Differences in the serum nonesterified fatty acid profile of young women associated with a recent history of gestational diabetes and overweight/obesity.

BACKGROUND: Nonesterified fatty acids (NEFA) play pathophysiological roles in metabolic syndrome and type 2 diabetes (T2D). In this study, we analyzed the fasting NEFA profiles of normoglycemic individuals at risk for T2D (women with a recent history of gestational diabetes (GDM)) in comparison to controls (women after a normoglycemic pregnancy). We also examined the associations of NEFA species with overweight/obesity, body fat distribution and insulin sensitivity. SUBJECTS AND METHODS: Using LC-MS/MS, we analyzed 41 NEFA species in the fasting sera of 111 women (62 post-GDM, 49 controls). Clinical characterization included a five-point oral glucose tolerance test (OGTT), biomarkers and anthropometrics, magnetic resonance imaging (n = 62) and a food frequency questionnaire. Nonparametric tests with Bonferroni correction, binary logistic regression analyses and rank correlations were used for statistical analysis. RESULTS: Women after GDM had a lower molar percentage of total saturated fatty acids (SFA; 38.55% vs. 40.32%, p = 0.0002) than controls. At an explorative level of significance several NEFA species were associated with post-GDM status (with and without adjustment for body mass index (BMI) and HbA1c): The molar percentages of 14:0, 16:0, 18:0 and 18:4 were reduced, whereas those of 18:1, 18:2, 20:2, 24:4, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) and total n-6 NEFA were increased. BMI and the amount of body fat correlated inversely with several SFA and MUFA and positively with various PUFA species over the whole study cohort (abs(ρ)≥0.3 for all). 14:0 was inversely and BMI-independently associated with abdominal visceral adiposity. We saw no correlations of NEFA species with insulin sensitivity and the total NEFA concentration was similar in the post-GDM and the control group. CONCLUSION: In conclusion, we found alterations in the fasting NEFA profile associated with a recent history of gestational diabetes, a risk marker for T2D. NEFA composition also varied with overweight/obesity and with body fat distribution, but not with insulin sensitivity

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: To metabolically characterize women with recent gestational diabetes (GDM), an at-risk cohort for T2D. Study participants: 147 consecutively recruited women 3-16 months after pregnancy, women who had GDM and women after a normoglycemic pregnancy (controls) in a 2:1 ratio Design: Mono-center cross-sectional analysis (PPS-Diab study) Methods: 5-point OGTT with calculation of insulin sensitivity (ISI) and disposition index (DI; validation by euglycemic clamp and IVGTT), anthropometrics, medical and family history, clinical chemistry and biomarkers, statistical modelling, MRI/MRS substudy (body fat distribution, liver and muscle fat; n=66) Results: Compared to control subjects, women post GDM had a reduced DI, higher levels of plasma fetuin-A and a lower ISI. A low ISI was also the major determinant of pathologic glucose tolerance after GDM. The factors most strongly predictive of low insulin sensitivity were high plasma leptin, BMI, triglycerides, and waist circumference. Ectopic lipids showed no BMI-independent associations with having had GDM or low insulin sensitivity in an MRI substudy. Conclusions: We found that beta cell function is already impaired in women with recent GDM, a young at-risk cohort for T2D. Additionally, 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