Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study

Background: The protective role of high HDL cholesterol levels against cardiovascular diseases has been recently questioned. Limited data are available on this specific topic in patients with type 2 diabetes mellitus (T2DM). We aimed to evaluate the association of HDL cholesterol concentrations with all-cause and cause-specific mortality in a historical cohort of T2DM patients with 14 years of follow-up. Methods: This is a retrospective population-based cohort study involving 2113 T2DM patients attending the Diabetic Clinic of Asti. Survival analyses were performed to assess hazard ratios for overall and specific-cause mortality by HDL cholesterol tertiles, using the middle HDL cholesterol tertile as a reference. Results: The mean age was 66 ± 11 years; 51.4% of patients had low HDL-cholesterol levels. After a 14-year follow-up, 973/2112 patients had died (46.1%). The HDL cholesterol tertile cut-off points were 37.5 and 47.5 mg/dL (males) and 41.5 and 52.0 mg/dL (females). No associations between lower and upper HDL cholesterol tertiles respectively and all-cause (HR = 1.12; 95% CI 0.96-1.32; HR = 1.11; 0.95-1.30), cardiovascular (HR = 0.97; 0.77-1.23; HR = 0.94; 0.75-1.18) or cancer (HR = 0.92; 0.67-1.25; HR = 0.89; 0.66-1.21) mortality were found. A significantly increased risk for infectious disease death was found both in the lower (HR = 2.62; 1.44-4.74) and the upper HDL-cholesterol tertiles (HR = 2.05; 1.09-3.85) when compared to the reference. Individuals in the upper tertile showed an increased risk for mortality due to diabetes-related causes (HR = 1.87; 1.10-3.15). Conclusions: Our results corroborate the hypothesis that HDL cholesterol levels are nonprotective in T2DM patients. The U-shaped association between HDL-cholesterol levels and mortality associated with infectious diseases should be verified by further studies.