Insulin-like growth factor (IGF) and Insulin-like growth factor binding proteins (IGFBP) as predictors of type 2 diabetes risk in obese adults

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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s40200-025-01753-y.