Influence of duration of obesity on the insulin resistance of obese non-diabetic patients

OBJECTIVE: To investigate whether duration of obesity has an independent impact on insulin resistance. DESIGN: Case-control study. SUBJECTS: 30 non-diabetic obese subjects (age, 34 ± 2 y, body mass index (BMI), 33.5 ± 0.8 kg·m-2) with a range (1-35 y) of self-reported duration of obesity, and 12 age- and gender-matched non-obese controls (BMI, 22.1 ± 0.6 kg·m-2). MEASUREMENTS: Oral glucose tolerance (40 g·m-2), insulin sensitivity (by the euglycaemic insulin clamp technique), and insulin secretion (as the product of post-hepatic insulin clearance and plasma insulin concentration). RESULTS: The obese group presented hyperinsulinaemia in the basal state and after glucose loading (insulin area = 58 ± 5 vs 33 ± 3 nmol·l-1·2 h, P = 0.005), insulin resistance (M value = 37.4 ± 4.8 vs 50.6 ± 2.6 μmol·min-1 kg FFM-1, P = 0.002), and insulin hypersecretion (61.9 ± 6.0 vs 33.9 ± 4.0 nmol·2 h, P = 0.007); endogenous glucose production was similar in the two groups. In the whole dataset, insulin resistance was directly related to BMI, the waist-to-hip ratio (WHR), endogenous glucose production, insulin secretion, and fasting serum triglycerides and uric acid concentrations. When the obese subjects were stratified by duration of obesity, insulin resistance was progressively lower with longer obesity duration (P = 0.04). When simultaneously adjusting by age, gender and BMI, obesity duration was independently associated with greater insulin sensitivity (P = 0.003), lower plasma insulin response to oral glucose (P = 0.001), and lower fasting and glucose-stimulated insulin release (P = 0.01 for both). CONCLUSIONS: In obese subjects with preserved glucose tolerance, duration of obesity is associated with better insulin sensitivity irrespective of the degree of overweight.