To investigate the association of folate and vitamin B 12 in early pregnancy with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODSThe data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B 12 measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks' gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association. RESULTSA total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B 12 were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19-2.53) (P 5 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ‡600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03-2.41) (P 5 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (P trend 5 0.021). Vitamin B 12 was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P 5 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B 12 with GDM was observed. CONCLUSIONSHigher maternal RBC folate and vitamin B 12 levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B 12 is not significantly associated with GDM.As one of the most common pregnancy complications, gestational diabetes mellitus (GDM) affects ;17% of pregnancies worldwide (1). In China, ;2.9 million pregnant women suffer from this disorder (2). GDM has long-term adverse outcomes in both mothers and offspring (3). Despite its serious complications, the diagnosis of GDM is

Chronic exposure of pancreatic β-cells to abnormally elevated levels of free fatty acids can lead to β-cell dysfunction and even apoptosis, contributing to type 2 diabetes pathogenesis. In pancreatic β-cells, SIRT6 has been shown to regulate insulin secretion in response to glucose stimulation. However, what roles SIRT6 play in β-cells in response to lipotoxicity remain poorly understood. Our data indicated that SIRT6 protein and mRNA levels were reduced in islets from diabetic and aged mice. High concentrations of palmitate also led to a decrease in SIRT6 expression in MIN6 β-cells and resulted in cell dysfunction and apoptosis. Knockdown of Sirt6 caused an increase in cell apoptosis and impairment in insulin secretion in response to glucose in MIN6 cells even in the absence of high palmitate. Furthermore, overexpression of SIRT6 alleviated the palmitate-induced lipotoxicity with improved cell viability and increased glucose-stimulated insulin secretion. In summary, our data suggest that SIRT6 can protect against palmitate-induced β-cell dysfunction and apoptosis.

Objective: To evaluate whether the associations of maternal liver dysfunction and liver function biomarkers (LFBs) with gestational diabetes mellitus (GDM) are independent of overweight. Design: Prospective cohort study.Methods: A sub-cohort of pregnant women with seven LFBs examined at 9-13 weeks of gestation and with complete GDM evaluation at mid-gestation were extracted from the prospective Shanghai Preconception Cohort Study. Associations of liver dysfunction, defined as having any elevated LFB levels, and individual LFB levels with GDM incidence were assessed by adjusting body mass index and other covariates in the multivariable logistic regression model. Odds ratios (ORs) and 95% CI were reported.

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD) + biosynthesis. Through its NAD + -biosynthetic activity, NAMPT influences the activity of NAD + -dependent enzymes, such as sirtuins. NAMPT is able to modulate processes involved in the pathogenesis of non-alcohol induced fatty liver disease (NAFLD), but the roles NAMPT plays in development of alcoholic liver disease (ALD) still remain unknown. Here, we show that ethanol treatment suppresses the expression of Nampt in hepatocytes. Consistently, chronic ethanol administration also reduces Nampt expression in the mouse liver. We next demonstrate that hepatocytes infected with Ad-NAMPT adenovirus exhibit significantly elevated intracellular NAD + levels and decreased ethanol-induced triglyceride (TG) accumulation. Similarly, adenovirus-mediated overexpression of NAMPT in mice ameliorates ethanol induced hepatic steatosis. Moreover, we demonstrate that SIRT1 is required to mediate the effects of NAMPT on reduction of hepatic TG accumulation and serum ALT, AST levels in ethanol-fed mice. Our results provide important insights in targeting NAMPT for treating alcoholic fatty liver disease.

<strong>OBJECTIVE</strong> <p>To investigate the association of folate and<b> </b>vitamin B₁₂in early pregnancy with gestational diabetes mellitus (GDM) risk.</p> <p> </p> <p><strong>RESEARCH DESIGN AND METHODS</strong> </p> <p><a></a><a>The data of this study were from a sub-cohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B₁₂ measurements at recruitment (between </a><a>9-13 gestational weeks</a>) and those with three samples available for glucose measurements under oral glucose tolerance test (OGTT). GDM was diagnosed between 24-28 weeks gestation. <a>Odds ratio (OR) </a>of having a GDM and 95% confidence interval (CI) was used to quantify the association. </p> <p> </p> <p><strong>RESULTS</strong> </p> <p><a></a><a>A total of 1,058 pregnancies were included and 180 GDM occurred (17.01%).</a> RBC folate and vitamin B₁₂were significantly higher in pregnancies with GDM than those without GDM (<i>P</i> values were 0.045 and 0.002 respectively), and positively correlated with 1-hour and 2-hour serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM, OR (95% CI) was 1.73 (1.19-2.53), <i>P</i>=0.004. Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ³600 ng/mL was associated with approximately 1.60-fold higher odds of GDM, the adjusted OR (95% CI) was 1.58 (1.03-2.41), <i>P</i>=0.033. A significant trend of risk effect on GDM risk across categories of RBC folate was observed (<i>P</i>_trend =0.021). Vitamin B₁₂ was significantly associated with GDM risk (OR =1.14 per 100 pg/ml, <i>P</i>=0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B₁₂ with GDM was observed.</p> <p> </p> <p><strong>CONCLUSIONS</strong> </p> <p><a>Higher </a>maternal RBC folate and vitamin B₁₂levelsin early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B₁₂ is not significantly associated with GDM.</p>