Objective: Impaired function of high-density lipoprotein (HDL) particles generates cardiometabolic disorders in people prone to impaired glucose tolerance for which clinical biomarkers need delineation. Study design: Prospective population-based study. Methods: Totally, data of 2725 adults followed-up over 7.3±3.0 years were analyzed by Cox regression analysis. C-reactive protein (CRP), complement C3 (C3), triglycerides (Trg) and HDL-cholesterol were tested to predict risk for incident diabetes or coronary heart disease (CHD). Results: Beyond atherogenic dyslipidemia, high-Trg/normal HDL-cholesterol category was associated with elevated CRP and diabetes risk in women. Normotriglyceridemic men with normal HDL-cholesterol showed higher apolipoprotein A-I levels and higher diabetes risk than men having low HDL-cholesterol. Diabetes risk doubled in hypertriglyceridemic women regardless of HDL-cholesterol. Trg/HDL-C>2 in men and Trg>1.7 mmol/L in women were best predictors of diabetes. C3>1.3 g/L served additively in women alone. Regarding CHD risk, not CRP, but C3 contributed independently to Trg/HDL>2 in men [RR 2.46 (95% CI 1.33; 4.53)]; a high ratio was merely additive to elevated CRP in women. Among five cut-off values, predictive values for diabetes were highest for CRP >2.5 mg/L in men, Trg>1.7 mmol/L and C3>1.3 g/dL in women. Conclusion: Trg/HDL-C ratio >2 and/or CRP >2.5 mg/L in men and Trg>1.7 mmol/L+C3>1.3 g/dL in women are most appropriate markers regarding impaired antiinflammatory or atheroprotective HDL function. In normotriglyceridemic men with normal HDL-cholesterol levels, diabetes risk may be elevated due to presumably dysfunctional apolipoprotein A-I.