No Correlation of Pancreatic Fat and ß-Cell Function in Young Women With and Without a History of Gestational Diabetes.

Context: Pancreatic steatosis may contribute to ß-cell dysfunction in type 2 diabetes (T2D), but data are controversial. Women who had gestational diabetes mellitus (GDM) are at high risk for developing T2D. Objective: To examine the association of pancreatic fat content with early/first-phase insulin secretion (as markers of ß-cell function). Design: Cross-sectional analysis of a subcohort of the monocentric, prospective cohort study titled Prediction, Prevention, and Subclassification of Type 2 Diabetes. Setting: Ludwig Maximilians University Hospital, Munich, Germany. Participants: Ninety-seven women, 3 to 16 months after pregnancy [41 normoglycemic women post-GDM, 19 women post-GDM with pathological glucose metabolism, and 37 normoglycemic women after a normoglycemic pregnancy (controls)]. Main Outcome Measures: Correlation of MRI-measured pancreatic fat content with early insulin release in an oral glucose tolerance test (OGGT) [insulin increment within the first 30 minutes of the OGTT (IR30)] and first-phase insulin response (FPIR) in an intravenous glucose tolerance test (n = 65), both adjusted for insulin sensitivity index (ISI). Results: Pancreatic fat content did not correlate with IR30 and FPIR adjusted for ISI. It correlated positively with body mass index, waist circumference, liver fat, and intraabdominal fat volume. Conclusion: Pancreatic fat content does not correlate with ß-cell function in a cohort of young women with different degrees of T2D risk.

The Diabetes Risk Phenotype of Young Women With Recent Gestational Diabetes.

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 ß-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.