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Medical Forum / Diseases and Disorders / Diabetes / March 2006Insulin for Non-insulin type 2 diabetics
Insulin therapy for Non-insulin dependent type 2 diabetics: Some people have advocated the use of insulin therapy for non-insulin dependant type 2 diabetics. I bought into this idea about 2 years ago and generally have normal fasting blood glucose readings. It is sort of an art rather than a simple mechanical application. Part of the issue is the quality of the blood test prior to the low dose insulin injection. One of my objectives was to keep islet amyloid polypeptide (IAPP) plaque at a minimum by keeping demand endogenous insulin secretion down. This is a logical deduction since amylin is co-secreted with insulin. Since reading more about amylin analogs like Symlin (pramlintide). "As might be expected, because of the co-localization of both hormones within ß-cells, patients with type 1 diabetes have an absolute deficiency of both insulin and amylin, whereas patients with type 2 diabetes have a relative deficiency of both hormones, including a markedly impaired amylin and insulin response to meals (Figure 2B).15,28,29 These findings have led to questions of whether amylin deficiency contributes to the metabolic derangements in patients with type 1 or type 2 diabetes and, if so, whether amylin replacement might convey clinical benefit when used in conjunction with insulin replacement. Extensive studies with amylin and amylin antagonists in rodents and with pramlintide in patients with type 1 or type 2 diabetes have provided a solid understanding of the role of amylin in glucose homeostasis. Preclinical data indicate that amylin acts as a neuroendocrine hormone that complements the actions of insulin in postprandial glucose homeostasis via several mechanisms. These include a suppression of postprandial glucagon secretion and a slowing of the rate at which nutrients are delivered from the stomach to the small intestine for absorption. The net effect of these actions is to mitigate the influx of endogenous (liver-derived) and exogenous (meal-derived) glucose into the circulation and thus to better match the rate of insulin-mediated glucose clearance from the circulation (Figure 3)." Amylin Replacement With Pramlintide in Type 1 and Type 2 Diabetes: A Physiological Approach to Overcome Barriers With Insulin Therapy - http://clinical.diabetesjournals.org/cgi/content/full/20/3/137 It is considered a progressive therapy by some endocrinologist to use insulin injections at least temporarily in newly diagnosed type 2 diabetics inorder to bring these patients out of glucotoxicity. That may be the way to go as long as blood glucose and retinas are monitored closely so that edemas of the retinas are not induced. That is a separate issue from a low dose insulin therapy used to tweak basal blood glucose levels to be more in a normal range. As to whether or not the beta-cells are given a rest by not putting as much demand on them for insulin secretion is yet another issue. If one could also low dose with a amylin analog this might be a more ideal approach and would in some ways be similar to Byetta therapy, yet it would not impact the gut incretin hormones like GLP-1 and GIP. See figure 2B in the article cited above. I am not saying I have the answer diabetes management, but some of this remains a question in my mind. ;) Frank > Insulin therapy for Non-insulin dependent type 2 diabetics: > [quoted text clipped - 59 lines] > > Frank I have been thinking of this along the same lines. After three months of using a low dose of a 24 hour insulin (Lantus) and Novolog, I am finding I can eat more carbs and using less short term insulin (Novolog). Presently I don't need to use the Novolog except for inflamations like a cold or other event. > Amylin Replacement With Pramlintide in Type 1 and Type 2 Diabetes: A > Physiological Approach to Overcome Barriers With Insulin Therapy - > http://clinical.diabetesjournals.org/cgi/content/full/20/3/137 This article is well worth a read! Thanks for posting the link. One thing that I have not gotten clear in my mind is the functional difference between Symlin and Byetta (what changes one makes that the other does not). I've gotten the impression that endos think Symlin should be given to Type 1s and Byetta to type 2s. My doctor was all over me to try Byetta, but that was before I discovered I have a type 1 response to insulin. I'm going back to see her in a few weeks, and because I'm still having trouble with my post-meal numbers even with the basal working, I've been wondering which of these drugs (if any) would be the right one for me. Both seem to slow gastric emptying, increase weight gain, and lower blood sugar--when they work. Byetta apparently stimulates the beta cells. Since I experienced response to Starlix that also does that, I'm tending to think Symlin would be better. But the problem for me could be that it causes hypos. Anyone have any ideas about this? --Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control > Both seem to slow gastric emptying, increase weight gain, and lower > blood sugar--when they work. Byetta apparently stimulates the beta > cells. Since I experienced response to Starlix that also does that, I'm > tending to think Symlin would be better. But the problem for me could be > that it causes hypos. > Typo! I meant "since I experienced NO response to Starlix . . . " --Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control > One thing that I have not gotten clear in my mind is the functional > difference between Symlin and Byetta (what changes one makes that the [quoted text clipped - 6 lines] > trouble with my post-meal numbers even with the basal working, I've been > wondering which of these drugs (if any) would be the right one for me. > --Jenny Hi, Jenny. It doesn't help the confusion factor that both are from Amylin Pharmaceuticals, and that they have some overlapping mechanisms. I've been interested in these drugs for the past few years, so I'll try to share my understanding. I know that you already know some of this stuff, but I'll be a bit longwinded for those who don't. Symlin, generic name pramlintide acetate, is a synthetic amylin; Byetta, generic name extenitide, is a synthetic version of GLP-1 (Glucose Like Peptide-1). Byetta has had some media zing because it was discovered as a component in gila monster saliva. In a person with normal glucose regulation, eating causes a number of effects. The first, caused by the physical filling of the stomach, is the excretion of the gastric incretins GLP-1, and GIP (Gastric Inhibitory Polypeptide)from the stomach and GI tract in cells called enteroendocrine K and L cells. GIP is kinda interesting, although we're still trying to figure out what it does and how it works. The GIP hormone is secreted most in the presence of a high carb and high fat meal. It looks to me like we will discover that it has a counter-regulatory effect with GLP-1. It is also being explored as a weight loss tool because it seems to prevent obesity. Both are suspected in stimulating beta-cell creation, which may play a role helping Type-2s early in the progression of DM to "fully recover". Notice I never used the word "cure". :-) The GLP-1 hormone has the effect of telling the pancreas that an increase in glucose is on the way, so start releasing insulin. The amount of insulin release is modulated by the BG, so this is of special interest to Type-2s. It's of no known use to Type-1s, as they usually have no beta-cells left to stimulate. This makes Byetta a drug targeted exclusively to Type-2s. When the fast carbs are converted from glucose in both the mouth and stomach, the increase in glucose also causes the beta-cells to release Phase-I (stored) insulin. When the beta cells create insulin, they also create amylin, which is also known as Insulin Amyloid PolyPeptide (IAPP). Until recently, we didn't really know what amylin was good for. We did know it was absent or low in Type-1s, just like insulin. In Type-2s, we know that there is hyperamylinemia along with the hyperinsulinemia. (There is some evidence that hyperamylinemia is connected with Alzheimer's Disease, as an AD patient's cerebral cortex is likely to show amyloid plaque.) The alpha-cells in the pancreatic islets produce glucagon. Glucagon tells the liver to make glucose, so it is counter regulatory to insulin. When insulin goes up, glucagon is supposed to go down. In many Type-2s, it doesn't. This glucagon causes the liver to continue to produce unnecessary glucose and this causes higher BG after eating. Both amylin and Byetta seem to help turn down glucagon production by the alpha-cells, or perhaps block its action. Symlin and Byetta show similar actions on stomach emptying. GLP-1 tells the stomach that food is present, so it can slow down processing. Amylin tells the stomach that insulin has been released in a response to an increase in BG, so it can slow down processing. Amylin, like insulin, tells the liver that it can turn off glucose production. Amylin seems to work better at this in Type-2s whose livers' turn-off mechanism seems to be broken. Byetta claims this same effect. Amylin also seems to have an effect on the satiety perception of the brain, making people feel fuller on less food, so they tend to eat less and lose weight. Byetta does this, too. Overall, I'm enthusiastic about the research into both GLP-1 and GIP. I think a GIP analogue might turn out to be another winner in the battle with Type-2 and obesity. There is a really good article about the gastric incretins at http://www.medscape.com/viewarticle/474380 . I'm still a little skeptical about Symlin. The statistical results from the trials quoted in the PI show that at six months: Type-2s using insulin Mean reduction in A1c (from 9.1% !!!) a whopping half percent Mean reduction in weight of 1.7kg Mean reduction in bolus insulin of 3% Mean reduction in basal insulin of 0.2% Type-1s [using insulin] Mean reduction in A1c (from 8.9% !!!) a whopping 1/3 percent Mean reduction in weight of 1.7kg Mean reduction in bolus insulin of 3.6% Mean INCREASE in basal insulin of 1.9% Amylin calls these improvements statistically significant. I don't. Sorry this got so long. Bottom line: if you're Type-1 try Symlin, but not Byetta. If you are Type-2, try Byetta first with another drug like a sulf or metformin. If that doesn't work, try Symlin. Jim ------BTW, I don't personally use either. Yet. > Sorry this got so long. Bottom line: if you're Type-1 try Symlin, but not > Byetta. If you are Type-2, try Byetta first with another drug like a sulf > or metformin. If that doesn't work, try Symlin. > > Jim > ------BTW, I don't personally use either. Yet. Thanks, Jim - that's a keeper. Nicky.  SignatureA1c 10.5/5.4/<6 T2 DX 05/2004 1g Metformin, 100ug Thyroxine 95/74/72Kg i think this post of Jim's belongs on the web page for asd........ it's thorough and explicit in it's content good post, Jim kate SignatureJoin us in the Diabetic-Talk Chatroom on UnderNet /server irc.undernet.org --- /join #Diabetic-Talk More info: http://www.diabetic-talk.org/ http://www.diabetic-talk.org/freeveggies.htm I have no medical qualifications beyond my own experience. Choose your advisers carefully, because experience can be an expensive teacher. > > Sorry this got so long. Bottom line: if you're Type-1 try Symlin, but not > > Byetta. If you are Type-2, try Byetta first with another drug like a sulf [quoted text clipped - 6 lines] > > Nicky. J.C., Thanks so much. That is by far the most cogent explanation of how Symlin and Byetta work that I've seen anywhere! I agree that the data for Symlin's efficacy is disappointing. Byetta, when it works, seems to work dramatically, but it is not at all clear to me if it is mainly because it forces people to cut way back on the foods that push up blood sugar. So many people posting on the Byetta blog don't get the dramatic bg lowering. The suggestion that it causes beta cells to grow appears to me, anyway, to be only a suggestion from always-suspect rodent research, though one that is being pushed very hard by the salespeople. I must confess that I am curious whether any of these might have some near-magical effect on my postprandial numbers. Being human, I do respond to the dream of the magical cure even knowing it is a dream. But with my near-endless supply of bizarre physiological reactions to ordinary drugs that everyone else can take, I know that it would not be a good idea to experiment with these until I've exhausted all other alternatives which isn't yet. OTOH, with my odd physiology there's always the off chance that maybe it does supply some mystery element that would fix everything right up. It would be so nice if I had a doctor who had just the slightest tinge of idea what is going on with my weird-beard diabetes, but that is another dream that isn't happening anytime soon. I should be glad that at least I've finally got a diagnosis, even if it is "You have a special form of diabetes about which we know almost nothing." ===== J.C. Hartmann wrote a long and extremely lucid explanation of how Byetta and Symlin work repeated below > Symlin, generic name pramlintide acetate, is a synthetic amylin; Byetta, > generic name extenitide, is a synthetic version of GLP-1 (Glucose Like [quoted text clipped - 83 lines] > Jim > ------BTW, I don't personally use either. Yet. Signature--Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control Hi Jenny: > I agree that the data for Symlin's efficacy is disappointing. Byetta, > when it works, seems to work dramatically, but it is not at all clear to > me if it is mainly because it forces people to cut way back on the foods > that push up blood sugar.(snipped) JC Hartman said: >> I'm still a little skeptical about Symlin. The statistical results >> from the trials quoted in the PI show that at six months: >> >> Type-2s using insulin >> Mean reduction in A1c (from 9.1% !!!) a whopping half percent >> Mean reduction in weight of 1.7kg This is a near confirmation of the study below and maybe what the PI used for it's 6 month reference. Note that the placebo group continued to gain weight, so that the net weight change would more likely be 2.1 kg or 4.6 lbs - still not great. "RESULTS—Treatment with pramlintide 120 µg BID led to a sustained reduction from baseline in HbA1c (-0.68 and -0.62% at weeks 26 and 52, respectively), which was significantly greater than that seen with placebo (P < 0.05). The proportion of patients achieving an HbA1c <8% was approximately twofold greater with pramlintide (120 µg BID) than with placebo (46 vs. 28%, P < 0.05). The glycemic improvement with pramlintide 120 µg BID was accompanied by a mean weight loss (-1.4 kg vs. +0.7 kg with placebo at week 52, P < 0.05) and occurred without an overall increase in the severe hypoglycemia event rate." Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes - http://care.diabetesjournals.org/cgi/content/full/26/3/784 What I have posted below I previously posted in another thread. Effects of Pramlintide on Postprandial Glucose Excursions and Measures of Oxidative Stress in Patients With Type 1 Diabetes - http://care.diabetesjournals.org/cgi/content/full/28/3/632 While the title of this article mentions type 1 diabetes a lot of the Discussion section relates to type 2 diabetes as well. I have not seen anything that can have such a dramatic effect on oxidative stress in diabetics of any stripe. With the antioxidant status maintained there will be less inflammation. Things like COX-2 will be at a lower level. "The plasma concentrations of glucose and markers of oxidative stress (nitrotyrosine, oxidized LDL [ox-LDL], and total radical-trapping antioxidant parameter [TRAP]) were measured at baseline and during the 4-h postprandial period. Following injections of insulin alone (placebo), meal-induced increases in plasma glucose concentrations were associated with concomitant generation of oxidative stress, evidenced by a marked postprandial rise in plasma nitrotyrosine and ox-LDL, as well as antioxidant consumption, reflected by reduced TRAP values(Fig. 1). In contrast, postprandial excursions of nitrotyrosine and ox-LDL were significantly reduced and TRAP was significantly preserved with pramlintide treatment compared with placebo (Fig.1). ... Pronounced effects of pramlintide on postprandial oxidative stress were demonstrated by reductions of 100% in plasma nitrotyrosine and ox-LDL and a 100% preservation in plasma TRAP. These findings, observed with three independent markers, present a consistent and conclusive profile of pramlintide-mediated improvement in oxidative status. ... Therefore, results from this study demonstrate that preprandial administration of pramlintide is accompanied by conditions favoring protection of antioxidant capacity (TRAP) and systemic reductions in atherogenic and cytotoxic agents (ox-LDL and nitrotyrosine) (8,21) in the postprandial period." New Insights on Oxidative Stress and Diabetic Complications May Lead to a "Causal" Antioxidant Therapy - http://care.diabetesjournals.org/cgi/content/full/26/5/1589 Is Oxidative Stress the Pathogenic Mechanism Underlying Insulin Resistance, Diabetes, and Cardiovascular Disease? The Common Soil Hypothesis Revisited - http://atvb.ahajournals.org/cgi/content/full/24/5/816 A High Wire search for A. Ceriello resulted in 231 finds - http://tinyurl.com/lmd26. A High Wire search for Ceriello+oxidative+stress resulted in 486 finds - http://tinyurl.com/n5kuz. >> Mean reduction in bolus insulin of 3% >> Mean reduction in basal insulin of 0.2% [quoted text clipped - 6 lines] >> >> Amylin calls these improvements statistically significant. I don't. One of the most significant findings of Symlin(pramlintide)therapy has to do with oxidative stress. Within cells this stress occurs significantly within the mitochondria (the energy producing component of cells). The oxidative stress occurs largely in the postprandial state. If there is an antioxidant-oxidant imbalance, the mitochondrea of cells such as the pancreatic beta-cells (which do not have a very good antioxidant defense from the natural antioxidants: glutathione, catalase, and superoxide dismutase) are subject to having NFkappaB move out of the mitochondria and into the cytoplasm. This in turn promotes inflammation and cell death (by apoptosis). While it may sometimes seem like micro managing when people use their glucose meters to identify foods that cause spikes within a shorter time frame and then subsequently modify their diets to moderate these spikes, they are trying to reduce the oxidative stress that occurs when glucose (energy) combusts and thereby minimize this undesirable postsprandial effect. The graphics in figure 4 shows the impact of Symlin in a short time frame of 3 hours in type 1 DMs. The change would not be as great in type 2 DMs with remaining amylin production. http://clinical.diabetesjournals.org/cgi/content/full/20/3/137/FIG4 "The effects of pramlintide therapy on long-term glycemic control in patients with insulin-requiring type 1 or type 2 diabetes have been investigated in four double-blind, placebo-controlled, parallel-group, multicenter studies of 12 months’ duration.52–55 In all of these studies, subcutaneous injections of pramlintide were administered in addition to the patients’ existing insulin regimens (add-on design)." The graphics in figure 5A and 5B show the impact of Symlin in a 52 week (1 year) period for both type 1 and 2 DMs on A1c mean change. "Mean changes (standard error) from baseline in A1C (A and B) ... for patients with type 1 (A and C) or type 2 (B and D) diabetes treated with placebo + insulin or pramlintide + insulin. Statistical significance is denoted by * (P < 0.05) and ** (P < 0.001). In both types of diabetes, addition of pramlintide to existing insulin therapy led to significant and sustained reductions in both A1C ... ." http://clinical.diabetesjournals.org/cgi/content/full/20/3/137/FIG5 The impact of Symlin may vary significantly amongst patients. A local diabetic educator has mentioned one person who reduced insulin doses nearly in half. Frank > This is a near confirmation of the study below and maybe what the PI > used for it's 6 month reference. Note that the placebo group continued > to gain weight, so that the net weight change would more likely be 2.1 > kg or 4.6 lbs - still not great. <much good stuff snipped> The thing that stands out to me in all this, is that all these studies done with "diabetics" make no attempt to factor out what makes these diabetics diabetic. Certainly for Type 2 there are so many different spots along the insulin/glucose pathway that can be broken, that it makes sense that a drug that fixes something will be much more useful for a person who has it broken, than for someone who doesn't. I suspect even with type 1s, there are different levels of damage to the entire system, which would explain why some Type 1s find control relatively easy even with less than perfect insulin regimens and others can't get good control no matter what they do. If we only had a diagnostic process that investigated more than insulin and blood sugar level but looked at things like our levels of amylin, GLP-1, IGF-1 etc we might be better able to know whether drugs that affect these chemicals would help us. But I don't see the slightest hint that anything like that might ever happen. They are only now starting to talk about individual differences in drug metabolism. A bunch of media articles recently talked about "slow metabolizers" and suggested that people someday could have their genes s tested so they could benefit better from medications . But the thing driving this is not a desire to help patients chose drugs wisely. It is that there are a number of drugs in the pipeline that could earn a lot of money for the drug companies except that clinical trials show that they are toxic to slow metabolizers. This usually keeps a drug from being approved, so the big drug companies are now trying to find a way around this--hence the emphasis popularizing the idea that people could be genetically tested to find the "right drug" for them. --Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control Hi Jenny: > The thing that stands out to me in all this, is that all these studies > done with "diabetics" make no attempt to factor out what makes these > diabetics diabetic. Certainly for Type 2 there are so many different > spots along the insulin/glucose pathway that can be broken, that it > makes sense that a drug that fixes something will be much more useful > for a person who has it broken, than for someone who doesn't. Agreed. The only type 2s that maybe identical are identical twins. (snipped) > If we only had a diagnostic process that investigated more than insulin > and blood sugar level but looked at things like our levels of amylin, [quoted text clipped - 13 lines] > around this--hence the emphasis popularizing the idea that people could > be genetically tested to find the "right drug" for them. I suspect you might even be considering variation in micronutrient needs, balances, etc. There are probably as many polymorphism as there are people. No two snow flakes alike theory. ;) In a Jul 23 2004 post I said: "Do you have a conceptual model for a matrix that would combine food and supplement intake that would result in an appropriate balance within the matrix? Given that some forms of vitamins are in a reserve form, time would be part of this kind of model, I presume. Enzymes play a part in the speed of reactions and the appropriate level of each vitamin intake that is a precursors to the coenzyme is a factor including their bioavailability. Since people have variable requirements, I'm just trying to get some notion of a general model." http://tinyurl.com/q6tvc Apparently some technology is evolving, but a database for each individual would be massive. Science fiction tech tommorrow. Measuring blood sugar with a wave of the arm - http://www.eurekalert.org/pub_releases/2004-06/acs-bs062804.php Sensor Letters - http://www.aspbs.com/sensorlett/ Article by Lester Packer - http://www.gotyournumber.com/_downloads/packer.html Main page: http://www.gotyournumber.com/main.html --- I first saw a demonstration of the device mentioned at a mall. The people were trying to sell vitamin supplements. Knowledge about how a persons body is functioning is necessary for a proactive approach to health. I had a scan done and it was no big deal. The problem as I see it was it was focused on one type of antioxidant - carotenoid antioxidants which are fat soluble. According to this test, I had a better than average antioxidant status. Resonance Raman detection of carotenoid antioxidants in living human tissues - http://www.nutritionfilecabinet.com/_downloads/4Tissue_Carotoids.pdf Coming back to the subject of this thread: The abstract for the following is available at the Diabetes site, but the full article won't be available there until June or July. We lucked out. I had the abstract of this one in my tickler file as a reminder. Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like Peptide 1 - http://www.medscape.com/viewarticle/523581_print Frank > Coming back to the subject of this thread: > The abstract for the following is available at the Diabetes site, but [quoted text clipped - 3 lines] > Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like > Peptide 1 - http://www.medscape.com/viewarticle/523581_print Yet another keeper! Thanks for hunting this stuff down for us! --Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control > "The plasma concentrations of glucose and markers of oxidative stress (nitrotyrosine, oxidized LDL [ox-LDL], and total radical-trapping antioxidant parameter [TRAP]) were measured at baseline and during the 4-h postprandial period. " I've seen a lot of plausible sounding arguments that LDL per se is of no particular consequence w.r.t atherosclerosis - it's the oxidized LDL that does the damage. Are there common lab tests for oxidized LDL, or is this just a test that research labs run? Are these tests standardized enough, or does one need a rich description of the "lab normal" outcomes in order to interpret the result? Is there one widespread test, or are there a bunch of different methods, with varying accuracies, to choose from? Is getting a reading after overnight fasting enough, or does one need multiple draws to get a meaningful measure? If I pressure my endo to test my oxidized LDL, am I asking for a $20 test or a $600 test? Anybody? Thanks Adam Becker This post not CC'd by email On 13 Mar 2006 14:04:25 -0800, "Adam Becker Sr" <adam_becker_sr@yahoo.com> wrote: >> "The plasma concentrations of glucose and markers of oxidative stress (nitrotyrosine, oxidized LDL [ox-LDL], and total radical-trapping antioxidant parameter [TRAP]) were measured at baseline and during the 4-h postprandial period. " > [quoted text clipped - 15 lines] >Thanks >Adam Becker G'day G'day Adam, There are sophisticated tests for oxidized LDL anti-bodies. Then there is the ASD quick and dirty test. Calculated the TG:HDL ratio. The TG:HDL ratio is an indicator of several related phenomenon; insulin resistance, small dense LDL (sd-LDL). LDL gets to be small dense and twice as nasty by being glycated and oxidised. I take it that what you are really wanting to know is how nasty you LDL is rather than to become some data point of one scientific experiment. If that is so then TG:HDL will get you the result you are looking for without requiring any other test so you should find the price attractive. Best wishes SignatureQuentin Grady ^ ^ / New Zealand, >#,#< [ / \ /\ "... and the blind dog was leading." http://homepages.paradise.net.nz/quentin > G'day G'day Adam, > [quoted text clipped - 9 lines] > result you are looking for without requiring any other test so you > should find the price attractive. Can you explain some more? Calculate the TG/HDL ratio & then do what to find out the oxidised LDL? >>G'day G'day Adam, >> [quoted text clipped - 12 lines] > Can you explain some more? Calculate the TG/HDL ratio & > then do what to find out the oxidised LDL? A TGL/HDL ratio under 3 (the lower the better) is a marker for larger, fluffier LDL. It's the small (VLDL) dense LDL which oxidizes and causes damage. Susan > x-no-archive: yes > [quoted text clipped - 18 lines] > fluffier LDL. It's the small (VLDL) dense LDL which oxidizes and > causes damage. So if someone has 100 TGL & 50 HDL & a high value of LDL, say 200, is it not bad? The ratio works out to 2 i.e. less than 3. Should one worry only when both the TGL & LDL are are high? > So if someone has 100 TGL & 50 HDL & a high value of > LDL, say 200, is it not bad? > The ratio works out to 2 i.e. less than 3. > Should one worry only when both the TGL & LDL are are > high? I would say it might not be bad and other factors should be examined. Additional factors to consider are bg (fasting and post prandial), HbA1c, CRP, fibrinogen, fasting insulin, etc... Susan > So if someone has 100 TGL & 50 HDL & a high value of > LDL, say 200, is it not bad? > The ratio works out to 2 i.e. less than 3. > Should one worry only when both the TGL & LDL are are > high? My total cholesterol hovers around 300, but my triglycerides are 106 and my HDL is 67 and that works out very well. I had genetic testing as part of a study, BTW, that confirmed that I have a gene for a kind of light fluffy cholesterol that is associated with longevity. My dad had the same gene and lived to be 100. His cholesterol in his 60s was 340. He did not die of heart disease. So yes, Total Cholesterol alone is not a good index to CV health. The reason doctors harp on it is that they have a drug that will lower LDL without doing anything for triglycerides or HDL. LDL Particle Size seems to be a much better indicator of risk. --Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control >> x-no-archive: yes >> [quoted text clipped - 24 lines] >Should one worry only when both the TGL & LDL are are >high? Hi Just I can't answer the question, except to say that when I was exactly in that position I chose to go back on lipitor20mg. On the more specific ratio of trigs to HDL, and it's implications for LDL components, this study gives some pointers. Note that the ratio of 1.33 mentioned here translates to a ratio of 3.0 for mg/dl users. http://care.diabetesjournals.org/cgi/reprint/23/11/1679.pdf Ratio of Triglycerides to HDL Cholesterol Is an Indicator of LDL Particle Size in Patients With Type 2 Diabetes and Normal HDL Cholesterol Levels RESEARCH DESIGN AND METHODS Sixty patients with type 2 diabetes with acceptable glycemic control and an HDL cholesterol level 1 mmol/l were recruited after cessation of lipid-altering treatments. LDL size was determined by 220% PAGE; patients having small LDL (n = 30) were compared with those having intermediate or large LDL (n = 30). RESULTS Clinical characteristics, pharmacological therapies, lifestyle, and prevalence of diabetes-related complications were similar in both patient groups. LDL size correlated negatively with plasma triglycerides (TGs) (R2 = 0.52) and positively with HDL cholesterol (R2 = 0.14). However, an inverse correlation between the TGtoHDL cholesterol molar ratio and LDL size was even stronger (R2 = 0.59). The ratio was 1.33 in 90% of the patients with small LDL particles (95% CI 79.3100) and 16.5% of those with larger LDL particles. A cutoff point of 1.33 for the TGtoHDL cholesterol ratio distinguishes between patients having small LDL values better than TG cutoff of 1.70 and 1.45 mmol/l. CONCLUSIONS The TGtoHDL cholesterol ratio may be related to the processes involved in LDL size pathophysiology and relevant with regard to the risk of clinical vascular disease. It may be suitable for the selection of patients needing an earlier and aggressive treatment of lipid abnormalities. Diabetes Care 23:16791685, 2000 .............. Cheers, Alan, T2, Australia. d&e, metformin 2x500mg SignatureEverything in Moderation - Except Laughter. This post not CC'd by email >> G'day G'day Adam, >> [quoted text clipped - 12 lines] >Can you explain some more? Calculate the TG/HDL ratio & >then do what to find out the oxidised LDL? G'day G'day Just, This seems to have been a popular thread and the existing answers are probably more than adequate for the intended purpose. Possibility A. You really want to test how much oxidised LDL you have. Sorry can't help. There are at least two approaches. One is to get the LDL fractionated. The small dense LDL is oxidised. Secondly get the antibodies to oxidised LDL measured. The body doesn't like oxidised LDL so produces antibodies to it. Ordinary LDL is doesn't stimulate the production of these antibodies. Possibility B. When I comes to spending cold cash you are really more interested in knowing how safe is your LDL. This is much easier and requires no extra tests to be performed. Divide the Triglyceride number by the HDL number. If American mg/100ml units are used then you are looking for a ratio less than 3. If the International mmol/L units are used then you are looking for a ratio less than 1.33 If the ratio is low, then it is a strong indicator that your LDL isn't oxidised. As a rough rule of thumb, fluffy non-oxidised LDL is half as dangerous as the oxidised stuff that is small dense and nasty. If you want to explore other issues you could probably get tests such as the C-reactive protein, CRP test done. Remember this, the latest guidelines for introducing statins are either elevated LDL or CRP. 2 parts per million of CRP is considered unhealthy. One way to deal with CRP is eat greens preferably cooked with extra virgin olive oil, have turmeric regularly or include some bromelain as a supplement. You have plenty of choices. Best wishes, SignatureQuentin Grady ^ ^ / New Zealand, >#,#< [ / \ /\ "... and the blind dog was leading." http://homepages.paradise.net.nz/quentin > Possibility B. When I comes to spending cold cash you are really more > interested in knowing how safe is your LDL. This is much easier and [quoted text clipped - 20 lines] > virgin olive oil, have turmeric regularly or include some bromelain as > a supplement. You have plenty of choices. Thank you, Quentin. > G'day G'day Adam, > > There are sophisticated tests for oxidized LDL anti-bodies. > Then there is the ASD quick and dirty test. > > Calculated the TG:HDL ratio. AIP values of -0.3 to 0.1 are associated with low, 0.1 to 0.24 with medium and above 0.24 with high CV risk. A friend just sent me this. The AIP is a souped up version of the TG:HDL ratio. It is log TG/HDL in MMOL/L. For Americans, you have to convert the TG into mmol/L (divide mg/dl by 89) and convert the HDL to mmol/L by dividing by 39. Then use a logarithm calculator to get the log. (There are several online.) [AIP--atherogenic index of plasma like significant predictor of cardiovascular risk: from research to practice] PG - 64-71 AB - BACKGROUND: Various indices have been used for the diagnosis and prognosis of cardiovascular disease (CVD). Atherogenic index of plasma (AIP) is a logarithmically transformed ratio of molar concentrations of triglycerides to HDL-cholesterol. The strong correlation of AIP with lipoprotein particle size may explain its high predictive value. Here we summarize data on AIP calculated in 8394 subjects from 6 population and clinical studies. RESULTS: AIP values increase with increasing CV risk. Thus umbilical cord, young children, healthy women have values below 0.1 while men and subjects with CV risk factors such as hypertension, diabetes, dyslipidemia have increasing values up to 0.4. Based on these data we suggest that AIP values of -0.3 to 0.1 are associated with low, 0.1 to 0.24 with medium and above 0.24 with high CV risk. In the population study men had higher AIP values than women. In a cohort undergoing coronary angiography AIP, in model that included age, BMI, waist circumference, type 2. DM, blood pressure, smoking, TG, TC, LDL-C, apoB, HDL-C, and TC/HDL-C, AIP was the best predictor of positive findings. AIP was also a highly sensitive marker of differences of lipoprotein profiles in families of patients with premature myocardial infarction and control families. Treatment with ciprofibrate, and combination of statin and niacin dramatically decreased AIP. Combination with hypoglycemic therapy that included pioglitazone decreased AIP in patiens with type 2. diabetes. CONCLUSIONS: AIP can be easily calculated from standard lipid profile. As a marker of lipoprotein particle size it adds predictive value beyond that of the individual lipids, and/or TC/HDL-C ratio. AD - Fyziologicky ustav Akademie ved Ceske republiky, dobias@biomed.cas.cz FAU - Dobiasova, M AU - Dobiasova M LA - cze PT - Journal Article TT - AIP--aterogenni index plazmy jako vyznamny prediktor kardiovaskularniho rizika: od vyzkumu do praxe. PL - Czech Republic TA - Vnitr Lek JT - Vnitr inverted question markni lekar inverted question markstvi. JID - 0413602 SB - IM EDAT- 2006/03/11 09:00 Signature--Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control >> G'day G'day Adam, >> [quoted text clipped - 5 lines] >AIP values of -0.3 to 0.1 are associated with low, 0.1 to > 0.24 with medium and above 0.24 with high CV risk. <snip> Hi Jenny, and anyone else interested in lipids. I played around with that in Excel, and came up with the following table: TG/HDL mmol/L TG/HDL mg/dl LogTG/HDL mmol/L 0.5 1.15 -0.3 1.26 2.9 0.1 1.74 4.0 0.24 So, "0.1" for the crossover from low to medium risk relates fairly closely to the other TG/HDL recommended ratio of less than 1.3 for mmol/L and 3.0 for mg/dl. Coincidence is an odd thing. I was looking for "The plasma parameter log (TG/HDL-C) as an atherogenic index" as part of preparing an answer for Just; that was the first time I'd heard of using the log of the TG/HDL ratio and FERHDL - and I read your post while waiting for Highwire to finish the search. I'm still trying to get time to read some of the results of this search - but I think you'll find it worthwhile to wander through some of the others that came up in that single search: Highwire: http://tinyurl.com/l3be7 There are some fascinating subject titles there; so much to read, so little time:-) Cheers, Alan, T2, Australia. d&e, metformin 2x500mg SignatureEverything in Moderation - Except Laughter. > AIP values of -0.3 to 0.1 are associated with low, 0.1 to > 0.24 with medium and above 0.24 with high CV risk. [quoted text clipped - 5 lines] > and convert the HDL to mmol/L by dividing by 39. Then use a logarithm > calculator to get the log. (There are several online.) log base what? I still have my old log charts from Way Back When (before portable calculators...& then there are the handheld versions called "slide rules".) & doing that stuff would be good for my brain-exercise-program anyway. :) bj >> AIP values of -0.3 to 0.1 are associated with low, 0.1 to >> 0.24 with medium and above 0.24 with high CV risk. >> >> A friend just sent me this. The AIP is a souped up version of the TG:HDL >> ratio. It is log TG/HDL in MMOL/L. > log base what? 10 I was once the proud owner of an expensive slide rule, too. <g> --Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control > I was once the proud owner of an expensive slide rule, too. <g> <sigh> I haven't seen mine around in years, & I have looked & kept an eye out for it when I do general clearouts which, over the years, have hit just about every nook & cranny in the house. I still hope it'll turn up. I do have my father's, though. I'm not sure of its vintage, but he graduated from USNA in 1938. I also have a cheapo (maybe a trade-show give-away eons ago) pocket size that *might* do for e-z-arithmetic. bj >>> AIP values of -0.3 to 0.1 are associated with low, 0.1 to >>> 0.24 with medium and above 0.24 with high CV risk. >>> >>> A friend just sent me this. The AIP is a souped up version of the TG:HDL >>> ratio. It is log TG/HDL in MMOL/L. >> log base what? > 10 <cough> It doesn't matter what the base is, if you're dividing one log by another. </cough> :-) SignatureChris Malcolm cam@infirmatics.ed.ac.uk +44 (0)131 651 3445 DoD #205 IPAB, Informatics, JCMB, King's Buildings, Edinburgh, EH9 3JZ, UK [http://www.dai.ed.ac.uk/homes/cam/] >>>> AIP values of -0.3 to 0.1 are associated with low, 0.1 to >>>> 0.24 with medium and above 0.24 with high CV risk. [quoted text clipped - 9 lines] > <cough> It doesn't matter what the base is, if you're dividing one log > by another. </cough> :-) But you're not -- at least the way it's written here -- you're taking the log of the result of a division, and comparing the result to various values. bj ><cough> It doesn't matter what the base is, if you're dividing one log >by another. </cough> :-) In the example I was giving the log of the result. Cheers, Alan, T2, Australia. d&e, metformin 2x500mg SignatureEverything in Moderation - Except Laughter. >> AIP values of -0.3 to 0.1 are associated with low, 0.1 to >> 0.24 with medium and above 0.24 with high CV risk. [quoted text clipped - 12 lines] >:) >bj I presumed standard base 10 (geez - dredging the memory from high school here) and those appeared to correlate well. I just put =log(term) into Excel. Cheers, Alan, T2, Australia. d&e, metformin 2x500mg SignatureEverything in Moderation - Except Laughter. >>log base what? >> > I presumed standard base 10 (geez - dredging the memory from > high school here) and those appeared to correlate well. geez, indeed! I've just gotten the first salvo of communications about my <mmmphieth> high school reunion. And I regularly browse my library for "what can I get rid of...." (with occasional success). My old log booklet (from mid-50's) & my college CRC continue to be keepers. I actually do use the CRC occasionally to look something up! bj >Sorry this got so long. I'm not:-) Thanks, Jim. Cheers, Alan, T2, Australia. d&e, metformin 2x500mg SignatureEverything in Moderation - Except Laughter. >> One thing that I have not gotten clear in my mind is the functional >> difference between Symlin and Byetta (what changes one makes that the [quoted text clipped - 102 lines] >Jim >------BTW, I don't personally use either. Yet. Thanks Jim, very helpful post. Sleepy ------------------------------------------------------------------ It is easier to make a saint out of a libertine than out of a prig. -George Santayana (1863-1952) ------------------------------------------------------------------ >> Amylin Replacement With Pramlintide in Type 1 and Type 2 Diabetes: A >> Physiological Approach to Overcome Barriers With Insulin Therapy - [quoted text clipped - 5 lines] > difference between Symlin and Byetta (what changes one makes that the > other does not). The way I see it, Byetta addresses more blood glucose related hormones than would an insulin and Symlin therapy. One aspect is that Byetta increases endogenous insulin secretion so that it will have an impact on the portal vein. "In the diabetic state, there is inadequate suppression of postprandial glucagon secretion (hyperglucagonemia)41,42 resulting in elevated hepatic glucose production (Figure 4). Importantly, exogenously administered insulin is unable both to restore normal postprandial insulin concentrations in the portal vein and to suppress glucagon secretion through a paracrine effect. This results in an abnormally high glucagon-to-insulin ratio that favors the release of hepatic glucose.43 These limits of exogenously administered insulin therapy are well documented in individuals with type 1 or type 2 diabetes and are considered to be important contributors to the postprandial hyperglycemic state characteristic of diabetes." Glucose Metabolism and Regulation: Beyond Insulin and Glucagon - http://spectrum.diabetesjournals.org/cgi/content/full/17/3/183 Both Byetta and Symlin effect the same area of the brain and thus suppress appetite. Both drugs slow the exit of food from the stomach to the small intestine. Symlin does not have all the incretin effects of a GLP-1 mimetic or a DPP-IV inhibitor. ("In addition to incretin mimetics, research indicates that DPP-IV inhibitors may improve glucose control by increasing the action of native GLP-1." op. cite) > I've gotten the impression that endos think Symlin should be given to > Type 1s and Byetta to type 2s. My doctor was all over me to try Byetta, > but that was before I discovered I have a type 1 response to insulin. I know you have relatively low insulin resistance for a type 2 DM, but so do I. I don't have any reason to suspect some form of MODY in my case however. Your insulin dose is about half of mine (5 units versus 10 units of long acting). Byetta does improve the proinsulin:insulin ratio which indicates an improved beta-cell function. It remains to be proven whether beta-cell mass is increased in human such as it is in some animal species. Upon reconsideration since I don't inject insulin with meals, the main secretion amylin would not be decreased by exogenous insulin. Yet any amylin that might be secreted throughout the night would be reduced together with any remaining pulsatile insulin secretion. Until you get either Byetta or Symlin, you will need to use metformin to keep glucse levels down by inhibiting gluconeogenesis and glycogenolysis. "Gluconeogenesis, glycogenolysis and glycogen synthesis can be altered by metformin, although in vivo, this also depends on the methodology. Component processes from substrate supply and liver uptake, through a number of glucogenic enzymes, as well as glycogen synthase and phosphorylase have all been shown to be affected. (iii) unifying concepts: reported actions of metformin on the mitochondrial respiratory chain, free fatty acid metabolism, AMP-activated protein kinase, and on membrane proteins directly may all explain subsets of actions that are seen, providing more integrated targets for consideration in the therapy of DM2." Metformin and its Liver Targets in the Treatment of Type 2 Diabetes - http://www.ingentaconnect.com/content/ben/cdtiemd/2003/00000003/00000002/art00006 Somewhat like GLP-1, Byetta does inhibit glucagon secretion. "Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic {alpha} cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogastrone in humans." Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans - http://gut.bmjjournals.com/cgi/content/abstract/55/2/243 Glucose homeostasis: roles of insulin, glucagon, amylin, and GLP-1 - http://spectrum.diabetesjournals.org/cgi/content/full/17/3/183/FIG3 Frank > One aspect is that Byetta > increases endogenous insulin secretion so that it will have an impact on > the portal vein. Back in August I was having overall good control (A1Cs running 4.8 to 5.2) but my FBG was climbing - many mornings 120-130 mg/dl. I was (and still am) taking 2000mg/d metformin and 5mg/d resulin. I asked my endo about taking an evening shot of insulin. He counseled me to try Byetta (exanitide) instead. I started on 5mcg 2X/d, increased to 10mcg after two months. He mentioned the same point Jefferson did - Exanitide not only restores insulin, but it does it in the most phsyiologicly (sp?) appropriate way (which injection doesn't.) Also, it restores the amylin, which injectible insulin doesn't. Byetta: This stuff is great! My FBGs usually run 90-110 now. Moreover, I've been able to add some fruit back into my breakfast routine and still keep my 1 and 2 hour postprandials well below 140. Plus I've lost another 5 lbs (and that's in addition to the 50 lbs I lost between my diagnosis 6+ yrs ago and when I started the Byetta.) The nausea is a problem. Most days I get no nausea. About once a month it's bad enough that I throw up. Another 3-4 times a month it's severe enough that I can't eat my dinner. But it's improved my glycemic control enough that I'm more than willing to put up with it. One other downside to it is that it changes my tastes. On Byetta, I can't handle really intense savory tastes like I used to. Last year, I was often eating a can of sardines for breakfast (and enjoying it!) On Byetta, I just can't hack the intense taste. Instead, I've been eating herring with sour cream. It's only available around here with some added sugar, but I find I can tolerate that now. Byetta allows me to tolerate more carb. OTOH, it makes me more hungry for carb. As I said, it's allowed me to add a substantial amount of fruit to my diet. One strange evening - back in mid-Feb, I completely fell off the wagon one evening and gorged on a pint of chocolate ice cream (about an hour after injecting Byetta.) Forty min later, I felt really weird, shaky. Checked my BG, expecting to be over 200. Instead I was running 48 mg/dl (?!) On a quick retest, it was 52. I ate a large orange and went out for a 2 mile walk; when I got back my BG was in the 90s, as it was a few hours later. I have indications that I probably could tolerate a lot more carb in my diet than I'm eating now. It's easier for me to eat no bread at all than a half a slice, though. So I'm still low carbing it, except for the fruit - especially citrus and apples, which I'd really missed. Even on evening when I've occaisonally skipped the Byetta, I have the impression that I handle some carb better. (Maybe some of my beta cells recovering? not sure, but I can hope.) I quit posting here back in July when my daughter was born. She's well and is darling. Just didn't have the time to post. I'm hoping to gradually start posting again. Cheers Adam Becker T2, 50 yrs > I quit posting here back in July when my daughter was born. She's well > and is darling. Just didn't have the time to post. I'm hoping to > gradually start posting again. Good to see you again, Adam - and nice to know things are going well for you. Nicky. SignatureA1c 10.5/5.4/<6 T2 DX 05/2004 1g Metformin, 100ug Thyroxine 95/74/72Kg >I quit posting here back in July when my daughter was born. She's well >and is darling. Just didn't have the time to post. I'm hoping to >gradually start posting again. Hi Adam Good to hear from you. Have the doctors given any advice on ways to solve the nausea problem? I know you're prepared to pay that price for control, but not everyone will. Cheers, Alan, T2, Australia. d&e, metformin 2x500mg SignatureEverything in Moderation - Except Laughter. congratulations to the new addition to the Becker family i'll look forward to you posting again Adam! kate SignatureJoin us in the Diabetic-Talk Chatroom on UnderNet /server irc.undernet.org --- /join #Diabetic-Talk More info: http://www.diabetic-talk.org/ http://www.diabetic-talk.org/freeveggies.htm I have no medical qualifications beyond my own experience. Choose your advisers carefully, because experience can be an expensive teacher. "Adam Becker Sr" <> wrote in message ... > I quit posting here back in July when my daughter was born. She's well > and is darling. Just didn't have the time to post. I'm hoping to [quoted text clipped - 3 lines] > Adam Becker > T2, 50 yrs > I know you have relatively low insulin resistance for a type 2 DM, but > so do I. I don't have any reason to suspect some form of MODY in my case > however. Your insulin dose is about half of mine (5 units versus 10 > units of long acting). Actually, my dose is between 3.5 and 4 units that's enough to keep me in the 80s fasting and 90s 1 hour after eating lunch and after a late afternoon snack. And to make a HUGE difference in my energy level. My insulin went bad last week and it took me a while to figure out that something was wrong with he insulin because I felt so sick and exhausted that I thought the higher blood sugars were because I was coming down with something. Finally, I noticed little crystals on the side of the vial yesterday and opened a new one today, and lo and behold 3 hours later I was so energetic I felt ready to tap dance my way down the street like Judy Garland in one of those Mickey Rooney movies. My blood sugar was 83 when I finally got home and tested instead of 115. So for me, something about the injected insulin makes my whole body happy in a way that must be doing other things than just lowering the blood sugar. So I'm not sure I really want to stimulate more of my homemade stuff since it doesn't make me feel good, and in fact, when it is high (when I spike) I feel poisoned. Always have. Thanks for pointing out the part about the insulin being secreted into the portal vein. That is important because the article makes it clear subcutaneous insulin does miss having some important effects on the liver. I do still take metformin. --Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control >So for me, something about the injected insulin makes my whole body >happy in a way that must be doing other things than just lowering the >blood sugar. Maybe you should buy it in the pharmacist instead of street-corners? (couldn't resist:-) Cheers, Alan, T2, Australia. d&e, metformin 2x500mg SignatureEverything in Moderation - Except Laughter. > Maybe you should buy it in the pharmacist instead of > street-corners? (couldn't resist:-) You're not the only one. You wouldn't believe the Junkie jokes I have to put up with around the house. <g> --Jenny http://www.phlaunt.com/diabetes Diabetes Info http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood Sugar Under Control |
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