Low plasma insulin-like growth factor-1 levels are associated with reduced insulin sensitivity and increased insulin secretion in nondiabetic subjects

Background and aim: Weight gain is associated with a decline in insulin sensitivity and a compensatory increase in insulin secretion. IGF-1 is a plausible candidate to explain these divergent phenomena. In this cross-sectional study, we analyzed the relationship between IGF-1 levels, insulin sensitivity and secretion in 110 nondiabetic subjects with a wide range of BMI to verify this hypothesis. Methods and results: Subjects underwent OGTT, IVGTT and euglycemic-hyperinsulinemic clamp. HOMA-beta, IVGTT-derived and OGTT-derived indexes for first-phase and second-phase insulin secretion were higher in obese as compared with overweight and normal-weight groups, while glucose disposal was lower. IGF-1 levels were negatively correlated with IVGTT-derived and OGTT-derived indexes first-phase and second-phase insulin secretion, and positively correlated with glucose disposal. These correlations were no longer significant after adjustment for BMI. In a multivariate analysis, the variables associated with glucose disposal were IGF-1, age, triglycerides, and 2-h post-load glucose accounting for 23.4% of its variation. When BMI was entered into the model, the variables associated with glucose disposal were triglycerides, 2-h post-load glucose and BMI accounting for 27.2% of variation. In a multivariate analysis, the only variable associated with IVGTT-derived first-phase and second-phase insulin secretion was IGF-1 accounting for 10.4% and 15.1% of variation, respectively. When BMI was entered into the model, it became the only variable associated with both first-phase and second-phase insulin secretion accounting for 25.7% and 37.6% of variation, respectively. Conclusion: These data suggest that progressive reduction in IGF-1 levels may be involved in obesity-related changes in both insulin sensitivity and secretion.