Impact of visit-to-visit glycemic variability on the risks of macrovascular and microvascular events and all-cause mortality in type 2 diabetes: the ADVANCE trial

Diabetes Care. 2014 Aug;37(8):2359-65. doi: 10.2337/dc14-0199. Epub 2014 May 8.

Abstract

Objective: There is no consensus on the importance of visit-to-visit glycemic variability in diabetes. Therefore, we assessed the effects of visit-to-visit variability (VVV) in HbA1c and fasting glucose on major outcomes in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial.

Research design and methods: ADVANCE was a factorial randomized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes. VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA1c and glucose taken 3-24 months after randomization. Outcomes were combined macro- and microvascular events and all-cause mortality occurring post 24 months. Sensitivity analyses were performed using other indices of variability and in the standard glucose treatment group.

Results: Among 4,399 patients in the intensive group, an increase in VVV of HbA1c was associated with an increased risk of vascular events (P = 0.01) and with mortality (P < 0.001): highest versus lowest tenth hazard ratio (95% CI) 1.64 (1.05-2.55) and 3.31 (1.57-6.98), respectively, after multivariable adjustment. A clear association was also observed between VVV of fasting glucose and increased risk of vascular events (P < 0.001; 2.70 [1.65-4.42]). HbA1c variability was positively associated with the risk of macrovascular events (P = 0.02 for trend), whereas glucose variability was associated with both macro- and microvascular events (P = 0.005 and P < 0.001 for trend, respectively). Sensitivity analyses using other indices, and patients in the standard glucose treatment group, were broadly consistent with these results.

Conclusions: Consistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT00145925.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Glucose / analysis
  • Blood Glucose / metabolism*
  • Cause of Death
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / mortality*
  • Diabetic Angiopathies / etiology*
  • Diabetic Angiopathies / mortality*
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Gliclazide / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Indapamide / therapeutic use
  • Male
  • Middle Aged
  • Office Visits / statistics & numerical data*
  • Perindopril / therapeutic use
  • Risk Factors

Substances

  • Blood Glucose
  • Drug Combinations
  • Hypoglycemic Agents
  • indapamide, perindopril drug combination
  • Indapamide
  • Gliclazide
  • Perindopril

Associated data

  • ClinicalTrials.gov/NCT00145925