HDL cholesterol is an independent predictor of β-cell function decline and incident type 2 diabetes: A longitudinal study

Background Experimental evidence indicates that high-density lipoprotein (HDL) may stimulate glucose uptake and improve beta-cell function. The aim of this study was to evaluate whether lower levels of HDL may affect the risk to develop type 2 diabetes. Methods Incident rate of type 2 diabetes and changes in insulin sensitivity and beta-cell function over 5.5-year follow-up were examined in 670 non-diabetic subjects stratified in tertiles according to basal HDL levels. Results As compared to the highest tertile of HDL, individuals with lower levels of HDL have an increased risk to develop type 2 diabetes independently from several cardiometabolic risk factors (odds ratio: 2.88, 95% confidence interval: 1.05-7.91), and exhibited a greater deterioration of beta-cell function, estimated by the disposition index, over 5.5-year follow-up. Conversely, changes in Matsuda index of insulin sensitivity over the follow-up were not significantly different amongst the three HDL groups. In a multivariable regression analysis model including age, sex, waist circumference, triglycerides, total cholesterol, C-reactive protein, fasting and 2-hour post-load glucose, family history of type 2 diabetes and smoking habit, HDL concentration at baseline was an independent predictor of beta-cell function decline over the follow-up (beta = .30, P = .0001). Mediation analysis showed that the association between lower HDL levels at baseline and increased risk of incident diabetes was mediated by beta-cell function deterioration during the follow-up (t = -3.32, P = .001). Conclusions Subjects with lower levels of HDL have an increased risk to develop type 2 diabetes likely due to a greater beta-cell function decline over time.