OBJECTIVE -Women with prior gestational diabetes mellitus (pGDM) are at increased risk of developing type 2 diabetes and associated vasculopathy. Because increased fat mass and inflammatory processes are angiopathic risk factors, the relationship between insulin sensitivity, parameters of subclinical inflammation, and plasma concentrations of adipocytokines was investigated in pGDM both at 3 months and 12 months after delivery.RESEARCH DESIGN AND METHODS -Insulin sensitivity (through a frequently sampled intravenous glucose tolerance test) and plasma concentrations of ultrasensitive C-reactive protein (CRP), adiponectin, plasminogen activator inhibitor (PAI)-1, tumor necrosis factor-␣, leptin, and interleukin-6 were measured in 89 pGDM (BMI 26.9 Ϯ 0.5 kg/m 2 , age 32 Ϯ 0.5 years) and in 19 women with normal glucose tolerance during pregnancy (NGT) (23.7 Ϯ 0.9 kg/m 2 , 31 Ϯ 1.3 years).RESULTS -pGDM showed lower (P Ͻ 0.0001) plasma adiponectin (6.7 Ϯ 0.2 g/ml) than NGT (9.8 Ϯ 0.6 g/ml) and a decreased (P Ͻ 0.003) insulin sensitivity index (S i ) and disposition index (P Ͻ 0.03), but increased plasma leptin (P Ͻ 0.003), PAI-1 (P Ͻ 0.002), and CRP (P Ͻ 0.03). After adjustment for body fat mass, plasma adiponectin remained lower in pGDM (P Ͻ 0.004) and correlated positively with S i (P Ͻ 0.003) and HDL cholesterol (P Ͻ 0.0001) but negatively with plasma glucose (2-h oral glucose tolerance test [OGTT]) (P Ͻ 0.0001), leptin (P Ͻ 0.01), CRP (P Ͻ 0.007), and PAI-1 (P Ͻ 0.0001). On regression analysis, only HDL cholesterol, postload (2-h OGTT) plasma glucose, and S i remained significant predictors of plasma adiponectin, explaining 42% of its variability. Of note, adiponectin further decreased (P Ͻ 0.05) only in insulin-resistant pGDM despite unchanged body fat content and distribution after a 1-year follow-up.CONCLUSIONS -Lower plasma adiponectin concentrations characterize women with previous GDM independently of the prevailing insulin sensitivity or the degree of obesity and are associated with subclinical inflammation and atherogenic parameters. Diabetes Care 27:1721-1727, 2004P lasma concentrations of adiponectin, an adipocyte-specific collagenlike molecule, are reduced in patients with obesity, coronary artery disease, and type 2 diabetes (1). Longitudinal studies indicate that a decrease in plasma adiponectin parallels the progression of the metabolic syndrome (2,3). Potentially, this observation suggests a predictive role of adiponectin also in the development of type 2 diabetes and atherosclerosis, where it could relate to insulin sensitivity and atherogenic parameters such as the lipid profile, cytokines, and subclinical inflammation. This concept is supported by low plasma adiponectin concentrations in states of enhanced insulin resistance in rhesus monkeys (4) and humans (5), when low plasma adiponectin precedes the decrease in whole-body insulin sensitivity (6,7). Moreover, adiponectin decreases both the attachment of monocytic THP-1 cells to human aortic endothelial cells and suppresses the secretion of tumo...

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Aims/hypothesis Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m 2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria.Methods Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m 2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. Results The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% Diabetologia (2017) 60:1913-1921 DOI 10.1007 of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24-28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35-37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. Conclusions/interpretation The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m 2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies.

recommendations leads to an increased prevalence of gestational diabetes mellitus (GDM) due to more stringent criteria and early screening of women at high risk for diabetes in pregnancy (DIP) (1,2). IADPSG members now recommend that their GDM criteria should not be used in early pregnancy but have not provided alternative criteria (3). We have compared the characteristics of overweight/obese women early in pregnancy, with and without GDM using the new criteria, to assess whether those testing positive are metabolically distinct.Pregnant women with a BMI $29.0 kg/m 2 underwent a 75-g oral glucose tolerance test in early pregnancy as part of enrollment into the DALI (Vitamin D And Lifestyle Intervention for GDM prevention) pilot and lifestyle Pan-European multicenter trials (4). GDM and DIP were diagnosed using WHO 2013 criteria. A high rate of GDM (237/1,035 or 22.9%: DIP 0.5%; total hyperglycemia in early pregnancy 23.4%) was found at a mean of 15.2 6 3.0 gestational weeks (interquartile range 13.4-16.8).A fasting glucose alone identified 190/242 (78.5%) women. The other 52 women (21.5%) were diagnosed with elevated

DM affects the length of gestation and incidence of spontaneous preterm birth.

ContextGenetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM).ObjectiveWe assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy.Methods960 pregnant women (after dropouts 820: case/control: m99’WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m’99WHO criteria based on standard OGTT values.ResultsThe most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m’99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT.ConclusionsWe confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99’WHO and the IADPSG GDM diagnostic criteria.

A team of experts from the fields of gynaecology and obstetrics, diabetology, internal medicine, paediatrics and midwifery from Germany, Austria and Switzerland produced a new version of the existing S3 guideline on gestational diabetes. It replaces the recommendations of the German Association for Gynaecology and Obstetrics and the German Diabetes Association on the diagnosis and treatment of gestational diabetes from 2011 and is valid for the three German-speaking countries. The primary aim of the guideline is to improve and standardise the prevention, screening, diagnosis, treatment and follow-up of gestational diabetes through evidence-based recommendations for the outpatient and inpatient area. A large number of new studies and data published in the last few years required a comprehensive revision of the 2011 guideline. The new aspects include early screening of pregnant women with a high risk for diabetes or gestational diabetes, the validity of two-stage screening in the third trimester by means of the 50-g challenge test, as specified in the maternity guidelines, use of metformin instead of or in addition to insulin in gestational diabetes, and birth planning with GDM and/or macrosomia. The recommendations are based on the evidence from the literature, which was selected through a systematic external literature search. All recommendations had to pass through a consensus process. The present text corresponds to the practice guideline on gestational diabetes, which is an action-oriented short version of the evidence-based S3 guideline that can be viewed on the internet.

Early manifestation of GDM is affected by insulin resistance that is partly explained by higher degree in obesity. However, ß-cell dysfunction was also detectable in GDMLate, indicating defective compensatory mechanisms emerging already in early pregnancy.