Baseline alterations in the insulin-like growth factor (IGF) system were associated with long-term markers of kidney function decline and mortality in adults with type 2 diabetes mellitus (T2DM), according to a longitudinal study published in Diabetic Medicine. The findings suggest that selected insulin-like growth factor binding proteins (IGFBPs) may help identify patients at higher risk for progressive renal complications.

The study evaluated 436 adults with T2D recruited from primary and secondary care between 2002 and 2004 through the Salford and Manchester Integrated Care Record. At entry, the mean age was 56.6 ± 9.4 years, and 59.3% were men. Participants were followed for a mean of 17.4 ± 5.2 years, with repeated laboratory assessments available for as long as 24 years. Baseline insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and IGF binding proteins (IGFBPs) were examined against 2 predefined outcomes: longitudinal change in urinary albumin-to-creatinine ratio (ACR) and longitudinal change in serum creatinine. Mortality was also assessed.

IGF-II and IGFBP-3 showed a strong correlation (Spearman rho=0.80) and were not entered together in multivariable models because of collinearity. Higher IGFBP-2 was independently associated with faster ACR progression (normalized beta, 0.007; P=0.002). Lower IGFBP-1 was associated with worsening ACR trend (B=-0.057; P=0.009) and greater creatinine increase (B=-0.038; P=0.04). Higher IGF-II was also associated with worsening ACR slope (B=0.005; P=0.013), whereas IGF-I showed no measurable association. Higher IGFBP-2 was independently associated with increased all-cause mortality (HR per 1 standard deviation increase, 1.306; 95% CI, 1.151-1.483; P=0.0001).

The analysis showed that higher baseline IGFBP-2, higher IGF-II, and lower IGFBP-1 were associated with a greater likelihood of albuminuria progression in T2D. Higher IGFBP-2 was also associated with higher mortality.