Changes in insulin secretion were investigated in a group of non obese subjects with combined familial hyperlipidemia (CFH), with normal glucose tolerance, relating the observed changes with plasma triglycerides and lipoprotein phenotype. METHODS The study was conducted with 21 subjects (16 males and 5 females; mean age: 45.9 +/- 9.1 years), diagnosed of CFH after the clinical and analytical study of patients and their first degree relatives (9 with phenotype IIa, 8 IIb, and 4 IV) and 21 healthy control subjects, of similar age, sex and body weight. In both groups, lipids, plasma lipoproteins, glucose, basal plasma insulin, and insulin after and oral glucose overload (OGO) were quantitated. RESULTS Diastolic blood pressure was higher (p < 0.01) in CFH group compared with controls (means: 132/80 vs 123/71 mmHg, respectively). TC, TG and Apo B were also higher in the CFH group. With OGO significantly higher serum insulin levels were observed at 0, 30, 60, 90 and 120 minutes in CFH subjects compared with control group. Basal serum insulin and the area under the curve of insulin secretion after OGO was higher in subjects with triglycerides (45,579 +/- 13,056 in controls, 61,385 +/- 22,254 in CFH IIa, 70,645 +/- 17,271 IIb and 124,884 +/- 36,944 in CFH IV. Insulin secretion correlated significantly (p < 0.01) with plasma triglycerides. As conclusion, hyperinsulinism is a finding in CFH non obese subjects and with normal glucose tolerance, and has an increasing frequency in subjects with high triglycerides levels.