Insulinresistenz und Inzidenz eines Gestationsdiabetes bei Kinderwunschpatientinnen mit und ohne PCO-Syndrom

Zusammenfassung

Jahren kinderlos. Ein Gestationsdiabetes wurde bei 25 Schwangeren (25,8 %) diagnostiziert (n = 11 [19,6 %] PCO+, n = 14 [34,1 %] PCO-); 9 PCO+- bzw. 14 PCO-Patientinnen davon zeigten im OGTT vor Konzeption eine Insulinresistenz. Bei den PCO-Patientinnen war eine positive Assoziation zwischen BMI und Insulinresistenz nachweisbar (p = 0,010), bei den PCO+ dagegen nicht. Schlussfolgerungen: Bei (insulinresistenten) Kinderwunschpatientinnen mit und ohne PCO-Syndrom ist das Risiko eines Gestationsdiabetes mit 20 bzw. 34 % hoch. Bereits präkonzeptionell sollte daher eine Insulinresistenz nachgewiesen werden, um Risikopatientinnen frühzeitig identifizieren zu können.

Abstract

Purpose: Polycystic ovary (PCO) syndrome is one of the main causes of sterility. Anovulation and hyperandrogenemia as well as insulin resistance are common findings in PCO syndrome. The aim of our study was to compare the incidence of gestational diabetes in sterile women with PCO syndrome (PCO+) with that of women at high risk of gestational diabetes without PCO syndrome (PCO-). Material and Methods: An oral glucose tolerance test (OGTT) was performed in 97 women who had not yet conceived (56 PCO+, 41 PCO-). During the test, blood samples were taken at 30 minute intervals up to 120 minutes and the insulin resistance was determined (as defined by Matsuda and DeFronzo). The women were subsequently followed up during pregnancy, and in early pregnancy another OGTT was performed with samples taken at 60 and 120 minutes after the administration of 75 g of oral glucose to diagnose or exclude gestational diabetes. Results: During follow-up 104 pregnancies and 78 deliveries with 92 children (which included ten twins and two sets of triplets) as well as 26 abortions (26.8 %) were documented, 19 (19.6 %) women remained childless. Gestational diabetes was diagnosed in 25 pregnant women (n = 11 [19.6 %] PCO+; n = 14 [34.1 %] PCO-); 9 (PCO+) and 14 (PCO-) of these patients had been found to be insulin resistant prior to conception. BMI was found to be positively correlated to insulin resistance in PCO- patients (p = 0.010) but not in PCO+ patients. Conclusion: In sterile, especially insulin resistant, PCO+ and PCO- women, the risk of gestational diabetes is high with an incidence of 20 % and 34 %, respectively. Therefore testing for insulin resistance should be carried out before conception, i.e., before ART (artificial reproductive technique), to identify patients at risk for gestational diabetes in later pregnancies.

OGTT - PCO‐Syndrom - Gestationsdiabetes - Insulinresistenz

OGTT - PCO syndrome - gestational diabetes - insulin resistance

Literatur

• 1 Emons G, Geisthövel F, Hinney B, Partsch C-J, Sippell W, Wuttke W H. Gynäkologische Endokrinologie. Lehnert H Rationelle Diagnostik und Therapie in der Endokrinologie, Diabetologie und Stoffwechsel. 2. Auflage. Stuttgart; Thieme 2003: 256-262
• 2 Polson D W, Adams J, Wadsworth J, Franks S. Polycystic ovaries - a common finding in normal women.  Lancet. 1998;  16 870-872
• 3 Taponen S, Ahonkallio S, Martikainen H, Koivunen R, Ruokonen A, Sovio U, Hartikainen A L, Pouta A, Laitinen J, King V, Franks S, McCarthy M I, Järvelin M R. Prevalence of polycystic ovaries in women with self-reported symptoms of oligomenorrhoea and/or hirsutism: Northern Finland Birth Cohort 1966 Study.  Hum Reprod. 2004;  19 1083-1088
• 4 Broekmans F J, Knauff E A, Valkenburg O, Laven J S, Eijkemans M J, Fauser B C. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO‐II anovulation and association with metabolic factors.  BJOG. 2006;  113 1210-1217
• 5 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.  Fertil Steril. 2004;  81 19-25
• 6 Hahn S, Benson S, Elsenbruch S, Pleger K, Tan S, Mann K, Schedlowski M, van Halteren W B, Kimming R, Janssen O E. Metformin treatment of polycystic ovary syndrome improves health-related quality-of-life, emotional distress and sexuality.  Human Reprod. 2006;  21 1925-1934
• 7 Palomba S, Falbo A, Orio Jr F, Manguso F, Russo T, Tolino A, Annamaria C, Dale B, Zullo F. A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination.  Hum Reprod. 2005;  20 2879-2886
• 8 Solomon C G. The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risk.  Endocrinol Metab Clin North Am. 1999;  28 247-263
• 9 Rouzi A A, Ardawi M S. A randomized controlled trial on the efficacy of rosiglitazone and clomiphene citrate versus metformin and clomiphene citrate in women with clomiphene citrate-resistant polycystic ovary syndrome.  Fertil Steril. 2006;  85 428-435
• 10 Khorram O, Helliwell J P, Katz S, Bonpane C M, Jaramillo L. Two weeks of metformine improves clomiphen citrate-induced ovulation and metabolic profiles in women with polycystic ovary syndrome.  Fertil Steril. 2006;  85 1448-1451
• 11 Sahin Y, Yirmibes U, Kelestimur F, Aygen E. The effect of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome.  Eur J Obstet Gynecol Reprod Biol. 2004;  113 214-220
• 12 Thatcher S S, Jackson E M. Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin.  Fertil Steril. 2006;  86 1002-1009
• 13 Claudi-Böhm S, Böhm (Hrsg) B O. Diabetes und Schwangerschaft - Prävention, Beratung, Betreuung vor, während und nach der Schwangerschaft. 1. Auflage. Heidelberg; Springer 2007
• 14 AWMF-Leitlinien Register Nr. 057/008: Empfehlungen zu Diagnostik und Therapie des Gestationsdiabetes (GDM), Erstellungsdatum Juni 2007. 
• 15 Boomsma C M, Eijkemans M J, Hughes E G, Visser G H, Fauser B C, Macklon N S. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.  Hum Reprod Update. 2006;  12 673-683
• 16 Bjercke S, Dale P O, Tanbo T, Storeng R, Ertzeid G, Abyholm T. Impact of insulin resistance on pregnancy complications and outcome in women with polycystic ovary syndrome.  Gynecol Obstet Invest. 2002;  54 94-98
• 17 Radon P A, McMahon M J, Meyer W R. Impaired glucose tolerance in pregnant women with polycystic ovary syndrome.  Obstet Gynecol. 1999;  94 194-197
• 18 Turhan N O, Seckin N C, Aybar F, Inegol I. Assessment of glucose tolerance and pregnancy outcome of polycystic ovary patients.  Int J Gynaecol Obstet. 2003;  81 161-168
• 19 Haakova L, Cibula D, Rezabek K, Hill M, Fanta M, Zivny J. Pregnancy outcome in women with PCOS and in controls matched by age and weight.  Hum Reprod. 2003;  18 1438-1441
• 20 Lesser K B, Garcia F A. Association between polycystic ovary syndrome and glucose intolerance during pregnancy.  J Matern Fetal Med. 1997;  6 303-307
• 21 Vollenhoven B, Clark S, Kovacs B, Burger H, Healy D. Prevalence of gestational diabetes mellitus in polycystic ovarian syndrome (PCOS) patients pregnant after ovulation induction with gonadotrophins.  Aust N Z J Obstet Gynaecol. 2000;  40 54-58
• 22 Yu C KH, Teoh T G, Robinson S. Obesity in pregnancy.  BJOG. 2006;  113 1117-1125
• 23 Matsuda M, DeFronzo R A. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.  Diabetes Care. 1999;  22 1462-1470
• 24 SPSS Inc, SPSS for Windows 95, V. 15.0. SPSS inc. Chicago; 2004
• 25 Haffner S M, Kennedy E, Gonzalez C, Stern M P, Miettinen H. A prospective analysis of the HOMA model. The Mexico City Diabetes Study.  Diabetes Care. 1996;  19 1138-1141
• 26 Haffner S M, Miettinen H, Stern M P. The homeostasis model in the San Antonio Heart Study.  Diabetes Care. 1997;  20 1087-1092
• 27 Onalan G, Goktolga U, Ceyhan T, Bagis T, Onalan R, Pabuccu R. Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic?.  Eur J Obstet Gynecol Reprod Biol. 2005;  123 204-211
• 28 Tang T, Glanville J, Orsi N, Barth J H, Balen A H. The use of metformin for PCOS undergoing IVF treatment.  Hum Reprod. 2006;  21 1416-1425
• 29 Khattab S, Mohsen I A, Foutouh I A, Ramadan A, Moaz M, Al-Inany H. Metformin reduces abortion in pregnant women with polycystic ovary syndrome.  Gynecol Endocrinol. 2006;  22 680-684
• 30 Kjostrod S B, von Düring V, Carlsen S M. Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study.  Hum Reprod. 2004;  19 1315-1322
• 31 Costello M F, Chapman M, Conway U. A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotrophin ovulation induction or IVF in women with polycystic ovary syndrome.  Hum Reprod. 2006;  21 1387-1399
• 32 Checa M A, Requena A, Salvador C, Tur R, Callejo J, Espinos J J, Fabregues F, Herrero J. Reproductive Endocrinology Interest Group of the Spanish Society of Fertility . Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome.  Hum Reprod Update. 2005;  11 375-390
• 33 Glueck C J, Goldenberg N, Pranikoff J, Loftspring M, Sieve L, Wang P. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy.  Hum Reprod. 2004;  19 1323-1330
• 34 Lee A J, Hiscock R J, Wein P, Walker S P, Permezel M. Gestational diabetes mellitus: clinical predictors and long-term risk of developing type 2 diabetes: a retrospective cohort study using survival analysis.  Diabetes Care. 2007;  30 878-883