Abstract. Xu W, Bi Y, Sun Z, Li J, Guo L, Yang T, Wu G, Shi L, Feng Z, Qiu L, Li Q, Guo X, Luo Z, Lu J, Shan Z, Yang W, Ji Q, Yan L, Li H, Yu X, Li S, Zhou Z, Lv X, Liang Z, Lin S, Zeng L, Yan J, Ji L, Weng J (The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou; Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing; Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing; Objective. Progressive b-cell dysfunction hinders the maintenance of glycaemic control in type 2 diabetes, but comparative data on b-cell-protective therapies are lacking in the early stage of type 2 diabetes. Here we evaluated the comparative glycaemic efficacy and impact on b-cell function of three antihyperglycaemic agents that have a b-cell-protective effect, exenatide, insulin and pioglitazone, in newly diagnosed patients with type 2 diabetes.Design and methods. In this 48-week, multicentre, parallel-group study, 416 patients newly diagnosed with type 2 diabetes were randomly assigned 1 : 1 : 1 to receive exenatide, insulin or pioglitazone. The primary end-point was the change in glycosylated haemoglobin (HbA1c) from baseline. Secondary end-points included effects on weight, blood pressure, lipid profiles and b-cell function assessed by homeostasis model assessment, fasting proinsulin:insulin (PI/I), disposition index (DI) and acute insulin response (AIR).Results. At week 48, mean [95% confidence interval (CI)] HbA 1c changes from baseline were À1.8% (À1.55% to À2.05%) with exenatide, À1.7% (À1.52% to À1.96%) with insulin and À1.5% (À1.23% to À1.71%) with pioglitazone. Treatment differences were À0.20% (95% CI À0.46% to 0.06%) for exenatide versus insulin (P = 0.185), and À0.37% (95% CI À0.63% to À0.12%) for exenatide versus pioglitazone (P = 0.002). Significant improvements from baseline in AIR, PI/I and DI were observed with all treatments, with the greatest improvements in DI, as well as weight, blood pressure and lipid profile, observed with exenatide.Conclusions. All three agents showed efficacy regarding glycaemic control and metabolic benefits; however, exenatide showed the greatest efficacy. b-cell function improved in all treatment groups; hence, early initiation of b-cell-protective therapy may halt the decline in b-cell function in type 2 diabetes.

The purpose of this study was to investigate the effects of maternal gestational diabetes mellitus (GDM) and breast feeding on childhood overweight and obesity in a mainland Chinese population. The incidence of and factors associated with overweight and obesity were compared between children of mothers with (n=1068) and without (n=1756) GDM. The independent roles of the associated factors were examined by multiple logistic regression analysis. The incidence of overweight was higher (16.6 v. 12.6%, P=0.002) in the GDM group, but that of obesity was not different (10.7 v. 12.0%, P=0.315). At age 1-2 and 2-5 years, no difference in overweight (11.0 v. 12.0%, P=0.917, and 15.7 v. 14.6%, P=0.693, respectively) was found, while obesity (8.0 v. 13.6%, P=0.019, and 8.4 v. 13.4%, P=0.014, respectively) was less frequent in the GDM offspring. At age 5-10 years, increased overweight (22.2 v. 12.1%, P<0.001) and obesity (15.9 v. 9.0%, P=0.001) were found in the GDM group, which was associated with maternal obesity, being born large-for-gestational age, male gender and formula feeding. After adjusting for confounding factors, GDM remained an independent determinant of offspring overweight and obesity (aOR 2.28, 95% CI 1.61-3.22), suggesting that the effects of GDM were independent of breast feeding, as well as of maternal obesity and birth size.

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.