Archive-name: diabetes/faq/part2
Posting-Frequency: biweekly
Last-modified: 24 December 2005

Changes: see part 1 of the FAQ for a list of changes to all parts.

------------------------------

Subject: READ THIS FIRST

Copyright 1993-2005 by Edward Reid. Re-use beyond the fair use provisions
of copyright law and convention requires the author's permission.

Advice given in m.h.d is *never* medical advice. That includes this FAQ.
Never substitute advice from the net for a physician's care. Diabetes is a
critical health topic and you should always consult your physician or
personally understand the ramifications before taking any therapeutic action
based on advice found here or elsewhere on the net.

------------------------------

Subject: Table of Contents

INTRODUCTION (found in all parts)
  READ THIS FIRST
  Table of Contents
GENERAL (found in part 1)
  Where's the FAQ?
  What's this newsgroup like?
  Abuse of the newsgroup
  The newsgroup charter
  Newsgroup posting guidelines
  What is glucose? What does "bG" mean?
  What are mmol/L? How do I convert between mmol/L and mg/dl?
  What is c-peptide? What do c-peptide levels mean?
  What's type 1 and type 2 diabetes?
  Is it OK to discuss diabetes insipidus here? What is it?
  How about discussing hypoglycemia?
  Helping with the diagnosis (DM or hypoglycemia) and waiting
  Exercise and insulin
BLOOD GLUCOSE MONITORING (found in part 2)
  How accurate is my meter?
  Ouch! The cost of blood glucose measurement strips hurts my wallet!
  What do meters cost?
  Comparing blood glucose meters
  How can I download data from my meter?
  I've heard of a non-invasive bG meter -- the Dream Beam?
  What's HbA1c and what's it mean?
  Why is interpreting HbA1c values tricky?
  Who determined the HbA1c reaction rates and the consequences?
  HbA1c by mail
  Why is my morning bg high? What are dawn phenomenon, rebound,
    and Somogyi effect?
TREATMENT (found in part 3)
  My diabetic father isn't taking care of himself. What can I do?
  Managing adolescence, including the adult forms
  So-and-so eats sugar! Isn't that poison for diabetics?
  Insulin nomenclature
  What is Humalog / LysPro / lispro / ultrafast insulin?
  Travelling with insulin
  Injectors: Syringe and lancet reuse and disposal
  Injectors: Pens
  Injectors: Jets
  Insulin pumps
  Type 1 cures -- beta cell implants
  Type 1 cures -- pancreas transplants
  Type 2 cures -- barely a dream
  What's a glycemic index? How can I get a GI table for foods?
  Should I take a chromium supplement?
  I beat my wife! (and other aspects of hypoglycemia) (not yet written)
  Does falling blood glucose feel like hypoglycemia?
  Alcohol and diabetes
  Necrobiosis lipoidica diabeticorum
  Has anybody heard of frozen shoulder (adhesive capsulitis)?
  Gastroparesis
  Extreme insulin resistance
  What is pycnogenol? Where and how is it sold?
  What claims do the sales pitches make for pycnogenol?
  What's the real published scientific knowledge about pycnogenol?
  How reliable is the literature cited by the pycnogenol ads?
  What's the bottom line on pycnogenol?
  Pycnogenol references
SOURCES (found in part 4)
  Online resources: diabetes-related newsgroups
  Online resources: diabetes-related mailing lists
  Online resources: commercial services
  Online resources: FTP
  Online resources: World Wide Web
  Online resources: other
  Where can I mail order XYZ?
  How can I contact the American Diabetes Association (ADA) ?
  How can I contact the Juvenile Diabetes Foundation (JDF) ?
  How can I contact the British Diabetic Association (BDA) ?
  How can I contact the Canadian Diabetes Association (CDA) ?
  What about diabetes organizations outside North America?
  How can I contact the United Network for Organ Sharing (UNOS)?
  Could you recommend some good reading?
  Could you recommend some good magazines?
RESEARCH (found in part 5)
  What is the DCCT? What are the results?
  More details about the DCCT
  DCCT philosophy: what did it really show?
  Is aspartame dangerous?
IN CLOSING  (found in all parts)
  Who did this?

------------------------------

Subject: How accurate is my meter?

bG (blood glucose) meters are not as accurate as the readings you get from
them imply. For example, you might think that 108 means 108 mg/dl, not 107 or
109. But in fact all meters made for home use have at least a 10-15% error
under ideal conditions. Thus you should interpret "108" as "probably between
100 and 120". (Similar considerations apply if you measure in units of
mmol/L.) This is a random error and will not be consistent from one
determination to the next. You cannot expect to get exactly the same reading
from two checks done one after the other, nor from two meters using the same
blood sample.

This is generally considered acceptable because variations in this range will
not make a major difference in treatment decisions. For example, the
difference between 100 and 120 may make no difference in how you treat
yourself, or at most might make a difference of one unit of insulin. With
present technology, more accurate meters would be much more expensive. This
expense is only justified in research work, where such accuracy might detect
small trends which could go undetected with less accurate measurements.

This discussion applies to ideal conditions. The error may be increased by
poor or missing calibration, temperatures outside the intended range,
outdated strips, improper technique, poor timing, insufficient sample size,
contamination, and probably other factors. Contamination is especially
serious since it can happen so easily and is likely to result in an overdose
of insulin. Glucose is found in fruits, juices, sodas, and many other foods.
Even a smidgen can seriously alter a reading.

When comparing meter readings with lab results, also note that plasma readings
are 15% higher than whole blood, and that capillary blood gives different
readings from venous blood.

Visually read strips are slightly less accurate than meters, with an error
rate around 20-25%.

For some meters, strips are available from manufacturers other than the meter
manufacturer. Some m.h.d. readers have compared the strips side-by-side and
found those from one manufacturer to read consistently lower than the strips
from another. The differences are not likely to make a significant difference
in your treatment, but are large enough to be noticeable and possibly
confusing. For this reason it is not a good idea to change strip
manufacturers without comparing the readings from one with the readings from
the other.

I've seen no such direct comparison of meters, but the possibility exists that
some meters might read consistently lower than others. Be careful when
changing meters.

By "error rate" I mean twice the standard deviation from the mean. An error
rate of 15% says that about 95% of the readings will be within 15% of the
actual value.

------------------------------

Subject: Ouch! The cost of blood glucose measurement strips hurts my wallet!

The cost of blood glucose measurement strips is a complex interaction
of R&D costs, manufacturing costs, marketing strategy, insurance
practices, and undoubtedly other factors. You can ask on the net if you
want; you'll get lots of comments but no answers.

There are a few of ways of reducing the cost of blood glucose
monitoring.

One is to seek out the best price for the strips; large stores such as
FEDCO often have good prices, as do some mail order suppliers (see mail
order section).

A second way is to choose a meter with lower cost strips. Your health
care team may be familiar with and prefer a particular meter, but it's
not likely that they considered cost in making their choice. If you
insist that you need a lower cost system, they should be willing to
work with you. All meters now on the market are adequately accurate for
home use.

A third way is to use visually read strips (Chemstrip bG and a couple of
lesser known brands) and cut them in half or even in thirds. Do the
cutting carefully with a pair of strong, *clean* scissors, and get the
strips back into the vial as quickly as possible. Some manufacturers
claim this procedure will cause problems, but those who have used the
technique report that it works well. Visually read strips are slightly
less accurate than meters. However, as of 1998, prices on visually read
strips are relatively high, and you will have to consider whether the
projected savings are worth the time to cut strips and the loss of the
convenience which meters give.

Do *not* cut strips when using them in meters. The results will be
totally incorrect.

Most discussion on m.h.d of the cost of blood glucose measurement strips
has centered on the US. I'm not sure why, though a good guess is that
differences in health care systems and national policies make this
issue more critical to the individual patient in the US. There is no
dearth of non-US participants on m.h.d.

------------------------------

Subject: What do meters cost?

The flip side of expensive blood glucose measurement strips is that
the manufacturers virtually (and sometimes literally) give away the
meters to hook you on their strips. Don't pay full price for a
meter; look for discounts, rebates, and giveaways. For example, as
of this writing I'm looking at a catalog that shows a Glucometer 3
for US$45, with a US$30 manufacturer's rebate *and* a US$30 trade-in
allowance if you already have a competing meter -- which means you
make US$15. There are similar deals on other meters.

But make sure you consider the cost of strips as well as the cost of
meters, and find out which your insurance will pay for. The most
fully featured meters, such as the One Touch II, don't have such
widely advertised deals, though you can probably find ways of
getting them at discount.

If you have insurance that pays for strips but not for the meter,
you should not have to pay anything for the meter. If it's worth the
time to you, call the meter manufacturers' customer service
departments or the mail order outfits (see "Where can I mail order
XYZ?" in part 4, Sources). They will find a way to get you the meter
for free.

As with strips, this discussion of costs applies to the US, and
there has been little discussion of meter costs outside the US on
m.h.d., probably because fewer tradeoffs are available in most
countries.

An Australian correspondent notes a much narrower choice and higher
cost of meters there, but subsidized (pardon, subsidised)
measurement strips.

In Britain, strips are covered by the National Health Service, but
meters may be expensive. However I've also heard of a limited-time
One Touch program providing a full refund for the meter if you
submit the strip wrappers. Likely other companies will compete.

Elsewhere? Please post. It's likely that the situation is continuing
to change rapidly, so if the cost of the meter is painful for you,
investigate other options before paying full price -- wherever you
live.

------------------------------

Subject: Comparing blood glucose meters

Here are three ways of getting a list of the specs for most currently
available meters.

1) Call Hospital Center Pharmacy in Boston, 1-800-824-2401 (US only).
They have a chart which they will gladly send you.

2) The ADA publishes a Buyer's Guide to Diabetes Products once a
year in the Resource Guide, a supplement to the January isue of
Diabetes Forecast. As of January 2000, the latest is the Resource
Guide 2000. The meters section lists meters and features in a table.
The ADA does not recommend one meter over another, but does include
some tips on choosing a meter.

3) The ADA has this same Buyer's Guide information online at

  http://diabetes.org/diabetesforecast/2000BuyersGuide/default.asp

This URL will change in future years.

The caveat is that you must be patient. The table is a huge scanned
graphic rather than text. It will take about ten minutes to download
all the graphics on the page on a good 28.8 modem connection, and
possibly much longer.

------------------------------

Subject: How can I download data from my meter?

You can get a cable to hook the One Touch II and Profile meters to a PC
from the meter manufacturer, LifeScan. The cable includes some
electronics, not just a cable, so you probably don't want to make your
own -- but if you do, check out the schematics at either of these
sites:

    http://www.sci.fi/~keytech/otcable.html
    http://www.geocities.com/SiliconValley/Haven/5371/indexe.html

In the US the cable is free (or nearly so -- some mhd readers report
being quoted a small fee). Elsewhere, LifeScan lets each international
office set its own policy on cable distribution, and some are charging
substantial fees. North American telephone numbers are:

    U.S.A.    1-800-227-8862
              +1 408 263 9789
    Canada    1-800-663-5521

LifeScan provides some software for downloading the data. The more
recent versions provide considerable additional analysis.

A wide variety of other software is available as of 1998. I can't keep
up with it. See Rick Mendosa's companion posting on software.

Most meter makers now offer some software to be used with their meters.
Third party software is more abundant for the One Touch meters because
LifeScan, unlike other makers, publishes the download protocol. You can
ask them to send you a copy of the specs, or download it from

   One Touch II:         ftp://vic.cc.purdue.edu/pub/lifescan.ot2
    One Touch Profile:    ftp://vic.cc.purdue.edu/pub/lifescan.pro

Since these are simple tty-oriented protocols, you can download the raw
data from your meter using a basic telecom program such as Kermit or
ZTerm.

I'll mention just one piece of software here. Vic Abell
<abe(AT)purdue.edu> has long provided a simple free DOS program to
download and analyze One Touch II and Profile data. Vic posts update
announcements to misc.health.diabetes and has been known to support his
program via the newsgroup. TOUCH2 interfaces to the RS-232 data port of
the One Touch, downloads the data on command, and provides a variety of
analytical displays. It's available in a couple of compressed forms via
anonymous ftp from vic.cc.purdue.edu in the /pub directory, or using a
web browser,

   ftp://vic.cc.purdue.edu/pub/

------------------------------

Subject: I've heard of a non-invasive bG meter -- the Dream Beam?

***The following information is incomplete, as another company has introduced
   a non-invasive meter for about $8000. It has been discussed in the
   newsgroup. Rumors of other non-invasive (and "non-evasive") meters abound.
   I won't be trying to keep this section up to date until the situation
   stabilizes. ***

There is at least one development project in hot pursuit of a bG monitor
which operates by shining light through flesh (through the thumbnail in one
case) and analyzing the light that passes through. Glucose doesn't affect
light much differently from many other substances in the body, so this is not
an easy task. Some field trials have been done, but the developers have a way
to go to reach acceptable accuracy. A successful product is far from
guaranteed, and may be several years away if it arrives at all.

One estimate is that such a meter might cost about US$1000. Assuming the
per-check cost is zero, this would pay for itself in 1-2 years for many
patients. Look for the insurance companies to throw up some roadblock to
achieving these savings, at least in the US.

------------------------------

Subject: What's HbA1c and what's it mean?

Hb = hemoglobin, the compound in the red blood cells that transports
oxygen. Hemoglobin occurs in several variants; the one which composes
about 90% of the total is known as hemoglobin A. A1c is a specific
subtype of hemoglobin A. The 1 is actually a subscript to the A, and
the c is a subscript to the 1. "Hemoglobin" is also spelled
"haemoglobin", depending on your geographic allegiance.

Glucose binds slowly to hemoglobin A, forming the A1c subtype. The
reverse reaction, or decomposition, proceeds relatively slowly, so any
buildup persists for roughly 4 weeks. Because of the reverse reaction,
the actual HbA1c level is strongly weighted toward the present. Some of
the HbA1c is also removed when erythrocytes (red blood cells) are
recycled after their normal lifetime of about 90-120 days. These
factors combine so that the HbA1c level represents the average bG level
of approximately the past 4 weeks, strongly weighted toward the most
recent 2 weeks. It is almost entirely insensitive to bG levels more
than 4 weeks previous.

In non-diabetic persons, the formation, decomposition and destruction of
HbA1c reach a steady state with about 3.0% to 6.5% of the hemoglobin
being the A1c subtype. Most diabetic individuals have a higher average
bG level than non-diabetics, resulting in a higher HbA1c level. The
actual HbA1c level can be used as an indicator of the average recent bG
level. This in turn indicates the possible level of glycation damage to
tissues, and thus of diabetic complications, if continued for years.

Interpreting HbA1c values can be tricky for several reasons. See the
following section for more details.

------------------------------

Subject: Why is interpreting HbA1c values tricky?

Interpreting HbA1c values is tricky for several reasons: differing lab
measurements, variation among individuals, and misapprehension of the
relevant timeframe.

First trick: several different lab measurements have been introduced
since 1980, measuring slightly different subtypes with different limits
for normal values and thus different interpretive scales.

A National Glycohemoglobin Standardization Program began in 1996,
sponsored by the American Diabetes Association and others. See
reference 1. This program certifies HbA1c assays which conform to the
method used in the DCCT. However, as of 1998 other versions are still
in use in many places, both in the US and elsewhere. When you get a lab
result, be sure to look at what the lab considers to be the normal
range. Most discussion of HbA1c values in m.h.d appears to be based on
the DCCT, where the normal range is approximately 3.0-6.1%. Caveat
lector. (See part 5, Research, of this FAQ for more information on the
DCCT, the Diabetes Control and Complications Trial.)

Second trick: HbA1c levels appear to vary by up to 1.0% among
individuals with the same average bG. See reference 2.

This is very recent research and its implications are not yet clear. The
actual reaction rates governing the formation of HbA1c may vary among
individuals. Some of the variation may be due to differences in
erythrocyte (red blood cell) survival times -- the rough 90-120 day
range noted earlier -- although other work limits this to a small part
of the total variation (see reference 5). Variations in the HbA1c
formation rate may or may not correlate with the rate of damage to
other tissues.

While we await further research, we can only say that differences of
1.0% from one individual to another may not be meaningful.

Although HbA1c varies among individuals with the same average bG, it is
very stable for any given individual. Thus a change of 1.0% in your own
HbA1c is definitely meaningful.

Third and final trick: most medical professionals have been given
incorrect information about the timeframe which HbA1c represents.
Even textbooks normally state the 90-120 day average, as does the
American Diabetes Association in its Position Statement on Tests of
Glycemia in Diabetes (see reference 1).

The longer estimate is based on the assumption that the conversion of
hemoglobin A to HbA1c is essentially irreversible. This was a
reasonable assumption before the reaction rates were actually measured.
See the following section for information about the research which
measured the reaction rates and simulated the consequences.

See the following section for the references mentioned above.

------------------------------

Subject: Who determined the HbA1c reaction rates and the consequences?

In the early 1980s, Henrik Mortensen and colleagues at Glostrup
University Hospital, in Denmark, measured the reaction rates in vitro.
Their results showed the assumption of irreversibility to be untrue. In
fact the reverse reaction (HbA1c to HbA and glucose) proceeds at about
1/8 the rate of the forward reaction, which is very far from
irreversible. Mortensen et alia also built a biokinetic model based on
the measurements, and validated the model by comparing its predictions
to actual patients. See references 3-5.

Among other things, Mortensen's work shows that after a change in
average bG level, the HbA1c level restabilizes after about 4 weeks.
This has several consequences. Clinically, the most important are
these:

First, the HbA1c is an exponentially weighted average of blood glucose
levels from the preceding 4 weeks, with the most recent 2 weeks being
by far the most important.

Second, measuring HbA1c less often than monthly results in unmonitored
gaps between measurements. To use HbA1c as a continuous monitoring
tool, you need to check it at least once a month.

Third, it is worthwhile checking the HbA1c of newly diagnosed patients
as often as once a week to determine the effectiveness of the newly
imposed treatment.

Reference 1: American Diabetes Association, Tests of Glycemia in
Diabetes, Diabetes Care 23:S80-S82, January 2000 Supplement 1.
This specific issue is no longer available online, but the most recent
version is available at http://diabetes.org/cpr/.

Reference 2: Kilpatrick ES, Maylor PW, Keevil BG:  Biological Variation
of Glycated Hemoglobin. Diabetes Care 21:261-264, February 1998.
Abstract available on the web at
http://care.diabetesjournals.org/cgi/content/abstract/21/2/261.

Reference 3: Mortensen HB, Christophersen C: Glucosylation of human
haemoglobin a in red blood cells studied in vitro. Kinetics of the
formation and dissociation of haemoglobin A1c. Clinica Chimica Acta
134:317-326, 15 November 1983.

Reference 4: Mortensen HB, Volund A, Christophersen C: Glucosylation of
human haemoglobin A. Dynamic variation in HbA1c described by a
biokinetic model. Clinica Chimica Acta 136:75-81, 16 January 1984.

Reference 5: Mortensen HB, Volund A: Application of a biokinetic model
for prediction and assessment of glycated haemoglobins in diabetic
patients. Scandinavian Journal of Clinical and Laboratory Investigation
48:595-602, October 1988.

------------------------------

Subject: HbA1c by mail

You may find it cheaper and/or more convenient to have your HbA1c
measurements done by mail -- and you collect the sample by fingerstick.

Diabetes Technologies provides a "Accu-Base A1c (tm) Glycohemoglobin
Testing System". The cost is $19.95 per kit plus S/H (I think it's $3.85
per order), which includes the laboratory analysis. All needed supplies
are provided, including postage to the lab. They normally ask for a
doctor's prescription before sending the kit -- not because it's
required but because they want to make sure to keep the doctors in the
loop. Unhappy doctors are not good for their business.

The procedure is simple: they provide a capillary tube already attached
to a clip. Stick your finger (using a one-use lancet they provide, if
you wish) and touch the end of the tube to the drop until the tube is
full -- a fraction of a second to a few seconds. Drop the tube into a
small vial with fluid in it (pre-filled) and shake for a few seconds.
Fill out a little paperwork. Pack the vial in a Biopack, padding and
package, all provided and even prestamped. Drop it in the mail. You
provide: writing pen, blood, tissue for the excess blood.

The lab analyzes the sample using HPLC (high performance liquid
chromotography). This is the same as the major labs use. In other words,
SmithKline takes an entire vial of blood and uses one drop.

Diabetes Technologies is in Thomasville, GA. Their phone number is
888-872-2443.

Express-Med used to make a kit which I used once, but they no longer
sell it.

Becton-Dickinson (BD) was advertising a HbA1c kit in 1998. However, the
last time I spoke with someone there, they were only distributing it
through health care organizations (such as HMOs) and plans for
individual sales were indefinite.

A personal note: I have used the Diabetes Technologies kit, and a
predecessor supplied by Diabetes Support Systems, since 1996. Without
this service, I probably would have had at most one HbA1c measurement
per year due to the cost and the inconvenience of visiting the lab or
doctor's office -- and I really needed the tests at times. I plan to
continue using the service.

(As of the start of 2003 there are some other options. I need to update
this section.)

------------------------------

Subject: Why is my morning bg high? What are dawn phenomenon, rebound,
           and Somogyi effect?

This section is written by Charles Coughran <ccoughran(AT)ucsd.edu>.

There are three main causes of high morning fasting bg. In decreasing order of
probability they are insufficient insulin, dawn phenomenon, and Somogyi
effect (aka rebound). Insufficient or waning insulin is simple. If the
effective duration of intermediate or long acting insulin ends sometime
during the night, the relative level of circulating insulin will be too low,
and your blood sugars will rise.

Dawn phenomenon refers to increased glucose production and insulin resistance
brought on by the release of counterregulatory hormones in the early morning
hours near waking. It happens in normal people as well as in diabetics; in
nondiabetics it shows up as measurably increased insulin secretion around
dawn. Dawn phenomenon is variable in strength both within the population and
over time in individuals. It can show up as either high fasting glucose
levels or an increased insulin requirement to cover breakfast compared to
equivalent meals at other times of day.

Somogyi effect refers to a rebound in bg after nocturnal hypoglycemia which
occurs during sleep with the patient not experiencing any symptoms. The
hypoglycemia triggers the release of counterregulatory hormones. Somogyi
effect appears to be less prevalent than previously thought. While it does
occur, some episodes of hyperglycemia following hypoglycemia are actually
waning insulin levels following an insulin peak with medium acting insulin.
This can be difficult to sort out.

The best way to sort it out is to test every couple of hours from bedtime to
morning.

    If your bg rises all, or much of the night, it is a lack of circulating
    insulin.

    If it is stable all night, but rises sharply sometime before you wake in
    the morning, it is dawn phenomenon.

    If your bg declines to the point of a hypoglycemic reaction, it is
    *possibly* Somogyi effect.

You may have to test on several nights to nail the problem. Once you have
figured out the problem you and your doctor can discuss changes in your
insulin regimen to correct it. The answer depends critically on your
particular circumstances.

Mayer Davidson, in _Diabetes Mellitus: Diagnosis and Treatment_ (p 252 in the
3rd edition) says that Somogyi effect rarely causes fasting hyperglycemia,
and cites studies.

------------------------------

Subject: Who did this?

Archive-name: diabetes/faq/part4
Posting-Frequency: biweekly
Last-modified: 30 April 2003

Changes: see part 1 of the FAQ for a list of changes to all parts.

------------------------------

Subject: READ THIS FIRST

Copyright 1993-2005 by Edward Reid. Re-use beyond the fair use provisions
of copyright law and convention requires the author's permission.

Advice given in m.h.d is *never* medical advice. That includes this FAQ.
Never substitute advice from the net for a physician's care. Diabetes is a
critical health topic and you should always consult your physician or
personally understand the ramifications before taking any therapeutic action
based on advice found here or elsewhere on the net.

------------------------------

Subject: Table of Contents

INTRODUCTION (found in all parts)
  READ THIS FIRST
  Table of Contents
GENERAL (found in part 1)
  Where's the FAQ?
  What's this newsgroup like?
  Abuse of the newsgroup
  The newsgroup charter
  Newsgroup posting guidelines
  What is glucose? What does "bG" mean?
  What are mmol/L? How do I convert between mmol/L and mg/dl?
  What is c-peptide? What do c-peptide levels mean?
  What's type 1 and type 2 diabetes?
  Is it OK to discuss diabetes insipidus here? What is it?
  How about discussing hypoglycemia?
  Helping with the diagnosis (DM or hypoglycemia) and waiting
  Exercise and insulin
BLOOD GLUCOSE MONITORING (found in part 2)
  How accurate is my meter?
  Ouch! The cost of blood glucose measurement strips hurts my wallet!
  What do meters cost?
  Comparing blood glucose meters
  How can I download data from my meter?
  I've heard of a non-invasive bG meter -- the Dream Beam?
  What's HbA1c and what's it mean?
  Why is interpreting HbA1c values tricky?
  Who determined the HbA1c reaction rates and the consequences?
  HbA1c by mail
  Why is my morning bg high? What are dawn phenomenon, rebound,
    and Somogyi effect?
TREATMENT (found in part 3)
  My diabetic father isn't taking care of himself. What can I do?
  Managing adolescence, including the adult forms
  So-and-so eats sugar! Isn't that poison for diabetics?
  Insulin nomenclature
  What is Humalog / LysPro / lispro / ultrafast insulin?
  Travelling with insulin
  Injectors: Syringe and lancet reuse and disposal
  Injectors: Pens
  Injectors: Jets
  Insulin pumps
  Type 1 cures -- beta cell implants
  Type 1 cures -- pancreas transplants
  Type 2 cures -- barely a dream
  What's a glycemic index? How can I get a GI table for foods?
  Should I take a chromium supplement?
  I beat my wife! (and other aspects of hypoglycemia) (not yet written)
  Does falling blood glucose feel like hypoglycemia?
  Alcohol and diabetes
  Necrobiosis lipoidica diabeticorum
  Has anybody heard of frozen shoulder (adhesive capsulitis)?
  Gastroparesis
  Extreme insulin resistance
  What is pycnogenol? Where and how is it sold?
  What claims do the sales pitches make for pycnogenol?
  What's the real published scientific knowledge about pycnogenol?
  How reliable is the literature cited by the pycnogenol ads?
  What's the bottom line on pycnogenol?
  Pycnogenol references
SOURCES (found in part 4)
  Online resources: diabetes-related newsgroups
  Online resources: diabetes-related mailing lists
  Online resources: commercial services
  Online resources: FTP
  Online resources: World Wide Web
  Online resources: other
  Where can I mail order XYZ?
  How can I contact the American Diabetes Association (ADA) ?
  How can I contact the Juvenile Diabetes Foundation (JDF) ?
  How can I contact the British Diabetic Association (BDA) ?
  How can I contact the Canadian Diabetes Association (CDA) ?
  What about diabetes organizations outside North America?
  How can I contact the United Network for Organ Sharing (UNOS)?
  Could you recommend some good reading?
  Could you recommend some good magazines?
RESEARCH (found in part 5)
  What is the DCCT? What are the results?
  More details about the DCCT
  DCCT philosophy: what did it really show?
  Is aspartame dangerous?
IN CLOSING  (found in all parts)
  Who did this?

------------------------------

Subject: Online resources: diabetes-related newsgroups

On the Usenet, the misc.health.diabetes newsgroup carries most of the
messages related to diabetes. Volume runs about 200-250 articles/day. Suppose
you obtained this FAQ by some method other than by reading m.h.d and you want
to participate. If you already have access to Usenet news, just subscribe to
misc.health.diabetes; the exact method depends on the software used at your
site, so you should inquire locally for details. If you do not have access to
Usenet news, inquire locally about obtaining such access. The key words are
"I want to participate in the Usenet newsgroup misc.health.diabetes". Usenet
is available at most colleges and universities, many companies, all of the
large commercial services (including Delphi, Netcom, America Online,
Compuserve, Prodigy), many smaller local services, most Freenet systems,
and many locally run BBSs. Some of these have selective news feeds, and you
will have to ask them to get misc.health.diabetes before you can subscribe
via their system.

m.h.d is not gatewayed to any mailing list, and to my knowledge is not
archived anywhere as such. However, DejaNews has all of Usenet from March
1995 to present online and available to the public, and plans to extend the
scope farther into the past. You can create a filter specifying only the
newsgroup you want, and then search for key words. See

   http://www.dejanews.com

Another newsgroup, alt.support.diabetes.kids, has a much smaller volume of
articles, about 2-3 per day. Being in the alt.* hierarchy of newsgroups, its
propagation is somewhat restricted compared to misc.health.diabetes. To
obtain access, follow the same instructions as for m.h.d, above.

Other Usenet newsgroups which might be relevant are

    rec.food and its subgroups
    the sci.med hierarchy
    the alt.support hierarchy, especially alt.support.diet
    bit.listserv.transplant (only available at sites that carry bit.* --
                             see the description below of the TRNSPLNT list)

------------------------------

Subject: Online resources: diabetes-related mailing lists

Several public electronic mailing lists have diabetes-related content. The
main alternative to a newsgroup is the DIABETIC list, which carries about
60-80 messages/day. Its charter is to be "a support and information group for
diabetics". The overall flavor and atmosphere are different from the m.h.d
newsgroup, so if you find that you are uncomfortable with one, try the other.
If you subscribe to the DIABETIC list, be prepared for the large volume of
messages. If you have not dealt with this volume of email before, it will be
quite disconcerting to see so many messages appear in your personal mailbox,
and I advise that you consider one of the following methods to avoid being
overwhelmed:

    -- set up a mailbox (aka userid, account, screen name) separate from
       your normal personal mailbox in which to receive the mailing list.
       You will have to ask locally whether this is possible on your system.
       You may also be able to use your mail program to filter mailing list
       messages into a separate mailbox.

    -- convert to the digest as soon as you have subscribed. The digest
       option collects messages into large postings called digests (a misuse
       of the word, as all messages are included in their entirety). This
       digest is sent daily, or when its size passes a limit (currently 2000
       lines). Convert to digest form by sending a message addressed to the
       listserv (see below) with a message body containing

           set diabetic mail digest

TYPE_ONE is a low to moderate volume mailing list for discussion of type 1
diabetes, intended primarily as a support group. It carries about 10
messages/day. There is no digest option. If you get any error messages from
"majordomo", be sure to write directly to the list owner,
jamyers(AT)netcom.com, as sometimes the software at netcom prevents him from
replying directly.

DIABETES-EHLB started as an Electronic HighLights Bulletin to distribute
information presented at the ADA conference in June 1996. It was carried
forward as a moderated mailing list. The moderator plans to try to keep
discussions focussed on specific topics.

TRNSPLNT is a low volume mailing list for discussion of organ transplants. It
carries about 10 messages/day. It is relevant to diabetes because
complications of diabetes often lead to kidney transplants. TRNSPLNT is
gatewayed with the newsgroup bit.listserv.transplant, which is available at
Usenet sites which carry the bit.* hierarchy of newsgroups.

DIABETES-NEWS is a one-way list provided by _Diabetes Interview_ magazine. It
provides a sample, one article per week, from the printed magazine. See the
section on "Could you recommend some good magazines?" for more information
about the printed magazine.

AUTOIMMUNE is a moderated, low volume list carrying technical information
about research on autoimmune disorders, including type 1 diabetes.

HYPO is a moderate volume mailing list for support and information on
hypoglycemia (as a medical condition as opposed to an insulin reaction).

To subscribe to the mailing list in the first column, send a message to the
email address in the second column (or to the alternate if given) containing
the command in the third column. Note that Firstname Lastname is your real
name, such as John Doe. The listserv software will use the email address in
your message header for your subscription. If you have trouble sending email
to the listserv, or if you receive no response, then you will need the help
of someone at your site.

  DIABETIC   listserv(AT)lehigh.edu     subscribe diabetic Firstname Lastname

  TYPE_ONE   listserv(AT)netcom.com     subscribe type_one

  DIABETES-EHLB
             listserv(AT)shrsys.hslc.org subscribe diabetes-ehlb Fstnm Lstnm

  TRNSPLNT   listserv(AT)wuvmd.bitnet   subscribe trnsplnt Firstname Lastname
             listserv(AT)wuvmd.wustl.edu

  DIABETES-NEWS
     diabetes-news-request(AT)lists.best.com    subscribe

  AUTOIMMUNE maiser(AT)ksg1.harvard.edu  Subscribe autoimmune_research

  HYPO       hypo-request(AT)iceblue.com.au  subscribe hypo

  NECROBIOSIS  necrobiosis-subscribe@yahoogroups.com [no command needed]
     web page: http://groups.yahoo.com/group/necrobiosis

For up to date information and more diabetes-related mailing lists, see
Rick Mendosa's Online Diabetes Resources FAQ at

  http://www.mendosa.com/faq.htm

------------------------------

Subject: Online resources: commercial services

Most of the information here comes from David Cohler <ar051(AT)lafn.org>, who
tried out all the online services and sent me his reviews. Thanks, David! I
don't have any information about commercial services in countries other than
the US.

CompuServe has a very active "Diabetes Forum." In many respects, it is the
single most comprehensive online resource for diabetics, featuring active
participation from several dozen countries, an extensive document library,
and an extensive software library. The moderators ("sysops") are quick to
pounce on misinformation and either correct it or delete it. No flaming
allowed. As of late 1995 the main drawback to CIS is price; even under a new
pricing policy, accessing the Diabetes Forum just 20 minutes a day could
result in charges of US$30 per month.

America Online has a diabetes support area. It is newer and smaller than
Compuserve's, but growing. The health forum has a number of information files
on diabetes which users can read and download. These files generally contain
good advice and some explanation, but not in-depth explanation.

Also on AOL, each Sunday evening at 8:30 Eastern Time (US) a diabetes support
group meets in a "private room" named "Diabetes". For more information, email
Jim Lewis <jblewis(AT)aol.com>.

Prodigy has a relatively small but active and very friendly support group
accessed by "jumping" to "Medical Support BB" and then selecting "diabetes"
as the bookmark configuration. The board is monitored by several CDEs.
Although there is some discussion of scientific research, etc., the
preponderance of posts concerns support for people having trouble with
self-management. This is an excellent place for newly-diagnosed diabetics who
still need a lot of basic information and emotional support. Moderated (no
flaming allowed).

Delphi has an active diabetes support forum, accessed by typing GO REL DIA.
Lisa Crawford <LISA_POOH(AT)delphi.com> is the host and forum manager.

Genie has a miniscule diabetes support area, configured as an RT ("Round
Table," Genie's term for BB). As of May 1995, traffic was at the rate of a
dozen posts per week.

------------------------------

Subject: Online resources: FTP

Demon Internet Services, a UK service provider, donated FTP space for
diabetes-related materials due to the urging and coordination of Ian
Preece <ianp(AT)darktower.com>. This cooperative endeavor was launched
with an empty directory in June 1994.

FTP has taken a back seat to the WWW. However, this site is one of the
very few soliciting donations as a cooperative endeavour.

Using the World Wide Web will be the easiest access to ftp for most new
users:

  ftp://ftp.demon.co.uk/pub/diabetes/

You can also use a traditional FTP program.

To submit material, upload it to the "incoming" directory. After making
a submission, send email to Ian Preece <ianp(AT)darktower.com> telling him
about the file you have submitted.

------------------------------

Subject: Online resources: World Wide Web

I list a few excellent starting points for diabetes information on the
web. The maintainers of these pages are putting a lot of effort into
providing good information and links to other sites, and I'm not going
to try to duplicate their work here.

One of the best starting points is Jeff Hitchcock's Children with
Diabetes. Don't judge Children with Diabetes by the title alone; it has
extensive links to diabetes information of all sorts and is by far the
most extensive compilation on diabetes that I've seen on the net.

   http://www.childrenwithdiabetes.com/

Rick Mendosa <mendosa(AT)cruzio.com> maintains a very extensive list of
online resources for diabetes, including many informational and
commercial web sites, and a list of BBSs. It is very likely the most
complete list available, and because it's simply a list, it is much
easier to read than sites with lots of complex internal links. Rick
also keeps one of the most thorough available lists of glycemic index
values for foods.

   http://www.mendosa.com

Another excellent compilation of links to diabetes-related web sites is
the Diabetes Monitor of the Midwest Diabetes Care Center. It's
maintained by William Quick and is exceptionally easy to navigate.

   http://www.diabetesmonitor.com

Yahoo has links on a huge variety of subjects, so if you want more than
just diabetes information you can shorten this URL:

   http://www.yahoo.com/Health/Diseases_and_Conditions/Diabetes

Ian Preece <ianp(AT)darktower.com> is maintaining a web site in
conjunction with the Demon FTP site described above:

   http://www.demon.co.uk/diabetic/

You can reach a WWW-formatted version of this FAQ via the URL

   http://www.faqs.org/faqs/diabetes/

or you can get the plain text by FTP from

   ftp://rtfm.mit.edu/pub/usenet/news.answers/diabetes/

The American Diabetes Association (ADA) has put its entire set of
Clinical Practice Recommendations online in full. For the most recent
version go to

   http://diabetes.org/cpr/

or start at the ADA home page and follow the link to "For Health Care
Professionals", then "Clinical Practice Recommendations".

Since these are oriented toward health care professionals, they provide
a wealth of detailed recommendations for actual health care practice.

Donald Lehn <dalehn@facstaff.wisc.edu> was probably the first to put a
server with diabetes information on the web. Lehn's Diabetes
Knowledgebase has been offline since August 1995, and is apparently
gone for good.

------------------------------

Subject: Online resources: other

Most online resources previously available via other means are now
available via the web. Since these are thoroughly cataloged by the best
of the diabetes web sites (see previous section on "Online resource:
World Wide Web), I've dropped this coverage from the FAQ.

------------------------------

Subject: Where can I mail order XYZ?

XYZ is most often blood glucose measurement strips, especially for those
who don't live near discount pharmacies and must pay cash for their
supplies. Mail order prices are not always lower than local prices.
Remember that there is an advantage to going to a single pharmacist for
all your drugs, if that pharmacist is knowledgeable about interactions
and tracks all the drugs you use. Adjustments will be slower if you mail
order. Never mail order unless you are certain about what you need.

That said, here are two starting points.

_Diabetes Forecast_ has a long advertising section, part of which is for
suppliers. Nowadays most list their web addresses in the ads. In
addition, each issue of _Diabetes Forecast_ contains a column
summarizing recommendations for ordering health supplies by mail.

Jeff Hitchcock's Children with Diabetes web site has links to quite a
list on suppliers with information online at
http://www.childrenwithdiabetes.com/d_06_900.htm.

I have removed the list formerly kept here because it was years out of
date and done better elsewhere. This leaves no information for those
outside the US, as the above links are mostly focused on US sources. In
the past, this has been much more of an issue in the US. However, web
search engines might be a great help -- googling "diabetes supplies
Australia", without the quotes, yields nearly a million hits. Just be
careful to evaluate what you find.

------------------------------

Subject: How can I contact the American Diabetes Association (ADA) ?

The ADA has local offices in many cities. Check your local phone book first.

To contact the national organization, call 1-800-232-3472 or +1 703 549 1500.
This will reach all departments. Or write

   American Diabetes Association
   1660 Duke Street
   Alexandria, VA 22314
   USA

The ADA offers aid to diabetic patients, books, and journals ranging
from general to research. All can be ordered by phone. They maintain
lists of physicians with special interest and/or training in diabetes.
New patients and their families needing advice are encouraged to call.
They may be able to help in dealing with bureaucratic problems.

The ADA is on the web at http://diabetes.org. The web site has a great
deal of useful information. It includes lists of ADA publications and
ordering information. One section that is particularly useful is the
ADA's Clinical Practice Recommendations, which are all online in full at

   http://diabetes.org/cpr/

or start at the ADA home page and follow the link to "For Health Care
Professionals", then "Clinical Practice Recommendations".

------------------------------

Subject: How can I contact the Juvenile Diabetes Foundation (JDF) ?

Check your phone book for a local office, or call 1-800-533-2873.

The JDF also has a web site at http://www.jdfcure.com/.

The JDF's motto is "finding a cure for diabetes", though apparently they only
mean for type 1 diabetes. They are rather obnoxious in their rejection of the
value of support and treatment other than a total cure. Despite this position,
the JDF in fact does a great deal of excellent support work.

------------------------------

Subject: How can I contact the British Diabetic Association (BDA) ?

    The British Diabetic Association
    10 Queen Anne Street
    London W1M 0BD
    Telephone 0171 323 1531  (+44 171 323 1531)
     CARELINE 0171 636 6112  for information about diabetes

The BDA produces a bi-monthly magazine for members called "Balance".
Membership is UKP 12 a year.

------------------------------

Subject: How can I contact the Canadian Diabetes Association (CDA) ?

The CDA has local offices in many cities. Check your local phone book first.

To contact the national organization, call +1 416 363 3373, or write

        Canadian Diabetes Association
        15 Toronto St, Suite 800
        Toronto, Ontario  M5C 2E3
        Canada

In Canada, call 1-800-847-SCAN.

The CDA is on the web at http://www.diabetes.ca.

The B.C. - Yukon Division of the CDA maintains an information center on the
Vancouver Freenet. It includes contact information for regional divisions of
the CDA. See the section "Online resources: other".

------------------------------

Subject: What about diabetes organizations outside North America?

I can't list them unless someone sends me the information.

Ian Preece <ianp(AT)darktower.com> has started a list, which now has
contact info for several European organizations, at

   http://www.demon.co.uk/diabetic/orgs.html

------------------------------

Subject: How can I contact the United Network for Organ Sharing (UNOS)?

UNOS (United Network of Organ Sharing) has a variety of information
concerning organ transplants and transplant centers. Contact UNOS at
(800)24-DONOR or +1 804 330 8602, or PO Box 13770, Richmond VA 23225, USA.

UNOS has a WWW page at

  http://www.unos.org

Email contact is Joel Newman <newmanjd(AT)comm5.unos.org>.

------------------------------

Subject: Could you recommend some good reading?

You mean to curl up with on the sofa? Oh, diabetes ... OK.

My favorite book is Mayer Davidson's _Diabetes Mellitus: Diagnosis and
Treatment_, published by Churchill Livingstone. Though written as a
medical text, anyone willing to plow through an occasional dense
passage and keep a dictionary handy will have no trouble with it. (See
below about medical terminology.) Being written mostly by a single
person, it is much better focussed than the "committee" books which are
so common. And it's very cheap for medical books, US$42 in 1994.

Charles Coughran <csc(AT)coast.ucsd.edu> recommends _Management of
Diabetes Mellitus Perspectives of Care Across the Lifespan_, Debra
Haire-Joshu (editor), Mosby Year Book, 1992, ISBN 0-8016-2429-0. He
says it's as good as Davidson, readable, and aimed at a similar audience.

Coughran and Steve Kirchoefer <swkirch(AT)chrisco.nrl.navy.mil> recommend
_Joslin's Diabetes Manual_ by Krall and Beaser, Lea&Febiger 1988.
Though somewhat lacking in consistency due to the multitude of writers,
it's a useful practical book. The Joslin Institute is world renowned
for its support of diabetes research and treatment, and the price of
the book is reasonable.

Coughran further recommends _Joslin's Diabetes Mellitus_ (13th edition)
edited by Kahn and Weir, 1994. It's another book that suffers a lack of
consistency due to the multitude of writers, but it contains a wealth
of information. Lots of biochemistry and also sections on practical
day-to-day management. Oriented toward health care professionals. 1068
pages, $125.

Terence Griffin <griffin(AT)cam.nist.gov> recommends _Therapy for
Diabetes Mellitus and Related Disorders_. It's a professional level book
compiled and published by the ADA, now in its second edition. See below
for ADA ordering information.

Steve Marschman <sc_marschman(AT)pnl.gov> recommends John Davidson's
_Clinical Diabetes Mellitus, A Problem-Oriented Approach_ (2nd
edition), published by Thieme Medical Publications, New York. Written
from a care-giver's perspective, it is an excellent technical resource
book with medical descriptions of diabetes mellitus, diagnosis,
treatment, complications, and concomitant problems. Price about US$150,
but often available used for much less. (As far as I know, the two
Davidsons, Mayer and John, are not related.)

The American Diabetes Association publishes a number of books with
basic diabetes information of various sorts -- self care, diet,
recipes, etc. Deb Martinson <llama(AT)drizzle.com> especially recommends
_The ADA Complete Guide to Diabetes_, about $6 in paperback and
published in 1996.  See the ADA's web site at

  http://www.diabetes.org

or use the phone numbers or address in the following section.

Any university library will have a large number of books on diabetes,
and they will be grouped together on the shelves. Go and browse. The
books mentioned above can be found in most university libraries.

The rest of what I have to talk about is periodicals. See the next
topic.

------------------------------

Subject: Could you recommend some good magazines?

_Diabetes Interview_ is a popular monthly tabloid with a variety of
news stories, interviews, and lots and lots of advertising. It's run by
a journalist, Scott King, and it shows. Authority, to this publication,
always lies in people they talk to. They don't appear to read
scientific or medical literature as the basis or support for stories.
They do publish research summaries, but these are at the newswire level
with no apparent critical reading. No critical commentary accompanies
interviews.

Publisher Scott King has pursued some valuable projects, such as
organizing letter-writing to Ann Landers after she tried to shove
dining-out diabetics into the closet -- Landers published King's own
excellent letter. He has certainly advanced the cause of open
discussion of diabetes in general. But _Diabetes Interview_ has been
sidetracked needlessly at times, such as by allocating seriously
inordinate abounts of space and attention to minor issues such as the
animal/human insulin debate. They also regularly run a paid
advertisement for an herbal product which claims to "restore pancreatic
function" -- probably an illegal claim in the US.

_Diabetes Interview_ offers a sample (one article per week) as an
electronic mailing list and many articles on their web site. See the
section on "Online resources: diabetes-related mailing lists" for
information on the mailing list.

_Diabetes Interview_ subscription information: one year, US$20 in the
US, US$31 in CA and MX, $46 in other countries. Cancel after the first
issue if you don't like it

   Diabetes Interview
   3715 Balboa Street
   San Francisco, CA 94121
   http://www.diabetesworld.com
   phone: +1 415 387 4002
              US 800-234-1218

_Diabetes Self-Management_ is a bimonthly magazine containing generally
detailed articles oriented to helping patients with techniques and
skills -- diet, exercise, treatment, outlook, etc. They go into areas
not often covered, such as a recent series by Ann Williams on
low-vision tools and coping skills. The writers tend to have in-depth
knowledge of their fields and the information is well balanced. The
magazine emphasizes practical skills over basic knowledge, and spreads
itself a bit thin by trying to address itself to all diabetics. Those
who dislike Diabetes Forecast will find similar coverage in Diabetes
Self-Management but with more depth and aimed at a better educated
audience.

The _Diabetes Self-Management_ web site has full text of numerous
articles from back issues, about two articles from each issue.

_Diabetes Self-Management_ costs US$14/yr, or US$36/yr outside the US
and CA. To order, mail payment, call, or look on their website. They'll
send a free trial issue if you wish.

   Diabetes Self-Management
   P. O. Box 52890
   Boulder, CO 80322
   http://www.diabetes-self-mgmt.com/
   US phone: 800-234-0923

Everything else I have to recommend comes from the ADA (see section on
ADA).

Here's what the ADA says about its own publications:

    _Diabetes_ -- the world's most-cited journal of basic diabetes
    research brings you the latest findings from the world's top
    scientists.

    _Diabetes Care_ -- the premier journal of clinical diabetes research
    and treatment. _Diabetes Care_ keeps you current with original
    research reports, commentaries, and reviews.

    _Diabetes Reviews_ (in memoriam) -- the comprehensive but concise
    review articles in ADA's newest journal are a convenient way for
    the busy clinician to keep up-to-date on what's truly new in
    research. Sadly, Diabetes Reviews ceased publication at the end
    of 1999, a victim of the fact that medical libraries face a
    crisis of rising subscription costs but flat budgets. The seven
    volumes which were published are still an invaluable resource.

    _Diabetes Spectrum_ -- translates research into practice for nurses,
    dietitians, and other health-care professionals involved in patient
    education and counseling.

    _Clinical Diabetes_ -- For the primary-care physician as well as
    other health-care professionals, this newsletter offers articles
    and abstracts highlighting recent advances in diabetes treatment.

    _Diabetes Forecast_ -- ADA's magazine for patients and their
    families features advice on diet, exercise, and other lifestyle
    changes, plus the latest developments in new technology and
    research. It is a valuable tool for patient education.

Now for my own opinions.

_Diabetes Forecast_ is the mass market magazine, intended to be readable
by all literate diabetics. For US$24/year you can hardly go wrong. The
biggest problem with DF is that in the attempt to reach almost
everyone, it aims at a very low reading level -- perhaps eighth grade,
I'm not sure. This makes it tonally annoying and dilutes the
information content. Still, it contains useful information and is
excellent at promoting self-care and a positive self-image for persons
with diabetes.

_Diabetes Forecast_ is also one of the best places to look for
advertisements for diabetes-related products.

The remaining journals are of interest if you want to follow what is new
and under investigation in medical practice and research. The journals
vary in difficulty of reading. Though some knowledge of statistics and
chemistry helps, a general acquaintance with scientific method is
perhaps more important, and a smattering of familiarity with medical
terminology helps most. Luckily, medical terminology is basically
simple -- it mostly consists of putting together roots and affixes to
make specific terms. Learn a few dozen roots and you can make out most
of it. Try to have a dictionary at hand at first.

_Diabetes Care_ publishes papers on clinical research. I find many of
the papers to be interesting and applicable to my own management. With
the demise of _Diabetes Reviews_, DC plans to publish more review
articles as well.

_Diabetes_ is the ADA's journal primarily for basic research. Some of
the articles are interesting, but they run much more toward
biochemistry and mechanisms of metabolism. As important as basic
research is, few of the reports say little of value directly to
patients.

_Diabetes Spectrum_ is oriented toward health care practitioners.
It consists of reprints of important articles (sometimes several on
a topic) and summaries of related articles, plus original
commentaries from other authors. As such, it provides a broad
overview of topics for readers who don't have time to track down
lots of separate original articles. If you only have time to read
one technical publication, _Diabetes Spectrum_ is perhaps the best
choice -- the only competitor for this place is _Clinical Diabetes_.

_Clinical Diabetes_ contains focussed articles written specifically
for health care practitioners. It's very readable and to to the
point, another good choice for those wanting higher level reading
but not research articles.

The ADA has price structures for regular members and professional
members. A basic regular membership with _Diabetes Forecast_ is
US$24/year (in the US, $41.93 in Canada, $39 in Mexico, $49 elsewhere,
all in US funds). The other ADA journals will set you back about
US$90-120/year apiece. A professional membership allows you to pick and
choose journals at the listed rates; if you plan to get either
_Diabetes_ or _Diabetes Care_ you should enter a professional
membership to get the best prices. Credentials are not required for a
professional membership.

The ADA takes checks, money orders, Visa, Mastercard and American
Excess. Unfortunately, orders of books from outside the USA incur an
additional $15 shipping charge.

You can get more ADA info online, including an online catalog for all
books and magazines, at

  http://www.diabetes.org

Phone numbers

   1-800-232-3472
   +1 703 549 1500
   +1 703 549 6995 fax

or write

   American Diabetes Association
   Subscription Services
   1660 Duke Street
   Alexandria, VA 22314
   USA

------------------------------

Subject: Who did this?

Archive-name: diabetes/faq/part5
Posting-Frequency: biweekly
Last-modified: 14 July 2005

Changes: see part 1 of the FAQ for a list of changes to all parts.

------------------------------

Subject: READ THIS FIRST

Copyright 1993-2005 by Edward Reid. Re-use beyond the fair use provisions
of copyright law and convention requires the author's permission.

Advice given in m.h.d is *never* medical advice. That includes this FAQ.
Never substitute advice from the net for a physician's care. Diabetes is a
critical health topic and you should always consult your physician or
personally understand the ramifications before taking any therapeutic action
based on advice found here or elsewhere on the net.

------------------------------

Subject: Table of Contents

INTRODUCTION (found in all parts)
  READ THIS FIRST
  Table of Contents
GENERAL (found in part 1)
  Where's the FAQ?
  What's this newsgroup like?
  Abuse of the newsgroup
  The newsgroup charter
  Newsgroup posting guidelines
  What is glucose? What does "bG" mean?
  What are mmol/L? How do I convert between mmol/L and mg/dl?
  What is c-peptide? What do c-peptide levels mean?
  What's type 1 and type 2 diabetes?
  Is it OK to discuss diabetes insipidus here? What is it?
  How about discussing hypoglycemia?
  Helping with the diagnosis (DM or hypoglycemia) and waiting
  Exercise and insulin
BLOOD GLUCOSE MONITORING (found in part 2)
  How accurate is my meter?
  Ouch! The cost of blood glucose measurement strips hurts my wallet!
  What do meters cost?
  Comparing blood glucose meters
  How can I download data from my meter?
  I've heard of a non-invasive bG meter -- the Dream Beam?
  What's HbA1c and what's it mean?
  Why is interpreting HbA1c values tricky?
  Who determined the HbA1c reaction rates and the consequences?
  HbA1c by mail
  Why is my morning bg high? What are dawn phenomenon, rebound,
    and Somogyi effect?
TREATMENT (found in part 3)
  My diabetic father isn't taking care of himself. What can I do?
  Managing adolescence, including the adult forms
  So-and-so eats sugar! Isn't that poison for diabetics?
  Insulin nomenclature
  What is Humalog / LysPro / lispro / ultrafast insulin?
  Travelling with insulin
  Injectors: Syringe and lancet reuse and disposal
  Injectors: Pens
  Injectors: Jets
  Insulin pumps
  Type 1 cures -- beta cell implants
  Type 1 cures -- pancreas transplants
  Type 2 cures -- barely a dream
  What's a glycemic index? How can I get a GI table for foods?
  Should I take a chromium supplement?
  I beat my wife! (and other aspects of hypoglycemia) (not yet written)
  Does falling blood glucose feel like hypoglycemia?
  Alcohol and diabetes
  Necrobiosis lipoidica diabeticorum
  Has anybody heard of frozen shoulder (adhesive capsulitis)?
  Gastroparesis
  Extreme insulin resistance
  What is pycnogenol? Where and how is it sold?
  What claims do the sales pitches make for pycnogenol?
  What's the real published scientific knowledge about pycnogenol?
  How reliable is the literature cited by the pycnogenol ads?
  What's the bottom line on pycnogenol?
  Pycnogenol references
SOURCES (found in part 4)
  Online resources: diabetes-related newsgroups
  Online resources: diabetes-related mailing lists
  Online resources: commercial services
  Online resources: FTP
  Online resources: World Wide Web
  Online resources: other
  Where can I mail order XYZ?
  How can I contact the American Diabetes Association (ADA) ?
  How can I contact the Juvenile Diabetes Foundation (JDF) ?
  How can I contact the British Diabetic Association (BDA) ?
  How can I contact the Canadian Diabetes Association (CDA) ?
  What about diabetes organizations outside North America?
  How can I contact the United Network for Organ Sharing (UNOS)?
  Could you recommend some good reading?
  Could you recommend some good magazines?
RESEARCH (found in part 5)
  What is the DCCT? What are the results?
  More details about the DCCT
  DCCT philosophy: what did it really show?
  Is aspartame dangerous?
IN CLOSING  (found in all parts)
  Who did this?

------------------------------

Subject: What is the DCCT? What are the results?

The Diabetes Control and Complications Trial was a large multi-center
trial involving over 1400 volunteer patients with type 1 diabetes. It
began in 1983, ramped up to full speed by 1989, and ended early in 1993
when the investigators felt the results were clear. The volunteers were
all undergoing "standard" treatment when they were recruited, meaning
one or two injections per day. They were randomly assigned to two
groups. One group continued as before. The other group received
intensive treatment aimed at achieving blood glucose (bG) profiles as
close as possible to normal. The intensive treatment involved multiple
bG checks per day, multiple injections and/or an insulin pump, and
access to and regular consultation with a team of treatment experts.

It is particularly important to note that intensive treatment was
defined as a collaborative effort involving the patient and a skilled
team of health care professionals. It was not defined by particular
techniques, although certain techniques were typically used. The
frequent consultations and availability of a professional team were
critical components of intensive therapy.

The results show that the intensive treatment group did indeed achieve
bG levels closer to normal, and that they experienced far fewer
diabetic complications though also more hypoglycemia. In particular,
patients who maintained HbA1c levels around 7% appear to be much better
off than those whose HbA1c hovers around 9%. (See caveats in the
section on HbA1c.) Though it is not possible to separate the effects of
all the aspects of the intensive treatment, it is reasonable to believe
that lowering average bG may be effective even in isolation from the
other aspects of the intensive treatment. In its position statement,
the ADA says

   Patients should aim for the best level of glucose control they can
   achieve without placing themselves at undue risk for hypoglycemia or
   other hazards associated with tight control.

Though type 2 patients were not included in the study, it is generally
believed that the results showing the benefits of tight control apply
to type 2 patients as well.

The entire position statement was published in most of the ADA's
publications (see "could you recommend some good reading") in the
summer and fall of 1993.

The formal report detailing the results was published in The New England
Journal of Medicine, aka NEJM, of September 30,1993 (v 329 pp 977-986).
The following discussion is based on that article.

Several DCCT subjects participate in m.h.d and are willing to answer
questions related to the personal aspects of DCCT participation.

------------------------------

Subject: More details about the DCCT

The study placed subjects into two cohorts, primary prevention or
secondary intervention, depending on duration of diabetes and existing
complications -- the primary prevention cohort were those with
essentially no complications.

Specifically: all subjects met these criteria:

    Insulin dependent as evidenced by deficient C-peptide secretion
    Age 13 to 39 years at entry to the study
    No hypertension, hypercholesterolemia, severe diabetic complications,
        or other severe medical conditions
    Meet the criteria for one of the cohorts

and were separated into the two cohorts by these criteria:

                              Primary          Secondary
                             Prevention       Intervention
                              Cohort            Cohort

    Duration of IDDM        1-5 yrs           1-15 yrs
    Retinopathy             none detectable   very mild to moderate
                                                  nonproliferative
    Urinary albumin         < 40 mg / 24 hr   < 200 mg / 24 hr

Within each cohort, the subjects were randomly assigned to either
conventional therapy or intensive therapy. Thus the study compared
intensive to conventional therapy in two different cohorts. The two
questions the study was mainly designed to answer were

  1) Will intensive therapy prevent the development of diabetic
     retinopathy in patients with no retinopathy (primary
     prevention), and
  2) Will intensive therapy affect the progression of early
     retinopathy (secondary intervention)?

Conventional therapy included one or two injections per day, daily self
monitoring of blood or urine glucose, education, quarterly
consultations, and intensive therapy during pregnancy. Intensive
therapy included three or more daily injections or an insulin pump, bG
monitoring at least 4x/day, adjustment of insulin dosage for bG level
and food and exercise, monthly personal consultations and more frequent
phone consultations.

To simplify a lot, the DCCT showed the following changes in the
intensive therapy groups compared to the conventional therapy groups.
Note that '-' shows a decrease, '+' shows an increase, in the number of
patients affected. Patients were judged as affected or not based on
binary criteria, so the results only say how many subjects were
affected, not how severely those subjects were affected.

Intensive therapy compared to conventional therapy:

                                Primary                    Secondary
  Complication                 Prevention    Combined     Intervention
  ------------                 ----------    --------     ------------
  Retinopathy(*)                 - 75%                       - 55%
  Nephropathy(*)                 - 35%                       - 45%
  Neuropathy(*)                  - 70%                       - 55%
  Hypoglycemia(*)                              +200%
  Weight gain(*)                               + 33%
  Hypercholesterolemia(*)                      - 35%

(*) This brief table begs many questions about what exactly was
measured and how. For more details, read the paper.

There were no detectable differences on several measures:

  Macrovascular disease
  Mortality
  Changes in neuropsychological function
    (a feared result of severe hypoglycemia)
  Quality of life (based on a questionnaire)

Some limitations of the study: type 1 only, patients young and with
short duration (under 15 years) of diabetes, and short duration of the
study (5-9 years). Measured only number of subjects affected according
to binary criteria, not by measurement of severity of complications.
Excluded patients who already had severe complications and who thus
might benefit the most. The difference between the groups increased
during the study, but there is no proof that the difference would
continue to increase with time.

It is tempting to extrapolate the results to all diabetic patients --
all types, ages, and durations -- and there is at least some support
for doing so. However, the DCCT by itself does not show results for
type 2 patients, older patients, patients who have had diabetes for
many years, or those who already have severe complications. On the
other hand, a different group of subjects might shows differences in
areas such as mortality and macrovascular disease, where the young DCCT
cohorts simply did not have significantly measurable incidence. The
DCCT subjects are being tracked in a followup study which may shed
light on some of the unanswered questions.

Secondary analysis of the data indicates that retinopathy decreases with
decreasing HbA1c. This measure was not part of the study design and is
more difficult to interpret, but still shows clearly a correlation
between HbA1c and retinopathy.

------------------------------

Subject: DCCT philosophy: what did it really show?

It is often stated that the DCCT proved that tight control or lowered
HbA1c reduces complications. This is not the case. The controlled
variable in the DCCT was intensive vs conventional therapy, and
intensive therapy was defined by several factors including a team of
skilled health care professionals acting in partnership with the
patient. The results show that intensive therapy results in both
lowered HbA1c and fewer complications, but do not show that one causes
the other. The lead authors provide a good summary of this point in a
followup (NEJM 330:642, March 3, 1994):

    We want to stress that the most valid interpretation of the trial
    is that intensive therapy, with the **goal** of achieving blood
    glucose concentrations as close to the nondiabetic range as
    possible, delays the onset and slows the progression of long-term
    diabetic complications. The secondary analyses support the notion
    that lower glycosylated hemoglobin values are associated with a
    lower risk of progression of retinopathy, but they do not prove
    that hyperglycemia in itself causes retinopathy. [emphasis added]

Many of us believe, and believed before the DCCT, that actually
achieving good control aids our health. The DCCT adds weight to this
case but does not prove the point.

------------------------------

Subject: Is aspartame dangerous?

In short, no, except for phenylketonurics.

Aspartame is one of the most intensively studied food additives ever,
and the overwhelming scientific evidence is that it poses no danger.

The many claims of harm are all either anecdotal and not supported by
adequate observation, or are based on serious lack of understanding of
how to demonstrate facts scientifically. One of the most egregious is
the claim that studies with aspartame in capsules are invalid and that
it's only dangerous in solution. But d'oh -- if you administer
aspartame in solution, the patient will know whether he/she is getting
aspartame or not. This unblinds the experiment. Refer to Reid's Third
Law: Never Underestimate the Power of Suggestion.

An good set of links to web pages on aspartame is at
http://urbanlegends.about.com/library/blasp3.htm. (Unfortunately the
links open framed by about.com's heading, an unfair practice eschewed
by the vast majority of web sites. Ten demerits for about.com.)

The well known low-calorie sweeteners are pretty much all safe:
cyclamates, saccharin, aspartame, acesulfame, sucralose. Yes, even
cyclamates and saccharin -- the studies which resulted in their banning
turned out to be non-reproducible. I don't list stevia because it has
not been adequately studied, but I know of no significant indications
of danger.

If you don't like a given sweetener, try another. If you think you
respond badly in some way to a sweetener, try another. But unless you
have at least a heterozygous gene for phenylketonuria, it's unlikely
that you'll have a verifiable response to aspartame.

------------------------------

Subject: Who did this?

Archive-name: diabetes/faq/part3
Posting-Frequency: biweekly
Last-modified: 15 October 2002

Changes: see part 1 of the FAQ for a list of changes to all parts.

------------------------------

Subject: READ THIS FIRST

Copyright 1993-2005 by Edward Reid. Re-use beyond the fair use provisions
of copyright law and convention requires the author's permission.

Advice given in m.h.d is *never* medical advice. That includes this FAQ.
Never substitute advice from the net for a physician's care. Diabetes is a
critical health topic and you should always consult your physician or
personally understand the ramifications before taking any therapeutic action
based on advice found here or elsewhere on the net.

------------------------------

Subject: Table of Contents

INTRODUCTION (found in all parts)
  READ THIS FIRST
  Table of Contents
GENERAL (found in part 1)
  Where's the FAQ?
  What's this newsgroup like?
  Abuse of the newsgroup
  The newsgroup charter
  Newsgroup posting guidelines
  What is glucose? What does "bG" mean?
  What are mmol/L? How do I convert between mmol/L and mg/dl?
  What is c-peptide? What do c-peptide levels mean?
  What's type 1 and type 2 diabetes?
  Is it OK to discuss diabetes insipidus here? What is it?
  How about discussing hypoglycemia?
  Helping with the diagnosis (DM or hypoglycemia) and waiting
  Exercise and insulin
BLOOD GLUCOSE MONITORING (found in part 2)
  How accurate is my meter?
  Ouch! The cost of blood glucose measurement strips hurts my wallet!
  What do meters cost?
  Comparing blood glucose meters
  How can I download data from my meter?
  I've heard of a non-invasive bG meter -- the Dream Beam?
  What's HbA1c and what's it mean?
  Why is interpreting HbA1c values tricky?
  Who determined the HbA1c reaction rates and the consequences?
  HbA1c by mail
  Why is my morning bg high? What are dawn phenomenon, rebound,
    and Somogyi effect?
TREATMENT (found in part 3)
  My diabetic father isn't taking care of himself. What can I do?
  Managing adolescence, including the adult forms
  So-and-so eats sugar! Isn't that poison for diabetics?
  Insulin nomenclature
  What is Humalog / LysPro / lispro / ultrafast insulin?
  Travelling with insulin
  Injectors: Syringe and lancet reuse and disposal
  Injectors: Pens
  Injectors: Jets
  Insulin pumps
  Type 1 cures -- beta cell implants
  Type 1 cures -- pancreas transplants
  Type 2 cures -- barely a dream
  What's a glycemic index? How can I get a GI table for foods?
  Should I take a chromium supplement?
  I beat my wife! (and other aspects of hypoglycemia) (not yet written)
  Does falling blood glucose feel like hypoglycemia?
  Alcohol and diabetes
  Necrobiosis lipoidica diabeticorum
  Has anybody heard of frozen shoulder (adhesive capsulitis)?
  Gastroparesis
  Extreme insulin resistance
  What is pycnogenol? Where and how is it sold?
  What claims do the sales pitches make for pycnogenol?
  What's the real published scientific knowledge about pycnogenol?
  How reliable is the literature cited by the pycnogenol ads?
  What's the bottom line on pycnogenol?
  Pycnogenol references
SOURCES (found in part 4)
  Online resources: diabetes-related newsgroups
  Online resources: diabetes-related mailing lists
  Online resources: commercial services
  Online resources: FTP
  Online resources: World Wide Web
  Online resources: other
  Where can I mail order XYZ?
  How can I contact the American Diabetes Association (ADA) ?
  How can I contact the Juvenile Diabetes Foundation (JDF) ?
  How can I contact the British Diabetic Association (BDA) ?
  How can I contact the Canadian Diabetes Association (CDA) ?
  What about diabetes organizations outside North America?
  How can I contact the United Network for Organ Sharing (UNOS)?
  Could you recommend some good reading?
  Could you recommend some good magazines?
RESEARCH (found in part 5)
  What is the DCCT? What are the results?
  More details about the DCCT
  DCCT philosophy: what did it really show?
  Is aspartame dangerous?
IN CLOSING  (found in all parts)
  Who did this?

------------------------------

Subject: My diabetic father isn't taking care of himself. What can I do?

We'll assume your father has type 2 diabetes. See separate section for
definition of types.

Type 2 diabetics, and those who care for them, are in a difficult situation.
Type 2 strikes late in life, so personal habits and patterns are already
formed and solidly engrained. Yet in most cases those habits and patterns are
exactly what must be changed if a newly-diagnosed diabetic is to care
properly for his or her health. This is a difficult psychological problem.

The cornerstones for treating type 2 diabetes are exercise, weight control,
and diet. A high percentage of type 2 patients who apply these therapies
assiduously can control the disease with these therapies alone, without
insulin or oral hypoglycemic drugs. Naturally these are also some of the most
difficult aspects of life to change. There can be no single or simple answer
of how to help or encourage a particular individual find a combination of
therapies which not only controls the disease but also is psychologically
acceptable and which can be incorporated as a lifetime pattern. Helping
depends on knowing the individual's habits, patterns, motivations, desires,
likes and dislikes, and working with all the existing conditions and
everything brought forward from past life.

Doctors and other health care professionals have a choice in treating
patients with type 2 diabetes. They can prescribe drugs (oral hypoglycemics)
and insulin, or they can try to get their patients to make the difficult
lifestyle changes described above. (Many patients need both.) The latter
effort is time consuming and often frustrating, as doctors too often see
patients failing to make any change at all.

Friends and family can help by learning about type 2 diabetes, and doing what
you can to encourage your loved one to make diet and lifestyle changes. If
this supports the plan a treatment team is urging the patient to follow, you
will add your support for difficult changes. If the doctor (or the whole
treatment team) falls down on the educational and motivational structure, you
can fill in some of the gaps. Your effort is well spent in either case.

In particular, if a doctor has left the impression that drugs and insulin are
the only treatments, make sure to counter that impression with information
about the value of exercise, diet, and weight control.

At the same time, it's important to remember that needing oral hypoglycemics
and/or insulin injections as additional tools isn't failure. On the contrary,
a patient who's been actively involved in self treatment already has an
excellent chance of using these additional tools successfully. Those who have
learned to use the exercise - weight control - diet triumvirate will also be
able to utilize insulin and oral drugs as additional treatments when needed.
Choose the appropriate tools and use them effectively.

These treatment choices can interact in positive ways as well. Bringing blood
glucose under control often increases the body's sensitivity to insulin. So
ironically, using insulin may decrease the need for insulin. This is a
positive change which can then be reinforced by the other, interacting
treatments.

You will need far more information than is appropriate for a Usenet FAQ
panel. As a start, call the ADA (see ADA section), get a subscription to
_Diabetes Forecast_ (see journals), and visit a university library and browse
in the diabetes section in the stacks.

Beyond the generalizations above, a few specifics are usually of value:

   Set a good example in your own life. Exercise and eat a good diet.
   The recommendations for diabetics are healthy choices for anyone.

   Share your example. Serve a tasty, low-fat diet to family and friends
   when they are your guests.

   Suggest joint activities. Suggest a walk instead of watching a
   ball game.

   Make sure your diet and activities are visibly enjoyable so your
   guests will accept your invitiation to join you.

------------------------------

Subject: Managing adolescence, including the adult forms

Adolescents have special problems in managing diabetes. These include a
variety of physiological problems related to puberty and rapid growth, social
problems related to growing up and the general social pressures of adolescent
life, and the psychological turmoil caused by the expectations of others. I'm
here today to talk about (hey, hold the eggs and tomatoes) expectations.

Actually, this all applies to adults as well, though the subtle points may
differ.

The most important thing to remember, for the adolescent, the parent, and the
health care provider, is

              All Blood Glucose Measurements Are Good.

              There Are No Bad Blood Glucose Readings.

If that doesn't sound right, then please take two steps. First, learn why it
is true. Then chant it like a mantra until you internalize it, so that you
never give off the slightest vibes to the contrary.

Why is it true?

There are two kinds of adolescents (to simplify life enormously): those who
rebel and those who want to please. Ironically, the rebellious are probably
easier to deal with in treating diabetes. "So my blood sugar is 350, so
what?" Bad? No, that's good: you know what's going on, and so does your
child. The point of blood glucose measurement is to respond -- not to be good
or bad -- and only with an accurate report can you and the patient respond.

  [Compulsory digression: 350 mg/dl = 20.0 mmol/L.]

Look what can happen to the eager-to-please child:

   Child: My blood sugar is 350.
   Adult: Oh, that's awful! You must try to be better!

      [next time:]

   Child: My blood sugar is ... um [to self: I must be good] 140 ...
   Adult: Oh, that's great!

In short order, the log book looks great but the HbA1c doesn't jibe.

This all happens with the best of intentions from all parties. The child is
trying to please, and is behaving in exactly the ways that elicit approval.
The adult is trying to care for the child's health in the most natural ways.
And the result is one that neither desires.

Thus the positive mantra to replace the half-negative one above:

              All Blood Glucose Measurements Are Good.

           Responding To Blood Glucose Readings Is Good.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

An excellent article entitled "Insulin Therapy in the Last Decade: A
Pediatric Perspective", by Julio Santiago, MD, of the St. Louis Children's
Hospital and the Washington University School of Medicine in St. Louis,
Missouri, appears in _Diabetes Care_, volume 16 supplement 3, December 1993,
pp. 143-154. The article discusses many aspects of treating pediatric
diabetes. Santiago spends several pages discussing how to establish realistic
and honest approaches to self-monitoring. I highly recommend the article.

------------------------------

Subject: So-and-so eats sugar! Isn't that poison for diabetics?

This is asked from both sides: the non-diabetic who doesn't understand
diabetes, and the diabetic who gets tired of hearing "I won't put any sugar
on the table" etc etc ad nauseum.

Diabetics should eat a high-quality, healthy diet very similar to that
recommended for everyone. This will include some sugar, and research
indicates that obtaining a moderate amount of carbohydrates in the form of
sugar makes little or no difference in controlling blood glucose levels. There
isn't room here to describe all the aspects of diabetes treatment that make
this so.

No one has suggested a really good, uniformly satisfying answer to the public
know-alls who insist they know more than you do. Feel free to add to this
list:

   That was true before insulin treatment became available in 1922.

   Fat is more dangerous than sugar because diabetics have a three-fold
   higher risk of heart disease.

   The whole point of injecting insulin is to balance carbohydrate intake.

   All carbohydrates are converted to sugar in the digestive tract anyway.

------------------------------

Subject: Insulin nomenclature

The major types of insulin have both generic designations and brand names
used by the manufacturers. Most of the brand names are close enough to the
generic ones that the correspondence is obvious. Novo uses totally different
names. In those parts of the world where Novo has most of the market, the
Novo brand names are used in place of the generic names. To facilitate
communication between Novo users and others, here is the correspondence:

   Generic      Novo           May also be known as
   -------      ----           --------------------
   Regular      Actrapid         Soluble
   NPH          Protophane       Isophane
   Lente        Monotard
   Ultralente   Ultratard        Zn (Zinc suspension)

The recently developed lispro (generic name) insulin is sold as Humalog by
Eli Lilly. Novo has no comparable insulin as of July 1996, although they
undoubtedly have research in progress.

------------------------------

Subject: What is Humalog / LysPro / lispro / ultrafast insulin?

Except as otherwise noted, this info comes from an article on p396 of the
March 1994 _Diabetes_ by researchers at Eli Lilly.

Insulin is a protein. Proteins consist of sequences of amino acids. Human
insulin has the amino acid lysine at position B28 and proline at position
B29.

Insulin molecules naturally pair off (like people) and combine into dimers.
The dimers interact with small amounts of zinc and combine into hexamers, the
form sold as "regular" insulin.

  From another source, now forgotten: the time required to disassociate the
  hexamer into the dimer, and then the dimer into the monomer so that it
  can be absorbed, is the main reason for the delay in the action of regular
  insulin and the reason for injecting it 30 to 45 minutes before meals.

Switching the B28 and B29 positions on the protein has no effect on the
normal activity of the insulin but inhibits the formation of the dimer and
the hexamer. Thus the insulin is in monomeric form when injected and can be
absorbed immediately.

The name LysPro comes from the names of the amino acids, lysine and proline,
that occupy the swapped positions. According to an article in the August 1996
Diabetes Forecast, the spelling 'lispro' is now preferred.

Challenges in the development include the biochemical process for swapping the
amino acids, and making the result reasonably stable in the monomeric form.

From another source, now forgotten: US FDA approval was not automatic, since
the insulin molecule has been modified. In fact, several other amino acid
exchanges have been tried and met with unacceptable side effects.

Some points from the article in the August 1996 Diabetes Forecast:

  Patients with gastroparesis, or taking acarbose, should be careful with
  lispro. Gastroparesis is a condition caused by neuropathy which causes
  the stomach to empty slowly and erratically. (See the section on
  gastroparesis later in this section.) Acarbose is a drug which slows
  the absorption of carbohydrates from the intestine. Either may result
  in lispro insulin acting too quickly.

  Response to lispro is variable. Some patients love it, others hate it.
  On the average, it does not change bg control either for better or for
  worse, but some patients definitely find it one or the other. Eli Lilly
  is promoting lispro for convenience, not for better control.

  Doctors and patients are still experimenting with the best regimens for
  using lispro insulin. "Best" clearly varies from one patient to another.
  Typically lispro insulin is injected very close to mealtime.

An obvious concern is that hypoglycemic reactions might be more common with a
faster acting insulin. A paper presented at the 1996 ADA Scientific Papers
conference studied this possibility:

  Reducing the Incidence of Hypoglycemia with a Novel Insulin Formulation
    J. Anderson, R. Brunelle, A Pfeutzner et al.
    Indianapoils, IN and Bad Homberg, Germany

In fact, they found the rate of hypoglycemic incidents slightly lower among
those using lispro insulin. They found no difference on most other measures,
including especially HbA1c. I've only seen the abstract of the paper, so I
know nothing about their methodology. (They also state the lispro forms
hexamers just like regular insulin but that the hexamers dissociate much more
quickly. I don't know who to believe, but from a practical point of view it
doesn't matter.)

------------------------------

Subject: Travelling with insulin

Insulin does not need to be kept cold.

Insulin is stable at body temperature. This is not surprising when you
realize that the beta cells often store the insulin they produce for
days before releasing it. (Specifically, according to Jens Brange's
_Stability of Insulin_, Regular/Actrapid insulin stored at 40C will
lose 5% of its potency after 14 weeks.)

A general guide to how long it is safe to store insulin at various
temperatures:

   Refrigerated          a few years
   Room temperature      several months
   Body temperature      a few weeks

Do not allow insulin to freeze. Do not expose insulin to temperatures
significantly above body temperature. I don't know how much heat is
required to destroy insulin, but leaving it in a closed car in the sun
would be a very bad idea. (Two readers have reported that solidly
frozen and rethawed regular insulin works just fine. I've been unable
to locate any studies documenting the degradation of insulin at extreme
temperatures.)

Short of such extremes, degradation is gradual. You should always be
alert for gradual changes in your blood glucose anyway, since
individual sensitivity to insulin changes over time for reasons
unknown. Your normal dosage adjustments will handle minor degradation
that might occur, say, from keeping insulin in a very hot room for
several weeks.

So why do drugstores (pharmacies) keep insulin refrigerated, and why are
"insulin cold packs" advertised? The drugstores are mosty just
following standard procedures. For them, it's a simple precaution not
worth violating..

As for cold packs, as long as anyone thinks they are needed, someone
will sell them. As noted, you do need to protect insulin from extremes
of temperature, and the cold packs can help at both extremes. In many
situations it may be just as effective to pack the insulin next to a
bottle of water, especially during outdoor activities when you are
carrying water anyway.

Always keep your insulin with you! Keep all your medical supplies with
you. Never pack them in checked luggage. Luggage may sit outside in hot
sun or freezing rain. If you are delayed, or your luggage is waylaid,
you could be without supplies packed in luggage.

Meter manufacturers recommend keeping meters and strips from freezing
and extreme heat.

------------------------------

Subject: Injectors: Syringe and lancet reuse and disposal

Disposable syringes can be safely reused as long as you take reasonable
precautions. Recap both ends between uses, and discard the syringe if
dropped, dirty, or damaged (especially if the needle is bent). Discard
it when it becomes uncomfortable to use. This varies a great deal,
being half a dozen uses for some patients and several dozen uses for
others. Comfort depends far less on sharpness than on the silicone
coating applied to the needle at manufacture. Never wipe the needle
with alcohol, as this will remove the silicone coating.

Lancets can also be reused safely with the same caveats.

Syringe disposal has proven controversial. If you want to be
conservative, buy a needle clipper, get a hard plastic bottle designed
for medical waste to put the syringes in, and take the full bottle to a
facility approved for handling medical waste. Your doctor's office, a
local hospital, or a pharmacy may be able to handle it for you.
Intermediate positions use one of these techniques. At the least
conservative, cap the needle carefully and discard in trash which will
not be subject to illicit searching and possible abuse. If you have
trouble capping the needle without sticking yourself, definitely get a
bottle to drop the uncapped syringes in; a bleach bottle may be
adequate.

Local or state regulations apply in many places and limit your choices.
Know the laws for your area! Where sharps containers are required, the
pharmacy where you purchase the container will probably dispose of the
full container for you.

------------------------------

Subject: Injectors: Pens

A pen injector is a device that holds a small vial of insulin and a
disposable needle, and injects an amount measured with a dial.
Advantages include being compact, convenient, easy to use circumspectly
in public, and accurate and simple in dose measurement. The pen device
clicks for each unit (or two depending on the manufacturer) dialed;
this can help those with impaired vision.

Some pen units only allow setting a multiple of two units of insulin,
which many find inadequate. Get a model which measures a multiple of
one unit, which should be easy to find among current models.

The primary disadvantage is cost, up to twice as much per unit of
insulin compared with standard vials. The special vials may be
difficult to obtain in remote areas, and widespread shortages have
occurred occasionally. Falling back to a standard syringe is always an
option.

Also, the special vial can be refilled from a standard vial using a
syringe, making sure the rubber stopper is not damaged, though the
manufacturer will not recommend this. If you do refill, make sure to
use the same concentration of insulin. This is not a problem in the US,
where only U100 concentration is used. In some parts of the world, U40
concentration is common, but pen refills are always U100. Make sure to
match the concentration.

Pens are more popular in Europe than in the US, but are being heavily
promoted in the US.

------------------------------

Subject: Injectors: Jets

A jet injector uses no needles, but instead squirts the substance being
injected through a narrow orifice under high pressure, producing a fine
stream which penetrates the skin as easily as a needle. Jets are popular
with anyone who is simply scared of needles, for any reason. The jet
disperses the insulin more than a needle does, which probably results in
faster absorption. This can be an advantage or a disadvantage, and
requires careful monitoring when first used. Technique is just as
important as with needles, so jets are no more appropriate than needles
for small children. If a jet is used to avoid needles, equipment failure
forcing a fallback to needles may be traumatic. High cost is a major
factor.

------------------------------

Subject: Insulin pumps

An insulin pump provides a Continuous Subcutaneous Insulin Infusion, or CSII,
via an indwelling needle or catheter. That is, a small needle (similar to
those on insulin syringes) or tube is inserted through the skin and fixed in
place for two or three days at a time. An external box pumps insulin through
the needle steadily.

Pumps don't solve all the problems of treating diabetes for two main reasons:

  1) The infusion is still subcutaneous, so the insulin still must be
     absorbed before it can be used. Insulin from the pancreas goes directly
     into the bloodstream and takes effect much more quickly.

  2) Current pumps are open-loop -- that is, there is no feedback from blood
     glucose (bG) to the pump. The patient must still self-monitor bG and
     program the pump.

Nonetheless, many patients get much better results with a pump than from
intensive therapy without a pump, and those patients tend to be
extremely happy with the pump. It isn't clear at present how to decide
whether a given patient should use a pump. Different studies have
obtained varying results, ranging from 85% success to 85% dropout!
Unfortunately, no studies seem to have been done since the mid-1980s,
and the manufacturers have little motivation to fund the studies, as
advertising is more cost-effective for them. It is likely that the pumps
and pump therapy have become much more consistently successful since
then. A few important factors seem clear, though:

  1) Motivation. A pump takes extra effort and attention.

  2) Knowledge. If you aren't already familiar with intensive therapy,
     think more than twice before jumping for a pump. You should
     probably try intensive therapy with multiple injections first.

  3) Treatment team. Successful users are backed by teams of physicians
     and educators who are experienced *with pumps*. Don't try a pump on
     your own (the manufacturers won't let you anyway), and don't try it
     with inexperienced providers -- these are recipes for unnecessary
     failure.

  4) Funding. Pumps represent a nontrivial capital outlay. If you don't
     have insurance or other public programs that will pay for the pump,
     you will need personal financial resources.

Most or all pump manufacturers allow a trial period, so you can try a pump
without financial risk. You will probably know fairly soon whether you want
to continue with the pump.

I have removed the oudated insulin pump discussion previously posted here.

------------------------------

Subject: Type 1 cures -- beta cell implants

Beta cells can be isolated and implanted, requiring only outpatient surgery
for implantation. But foreign beta cells are quickly rejected without
immunosuppressant drugs. Even with the recent advances in drugs, especially
cyclosporin, using immunosuppressants is much more dangerous than living with
diabetes. As a result, beta cell implantation is not currently used to treat
diabetes.

Current research is investigating two general methods of implanting beta
cells without the use of immunosuppressant drugs. The first (immunoisolation)
encapsulates the beta cells within a barrier so that nutrients, glucose, and
insulin can pass freely through the barrier but the proteins which provoke
the immune response, and the cells which respond, cannot pass. The second
(immunoalteration) involves altering the proteins on the surface of the cells
which provoke the immune response. The first human trial began early in 1993
on immunoisolated beta cells, and human trials were scheduled to begin late
in 1993 on immunoaltered beta cells. (As of early 1997, I haven't had the
opportunity to try to locate the followup to these trials.)

An article in the Journal of Clinical Investigation, September 1996,
describes a successful experiment which implanted immunoisolated porcine
(pig) islets into monkeys. An accompanying editorial describes the state of
islet transplantation. Both are online in full, linked from the issue
contents page at

  http://www.jci.org/content/vol98/issue6/

In early 2000, a lot of hype appeared about the "Edmonton protocol" trials.
While an important step, this is still only a small step on a long journey.
They made improvements in technique and graft survival, but no progress on
the serious problems of beta cell supply (each patient needed beta cells
from two cadaver donors) or of immunosuppressant use (they used drugs,
albeit carefully).

Don't expect these treatments to be available on a standard basis any time
soon. I've been reading about this research since the mid-1970s, and the
results are always just around the corner. Serious problems remain to be
solved: safety of the immunoisolated implants, long-term survival, ability to
use beta cells from non-human species or grow usable cells for grafting in
the laboratory, perfection of both techniques -- all
these must be resolved before beta cell implantation moves beyond the
experimental stage. Other problems will likely be encountered along the way,
since this is cutting edge medical research. I'll be surprised if it gets out
of the lab before the year 2005; 2015 is probably a better guess. And it may
fail -- it's always possible that unsolvable problems will yet arise.

Finally, it's not yet clear that even completely normal bG profiles will cure
all the problems of type 1 diabetes. Some may be related to the autoimmune
reaction that is the immediate cause of diabetes. This question cannot be
answered until it is possible to normalize bG levels for a period of many
years.

------------------------------

Subject: Type 1 cures -- pancreas transplants

Whole pancreas transplants have the same rejection problems as beta
cell implants, and also require major surgery. For these reasons, whole
pancreas transplants are only used 1) in desperate cases in medical
schools with exceptional capabilities, and 2) in conjunction with
kidney transplants.

Kidney transplants are (relatively) common in diabetics with advanced
complications. A kidney recipient is taking immunosuppressant drugs
anyway, and the same surgery that implants the kidney can stick in a
pancreas with little extra effort or trauma. As a result, the double
transplant is now recommended, at least for consideration, for any
diabetic patient who requires a kidney transplant.

The only disadvantage would seem to be that the pancreas donor must be
dead; whereas a living kidney donor is feasible. Even this is not
strictly true, as a kidney-plus-partial-pancreas transplant from a
living donor is possible, and the partial pancreas contains enough beta
cells to produce insulin for the recipient. However, this procedure is
seldom performed.

Combination kidney/pancreas transplants are listed in a different queue
than kidney-only. Since the number of people waiting for donor kidneys
is quite long (anywhere from a few months to seven or eight years), the
kidney/ pancreas list is often a quicker means of receiving a
transplant. For example, in January 1998 there were 38,380 people on
the UNOS [see below] registrations for a kidney transplant. There were
only 355 registrations for a pancreas transplant and 1604 registrations
for a kidney-pancreas transplant. [Based on UNOS Scientific Registry
data as of January 28, 1998.]

Kidney/pancreas transplants, while still considered experimental at some
institutions, have been approved by Blue Cross/Blue Shield in the
following centers: University of Iowa Hospitals and Clinics, Iowa City;
University of Minnesota Hospital and Clinic, Minneapolis; Ohio State
University Hospitals, Columbus; and University of Wisconsin Hospital
and Clinics, Madison. Though this is for BC/BS only, other insurance
companies may follow the BC/BS lead if pushed. [Information from January
2000. Check to see whether additional centers have been approved.]

UNOS (United Network of Organ Sharing) has a list of 124 transplant
centers that have pancreas transplant programs. For more information,
contact UNOS at (800)24-DONOR or see their web page at

  http://www.unos.org

(See the section on sources for additional contact info.)

The UNOS handles transplant registrations only in the USA, but can
provide contact information for organ-donation agencies around the
world. Organ allocation became a political football in the US in the
late 1990s, and the details of allocation and waiting lists may change.

The transplant mailing list is an excellent resource. See the section on
online resources: mailing lists.

(Thanks to Alexandra Bost for much of the information in this section.)

------------------------------

Subject: Type 2 cures -- barely a dream

The treatments described in the preceding sections apply only to type 1
diabetes. Type 2 diabetes is the result of insulin resistance or other forms
of improper use of insulin within the body, not in general to an absolute
lack of insulin. Type 2 patients usually have normal beta cells at the start,
with beta cell insufficiency developing later while the insulin use defects
continue. There is nothing on the horizon for type 2 diabetes with promise
comparable to that of beta cell transplants for type 1. The sequencing of the
human genome, completed in 2000, provides information for research which is
likely to help, but that is for the very long term.

This is distinct from the *treatment* of type 2 diabetes, which has improved
quite significantly even since I first wrote the above paragraph. New drugs
are available which improve insulin sensitivity. The UKPDS directly, and the
DCCT indirectly, have convinced many more doctors that intensive treatment
of type 2 diabetes is worth the trouble and expense. Support and education
programs continue to expand. The UKPDS showed clearly that medical nutrition
therapy (MNT, diet with proper medical team support) helps type 2 diabetics
greatly even without weight loss, and so more doctors are providing the
necessary aid.

But all this is treatment, not cure.

------------------------------

Subject: What's a glycemic index? How can I get a GI table for foods?

The glycemic index, or GI, is a measure of how a given food affects
blood glucose (bG). Some complex carbohydrates affect bG much more
drastically than others. Some, such as white bread, affect bG even more
than sugar (sucrose).

This was quite a surprise when the research was first published in 1981.
It really should not have been such a surprise. "Sugar", meaning
sucrose, decomposes in the gut to equal parts of glucose and fructose.
Fructose, as expected, has only a small effect on bG. Even
professionals, it turns out, were swayed in their thinking by the evil
charm of the word "sugar" and failed to take into account the
differences among the many kinds of sugar found in foods.

To use the glycemic index in a real-life diet, you must combine the GI
of various foods using a weighted average. Rick Mendosa's article (see
below) has information on simple calculations for mixed meals, which
recent research has shown to be reliable.

It remains difficult to predict the GI of high fat meals because of the
multiple affects of the fat, especially the way it slows the gut. For
example, a baked potato has a very high GI (one of the famous,
unexpected examples), but adding butter to it lowers the GI greatly.
This is a good reason to reduce dietary fat (if you needed another
reason), since doing so makes the effect of carbohydrates more
predictable.

If you don't want to go to the effort of full GI calculations, the
important thing is to understand that foods may affect your bG profile
in ways that you wouldn't expect from categorizations such as "simple
sugar" and "complex carbohydrate". Build your knowledge about your own
response to different foods and meals by monitoring and keeping
records, and avoid assumptions.

Rick Mendosa <mendosa(AT)mendosa.com> has written an excellent and thorough
article about the glycemic index. He also  maintains a glycemic index
list. I highly recommend that you check out

  http://www.mendosa.com/gi.htm

[Thanks to Rick for information he provided for this section.]

------------------------------

Subject: Should I take a chromium supplement?

The short answer is "no". I'll quote the ADA's longer answer, from the May
1994 _Diabetes Forecast_, p.73. The ADA's editorial board says:

    Some popular books on diabetes have claimed that chromium, which is
    found in many common foods such as animal meats, grains, and
    brewer's yeast, is good for people with diabetes. Not so. Though
    chromium supplements may benefit people who are significantly
    malnourished and have an actual chromium deficiency, there is no
    significant evidence that consuming extra chromium helps people
    with diabetes who are even close to being well nourished.

    Taken at the dosages listed on the bottle, however, chromium is not
    likely to be harmful. But your money is better spent on more useful
    items!

------------------------------

Subject: I beat my wife! (and other aspects of hypoglycemia)

(not yet written)

------------------------------

Subject: Does falling blood glucose feel like hypoglycemia?

Sometimes. Symptoms of hypoglycemia are divided into the adrenergic and the
neuroglycopenic.  Adrenergic responses are caused by increased activity of
the autonomic nervous system and may be triggered by a rapid fall in blood
glucose (bG) or by low absolute bG levels; symptoms include

  weakness
  sweating
  tachycardia
  palpitations
  tremor
  nervousness
  irritability (sound familiar?)
  tingling of mouth and fingers
  hunger
  nausea or vomiting (unusual)

The autonomic nervous system activity also causes the secretion of epinephrine,
glucagon, cortisol and growth hormone.  The first two are secreted rapidly and
eliminated rapidly.  The second two are secreted slowly and remain active for
4-6 hours, and may cause reactive hyperglycemia.

Neuroglycopenic responses are caused by decreased activity of the central
nervous system and are triggered only by low absolute bG levels; symptoms
include

  headache
  hypothermia
  visual disturbances
  mental dullness
  confusion
  amnesia
  seizures
  coma

The above information is from Mayer Davidson's _Diabetes Mellitus: Diagnosis
and Treatment_.

Remember, as always, that individual responses vary greatly. The exact set of
symptoms encountered will vary. It's not impossible that some of the symptoms
will fall in the other category for some individuals.

------------------------------

Subject: Alcohol and Diabetes

This section provided by Peter Stockwell <peter(AT)sanger.otago.ac.nz>.

Having diabetes does not prevent the consumption of alcoholic drinks,
but there are some considerations:
  - Alcohol can metabolised to produce energy and so has dietary
      consequences.
  - Alcohol promotes the uptake of blood glucose into liver glycogen
      causing a drop in bG.
  - Many alcoholic drinks contain sugar, particularly mixed drinks.
  - The symptoms of drunkenness and hypoglycaemia are similar - alcohol
      may mask the effects of a hypo.
  - Diabetics must remain sober enough to care for themselves (perform
      injections on schedule, etc).
  - Excess alcohol consumption can cause increased serum triglycerides.

Few difficulties arise if following points are observed.

Acceptable in moderation:
  - Red wines.
  - Dry or medium-dry white wines.
  - Dry sherries.
  - Dry light beers (lagers, light ales fermented with low residual
      sugar).
  - Spirits (whiskey, gin, vodka, etc) with "diet" mixers.

Use with extreme caution due to high sugar content:
  - Sweet wines or sherries.
  - Ports.
  - Heavy or dark sweetened beers (stout, porters, etc which have
      high residual sugar).
  - Wine coolers.
  - Spirits with normal mixers.
  - Cocktails.
  - Liqueurs.

Use with extreme caution due to very high alcohol concentration:
  - Neat (undiluted) spirits.

General rules:
  - Simple drinks (wine, beer) are more reliable than complex mixed
      drinks, especially in company where you have less control over
      the contents or concentration.
  - Drink with or after food to avoid hypo problems.
  - Approach anything with caution if you are in doubt.
  - Low alcohol beers are not necessarily preferred - many of them are
      rather sweet.
  - Alcohol provides about 7 cal/g of food energy. Some is lost in the
      urine, but most is converted by the liver into forms which can be
      used for energy elsewhere in the body or stored as fat.

Clearly these succinct rules are simplified and there are exceptions to
them (for example, there are dry ports) but they are intended as a
general guide.  I make no attempt to define the term moderation, this
will depend on the individual.

------------------------------

Subject: Necrobiosis lipoidica diabeticorum

Necrobiosis lipoidica diabeticorum (NLD) consists of oval plaques, usually on
the lower legs. It may start as small red spots or raised areas, which
develop a shiny, porcelain-like appearance. The plaques often turn a light
color due to extracellular fat (the "lipoidica"). They are often itchy or
painful. Typically the spots turn a brownish color, which fades slowly but
is permanent.

NLD is not related to any other complication of diabetes. In particular, NLD
does not presage eye, kidney or vascular problems.

NLD is much more common in diabetics, who account for perhaps 2/3 of all
cases. Many of the remainder develop diabetes, and NLD should be considered a
warning sign of diabetes. Reports vary widely on exactly who is most at risk.
About 1% of diabetics have some degree of NLD ... plus or minus 1%, depending
on which report you read. Some reports say NLD occurs more often in young
women, but some textbooks disagree.

The real dangers seem to be ulceration, infection, and the stress from the
appearance. Ulceration sometimes occurs spontaneously, and often as a result
of trauma.

Ulceration is often a result of scratching or trauma, and the ulceration from
scratching sometimes heals very slowly. Thus avoiding scratching and trauma
decreases the amount of ulceration, though some ulceration will occur anyway.

There are some images of NDL lesions at

  http://tray.dermatology.uiowa.edu/DermImag.htm

No particularly good treatment seems to be known. Topical steroids (that is,
creams) are the most common first choice. The ulcerations usually heal if
cared for properly, and drastic measures are not called for in most cases.
William Biggs reports that skin grafts may be necessary in cases of severe
ulceration, but do not tend to give results that are cosmetically attractive.

Other treatments reported to help sometimes are oral aspirin, pentoxifylline,
dipyridamole, locally injected steroids, and systemic steroids. No one claims
to be able to predict what will work on any given patient, and often not much
of anything is effective. However, the ulcers usually heal if given
supportive treatment. Surgery should be avoided. Ineke van der Pol reports
finding relief in Chinese herbal treatments.

STEROID WARNING: locally injected and systemic steroids raise blood glucose
and cause severe problems regulating blood glucose. These should be used only
as a last resort. Topical steroids (creams and inhalers) cause no such
problems.

Note that treatment is not a medical necessity except for ulcerations and
infections. Otherwise, the purpose of treatment is to prevent ulcerations
and infections, decrease pain and itching, and improve the appearance.

NLD is the subject of occasional articles in scientific journals on diabetes
and on dermatology. Betsy Butler has researched the medical journals, finding
little beyond what I've reported above -- in her words, "no good answers".
_Therapy for Diabetes Mellitus and Related Disorders_, published by the ADA,
has a section on necrobiosis lipoidica diabeticorum and its treatment.

Ineke van der Pol has started a mailing list about NLD at
http://groups.yahoo.com/group/necrobiosis.

I thank the following people, especially Betsy, who posted the information
from which I derived this section:

    Betsy Butler Polley (who says sorry, she doesn't have any information
                         besides what's here)
    William Biggs <reddy_biggs(AT)msn.com>
    Tari M. Birch <tm_birch(AT)pnl.gov>
    Terence Griffin (who also says he doesn't have any other info)
    Bill Barner <barner(AT)mail.loc.gov>
    Ineke van der Pol <fluo(AT)chello.nl> (who has no further information
        but is happy to correspond about NLD if you wish)

------------------------------

Subject: Has anybody heard of frozen shoulder (adhesive capsulitis)?

Short answers: adhesive capsulitis, aka frozen shoulder, is a painful
condition that limits motion in one shoulder or both. It's not found
exclusively in conjunction with diabetes, but occurs sufficiently more often
with diabetes to be considered a diabetic complication. Don't be surprised,
though, if your doctor isn't aware of this connection. Avoid surgery (which
seldom helps) and cortisone (which plays havoc with blood glucose control);
take physical therapy seriously; expect to take about two years to recover.

Lee Boylan <lboylan(AT)cisco.com> wrote:

  There are three treatments usually offered for frozen shoulder: surgery,
  cortisone shots and exercises. Surgery offers the best transfer of money to
  a surgeon but the patient ends up needing to do exercises anyway.

  Cortisone offers quick pain relief but not full shoulder relief, so the
  patient is told to do exercises. Also, a DMer has drastically changed
  insulin requirements after taking a cortisone injection.

  Exercise, with alternating hot and cold packs and optional NSAIDs, offers
  slow and sometimes painful therapy that gets full or nearly full
  restoration of movement. Just don't let it discourage you, because
  improvement comes slowly. Keep at it! Eventually, you will have pain-free
  motion in your arm.

And I'll re-emphasize what Lee says: DON'T TAKE STEROIDS LIGHTLY. Including
cortisone. This warning should not be necessary, but unfortunately some
doctors are unaware of what steroids do to blood glucose. If your doctor
doesn't understand how serious a problem this is, insist on including an
endocrinologist in your medical team.

Lyle Hodgson <lyle(AT)world.std.com>, who has been through adhesive
capsulitis in both shoulders, wrote:

  I suggest anybody who really wants to know about it who can visit Boston go
  to see Dr. Gordon Lupien, who used to be an orthopedic surgeon at Joslin
  and, according to a couple doctors I asked, knows more about adhesive
  capsulitis in diabetics than anyone else, period.

  Factoids:

  o Diabetics get "frozen shoulder" more than non-diabetics.

  o Women get "frozen shoulder" more than men.

  o Everybody I talked to who had ever treated "frozen shoulder" said that
    every patient they'd seen with it got over it in two years, no matter
    whether they did the exercises or not.

  o The exercises and ESPECIALLY PHYSICAL THERAPY help tremendously in
    retaining what range of motion you still have and in keeping the pain
    (which can be incredible) to a minimum.

  o The exact cause and pathology is completely unknown, but often adhesive
    capsulitis follows an untreated injury, or bursitis or tendonitis or even
    a period of no stretching exercises.

  o Adhesive capsulitis is often mis-diagnosed as a torn rotator cuff, which
    may well be involved but which will heal without the surgery most
    orthopedic surgeons prescribe for it. What's more, an often undiscussed
    side-effect of the surgery is permanently reduced range of motion,
    because tendons are snipped and resewn, and thus shortened.

  o If the exact pathology is unknown, it is certain that it involves
    scarification of the tissues in the shoulder "capsule", and from what I
    understand scar tissue is at least partly caused by  glycosulation of
    tissues, so good control is (once again) the best prevention .

  o Cortisone is often prescribed for non-diabetic patients, and only for
    diabetic patients by doctors unfamiliar with the dramatic effect
    cortisone has on bloodsugar levels. Dr. Lupien told me cortisone doesn't
    even really have any long-term effect except to reduce the pain for
    awhile, and should be avoided completely since it could also permanently
    screw up how your body deals with cortisone.

  o Recommended treatment: daily exercises, biweekly physical therapy, daily
    (if possible) swimming, and acetaminephen (Tylenol). Extensive use of
    non-steroidal anti-inflammatories is not recommended. These include
    aspirin, ibuprofen (Advil/Motrin), and naproxen.

  Here's a sort-of-a- self test for adhesive capsulitis:

  1. Lay on the floor on your back. Can you raise your arm over your head in
     a 180-degree arc and rest it on the floor without pain or *too* much
     stretching?

  2. Stand sideways next to a wall, and walk your fingers up the wall until
     you can't reach any more. Can you almost press your armpit to the wall?

  If either of these gives you significant trouble -- you can't quite reach
  the floor behind your head, you can't touch the wall with your elbow, and
  either or both gives you pain -- you may (MAY, MAYBE, MIGHT) have adhesive
  capsulitis.

  Two doctors and one physical therapist told me that shoulders tend not to
  get the regular stretching that other joints get: a person can go for long
  periods of time without moving the shoulder much out of its usual hanging
  position, and then often the movement doesn't count for much. Hips are
  stretched at least a little several or many times a day, even  with
  sedentary types who only sit, stand, sit, stand, walk a little, sit, etc.:
  the tissues are still fairly regularly manipulated so that it is much
  harder for them to freeze up.

  Lyle, who is always interested to hear what else anyone has learned about
  this little-studied, little-mentioned condition

------------------------------

Subject: Gastroparesis

J K Drummond (no longer on the net, but well) contributed this section.

Gastroparesis (gastroparesis diabeticorum if a diabetes complication) is
nerve damage caused delayed gastric emptying. This more common than
recognized irregular digestive slowdown interferes with blood glucose
regulation and oral medicine absorption.

Severity ranges from occasionally recurring bothersome symptoms like
nausea, vomiting, constipation and diarrhea to total "stomach paralysis"
-- the inability to consume/absorb any food. This worst stage requires
tube feedings as the sole source of nutrition, IVs for hydration, and
gastric suction for waste elimination. Be aware that "stomach trouble" may
be more serious for one with diabetes and report digestive problems to
your physician. Do not wait until you have had gastroparesis for several
years or end up in the emergency room because you cannot eat. If you
are a health professional, please routinely ask diabetics if they have
digestive problems.

Many with gastroparesis are undiagnosed or misdiagnosed and find little
information about it. Often they have been used as guinea pigs in
guessing games of hit or miss treatment trials. The scary quest has
only just begun to find answers, reason, and solutions to this lesser
known and mystifying complication of diabetes. There are people who
have found answers in their lonely struggle with gastroparesis.

Most folks with gastroparesis are female, with type 1 diabetes for 20-25
years and are age 25-45 at onset of gastroparesis.

These incomplete lists of symptoms, treatments, helpful & stressful
foods, and social aspects have been compiled mostly from patient reports.
There is no all-patient guarantee of experience. CHECK WITH YOUR DOCTOR!

            S Y M P T O M S

Physical                Psychological

nausea                  fatigue- muscle weakness
vomiting                fear
constipation            frustration
diarrhea                stress
bloating
lack of hunger
indigestion
high stomach acidity
reflux
weight loss
inability to control blood sugars

            DIAGNOSIS**

Symptoms together with gender &/or years of diabetes (clinical intuition)
Gastric Mobility Transit Test
Manometric Motility Study

Diabetics are also subject to all forms of non-diabetic gastropathy so be
aware that tests are necessary to eliminate and/or verify other diagnoses.

            TREATMENTS

NUTRITION - MALNUTRITION  Dietitians recommend 6 small meals daily

Foods more easily digested   Foods increasing symptoms

fruit juices                 protein foods - meat, eggs
canned fruits & vegetables   raw fruits & vegetables
soft starches (white bread   dairy products
  & rice, mashed potatoes,
  cereals)                   caffeine, chocolate
soups                        nuts & seeds
baby foods
non-carbonated beverages
jello

      Liquid Nutritional Supplement Drinks

   Diabetic: Choice dm (Mead-Johnson), Glucerna (Ross Labs)
             Ensure Glucerna OS (Ross Labs)
   Non-diabetic:  Ensure/Ensure plus,  Sustacal (Ross Products Div)

      Nutrition via:

   IVs (fluids or TPN)
   Tube feedings (eq. Osmolite or Supplena)

PHYSICAL - Remaining upright at least a half hour after eating,
stomach massage, enemas, glycerine suppositories, stool softeners
(for example, psyllium husk powder: Metamucil and other brands)

DRUGS - May have adverse side effects on other conditions.  Ask your MD!

Reduce stomach acid: Zantac, Pepcid, Prilosec, Axid, Cytotec
Increase motility:
   Reglan (metoclopramide)
   erythromycin
   Propulsid (cisapride) (in U.S. only under compassionate use protocol)
   bethanechol
   domperidone (U.S. availability: compassionate use only, and for veterinary
      use -- it's used to treat fescue toxicosis in horses)
   Zelnorm (tegaserod maleate), labeled in the US as of 2002 to treat
      women with irritable bowel syndrome (IBS) dominated by
      constipation. Zelnorm increases serotonin activity in the bowel by
      activating some 5HT4 receptors, which increases serotonin in the
      bowel and increases motility. The percentage of IBS patients who
      benefit is small but significant. It's not clear why the labeling
      is limited to women, though it seems likely to be a combination of
      the fact that 2/3 of IBS patients are women and the clinical
      studies barely reached statistical significance. If the effects in
      gastroparesis follow those in IBS, a small percentage of patients
      will see improvement, and some of those will be helped a lot.
      Information from the Zelnorm prescribing information on the
      http://www.zelnorm.com web site.
Reduce digestive system spasm: dicyclomine
Diarrhea: immodium, clonidine
Nausea/vomiting: marinol, thorazine, ativan, inapsine, zephran, phenergan

   Surgical (physical implants or alterations)

portacath or Hickman - IV hydration or Total Peritoneal Nutrition
jejunostomy - tube feedings
gastrostomy - for stomach suction (PEG tube)
gastric resectioning or stomach removal
gastric pacing - digestive pacemakers (experimental). Enterra Therapy by
  Medtronic, gastric electrical stimulation (GES) neurostimulator implants
  are approved as a humanitarian use device (HUD) since severe gastroparesis
  (refractory to drugs) has less then 4,000 cases per year. More info at
    http://www.medtronic.com/neuro/enterra/patient.html
insulin pumps

      SOCIAL & PSYCHOLOGICAL ASPECTS

Frustration for patient and physician from the difficulty in balancing
insulin dosages and food intake to achieve level blood sugars with
unpredictable slowed digestion.

Additional psychological impact from delayed treatment due to relative
medical unrecognition causing underdiagnosis and even misdiagnosis (ex. as
anorexia nervosa if accompanied by vomiting).

Lack of ostomy education.

If/when eating ability returns following thinking that a normal diet could
never again be eaten it may cause physical & emotional anorexia.

Often felt burden to friends and family.

Most information was collected by the pioneering health professionals of
the defunct Gastroparesis Communication Network, updated by J K Drummond.

There's an excellent web page on gastroparesis at

  http://www.uoflhealthcare.org/digestivehealth/gastroparesis.htm

** If you have been or are out of work pursue Medicare/Medicaid & Social
Security Options IMMEDIATELY!

------------------------------

Subject: Extreme insulin resistance

Mayer Davidson writes several pages about insulin resistance in his
book _Diabetes Mellitus: Diagnosis and Treatment_. Except for what's in
[brackets], the following information is from pp 126-132 of the third
edition or pp 112-119 in the fourth edition. I'd recommend finding a
copy. Most university libraries will have it, even those without
medical schools. It's about $65; if necessary you can order from the
Rittenhouse Medical Bookstore in Philadelphia at 215-545-6072.

In this context, "insulin resistance" refers to patients requiring more
than the arbitrary amount of 200 units/day. Davidson uses the term
"insulin antagonism" for the phenomenon which is commonly part of type
2 diabetes.

Davidson cites ten major causes of insulin resistance. The first eight
are obvious major medical problems that you would immediately suspect
were related, so I won't bother listing those. Rarely, insulin is
destroyed at the subcutaneous injection site; this form can be treated
with normal amounts of insulin administered intravenously or
intraperitoneally.

The most common form of insulin resistance is immune-mediated. Everyone
taking injected insulin develops IgG antibodies to insulin. In most,
the antibody levels are low. In about 1 in 1000, the levels are much
higher, from 5 to over 1000 times higher than usual. In Davidson's
words:

    The reason for this markedly enhanced response and the
    subsequent decline to normal levels is completely unknown.

The antibodies bind to, and neutralize, the insulin.

At one time it was thought that the antibodies resulted from impurities
in the insulin preparations, and that using highly purified
preparations would avoid the problem. This has proven not to be the
case; purified insulin helps but usually does not resolve the problem,
[though it seems to be worth trying].

Also, switching to a different insulin does not help, as the antibodies
bind to beef, pork and human insulin. They may bind to one more than
the others, but the titers of antibody are so high as to neutralize
virtually all of any of the insulins.

Two treatments which are effective are not generally available in the
US.

First, insulin can be treated with sulfuric acid. The modified molecule
retains some biological activity but has reduced affinity for binding
to the IgG antibodies to insulin. This treatment was tested by a
Canadian laboratory in the late 1960s but is available in the US only
by special petition to the FDA. Novo Nordisk Pharmaceutical can provide
information at 609-987-5800.

Second, fish insulin works in humans but does not bind to the
antibodies. Cod insulin, for example, differs from human insulin in 33
amino acid positions compared with 3 differences for beef insulin. But
nonmammalian insulins are not available in the US at all.

This leaves the two treatments that are actually used on a regular
basis, and a promising new treatment.

Because this condition is rare, there's been little experience treating
it with lispro insulin (Humalog). That experience is promising; it
appears that the structural change in lispro may inhibit the antibody
binding. If this is borne out by further experience, lispro will be the
treatment of choice for extreme insulin resistance.

Glucorticoids such as prednisone decrease the extreme insulin
resistance, possibly by inhibiting the production of IgG antibodies. As
the antibodies have a half life of 3-4 weeks, the response is delayed,
during which time bg control is even more difficult due to the effects
of the glucocorticoids. After several weeks the dosage can be reduced
to maintenance levels or eliminated, but relapse is common. Since
glucocorticoids have other nasty effects in addition to the problems
listed above, there are significant problems with this course of
treatment.

Davidson's recommendation is based on The Good News: insulin resistance
is self-limited and only lasts a few months to a year. He simply uses
as much insulin as is needed in the meantime. U-500 concentration is
available for this purpose. The antibodies delay the action, so even
though U-500 is regular insulin it acts like a lente or semilente in
resistant patients. For unknown reasons, much less U-500 is needed than
the equivalent amount of U-100, 50% to 75% less. Since the situation is
difficult to manage and is temporary, Davidson advises not trying for
good bg control, but just avoiding ketosis and the overt symptoms of
hyperglycemia (thirst, excess urination, infections).

When insulin sensitivity returns, it can happen quite suddenly.
Davidson starts reducing the high insulin doses when fasting bg is
under 200 mg/dl (11.0 mmol/L). At these times, large amounts of insulin
previously bound to the antibodies may be released, so avoiding
hypoglycemia is a major concern. The return to normal sensitivity will
take at least several weeks due to the half-life of the antibodies, and
insulin requirements may fluctuate a great deal during this time. A
fast response to U-500 insulin (2-4 hours from injection to measurably
lower bg) may indicate the decline of insulin resistance.

[This was the movie. Now go read the book.]

------------------------------

Subject: What is pycnogenol? Where and how is it sold?

All sections on pycnogenol are written by Laura Clift <LauraRuss(AT)aol.com>.
Numbers in parentheses refer to the section on "Pycnogenol references".

Pycnogenol, a.k.a. Revenol, is a substance that has been mentioned in
misc.health.diabetes as an aid/cure for several diabetic complications.
Pycnogenol is a bioflavanoid, also identified as an oligomeric
proanthocyanidin (OPC) and a procyanidin, which is found in the bark of
conifers, specifically the maritime pine (_Pinus maritima_) and the Canadian
spruce (_Tsuga canadensis_) and in grape seeds. The substance was patented in
the US (patent 4,698,360) in 1985 by J. Masquelier of France.

Pycnogenol is sold on several web sites in addition to health food stores. The
web sites are set up in a pyramid scheme with the claims of quick riches for
new distributors. Most of the sales pitches rely on first-person
"testimonials". Some pitches include a list of published scientific studies
that, according to the pitch, support the claims of the ad. In the following
sections I examine the sales claims, investigate the ad's publication list,
and establish a bottom line.

------------------------------

Subject: What claims do the sales pitches make for pycnogenol?

Written by Laura Clift.

Pycnogenol or Revenol (super-enriched pycnogenol) claim to be the world's
most powerful anti-oxidant (vitamin C and E are anti-oxidants). The ads state
pycnogenol is non-toxic, non-mutagenic, has high bioavailability, crosses the
blood-brain barrier, enables vitamin C to remain in the body for 3 days as
opposed to 3 hours, increases capillary resistance, decreases capillary
fragility and permeability, decreases lower leg volume, strengthens collagen,
and remains active in the body for 72 hours.

Ads make claims that pycnogenol prevents, aids and/or cures the following
conditions:

  arthritis, cancer, AIDs, stomach pains, aches and pains, aging, abnormal
  menstrual bleeding, asthma, atherosclerosis, bruises, diabetic
  retinopathies, dry skin, edemas, excessive blood sugar, fatigue, hay fever,
  heart attacks due to vascular accidents, hemorrhoids, inflamed tissue,
  internal bleeding, jet lag, kidney disease, menstrual cramps, phlebitis,
  poor circulation, skin elasticity, strokes due to cerebral accidents,
  stress, ulcers, varicose veins, multiple sclerosis, prostate problems,
  sleep disorders, dog and horse cancers, attention deficit disorders, and
  increased physical endurance.

------------------------------

Subject: What's the real published scientific knowledge about pycnogenol?

Written by Laura Clift. (refs) point to "pycnogenol references" section.

In a study examining the anti-oxidant action of several bioflavanoids,
(-)-epicatechin 3-O-gallate and (-)-epigallocatechin 3-O-gallate were both
more potent than pycnogenol against the free radicals DPPH, superoxide anion,
OH, and OOH, although not by much (1).

The toxicity of pycnogenol is not established in published reports.
Proanthocyanidin mutagenicity is tricky, if it is completely pure it is
considered non-mutagenic. However, there is an impurity that is very similar
and hard to remove in the purification of proanthocyanidin that is mutagenic
(2).

No published work could be found on the bioavailability of pycnogenol in
particular, but oral ingestion of bioflavanoids in general results in a low
bioavailability (3).

Pycnogenol does cross the blood-brain barrier in rats when given as an
intraperitoneal injection (4). The same study seems to indicate that
pycnogenol can increase capillary resistance and decrease capillary
permeability in rats. A clinical study on 25 patients indicated an increase
in capillary resistance (5). When administered by intraperitoneal injection
to rats, chemically induced edema of the paw was decreased (6).

There are no published studies on pycnogenol's interaction with vitamin C and
most of the preventions, aids and/or cures claimed. However, procyanidol
oligomers offered no protection for venous disease from hypoxia (lack of
oxygen) (7).

------------------------------

Subject: How reliable is the literature cited by the pycnogenol ads?

Written by Laura Clift.

Masquelier J, Michaud J, Laparra J, Dumon MC. Flavanoids et pycnogenols. Int
J Vit Nutr Res 1979;49(3):307-11.

  Article in French. Abstract states that the article describes pycnogenol
  chemically designating the compound as "pycnogenol" to distinguish it from
  the hundreds of other bioflavanoinds.

Uchida S, Edamastu R, Hiramatsu M, et al. Condensed tannins scavenge active
oxygen free radicals. Med Sci Res 1987;15:831-2.

  Pycnogenol is a free radical scavenger (anti-oxidant) in vitro (outside of
  a living animal, or, in a petri plate).

Lagrue G, Oliver-Martin F, Grillot A. Etude des effects des oliomeres du
procyanidol sur la resistance capillaire dans l'hypertension arterielle et
certains nephropathies. La semaine des Hopitaux de Paris 1981; 57:1399-1401.

  French article. Abstract states capillary resistance increased in 25
  patients. No dose amount or route of administration in the abstract.

Cahn J, Borzeix MG. Etude de l'administration des oligomeres du
procyanidoliques chez le rat: Effets observes sur les alterations de la
permeabilite de la barrier hematoencephalique. La semaine des Hopitaux de
Paris 1983;59:2031-4.

  French article. Abstract states that pycnogenol crosses the blood-brain
  barrier in the rat and affects capillary permeability. Route and dose not
  presented in abstract.

Tixier JM, Godeau G, Rober AM, Hornebeck W. Evidence by in vivo and in vitro
studies that binding of pycnogenols to elastin affects its rate of
degradation by elastases. Biochem Pharmacol 1984;33(24):3933-9.

  Study with (+) catechin and pycnogenol (states they are related substances,
  but act differently, including the results of this study). Pycnogenol
  prevents the break down of elastin in vitro and in rabbits.

Kuttan R, Donnelly PV, DiFerrainte N. Collagen treated with (+)-catechin
becomes resistant to the action of mammalian aollagenase. Experentia
1981;37:221-3.

  (+) catechin is not pycnogenol (see above). Study does not investigate
  pycnogenol.

Reimann HJ, Lorenz W, Fischer M, et al. Histamine and acute hemorrhagic
lesions in rat gastric mucosa: prevention of stress ulcer formation by
(+)-catechin, an inhibitor of specific histidine decarboxylase in vitro.
Agents and Actions 1977;71:69-72.

  (+) catechin is not pycnogenol (see above). Study does not investigate
  pycnogenol.

Markle RA, Hollis TM. Rabbit aortic endothelial and medical histamine
synthesis following short-term cholesterol feeding. Exp Mol Pathol
1975;23:117-23.

Markle RA, Hollis TM. Variations in rabbit aortic endothelial and medical
histamine synthesis in pre- and early experimental atherosclerosis. Proc Soc
Exp Biol Med 1977;155:365-8.

Hollis TM, Furniss JV. Relationship between aortic histamine formation and
aortic albumin permeability in atherogenesis. Proc Soc Exp Biol Med
1980;165:271-4.

  Does not study pycnogenol or any bioflavanoid. Logic may go like this:
  pycnogenol is similar to (+) catechin which can effect histamines. Here are
  some cardiac/circulatory problems that are affected by histamine.
  Therefore, pycnogenol will prevent these diseases. Logic may be OK for a
  hypothesis but is flawed as a conclusion, especially since (+) catechin and
  pycnogenol act differently in most studies (see above).

Feine-Haake G. A new therapy for venous diseases with
3,3,4,4,5,7-hexa-dihydro-flauan. Z Allgemeinmed 1975;51(18):839.

  German article, no abstract translation; chemical name implies (+)-catechin
  was studied.

Blazso G, Gabor M. Oedema-inhibiting effect of procyanidin. Acta Physiol Acad
Sci Hung 1980;56(2):235-40.

  Chemically induced edema of a rat's paw was decreased with intraperitoneal
  injections of pycnogenol.

------------------------------

Subject: What's the bottom line on pycnogenol?

Written by Laura Clift. (refs) point to "pycnogenol references" section.

All bioflavanoids are anti-oxidants (1,8,9) and may effect capillary
hyperpermeability (8,9), inflammations (3,8), and edemas (8). However, there
is no bioflavanoid deficiency condition, and they have "no accepted
preventive or therapeutic role in vascular purpura, hypertension,
degenerative vascular disease, rheumatic fever, arthritis, cancer, or any
other condition" (9). This was as of 1988; no mention of bioflavanoids is
made in the 1994 edition of this reference. Most pycnogenol studies and/or
claims come from the early 70's to mid 80's. Promising starts are never
followed up on. Most later studies seem negative (both pycnogenol and
bioflavanoids), especially about the oral route. With all but one study
performed in rodents, there is a very definite lack of information on how
this substance acts in humans and what possible side-effects it produces.

The sales pitch seems to be taken from the 1985 patent. Filing a medical
patent doesn't mean the substance is thoroughly studied and its applications
are determined. A patent is filed when preliminary studies look promising and
you try to come up with every possibly use for the compound, no matter how
far out in left field it may be. If you do not hold the patent for the
application, someone else could conceivably use your compound for that
application and owe you nothing or a very reduced royalty.

In short, patent claims have no medical significance.

------------------------------

Subject: Pycnogenol references

Written by Laura Clift. This is the section to which the (refs) point.

1. Uchida S, Edamastu R, Hiramatsu M, et al. Condensed tannins scavenge active
oxygen free radicals. Med Sci Res 1987;15:831-2.

2.Yu CL, Swaminathan B. Mutagenicity of proanthocyanidins. Food Chem Toxicol
1987;25(2):135-9.

3. Namgoong SY, Son KH, Chang HW, Kang SS, Kim HP. Effects of naturally
ocurring flavanoids on mitogen-induced lymphocyte proliferation and mixed
lymphocyte culture. Life Sci 1994;54(5):313-20.

4. Cahn J, Borzeix MG. Etude de l'administration des oligomeres du
procyanidoliques chez le rat: Effets observes sur les alterations de la
permeabilite de la barrier hematoencephalique. La semaine des Hopitaux de
Paris 1983;59:2031-4.

5. Lagrue G, Oliver-Martin F, Grillot A. Etude des effects des oliomeres du
procyanidol sur la resistance capillaire dans l'hypertension arterielle et
certains nephropathies. Las semaine des Hopitaux de Paris 1981; 57:1399-1401.

6. Blazso G, Gabor M. Oedema-inhibiting effect of procyanidin. Acta Physiol
Acad Sci Hung 1980;56(2):235-40.

7. Michiels C, Arnould T, Houbion A, Remacle J. A comparative study of the
protective effect of different phlebotonic agents on endothelial cells in
hypoxia. Phlebologie 1991;44(3):779-86.

8. Lonchampt M, Guardiola B, Sicot N et al. Protective effect of a purified
flavanoid fraction against reactive oxygen radicals. in vivo and in vitro
study. Arzneimittelforschung 1989;39(8):882-5.

9. Shils ME. Modern nutrition in health and disease. Philadelphia: Lea and
Febiger, 1988. p472.

------------------------------

Subject: Who did this?