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.

Context Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine that improves insulin sensitivity in animals. However, serum ANGPTL6 concentration was found to be higher in human participants with diabetes or metabolic syndrome in cross-sectional studies, implying that ANGPTL6 may be induced to counteract hyperglycemia. Objective To investigate whether serum ANGPTL6 can predict incident diabetes and explore whether glucose or insulin can regulate ANGPTL6 expression and secretion. Design This cohort study included adults without diabetes at baseline who were followed every 2 years for incident diabetes. Serum ANGPTL6 concentrations were measured at baseline and during oral glucose tolerance tests (OGTTs). A hepatic cell line, HepG2, and diet-induced obesity mouse model were used to evaluate the response of ANGPTL6 expression and secretion to hyperglycemia and the metabolic syndrome. Results We recruited 1103 participants without diabetes at baseline. During the 4.22-year follow-up, 113 (10.2%) participants developed incident diabetes. Serum ANGPTL6 was negatively associated with the incidence of diabetes (adjusted hazard ratio, 0.77; P = 0.042). However, serum ANGPTL6 level was higher in participants with prediabetes (P = 0.018) and was elevated during OGTT. In HepG2 cells, treatment with glucose, but not insulin, induced ANGPTL6 expression. Hepatic ANGPTL6 expression and serum ANGPTL6 concentrations were significantly higher in mice fed with a high-fat diet than in those fed with a standard chow (both P &lt; 0.05). Conclusion A high serum ANGPTL6 level is associated with a low incidence of diabetes in humans. ANGPTL6 is expressed and secreted in response to hyperglycemia to maintain glucose homeostasis.

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Background: Advanced maternal age (AMA) is correlated with a higher risk of metabolic disorders during pregnancy, including gestational diabetes (GDM), gestational hypertriglyceridemia (GHTG), pregnancy-induced hypertension (PIH), and preeclampsia while the pathophysiology remains unclear. Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor which participates in the pathophysiology of metabolic disorders in non-pregnant population. We explored the role of ANGPTL4 in the link between AMA and metabolic disorders during pregnancy. Method: We recruited 571 pregnant women from November 2013 to April 2018 in National Taiwan University Hospital, Taiwan. ANGPTL4 expression level in placenta and maternal plasma ANGPTL4 level were measured. The correlations among age, plasma ANGPTL4 level, metabolic disorders during pregnancy, and adverse pregnancy outcome were analyzed. Result: Compared with women aged &lt;30 years, women aged ≥40 years had higher body mass index (BMI), fasting plasma glucose, hemoglobin A1c, insulin resistance index, plasma triglyceride, blood pressure, and plasma ANGPTL4 level in the first trimester. The expression level of ANGPTL4 were higher in the placenta of women with AMA than in the placenta of women aged &lt;30 years. The pregnant women with the highest quartile of plasma ANGPTL4 level had more metabolic disorders during pregnancy. Besides, higher plasma ANGPTL4 was associated with a higher risk of delivering neonates with large for gestational age and the presence of adverse pregnancy outcomes. Conclusion: Plasma ANGPTL4 is higher in women with AMA and is associated with metabolic disorders during pregnancy and the risk of adverse pregnancy outcomes. Disclosure I.Yen: None. H.Li: None.