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Exp Clin Endocrinol Diabetes 2006; 114(10): 577-583
DOI: 10.1055/s-2006-948308
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

Low Serum 25-Hydroxyvitamin D Concentrations are Associated with Insulin Resistance and Obesity in Women with Polycystic Ovary Syndrome

S. Hahn 1 , U. Haselhorst 2 , S. Tan 3 , B. Quadbeck 4 , M. Schmidt 5 , S. Roesler 1 , R. Kimmig 5 , K. Mann 3 , O. E. Janssen 3
  • 1Endokrinologikum Ruhr, Center for metabolic and endocrine diseases, Bochum, Germany
  • 2Laboratory Associates, Recklinghausen, Germany
  • 3Division of Endocrinology, Department of Medicine, University of Duisburg-Essen, Essen, Germany
  • 4Private Practice, Haus der Medizin, Essen, Germany
  • 5Department of Obstetrics and Gynaecology, University of Duisburg-Essen, Essen, Germany
Further Information

Publication History

Received: November 11, 2005 First decision: May 24, 2005

Accepted: June 6, 2006

Publication Date:
19 December 2006 (online)

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Abstract

Insulin resistance (IR) and central obesity are common features of the polycystic ovary syndrome (PCOS). Vitamin D is thought to play a role in the pathogenesis of type 2 diabetes by affecting insulin metabolism. The aim of our study was to investigate the effect of 25-hydroxyvitamin D (25-OH-VD) on metabolic parameters and IR in PCOS. In 120 untreated PCOS patients (median age 28 years) levels of 25-OH-VD (radioimmunoassay method provided by DiaSorin), calcium and anorganic phosphate were measured. In addition, endocrine and metabolic variables were evaluated and a glucose tolerance test was performed to assess indices of IR. In the entire PCOS cohort, 25-OH-VD concentrations were negatively correlated with body mass index (r=-0.2765), body fat (r=-0.2490), HOMA-IR (r=-0.1947), hyperinsulinemia (r=-0.1892) and leptin levels (r=-0.2834), and positively correlated with HDL cholesterol (r=0.2630) (all p<0.05). Subgroup analysis of lean, overweight and obese women revealed significant higher 25-OH-VD levels in lean women. Differences remained significant when women were divided according to their 25-OH-VD levels. Women with hypovitaminosis D (<9 ng/ml) had higher mean BMI, indices of IR and leptin levels compared to women with normal serum levels (all p<0.05). Analysis of vitamin D and biochemical endocrine PCOS features revealed a significant correlation only between 25-OH-VD and sex hormone-binding globulin as well as the free androgen index. In conclusion, in PCOS women, low 25-OH-VD levels are associated with obesity and insulin resistance but not with PCOS per se.

Key words

PCOS - 25-hydroxyvitamin D - insulin resistance - obesity

References

  • 1 Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland).  Cancer Causes Control. 2000;  11 847-852
    CrossrefPubMedSearch in Google Scholar
  • 2 Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2005;  90 1929-1935
    CrossrefPubMedSearch in Google Scholar
  • 3 Aronne LJ, Segal KR. Adiposity and fat distribution outcome measures: assessment and clinical implications.  Obes Res. 2002;  10 (Suppl 1) 14S-21S
    PubMedSearch in Google Scholar
  • 4 Bender R, Lange S, Ziegler AG. Wichtige Signifikanztests.  Dtsch Med Wochenschr. 2002;  127 T1-T3
    PubMedSearch in Google Scholar
  • 5 Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients.  Int J Clin Pract. 2003;  57 258-261
    PubMedSearch in Google Scholar
  • 6 Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis.  Proc Natl Acad Sci U S A. 1996;  93 7861-7864
    CrossrefPubMedSearch in Google Scholar
  • 7 Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction.  Am J Clin Nutr. 2004;  79 820-825
    PubMedSearch in Google Scholar
  • 8 Compston JE, Vedi S, Ledger JE, Webb A, Gazet JC, Pilkington TR. Vitamin D status and bone histomorphometry in gross obesity.  Am J Clin Nutr. 1981;  34 2359-2363
    PubMedSearch in Google Scholar
  • 9 de Souza Santos R, Vianna LM. Effect of cholecalciferol supplementation on blood glucose in an experimental model of type 2 diabetes mellitus in spontaneously hypertensive rats and Wistar rats.  Clin Chim Acta. 2005;  358 146-150
    CrossrefPubMedSearch in Google Scholar
  • 10 Del Pino-Montes J, Benito GE, Fernandez-Salazar MP, Covenas R, Calvo JJ, Bouillon R, Quesada JM. Calcitriol improves streptozotocin-induced diabetes and recovers bone mineral density in diabetic rats.  Calcif Tissue Int. 2004;  75 526-532
    CrossrefPubMedSearch in Google Scholar
  • 11 Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome.  Diabetes. 1989;  38 1165-1174
    CrossrefPubMedSearch in Google Scholar
  • 12 Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.  Diabetes Care. 1999;  22 141-146
    CrossrefPubMedSearch in Google Scholar
  • 13 Ehrmann DA, Schwarz PE, Hara M, Tang X, Horikawa Y, Imperial J, Bell GI, Cox NJ. Relationship of calpain-10 genotype to phenotypic features of polycystic ovary syndrome.  J Clin Endocrinol Metab. 2002;  87 1669-1673
    CrossrefPubMedSearch in Google Scholar
  • 14 ESHRE/ASRM . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.  Fertil Steril. 2004;  81 19-25
    PubMedSearch in Google Scholar
  • 15 Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults.  Diabetes Care. 2005;  28 1228-1230
    CrossrefPubMedSearch in Google Scholar
  • 16 Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men.  Lancet. 1985;  1 307-309
    PubMedSearch in Google Scholar
  • 17 Goodarzi MO, Erickson S, Port SC, Jennrich RI, Korenman SG. Relative impact of insulin resistance and obesity on cardiovascular risk factors in polycystic ovary syndrome.  Metabolism. 2003;  52 713-719
    CrossrefPubMedSearch in Google Scholar
  • 18 Hahn S, Fingerhut A, Khomtsiv U, Khomtsiv L, Tan S, Quadbeck B, Herrmann BL, Knebel B, Muller-Wieland D, Mann K, Janssen OE. The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is associated with a lower hirsutism score and increased insulin sensitivity in women with polycystic ovary syndrome.  Clin Endocrinol (Oxf). 2005;  62 573-579
    CrossrefPubMedSearch in Google Scholar
  • 19 Hahn S, Tan S, Elsenbruch S, Quadbeck B, Herrmann BL, Mann K, Janssen OE. Clinical and biochemical characterization of women with polycystic ovary syndrome in North Rhine-Westphalia.  Horm Metab Res. 2005;  37 438-444
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Holte J, Gennarelli G, Berne C, Bergh T, Lithell H. Elevated ambulatory day-time blood pressure in women with polycystic ovary syndrome: a sign of a pre-hypertensive state?.  Hum Reprod. 1996;  11 23-28
    PubMedSearch in Google Scholar
  • 21 Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study.  Lancet. 2001;  358 1500-1503
    CrossrefPubMedSearch in Google Scholar
  • 22 Isaia G, Giorgino R, Adami S. High prevalence of hypovitaminosis D in female type 2 diabetic population.  Diabetes Care. 2001;  24 1496
    CrossrefPubMedSearch in Google Scholar
  • 23 Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans.  J Clin Endocrinol Metab. 2000;  85 2402-2410
    CrossrefPubMedSearch in Google Scholar
  • 24 Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study.  J Clin Endocrinol Metab. 2005;  90 3236-3242
    CrossrefPubMedSearch in Google Scholar
  • 25 Ludwig E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex.  Br J Dermatol. 1977;  97 247-254
    CrossrefPubMedSearch in Google Scholar
  • 26 Manco M, Calvani M, Nanni G, Greco AV, Iaconelli A, Gasbarrini G, Castagneto M, Mingrone G. Low 25-hydroxyvitamin d does not affect insulin sensitivity in obesity after bariatric surgery.  Obes Res. 2005;  13 1692-1700
    PubMedSearch in Google Scholar
  • 27 Matsuda M, DeFronzo R. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.  Diabetes Care. 1999;  22 1462-1470
    CrossrefPubMedSearch in Google Scholar
  • 28 Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
    Search in Google Scholar
  • 29 Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study.  Arthritis Rheum. 2004;  50 72-77
    CrossrefPubMedSearch in Google Scholar
  • 30 Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS, Clore JN, Blackard WG. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome.  J Clin Endocrinol Metab. 1991;  72 83-89
    CrossrefPubMedSearch in Google Scholar
  • 31 Orio Jr. F, Lucidi P, Palomba S, Tauchmanova L, Cascella T, Russo T, Zullo F, Colao A, Lombardi G, De Feo P. Circulating ghrelin concentrations in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 2003;  88 942-945
    CrossrefPubMedSearch in Google Scholar
  • 32 Panidis D, Balaris C, Farmakiotis D, Rousso D, Kourtis A, Balaris V, Katsikis I, Zournatzi V, Diamanti-Kandarakis E. Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome.  Clin Chem. 2005;  51 1691-1697
    CrossrefPubMedSearch in Google Scholar
  • 33 Panidis D, Rousso D, Kourtis A, Tsimas V, Papathanasiou K, Makedos G. Serum leptin levels in normal-weight and overweight women with polycystic ovary syndrome.  Clin Exp Obstet Gynecol. 2003;  30 207-210
    PubMedSearch in Google Scholar
  • 34 Peiris AN, Sothmann MS, Aiman EJ, Kissebah AH. The relationship of insulin to sex hormone-binding globulin: role of adiposity.  Fertil Steril. 1989;  52 69-72
    PubMedSearch in Google Scholar
  • 35 Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey.  Diabetes Care. 2004;  27 2813-2818
    CrossrefPubMedSearch in Google Scholar
  • 36 Simpson RU, Thomas GA, Arnold AJ. Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle.  J Biol Chem. 1985;  260 8882-8891
    PubMedSearch in Google Scholar
  • 37 Spranger J, Mohlig M, Wegewitz U, Ristow M, Pfeiffer AF, Schill T, Schlosser HW, Brabant G, Schofl C. Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome.  Clin Endocrinol (Oxf). 2004;  61 738-746
    CrossrefPubMedSearch in Google Scholar
  • 38 Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, Rahe S, Staiger H, Maerker E, Haring H, Stumvoll M. Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism.  Diabetes. 2003;  52 239-243
    CrossrefPubMedSearch in Google Scholar
  • 39 Urbanek M, Legro RS, Driscoll DA, Azziz R, Ehrmann DA, Norman RJ, Strauss JF, Spielman RS, Dunaif A. Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin.  Proc Natl Acad Sci U S A. 1999;  96 8573-8578
    CrossrefPubMedSearch in Google Scholar
  • 40 Vague J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease.  Am J Clin Nutr. 1956;  4 20-34
    PubMedSearch in Google Scholar
  • 41 Wijeyaratne CN, Balen AH, Barth JH, Belchetz PE. Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among South Asians and Caucasians: is there a difference?.  Clin Endocrinol (Oxf). 2002;  57 343-350
    CrossrefPubMedSearch in Google Scholar
  • 42 Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity.  Am J Clin Nutr. 2000;  72 690-693
    PubMedSearch in Google Scholar
  • 43 Yildiz BO, Yarali H, Oguz H, Bayraktar M. Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2003;  88 2031-2036
    CrossrefPubMedSearch in Google Scholar
  • 44 Yki-Jarvinen H, Makimattila S, Utriainen T, Rutanen EM. Portal insulin concentrations rather than insulin sensitivity regulate serum sex hormone-binding globulin and insulin-like growth factor binding protein 1 in vivo.  J Clin Endocrinol Metab. 1995;  80 3227-3232
    CrossrefPubMedSearch in Google Scholar
  • 45 Zella JB, McCary LC, DeLuca HF. Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus.  Arch Biochem Biophys. 2003;  417 77-80
    PubMedSearch in Google Scholar
  • 46 Zemel MB. Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications.  J Am Coll Nutr. 2002;  21 146S-151S
    PubMedSearch in Google Scholar
  • 47 Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC. Regulation of adiposity by dietary calcium.  Faseb J. 2000;  14 1132-1138
    PubMedSearch in Google Scholar
  • 48 Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Korfer R, Stehle P. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure?.  J Am Coll Cardiol. 2003;  41 105-112
    PubMedSearch in Google Scholar

Correspondence

Susanne HahnMD 

Endokrinologikum Ruhr·Center for metabolic and endocrine diseases

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