Pre-diabetes, diabetes and fluctuations of glucose tolerance after gestational diabetes mellitus: 5-year follow-up of a contemporary, prospective study in Germany.

INTRODUCTION: Ten years ago, Germany started offering screening for gestational diabetes mellitus (GDM) to all pregnant women. This approach revealed more but also, on average, less severe cases of GDM than the risk-based screening practiced previously. We now examined the incidence of pre-diabetes and diabetes following a GDM diagnosis in the era of universal screening in Germany and compared our results with studies in the previous period. Additionally, we examined the year-to-year fluctuations of glucose tolerance after a pregnancy complicated by GDM. RESEARCH DESIGN AND METHODS: We report 5-year follow-up data from 202 women in the prospective, monocenter, postpartum study PPSDiab. Consecutive recruitment took place in Munich, Germany between 2011 and 2016. In the study, we conducted yearly examinations that included anthropometrics, laboratory chemistry and oral glucose tolerance testing. RESULTS: During the first 5 years post partum, 111 (55%) and 12 (6%) of the women developed pre-diabetes and type 2 diabetes, respectively, while 2 (1%) developed type 1 diabetes. Impaired fasting glucose (IFG) was the most common first manifestation of disturbed glucose tolerance, followed by impaired glucose tolerance (IGT), the combination of IFG and IGT, and diabetes. Glucose tolerance did not deteriorate steadily in most women but fluctuated from year to year. CONCLUSIONS: In our analysis, the incidence of diabetes, both type 1 and type 2, after GDM diagnosed in universal screening was substantially lower than in studies from the previous period of risk-based screening. Nevertheless, the high incidence of pre-diabetes we observed after GDM still confirms the importance of this diagnosis as a risk marker. Additionally, we documented frequent fluctuations of glucose tolerance from 1 year to the next. Therefore, a single postpartum glucose tolerance test, as currently practiced in routine care, may be insufficient for reliable risk stratification after GDM.

Distribution of RET proto-oncogene variants in children with appendicitis.

BACKGROUND: In addition to patient-related systemic factors directing the immune response, the pathomechanisms of appendicitis (AP) might also include insufficient drainage leading to inflammation caused by decreased peristalsis. Genetic predisposition accounts for 30%-50% of AP. M. Hirschsprung (HSCR), also characterized by disturbed peristalsis, is associated with variants in the RET proto-oncogene. We thus hypothesized that RET variants contribute to the etiology of AP. METHODS: DNA from paraffin-embedded appendices and clinical data of 264 children were analyzed for the RET c.135A>G variant (rs1800858, NC_000010.11:g.43100520A>G). In 46 patients with gangrenous or perforated AP (GAP), peripheral blood DNA was used for RET sequencing. RESULTS: Germline mutations were found in 13% of GAP, whereas no RET mutations were found in controls besides the benign variant p.Tyr791Phe (NC_000010.11:g.43118460A>T). In GAP, the polymorphic G-allele in rs2435352 (NC_000010.11:g.43105241A>G) in intron 4 was underrepresented (p = 0.0317). CONCLUSION: Our results suggest an impact of the RET proto-oncogene in the etiology of AP. Mutations were similar to patients with HSCR but no clinical features of HSCR were observed. The pathological phenotypes in both populations might thus represent a multigenic etiology including RET germline mutations with phenotypic heterogeneity and incomplete penetrance.

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.