Insulin-like Growth Factor (IGF) and Insulin-like Growth Factor Binding Proteins (IGFBP) as Predictors of Type 2 Diabetes Risk in Obese Adults

Abstract Aim: Obesity predisposes to Type 2 Diabetes, however, not all obese persons progress to diabetes; thus, risk stratification among non-diabetes people with obesity is important. Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Proteins modulate metabolism and may predict diabetes in high-risk adults. We aim to investigate whether their levels predict future diabetes risk in non-diabetes individuals with obesity. Methods: In this case-cohort analysis nested within the Johns Hopkins GeneSTAR study, 40 incident diabetes cases and 40 random cohort sample with a BMI ≥30 kg/m² at baseline (38% males, 50% African Americans, age range 22-69 years) were followed for incident diabetes for ≥10 years. Sampling-weighted logistic regression assessed the relationship between baseline IGF/IGFBP biomarkers measured by ELISA and diabetes risk. Results: Higher baseline levels of IGF1, IGFBP1, IGFBP2, IGFBP3, and IGFBP6 predicted decreased odds of developing diabetes over 10 years when adjusted for sex, race, baseline age, and follow-up time. This association remained statistically significant for IGFBP2, IGFBP3, and IGFBP6 after adjusting for fasting baseline glucose. Conclusions: IGF/IGFBP complex proteins may serve as early indicators for diabetes risk beyond fasting glucose levels. Future studies should investigate the functional role of the IGF/IGFBP system in obesity, glucose metabolism, and diabetes prevention.