To determine the most frequent dyslipidemias among first-degree relatives of NIDDM patients, and its association with their glucose-tolerance status and hyperinsulinemia, we have started to examine members of NIDDM pedigrees, according to American Diabetes Association guidelines for nuclear family studies. In a large family with 2 NIDDM siblings in the 2nd generation, and 4 siblings with NIDDM in the 3rd generation, we have evaluated 14 first degree relatives and also 15 sex and aged matched healthy control subjects without family history of diabetes. The NIDDM relative group presented BMI = 31.8 +/- 3.9 kg/m2, SBP = 128 +/- 18.2 mmHg, DBP = 84 +/- 12.7 mmHg. Both relatives and controls were subjected to a 2h 75g OGTT for glucose and insulin determinations. Although none of NIDDM relatives has IGT, both Glycemic Area (GA) and Insulin Area (IA) were greater (p < 0.01) in the NIDDM relative group. The Insulin/Glucose ratio was also higher (p < 0.01) at 0 and 120 min of OGTT, this might be indirect evidence of Insulin- Resistance. Fasting serum lipids in the NIDDM relatives were TG = 148 +/- 24mg/dl, T-Chol = 244 +/- 10.7mg/dl, HDL-C = 34.2 +/- 2.5mg/dl; lipids in the control group were TG = 84.8 +/- 10.1mg/dl, T-Chol = 167 +/- 10.2mg/dl, HDL-C = 44.4 +/- 2.6mg/dl. Electrophoretic pattern showed type IIa (30.7%) and IIb (61.5%) hyperlipidemias in the NIDDM relatives. In this group, there was a positive and significant association between basal insulin and DBP (r = 0.67; p < 0.01), and between DBP and both TG (r = 0.74; p < 0.01)) and VLDL-C (r = 0.58; p < 0.05). It was also obtained a negative association between basal insulin and HDL-C (r = -0.89; p < 0.001). These data suggest that hyperinsulinemia in association with lipid abnormalities could appear early (before the development of Impaired Glucose Tolerance and Diabetes) in first degree relatives of NIDDM patients.