Clinical implications and pharmacological considerations of glycemic variability in patients with type 2 diabetes mellitus

Glycemic variability (GV), independently of glycemic control, has emerged as a prognostic marker in patients with type 2 diabetes mellitus (DM). In this study, we assessed the prognostic value of long-term GV for predicting major adverse cardiovascular events (MACE) in our local population. We also assessed its prognostic value for diabetic microvascular complications (DMC) and its relationships with antidiabetic medications. This was a retrospective cohort study that recruited 680 patients with type 2 DM across 2015-2017. MACE were defined as: the composite of; total death, myocardial infarction (MI), stroke, hospitalization due to heart failure, and revascularization. GV was calculated for two glycemic control markers: glycated hemoglobin (G-Hb) and fasting blood sugar (FBS); via three metrics- standard deviation (SD), coefficient of variation (CV), and variability independent from the mean (VIM). Cox proportional hazard models and Kruskal-Wallis tests were used in the statistical analysis. 105 events classified as MACE were identified in 86 patients and 104 DMC in 98 patients in an average follow-up period of 78.43 months. Long-term GV was found to be an independent predictor of MACE, particularly for FBS-CV but not a predictor of DMC. FBS-CV ≥ 17.51% as compared with < 17.51% was a significant and independent predictor of MACE, with HR 1.589 (95% CI; 1.022, 2.472) (P = 0.040). DMC were predicted mainly by the duration of type 2 DM, and by the glycemic control; similarly represented by G-Hb and FBS. Patients on metformin, and dipeptidyl peptidase (DPP) 4 inhibitors, had the lowest GV, as compared with patients whose treatments included insulin/sulphonylureas (P < 0.001). In our population, long-term GV predicted MACE: with FBS-CV superior to the "gold standard" glycemic control marker G-Hb. Further, GV may be explained, partially at least, by the choice of antidiabetic medications: this finding might contribute to the cardiovascular protection attributed to one class rather than another.