Effects of Glycemic Variability on Regulatory T Cells in Patients with Type 2 Diabetes and Kidney Disease

Abstract

Purpose To investigate the pathogenesis of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM), we evaluated the effects of short-term glycemic variability (GV) on the profile of T cell subpopulations. Methods A total of 47 T2DM patients with normoalbuminuria, 47 microalbuminuria, and 49 macroalbuminuria were enrolled. The continuous glucose monitoring (CGM) determined the GV of enrolled patients. Flow cytometry was used to determine the proportion of T cell subpopulations. Results The frequency of T helper (Th) 17 and Th1 cells significantly increased while regulatory T cells (Tregs) significantly decreased in the macroalbuminuria group compared to normoalbuminuria and microalbuminuria groups ( P < 0.01). The suppressive function of Tregs was significantly lower in the macroalbuminuria group than the normoalbuminuria group ( P < 0.05). Compared with the normoalbuminuria group, the mean amplitude of glucose excursions (MAGE) of the macroalbuminuria group was significantly higher ( P <0.05). Furthermore, there were negative associations between the proportion of Tregs and MAGE. Conclusions Increased GV could decrease the proportion of Tregs and may impair their function. This may lead to increases in Th1 and Th17 cells, and some inflammatory cytokines, which might contribute to the development and progression of DKD in T2DM.

Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study

“…Obesity-associated chronic in ammation is an important factor in the predisposition to T2D 44,50 . Multiple studies have shown that an imbalance between Treg and Th17 cells, speci cally a de ciency of Tregs and an excess of Th17 cells, is linked to obesity, insulin resistance, and T2D [51][52][53] . Some studies have suggested that systemic Treg defects are associated with diabetic nephropathy, retinopathy, and diabetic foot ulcers 54,55 .…”