Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis

OBJECTIVEGlycemic variability is emerging as a measure of glycemic control, which may be a reliable predictor of complications. This systematic review and meta-analysis evaluates the association between HbA(1c) variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes.RESEARCH DESIGN AND METHODSMedline and Embase were searched (2004-2015) for studies describing associations between HbA(1c) variability and adverse outcomes in patients with type 1 and type 2 diabetes. Data extraction was performed independently by two reviewers. Random-effects meta-analysis was performed with stratification according to the measure of HbA(1c) variability, method of analysis, and diabetes type.RESULTSSeven studies evaluated HbA(1c) variability among patients with type 1 diabetes and showed an association of HbA(1c) variability with renal disease (risk ratio 1.56 [95% CI 1.08-2.25], two studies), cardiovascular events (1.98 [1.39-2.82]), and retinopathy (2.11 [1.54-2.89]). Thirteen studies evaluated HbA(1c) variability among patients with type 2 diabetes. Higher HbA(1c) variability was associated with higher risk of renal disease (1.34 [1.15-1.57], two studies), macrovascular events (1.21 [1.06-1.38]), ulceration/gangrene (1.50 [1.06-2.12]), cardiovascular disease (1.27 [1.15-1.40]), and mortality (1.34 [1.18-1.53]). Most studies were retrospective with lack of adjustment for potential confounders, and inconsistency existed in the definition of HbA(1c) variability.CONCLUSIONSHbA(1c) variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA(1c) level and might play a future role in clinical risk assessment.