Graves' disease is the leading cause of hyperthyroidism affecting 1.0–1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves' disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 × 10−32) and HLA-DRB1*08:03 (Pcombined=1.83 × 10−9) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13–41.48) and 6.13 (95% confidence interval=3.28–11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 × 10−21, 95% confidence interval=21.66–108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.

Aims/IntroductionThe International Association of the Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes are associated with increased prevalence. However, it remains unknown if intervention for more women with gestational diabetes mellitus by the IADPSG criteria results in better pregnancy outcomes than adopting the Carpenter and Coustan (C&C) criteria in Asian populations.Materials and MethodsThis was a retrospective cohort study. A total of 1,840 women, 952 subjects by the IADPSG criteria and 888 subjects by the C&C criteria, who delivered singletons in 2011 in a single tertiary center, were included in the study. The same therapeutic interventions were offered to women with gestational diabetes mellitus by the two criteria. Maternal and neonatal outcomes were evaluated.ResultsAdopting the IADPSG criteria increased the prevalence of gestational diabetes mellitus diagnosis to 13.44%, compared with 2.59% by the C&C criteria. The diagnosis was made 3 weeks earlier by the IADPSG criteria (27 vs 30.5 weeks, P < 0.0001). Adopting the IADPSG criteria was associated with reduced risk of primary cesarean section (adjusted odds ratio 0.79, 95% confidence interval 0.63–0.998, P < 0.05) and having any one of the adverse fetal outcomes (adjusted odds ratio 0.79, 95% confidence interval 0.64–0.998, P < 0.05), including birthweight >90th percentile, jaundice, admission to neonatal intensive care unit, birth trauma, neonatal hypoglycemia and fetal death.ConclusionsAdopting the IADPSG criteria is associated with improved pregnancy outcomes, at the expense of increased prevalence of gestational diabetes mellitus diagnosis.

AimOverweight and obesity are important risk factors of gestational diabetes mellitus (GDM). Clustering of metabolic risk factors in early pregnancy may be a potential pathogenesis between the link of overweight/obesity and GDM. Since it remains unexplored, we investigated if overweight and obesity are associated with clustering of metabolic risk factors in early pregnancy and the risk of GDM in this cohort study.MethodsTotal 527 women who visited National Taiwan University Hospital for prenatal care in between November 2013 to April 2018 were enrolled. Risk factors of GDM in the first prenatal visit (FPV) were recorded. Overweight/obesity was defined if body mass index ≥24 kg/m2. GDM was diagnosed from the result of a 75g oral glucose tolerance test in 24–28 gestational weeks.ResultsOverweight/obesity was associated with clustering of metabolic risk factors of GDM, including high fasting plasma glucose, high HbA1c, insulin resistance, high plasma triglyceride and elevated blood pressure in FPV (p<0.05). There was a positive relationship between the number of metabolic risk factors and the incidence of GDM (p <0.05). The odds ratios of HbA1c and diastolic blood pressure were higher in overweight/obese women, compared with those in normal-weight women.ConclusionsOverweight/obesity is associated with clustering of metabolic risk factors in early pregnancy, which is correlated with higher risk of GDM. Our findings suggest that metabolic risk factors during early pregnancy should be evaluated in overweight/obese women.

ObjectiveUsing a specific cutoff of fasting plasma glucose (FPG) to screen gestational diabetes mellitus (GDM) can reduce the use of oral glucose tolerance tests (OGTT). Since the prevalence of GDM increases with age, this screening method may not be appropriate in healthcare systems where women become pregnant at older ages. Therefore, we aimed to develop a screening algorithm for GDM that takes maternal age into consideration.MethodsWe included 945 pregnant women without history of GDM who received 75g OGTT to diagnose GDM in 2011. Screening algorithms using FPG with or without age were developed. Another 362 pregnant women were recruited in 2013–2015 as the validation cohort.ResultsUsing FPG criteria alone, more GDM diagnoses were missed in women ≥35 years than in women <35 years (13.2% vs. 5.8%, p <0.001). Among GDM women ≥35 years, 63.6% had FPG <92 mg/dL (5.1 mmol/L). Use of the algorithm with an “age plus FPG” cutoff could reduce the use of OGTT (OGTT%) from 77.6% to 62.9%, while maintaining good sensitivity (from 91.9% to 90.2%) and specificity (from 100% to 100%). Similar reduction in OGTT% was found in the validation cohort (from 86.4% to 76.8%). In the simulation, if the percentage of women ≥35 years were 40% or more, the screening algorithm with an “age plus FPG” cutoff could further reduce OGTT% by 11.0%-18.8%.ConclusionsA screening algorithm for GDM that takes maternal age into consideration can reduce the use of OGTT when women become pregnant at older ages.