Glycaemic variation is a predictor of all-cause mortality in the Veteran Affairs Diabetes Trial

Diab Vasc Dis Res. 2019 Mar;16(2):178-185. doi: 10.1177/1479164119827598.


Diabetes is associated with substantially increased mortality. Classic risk factors explain a portion of the excess of mortality in type 2 diabetes. The aim of this study was to examine whether visit-to-visit variation in fasting glucose and haemoglobin A1c values in the Veteran Affairs Diabetes Trial were associated with all-cause mortality in patients with type 2 diabetes in addition to other comorbidity conditions, hypoglycaemic events and adverse lifestyle behaviours. The Veteran Affairs Diabetes Trial was a randomized trial that enrolled 1791 military veterans who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. During the Veteran Affairs Diabetes Trial, fasting glucose and haemoglobin A1c were measured quarterly for up to 84 months. Variability measures included coefficient of variation and average real variability. We found that variability measures (coefficient of variation and average real variability) of fasting glucose were predictors of all-cause mortality, even after adjusting for comorbidity index, mean fasting glucose and adverse lifestyle behaviour during the study. Accounting for severe hypoglycaemia did not weaken this association. Our analysis indicates that in the Veteran Affairs Diabetes Trial, longitudinal variation in fasting glucose was associated with all-cause mortality, even when accounting for standard measures of glucose control as well as comorbidity and lifestyle factors.

Keywords: Mortality; glycaemic control; hypoglycaemia; long-term glycaemic variability; type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Cause of Death
  • Comorbidity
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / mortality*
  • Fasting / blood
  • Female
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Life Style
  • Male
  • Middle Aged
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • United States / epidemiology
  • United States Department of Veterans Affairs
  • Veterans Health*


  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human