Change in the Amount of Body Fat and IL-6 Levels is Related to Altered Insulin Sensitivity in Type 1 Diabetes Patients with or without Diabetic Nephropathy

Abstract

Insulin resistance (IR) is found early-on in renal disease. The aim of this study was to prospectively evaluate if a change in glomerular filtration rate (GFR) or in endocrine and inflammatory factors over time alters insulin sensitivity in patients with type 1 diabetes (T1D) or without diabetic nephropathy (DN) at baseline. 20 T1D with (DN+, n = 12) or without DN (DN-, n = 8) were re-examined after 5.0 ± 0.4 years. GFR was determined by ⁵¹Cr-EDTA clearance. Insulin sensitivity was assessed by hyperinsulinemic (56 mU/m²/min), euglycemic clamp (M-value at steady state during clamp) and calculated per lean body mass. Body composition was determined by bioimpedance. No association was found between change in GFR and change in M-value over time. Instead, change in M-value was associated to change in fat mass (%) and change in IL-6 levels in all subjects taken together (r = -0.55, p = 0.012 and r = -0.62, p = 0.006). These association were verified in the multivariate regression analyses. Findings were similar in DN - and DN +, respectively, but the change in IL-6 was only significantly associated with altered M-value in DN+ subjects. This prospective study indicates that change in amount body fat and levels of inflammatory cytokines, such as IL-6, contribute to change in insulin resistance over time in type 1 diabetes patients with and without diabetic nephropathy.