Background Hyperglycemia during pregnancy increases the risk of adverse perinatal outcomes and birth defects. Evidence regarding the long-term safety of antidiabetic drugs during pregnancy is still lacking.
Methods A two-sample Mendelian randomization (MR) study was performed to assess the causal association between six antidiabetic drug targets (ABCC8, DPP4, INSR, GLP1R, PPARG, and SLC5A2) and seven adverse perinatal outcomes and five congenital malformation outcomes. Inverse variance weighted (IVW) was adopted as the main MR method, and sensitivity analysis using traditional MR methods was performed to evaluate the robustness of the results.
Results We observed strong evidence that sodium-glucose cotransporter 2 (SGLT2) inhibitors (odds ratio [OR], 0.084; 95% confidence interval [CI], 0.009 to 0.834; P=0.034) reduces the risk of preterm birth; genetic variation in sulfonylurea drug targets (OR, 0.015; 95% CI, 2.50E-04 to 0.919; P=0.045) and genetic variation in thiazolidinedione drug targets (OR, 0.007; 95% CI, 4.16E-04 to 0.121; P=0.001) reduced the risk of eclampsia/preeclampsia; glucagon-like peptide 1 (GLP-1) analogues target (β=–0.549; 95% CI, –0.958 to –0.140; P=0.009) was inversely associated with fetal birth weight; thiazolidinedione target was inversely associated with gestational age (β=–0.952; 95% CI, –1.785 to –0.118; P=0.025); SGLT2 inhibitors reduced the risk of cardiocirculatory malformations (OR, 0.001; 95% CI, 8.75E-06 to 0.126; P=0.005).
Conclusion Most antidiabetic drugs are safe when used during the perinatal period. Of note, GLP-1 analogues may lead to a risk of low birth weight, while thiazolidinediones may lead to a reduction in fetal gestational age.
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Background Our previous studies have investigated the role of hepatic insulin resistance (hepatic IR) and islet β-cell function in the pathogenesis of diabetes. This study aimed to explore the contributions of hepatic IR and islet β-cell dysfunction to the blood glucose spectrum in patients with newly diagnosed type 2 diabetes mellitus.
Methods Hepatic IR was assessed by the hepatic insulin resistance index (HIRI). Islet β-cell function was assessed by insulin secretion- sensitivity index-2 (ISSI2). The associations between blood glucose spectrum and hepatic IR and ISSI2 were analyzed.
Results A total of 707 patients with new-onset diabetes were included. The fasting blood glucose (FBG) and 30 minutes postload blood glucose elevated with rising HIRI (both P for trend <0.001). The FBG, 30 minutes, 2 hours, and 3 hours post-load blood glucose elevated with decreasing ISSI2 quartiles (all P for trend <0.001). There was a negative correlation between ISSI2 and HIRI after adjusting blood glucose levels (r=–0.199, P<0.001).
Conclusion Hepatic IR mainly contributed to FBG and early-phase postprandial plasma glucose, whereas β-cell dysfunction contributed to fasting and postprandial plasma glucose at each phase.
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Methods This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed.
Results During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders.
Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.
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