2005-07-28, Responding to ironjustice@aol.com...

Time for your meds again Tommy.

http://tinyurl.com/4thvq

This is interesting, right now I know a woman who is being treated for
excessive storage of iron, they actually bleed her, like the old
fashioned leaching!  She meets most of the criteria  I on the other
hand meet all of the criteria and am iron defficient.  Go figure.--fran

Body iron stores are increased in overweight and obese women with polycystic
ovary syndrome.(BRIEF REPORT: Pathophysiology/Complications)
Diabetes Care; 8/1/2005; San Millan, Jose L.

Increased body iron stores are associated with insulin resistance and type 2
diabetes. In conceptual agreement, increased serum ferritin levels are
positively associated with the prevalence of the metabolic syndrome in men
and adult pre-and postmenopausal women (1) and with an increased risk of
type 2 diabetes in both men (2) and women (2,3). Given that insulin
resistance and an increased risk of type 2 diabetes are frequent in patients
with polycystic ovary syndrome (PCOS) (4,5), we hypothesize that body iron
stores might be especially increased in these women.
RESEARCH DESIGN AND METHODS--We studied 78 patients with PCOS and 43
nonhyperandrogenic control subjects matched for BMI and degree of obesity
(6). Women were phenotyped to determine clinical, anthropometrical hormonal
and metabolic variables as described previously (7). Serum ferritin and
C-reactive protein (CRP) concentrations were measured by automated
immunochemiluminescence (Immulite 2000 Ferritin and High Sensitivity CRP;
Diagnostic Products, Los Angeles, CA) with lower limits of detection of 0.9
pmol/l and 0.1 mg/l, respectively. None of the women had a history of
abnormal glucose tolerance or had taken insulin sensitizers in the previous
6 months. The ethics committee of Hospital Ramon y Cajal approved the study,
and informed consent was obtained from all participants.
Data were analyzed by general linear model after ensuring a normal
distribution of the variables by logarithmic or square-root transformations,
introducing PCOS or control status and degree of obesity or abnormal glucose
tolerance as independent variables and age as a covariate. P < 0.05 was
considered statistically significant.
RESULTS--Ferritin levels were increased in overweight and obese women with
PCOS compared with overweight and obese control subjects, given that a
significant interaction (F = 3.694, P = 0.028) between PCOS status and the
degree of obesity was found (Fig. 1A). However, no difference independent of
obesity was found between the PCOS patients and the control subjects (F =
1.395, P = 0.240), and no difference independent of PCOS status was found
between the lean, overweight, and obese women (F = 2.244, P = 0.111) (Fig.
1A).
[FIGURE 1 OMITTED]
Ferritin is considered an inflammatory marker. We therefore measured the
serum levels of the inflammatory marker CRP in these women to assess the
potential confounding effect of chronic inflammation on the observed
increase in ferritin levels.
CRP levels increased steadily from lean women to overweight and obese
individuals, irrespective of their PCOS or control status (F = 29.285, P <
0.001), and no differences were found between PCOS patients and control
subjects (F = 0.545, P = 0.462), suggesting that the increased ferritin
levels observed in overweight and obese PCOS patients were independent from
chronic inflammation (Fig. 1B).
Undiagnosed type 2 diabetes (2-h oral glucose tolerance test serum glucose
[greater than or equal to] 11.1 mmol/l) was present in three PCOS patients
(3.8%) and in no control subjects, whereas glucose intolerance (2-h oral
glucose tolerance test serum glucose 7.8-11.0 mmol/l) was found in six PCOS
patients (7.7%) and in three control subjects (7.0%). All of the women
presenting with a disorder of glucose tolerance were overweight or obese.
Ferritin levels were increased in the 12 women with abnormal glucose
tolerance compared with the 109 euglycemic subjects (F = 5.468, P = 0.021),
irrespective of PCOS or control status (F = 0.289, P = 0.592) (Fig. 1C).
Because the periodic blood loss resulting from regular menstruation protects
premenopausal women against excessive iron accumulation, oligomenorrhea and
amenorrhea might contribute to the increase in ferritin observed in
overweight and obese PCOS patients. When studying PCOS patients and control
subjects as a whole, ferritin levels were increased in women with amenorrhea
compared with women with regular menstrual cycles, whereas women with
oligomenorrhea presented with intermediate values (means + SD: amenorrhea
159 [+ or -] 144 pmol/l, oligomenorrhea 114 [+ or -] 95 pmol/l, and regular
menstrual cycles 83 [+ or -] 51 pmol/l; F = 3.295, P = 0.040).
CONCLUSIONS--Our present findings suggest for the first time that increased
body iron stores, expressed as increased serum ferritin concentrations, are
present in overweight and obese women with PCOS but not in lean patients.
These increased iron stores might contribute to the insulin resistance and
[beta]-cell dysfunction frequently found in PCOS patients, as has been
proposed for insulin resistance, the metabolic syndrome, and type 2 diabetes
(1-3,8,9).
However, the increase in serum ferritin levels in PCOS may be a secondary,
not a pathogenic, event in PCOS. The absence of regular menstrual blood loss
in PCOS patients might contribute to iron overload, as serum ferritin levels
were increased in our amenorrheic patients compared with regularly
menstruating women. Oxidative stress increases ferritin synthesis, partly to
avoid further oxidative damage, given that ferritin neutralizes the highly
toxic unbound iron (10), and oxidative stress may be increased in PCOS women
(7,11). Also, the hyperinsulinemia resulting from insulin resistance may
contribute to increased body iron stores and serum ferritin levels because
insulin may stimulate intestinal iron absorption by upregulating activity of
hypoxia-inducible factor-1[alpha] (12).
Yet several of these factors might collaborate in the increased body stores
observed in overweight and obese PCOS patients. As proposed for type 2
diabetes (10), the insulin resistance intrinsic to PCOS, exacerbated by
obesity and perhaps dietary influences, may facilitate iron absorption and
deposition in tissues, a mechanism possibly amplified by the reduced
menstrual losses of PCOS patients. Iron deposition in certain tissues
increases insulin resistance, closing the vicious circle of iron overload
and predisposing these women to disorders of glucose tolerance and other
components of the metabolic syndrome.
In summary, serum ferritin levels are increased in overweight and obese
women with PCOS and are associated with disorders of glucose tolerance in
premenopausal women.
Acknowledgments--This study was supported by grants FIS02/0741 and RGDMG03/
212 from the Fondo de Investigacion Sanitaria, Instituto de Salud Carlos
III, and by grant GR/SAL/0137/2004 from Comunidad de Madrid, Spain.
References
(1.) Jehn M, Clark JM, Guallar E: Serum ferritin and risk of the metabolic
syndrome in U.S. adults. Diabetes Care 27:2422-2428, 2004
(2.) Ford ES, Cogswell ME: Diabetes and serum ferritin concentration among
U.S. adults. Diabetes Care 22:1978-1983, 1999
(3.) Jiang R, Ma J, Ascherio A, Stampfer MJ, Willett WC, Hu FB: Dietary iron
intake and blood donations in relation to risk of type 2 diabetes in men: a
prospective cohort study. Am J Clin Nutr 79:70-75, 2004
(4.) Dunaif A: Insulin resistance and the polycystic ovary syndrome:
mechanism and implications for pathogenesis. Endocr Rev 18:774-800, 1997
(5.) Ehrmann D, Barnes R, Rosenfield R, Cavaghan M, Imperial J: Prevalence
of impaired glucose tolerance and diabetes in women with polycystic ovary
syndrome. Diabetes Care 22:141-146, 1999
(6.) Clinical guidelines on the identification, evaluation, and treatment of
overweight and obesity in adults: the evidence report: National Institutes
of Health. Obes Res 6 (Suppl. 2):51S-209S, 1998
(7.) San Millan JL, Corton M, Villuendas G, Sancho J, Peral B,
Escobar-Morreale HF: Association of the polycystic ovary syndrome with
genomic variants related to insulin resistance, type 2 diabetes mellitus,
and obesity, d Clin Endocrinol Metab 89:2640-2646, 2004
(8.) Haap M, Fritsche A, Mensing HJ, Haring HU, Stumvoll M: Association of
high serum ferritin concentration with glucose intolerance and insulin
resistance in healthy people. Ann Intern Mec1139:869-871, 2003
(9.) Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB: Body iron stores in
relation to risk of type 2 diabetes in apparently healthy women. JAMA
291:711-717, 2004
(10.) Fernandez-Real JM, Lopez-Bermejo A, Ricart W: Cross-talk between iron
metabolism and diabetes. Diabetes 51:2348-2354, 2002
(11.) Fenkci V, Fenkci S, Yilmazer M, Serteser M: Decreased total
antioxidant status and increased oxidative stress in women with polycystic
ovary syndrome may contribute to the risk of cardiovascular disease. Fertil
Steril 80:123-127, 2003
(12.) McCarty MF: Hyperinsulinemia may boost both hematocrit and iron
absorption by up-regulating activity of hypoxia-inducible factor-lalpha.
Meal Hypotheses 61:567-573, 2003
HECTOR F. ESCOBAR-MORREALE, MD, PHD (1) MANUEL LUQUE-RAMIREZ, MD (1)
FRANCISCO ALVAREZ-BLASCO, MD (1) JOSE I. BOTELLA-CARRETERO, MD, PHD (1) JOSE
SANCHO, MD, PHD (1) JOSE L. SAN MILLAN, PHD (2)
From the (1) Department of Endocrinology, Hospital Ramon y Cajal, Madrid,
Spain; and the (2) Department of Molecular Genetics, Hospital Ramon y Cajal,
Madrid, Spain.
Address correspondence and reprint requests to Hector F. Escobar-Morreale,
Department of Endocrinology, Hospital Ramon y Cajal, Carretera de Colmenar
km 9'1, Madrid E-28034, Spain. E-mail: hescobarm. hrc@saludmadrid.org
Received and accepted for publication 26 April 2005.
Abbreviations: CRP, C-reactive protein; PCOS, polycystic ovalT syndrome.
A table elsewhere in this issue shows conventional and Systeme International
(SI) units and conversion factors for many substances.
COPYRIGHT 2005 American Diabetes Association

Who loves ya.
Tom

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