Marietta Rottenkolber1, Uta Ferrari1, Lukas Holland1, Stephanie Aertsen1, Nora N Kammer1, Holger Hetterich1, Marina Fugmann1, Friederike Banning1, Michaela Weise1, Vanessa Sacco1, Denise Kohn1, Ines Freibothe1, Stefan Hutter1, Uwe Hasbargen1, Rainer Lehmann1, Harald Grallert1, Klaus G Parhofer1, Jochen Seissler1, Andreas Lechner1. 1. Institute of Medical Information Sciences, Biometry, and Epidemiology (M.R., D.K.), Diabetes Research Group, Medical Department 4 (U.F., L.H., S.A., M.F., F.B., M.W., V.S., I.F., J.S., A.L.), Institute for Clinical Radiology (N.N.K., H.H.), Department of Gynaecology and Obstetrics (S.H., U.H.), and Medical Department 2 (K.G.P.), Klinikum der Universitaet Muenchen, Ludwig-Maximilians-Universitaet Muenchen, 80539 Munich, Germany; Clinical Cooperation Group Type 2 Diabetes (U.F., L.H., S.A., M.F., F.B., M.W., V.S., I.F., H.G., J.S., A.L.) and Research Unit of Molecular Epidemiology, Institute of Epidemiology II (H.G.), Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany; German Center for Diabetes Research (U.F., L.H., S.A., M.F., F.B., M.W., V.S., I.F., R.L., J.S., A.L.), 85764 Neuherberg, Germany; and Division of Clinical Chemistry and Pathobiochemistry, Department of Internal Medicine IV (R.L.), University Hospital Tübingen, 72076 Tübingen, Germany.
Abstract
CONTEXT: The pathogenesis of type 2 diabetes (T2D) is still incompletely understood. In-depth phenotyping of young individuals at risk for T2D can contribute to the understanding of this process. OBJECTIVE: The purpose of this study was to metabolically characterize women with recent gestational diabetes (GDM), an at-risk cohort for T2D. STUDY PARTICIPANTS: Participants were 147 women consecutively recruited 3 to 16 months after pregnancy: women who had GDM and women after a normoglycemic pregnancy (control subjects) in a 2:1 ratio. DESIGN: This was a monocenter cross-sectional analysis (Prediction, Prevention and Subclassification of Type 2 Diabetes Study [PPS-Diab]). METHODS: A 5-point oral glucose tolerance test with calculation of the insulin sensitivity index and disposition index (validation by euglycemic clamp and intravenous glucose tolerance test) was performed. In addition, anthropometrics, medical and family history, clinical chemistry and biomarkers, statistical modeling, and a magnetic resonance imaging/magnetic resonance spectroscopy substudy (body fat distribution and liver and muscle fat; n = 66) were obtained. RESULTS: Compared with control subjects, women after GDM had a reduced disposition index, higher levels of plasma fetuin-A, and a lower insulin sensitivity index. A low insulin sensitivity index was also the major determinant of pathological glucose tolerance after GDM. The factors most strongly predictive of low insulin sensitivity were high plasma leptin, body mass index, triglycerides, and waist circumference. Ectopic lipids showed no body mass index-independent associations with having had GDM or low insulin sensitivity in a magnetic resonance imaging substudy. CONCLUSIONS: We found that β-cell function is already impaired in women with recent GDM, a young at-risk cohort for T2D. In addition, our data suggest that fetuin-A and leptin signaling may be important early contributors to the pathogenesis of T2D, at this disease stage equally or more relevant than ectopic lipids and low-grade inflammation.
CONTEXT: The pathogenesis of type 2 diabetes (T2D) is still incompletely understood. In-depth phenotyping of young individuals at risk for T2D can contribute to the understanding of this process. OBJECTIVE: The purpose of this study was to metabolically characterize women with recent gestational diabetes (GDM), an at-risk cohort for T2D. STUDY PARTICIPANTS: Participants were 147 women consecutively recruited 3 to 16 months after pregnancy: women who had GDM and women after a normoglycemic pregnancy (control subjects) in a 2:1 ratio. DESIGN: This was a monocenter cross-sectional analysis (Prediction, Prevention and Subclassification of Type 2 Diabetes Study [PPS-Diab]). METHODS: A 5-point oral glucose tolerance test with calculation of the insulin sensitivity index and disposition index (validation by euglycemic clamp and intravenous glucose tolerance test) was performed. In addition, anthropometrics, medical and family history, clinical chemistry and biomarkers, statistical modeling, and a magnetic resonance imaging/magnetic resonance spectroscopy substudy (body fat distribution and liver and muscle fat; n = 66) were obtained. RESULTS: Compared with control subjects, women after GDM had a reduced disposition index, higher levels of plasma fetuin-A, and a lower insulin sensitivity index. A low insulin sensitivity index was also the major determinant of pathological glucose tolerance after GDM. The factors most strongly predictive of low insulin sensitivity were high plasma leptin, body mass index, triglycerides, and waist circumference. Ectopic lipids showed no body mass index-independent associations with having had GDM or low insulin sensitivity in a magnetic resonance imaging substudy. CONCLUSIONS: We found that β-cell function is already impaired in women with recent GDM, a young at-risk cohort for T2D. In addition, our data suggest that fetuin-A and leptin signaling may be important early contributors to the pathogenesis of T2D, at this disease stage equally or more relevant than ectopic lipids and low-grade inflammation.
Authors: Anne L Potzel; Christina Gar; Friederike Banning; Vanessa Sacco; Andreas Fritsche; Louise Fritsche; Karsten Müssig; Laura Dauben; Jochen Seissler; Andreas Lechner Journal: PLoS One Date: 2022-04-27 Impact factor: 3.752
Authors: Marina Fugmann; Olaf Uhl; Christian Hellmuth; Holger Hetterich; Nora N Kammer; Uta Ferrari; Klaus G Parhofer; Berthold Koletzko; Jochen Seissler; Andreas Lechner Journal: PLoS One Date: 2015-05-26 Impact factor: 3.240
Authors: Laura Stirm; Peter Huypens; Steffen Sass; Richa Batra; Louise Fritsche; Sara Brucker; Harald Abele; Anita M Hennige; Fabian Theis; Johannes Beckers; Martin Hrabě de Angelis; Andreas Fritsche; Hans-Ulrich Häring; Harald Staiger Journal: Sci Rep Date: 2018-01-22 Impact factor: 4.996
Authors: C Gar; M Rottenkolber; H Grallert; F Banning; I Freibothe; V Sacco; C Wichmann; S Reif; A Potzel; V Dauber; C Schendell; N N Sommer; B Wolfarth; J Seissler; A Lechner; U Ferrari Journal: PLoS One Date: 2017-06-13 Impact factor: 3.240