Coronary artery disease severity modifies associations between glycemic control and both mortality and myocardial infarction

J Diabetes Complications. 2018 May;32(5):480-487. doi: 10.1016/j.jdiacomp.2018.01.010. Epub 2018 Jan 31.


Aims: This study examined whether the association between hemoglobin A1c (HbA1c) and short-term clinical outcomes is moderated by CAD severity.

Methods: We studied 17,394 US Veterans with type 2 diabetes who underwent elective cardiac catheterization between 2005 and 2013. CAD severity was categorized as obstructive, non-obstructive, or no CAD. Using multivariable Cox proportional hazards regression, we assessed associations between time-varying HbA1c and two-year all-cause mortality and non-fatal MI, with an interaction term between HbA1c and CAD severity.

Results: 61%, 22%, and 17% of participants had obstructive, non-obstructive, and no CAD, respectively. CAD severity modified the relationship between HbA1c and each outcome (interaction p-value 0.0005 for mortality and <0.0001 for MI). Low HbA1c (<42 mmol/mol) was associated with increased mortality, relative to HbA1c of 48-52 mmol/mol, in individuals with obstructive CAD (HR 1.52 [1.17, 1.97]) and non-obstructive CAD (HR 2.61 [1.61, 4.23]), but not in those with no CAD (HR 0.91 [0.46, 1.79]). In contrast, higher HbA1c levels (≥53 mmol/mol) were associated with increased MI risk only in individuals with obstructive CAD.

Conclusions: The associations between HbA1c and mortality and MI were moderated by CAD severity. Measures of cardiovascular disease severity may inform optimal individualized diabetes management.

Keywords: Cardiovascular risk factor; Coronary artery disease; Glycemic control; Heart disease; Interaction.

Publication types

  • 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
  • Blood Glucose / metabolism
  • Cardiac Catheterization
  • Comorbidity
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / mortality*
  • Coronary Artery Disease / therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / mortality*
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mortality
  • Myocardial Infarction / blood
  • Myocardial Infarction / complications
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / mortality*
  • Risk Factors
  • Severity of Illness Index
  • United States / epidemiology
  • Veterans / statistics & numerical data


  • Blood Glucose
  • Glycated Hemoglobin A