Abstract
BACKGROUND: Type 2 diabetes is increasing worldwide. Traditionally, only hypertriglyceridemia is considered a risk factor. We investigated whether also normal triglycerides prospectively associate with incident type 2 diabetes in healthy subjects. METHODS: Incident type 2 diabetes was determined in healthy individuals with normal triglyceride levels from a prospective longitudinal cohort study (PREVEND, n = 2085, 11.4-year median follow-up). RESULTS: Type 2 diabetes incidence was 3.8%. In linear regression analysis baseline insulin, HOMA-IR, total cholesterol, HDL cholesterol, eGFR, systolic blood pressure (all p < 0.001), glucose, age and creatinine (all p < 0.01) independently associated with triglycerides within the normal range, comparable to what would be expected from associations with increased triglycerides. In Kaplan-Meier analysis sex-stratified tertiles of normal triglycerides prospectively associated with de novo type 2 diabetes (p < 0.001). Cox regression confirmed a significant prospective association independent of HOMA-IR [HR (95% CI), 1.39 (1.12, 1.74), p = 0.002] and several other recognized risk factors. CONCLUSIONS: Even in healthy subjects without metabolic syndrome increasing triglyceride levels within the normal range confer a continuous increase in type 2 diabetes incidence. These data indicate that virtually everyone could potentially benefit from triglyceride lowering, further encouraging implementation of lifestyle changes in the general population.