Serum insulin-like growth factor binding protein 6 (IGFBP6) is increased in patients with type 1 diabetes and its complications

Abstract

Insulin-like growth factor binding proteins (IGFBPs) are associated with insulin resistance and accelerated micro- and macro-vascular complications of diabetes. We investigated the relationship between serum levels of IGFBP6 in type-1 diabetes (T1D) patients and diabetic complications. In this study, IGFBP6 was measured in the sera from 697 T1D patients and 681 healthy controls using a Luminex assay. Mean serum levels of IGFBP6 were higher in T1D patients than controls matched for sex and age (119.7 vs 130.6 ng/ml, p < 10(-4)). Subject age, sex and duration of disease have a significant impact on serum IGFBP6 levels in both T1D patients and healthy controls. Patients with complications have significantly higher mean serum IGFBP6 than patients without any complication (p = 3.5x10(-6)). More importantly, conditional logistic regression analysis suggested that T1D patients are more likely to have very high levels of serum IGFBP6 (in the 4(th) quartile) (OR = 1.7) than healthy controls. Furthermore, T1D patients with various complications are more likely to have very high levels of serum IGFBP6 (in the 4(th) quartile) than patients without any complication (OR = 1.7 - 22.9). These results indicate the clinical importance of measuring IGFBP6 to the better management of T1D patients.

Keywords: Insulin-like growth factor binding proteins (IGFBPs); complications; diabetes; insulin resistance.

Figure 1

Regression graphs showing the correlation between serum IGFBP6 levels and age of subjects. Relative levels of IGFBP6 as a function of age in the total control group (a, β=0.013, p=3x10^-9), female controls (b, β=0.009, p=0.006), male controls (c, β=0.02, p= 6.6x10^-11), and regression lines for control males and females on same plot (d). Relative levels of IGFBP6 as a function of age in the total T1D group (e, β=0.018, p=1x10^-16), female T1D (f, β=0.016, p=1x10^-13), male T1D (g, β=0.021, p= 8.3x10^-14), and regression lines for T1D males and females on same plot (h).

Figure 2

Regression plots of IGFBP6 levels with the duration of disease for all T1D patients (a; β=0.023, p=1x10^-16), female T1D (b, β=0.024, p=3.1x10^-12), male T1D (c, β=0.023, p=1x10^-11), and regression lines for both genders on same plot (d).

Figure 3

The distribution of serum IGFBP6 levels in T1D and control groups after matching for sex and age. Dash lines mark the 95^th percentile value in T1D patients. Solid lines and values on the right side represent the mean values of serum IGFBP6 in the respective groups. IGFBP6 serum levels in total T1D and control subjects (a). After separating both T1D and control groups into female and male subjects (b).

Figure 4

Boxplots showing serum IGFBP6 differences between T1D without any complications (NoC) and T1D with complications (Comp).