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 β-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 β-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 β-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 β-cell function decline over the follow-up (β = .30, P = .0001). Mediation analysis showed that the association between lower HDL levels at baseline and increased risk of incident diabetes was mediated by β-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 β-cell function decline over time.