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

Diabetes Care. 2015 Dec;38(12):2354-69. doi: 10.2337/dc15-1188.

Abstract

Objective: Glycemic 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 HbA1c variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes.

Research design and methods: Medline and Embase were searched (2004-2015) for studies describing associations between HbA1c 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 HbA1c variability, method of analysis, and diabetes type.

Results: Seven studies evaluated HbA1c variability among patients with type 1 diabetes and showed an association of HbA1c 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 HbA1c variability among patients with type 2 diabetes. Higher HbA1c 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 HbA1c variability.

Conclusions: HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Blood Glucose / analysis
  • Cardiovascular Diseases / complications
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / mortality
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / complications*
  • Glycated Hemoglobin / analysis
  • Humans
  • Risk Factors

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human