Diagnostic Thresholds for Pre-Diabetes Mellitus and Diabetes Mellitus and Subclinical Cardiac Disease in the General Population: Data From the ACE 1950 Study

J Am Heart Assoc. 2021 Jun;10(11):e020447. doi: 10.1161/JAHA.120.020447. Epub 2021 May 17.


Background Diabetes mellitus (DM) is associated with left ventricular remodeling and incident heart failure, but the association between glycated hemoglobin A1c (HbA1c) and subclinical cardiac disease is not established. We aimed to determine the associations between HbA1c and (1) echocardiographic measures of left ventricular structure and function, and (2) cardiovascular biomarkers: cardiac troponin T, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and CRP (C-reactive protein). Methods and Results Participants (n=3688) born in 1950 from the population-based ACE (Akershus Cardiac Examination) 1950 Study were classified as DM (HbA1c≥6.5% or self-reported DM), pre-DM (HbA1c 5.7%-6.5%), and no-DM (HbA1c<5.7%). DM, pre-DM, and no-DM were classified in 380 (10%), 1630 (44%), and 1678 (46%) participants, respectively. Mean age was 63.9±0.7 years, mean body mass index was 27.2±4.4 kg/m2, and 49% were women. Higher HbA1c was associated with worse left ventricular systolic (ejection fraction and global longitudinal strain) and diastolic (E/e'-ratio) function, myocardial injury (cardiac troponin T), inflammation (CRP), and impaired neurohormonal homeostasis (NT-proBNP) (P<0.001 in unadjusted and P<0.01 in adjusted analysis for all). The associations between HbA1c and cardiovascular biomarkers were independent of the echocardiographic variables, and vice versa. Associations were nonlinear (P<0.05 for nonlinearity) and appeared stronger in the pre-DM range of HbA1c than the no-DM and DM range. Conclusions HbA1c was associated with indexes of subclinical cardiovascular disease, and this was more pronounced in pre-DM. Our results suggest that cardiovascular preventive measures should be considered also in subjects with hyperglycemia and HbA1c below the established DM cutoff. Registration clinicaltrials.gov. Identifier: NCT01555411.

Keywords: biomarker; diabetes mellitus; echocardiography; hemoglobin A1c; troponin.

Publication types

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

MeSH terms

  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Diabetes Mellitus / diagnosis*
  • Diastole
  • Echocardiography, Doppler / methods*
  • Female
  • Glycated Hemoglobin / metabolism*
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / physiopathology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Norway / epidemiology
  • Peptide Fragments / blood
  • Prediabetic State / diagnosis*
  • Protein Precursors
  • Stroke Volume / physiology*
  • Systole
  • Troponin T / blood
  • Ventricular Remodeling / physiology*


  • Biomarkers
  • Glycated Hemoglobin A
  • Peptide Fragments
  • Protein Precursors
  • Troponin T
  • hemoglobin A1c protein, human
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT01555411