To identify the associated risk factors to the increase of early insulin response in healthy Hispanic-Mexican subjects.Comparative cross-sectional study including 130 nonpregnant women and 54 men older than 30 years of age, randomly selected from Durango City, an urban population from the North of Mexico. According to the insulinogenic index value that assesses the early insulin response, subjects were distributed into quartiles. Subjects with increased insulin response (4th quartile) were compared against a control group (2nd and 3rd quartile).There were no significant differences by obesity (body mass index 29.2 +/- 5.1 vs. 28.7 +/- 4.5 kg/m2), nor fasting nor 2-h post dose glucose (85.2 +/- 16.1 vs 82.1 +/- 10.4 mg/dL, and 95. +/- 25.5 vs. 99.1 +/- 23.1 mg/dL) between subjects in the 4th quartile vs. subjects in the 2nd and 3rd quartile, respectively. The family history of diabetes (FHD) (Odds ratio 3.9; C1(95%) 1.3-9.1, p < 0.01) was a powerful risk factor associated to increased early insulin response.FHD is an independent predictor for increased early insulin response in Hispanic-Mexican subjects.