Excessive visit-to-visit glycemic variability independently deteriorates the progression of endothelial and renal dysfunction in patients with type 2 diabetes mellitus

BACKGROUND: Glycemic variability (GV) creates challenges to glycemic control and may be an independent marker for unfavorable outcome in management of patients with diabetes. This study was designed to investigate the effect of excessive visit-to-visit GV on the progression of endothelial and renal dysfunction in patients with type 2 diabetes mellitus (T2DM). METHODS: Two hundred and thirty nine patients with T2DM, who were recruited from outpatient, completed 48-month follow-up visit. Visit-to-visit GV was calculated by the standard deviation (SD) and coefficient of variation (CV) of serially measured HbA1c and fasting plasma glucose (FPG). Endothelial and renal function was assessed at baseline and end of follow-up. RESULTS: At end of follow-up, brachial flow-mediated dilation (FMD), nitric oxide (NO), creatinine-based estimated glomeruar filtration rate (eGFR-Cr), and cystatin C-based estimated glomeruar filtration rate (eGFR-Cys C) increased, and endothelin-1 and urine albumin/creatinine ratio (ACR) declined as compared with baseline in overall (P < 0.05). The increment of FMD, NO, eGFR-Cr, and eGFR-Cys C and the decrement of endothelin-1 and ACR in first tertile group were significantly greater than those in third tertile group classified by tertile of either SD of HbA1c or SD of FPG. Change percentage of FMD, NO, eGFR-Cr, and eGFR-Cys C were positively, and change percentage of endothelin-1 and ACR were negatively correlated with SDs of HbA1c and FPG, and CVs of HbA1c FPG (P < 0.01, respectively). After adjusted for mean HbA1c, mean FPG, baseline demographic, and clinical characteristics, SD of HbA1c and SD of FPG were always statistically correlated with change percentage of FMD, NO, endothelin-1, ACR, eGFR-Cr, and eGFR-Cys C. CONCLUSION: Excessive visit-to-visit GV independently deteriorates the progression of endothelial and renal dysfunction in patients with T2DM.