Pancreatic β-cell function relates positively to HDL functionality in well-controlled Type 2 diabetes mellitus

BackgroundHigh density lipoproteins (HDLs) have been implicated in glucose homeostasis. Among subjects with normal fasting glucose (NFG), impaired fasting glucose (IFG) and Type 2 diabetes mellitus (T2DM) we tested whether pancreatic β-cell function relates to HDL functionality, as determined by HDL anti-oxidative capacity and cellular cholesterol efflux to plasma.Subjects and methodsHDL anti-oxidative capacity (inhibition of LDL oxidation in vitro), cellular cholesterol efflux (the ability of plasma to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single human donor), glucose and insulin were determined in fasting plasma samples from 37 subjects with NFG, 36 with IFG and 22 with T2DM (no glucose lowering drug or insulin treatment; HbA1c 6.0 ± 1.0%). Homeostasis model assessment was used to estimate pancreatic β-cell function (HOMA-β) and insulin resistance (HOMAir).ResultsHOMA-β was lowest, whereas HOMAir was highest in T2DM (P < 0.01 and P < 0.001 vs. NFG). HDL anti-oxidative capacity and cellular cholesterol efflux did not differ significantly according to glucose tolerance category. In univariate analysis and after controlling for HOMAir both HDL anti-oxidative capacity (P < 0.05) and cellular cholesterol efflux (P < 0.01) were positively correlated with HOMA-β in T2DM, but not in NFG and IFG. In age-, sex- and HOMAir-adjusted analyses, T2DM status interacted positively with HDL anti-oxidative capacity (P = 0.001) and cellular cholesterol efflux (P = 0.042) on HOMA-β. HbA1c interacted similarly with HDL functionality measures on HOMA-β.ConclusionsPancreatic β-cell function relates to pathophysiologically relevant measures of HDL function in T2DM, but not in NFG and IFG. Better HDL functionality may contribute to maintenance of β-cell function in subjects with well-controlled T2DM.

► Abnormalities in HDL functionality may affect β-cell function. ► HDL functionality was assessed as its anti-oxidative capacity and cholesterol efflux to plasma. ► β-cell function was related to these HDL functionality measures in well-controlled Type 2 diabetes. ► Such relationships were not observed in subjects with normal and impaired fasting glucose. ► Better HDL functionality may contribute to maintenance of β-cell function in Type 2 diabetes.