Association of Glycemic Control Trajectory with Short-Term Mortality in Diabetes Patients with High Cardiovascular Risk: a Joint Latent Class Modeling Study

J Gen Intern Med. 2020 Aug;35(8):2266-2273. doi: 10.1007/s11606-020-05848-5. Epub 2020 Apr 24.


Background: The relationship between risk factor or biomarker trajectories and contemporaneous short-term clinical outcomes is poorly understood. In diabetes patients, it is unknown whether hemoglobin A1c (HbA1c) trajectories are associated with clinical outcomes and can inform care in scenarios in which a single HbA1c is uninformative, for example, after a diagnosis of coronary artery disease (CAD).

Objective: To compare associations of HbA1c trajectories and single HbA1c values with short-term mortality in diabetes patients evaluated for CAD DESIGN: Retrospective observational cohort study PARTICIPANTS: Diabetes patients (n = 7780) with and without angiographically defined CAD MAIN MEASURES: We used joint latent class mixed models to simultaneously fit HbA1c trajectories and estimate association with 2-year mortality after cardiac catheterization, adjusting for clinical and demographic covariates.

Key results: Three HBA1c trajectory classes were identified: individuals with stable glycemia (class A; n = 6934 [89%]; mean baseline HbA1c 6.9%), with declining HbA1c (class B; n = 364 [4.7%]; mean baseline HbA1c 11.6%), and with increasing HbA1c (class C; n = 482 [6.2%]; mean baseline HbA1c 8.5%). HbA1c trajectory class was associated with adjusted 2-year mortality (3.0% [95% CI 2.8, 3.2] for class A, 3.1% [2.1, 4.2] for class B, and 4.2% [3.4, 4.9] for class C; global P = 0.047, P = 0.03 comparing classes A and C, P > 0.05 for other pairwise comparisons). Baseline HbA1c was not associated with 2-year mortality (P = 0.85; hazard ratios 1.01 [0.96, 1.06] and 1.02 [0.95, 1.10] for HbA1c 7-9% and ≥ 9%, respectively, relative to HbA1c < 7%). The association between HbA1c trajectories and mortality did not differ between those with and without CAD (interaction P = 0.1).

Conclusions: In clinical settings where single HbA1c measurements provide limited information, HbA1c trajectories may help stratify risk of complications in diabetes patients. Joint latent class modeling provides a generalizable approach to examining relationships between biomarker trajectories and clinical outcomes in the era of near-universal adoption of electronic health records.

Keywords: cardiovascular disease; diabetes; hemoglobin A1c trajectory; mortality.

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

  • Blood Glucose
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Diabetes Mellitus, Type 2*
  • Glycated Hemoglobin / analysis
  • Glycemic Control
  • Heart Disease Risk Factors
  • Humans
  • Retrospective Studies
  • Risk Factors


  • Blood Glucose
  • Glycated Hemoglobin A