Cardiovascular and Kidney Outcomes Across the Glycemic Spectrum: Insights From the UK Biobank

J Am Coll Cardiol. 2021 Aug 3;78(5):453-464. doi: 10.1016/j.jacc.2021.05.004. Epub 2021 May 17.

Abstract

Background: Treatment guidelines for prediabetes primarily focus on glycemic control and lifestyle management. Few evidence-based cardiovascular and kidney risk-reduction strategies are available in this population.

Objectives: This study sought to characterize cardiovascular and kidney outcomes across the glycemic spectrum.

Methods: Among participants in the UK Biobank without prevalent type 1 diabetes, cardiovascular disease, or kidney disease, Cox models tested the association of glycemic exposures (type 2 diabetes [T2D], prediabetes, normoglycemia) with outcomes (atherosclerotic cardiovascular disease [ASCVD], chronic kidney disease [CKD], and heart failure), adjusting for demographic, lifestyle, and cardiometabolic risk factors.

Results: Among 336,709 individuals (mean age: 56.3 years, 55.4% female), 46,911 (13.9%) had prediabetes and 12,717 (3.8%) had T2D. Over median follow-up of 11.1 years, 6,476 (13.8%) individuals with prediabetes developed ≥1 incident outcome, of whom only 802 (12.4%) developed T2D prior to an incident diagnosis. Prediabetes and T2D were independently associated with ASCVD (prediabetes: adjusted HR [aHR]: 1.11; 95% CI: 1.08-1.15; P < 0.001; T2D: aHR: 1.44; 95% CI: 1.37-1.51; P < 0.001), CKD (prediabetes: aHR: 1.08; 95% CI: 1.02-1.14; P < 0.001; T2D: aHR: 1.57; 95% CI: 1.46-1.69; P < 0.001), and heart failure (prediabetes: aHR: 1.07; 95% CI: 1.01-1.14; P = 0.03; T2D: aHR: 1.25; 95% CI: 1.14-1.37; P < 0.001). Compared with hemoglobin A1c (HbA1c) <5.0%, covariate-adjusted risks increased significantly for ASCVD above HbA1c of 5.4%, CKD above HbA1c of 6.2%, and heart failure above HbA1c of 7.0%.

Conclusions: Prediabetes and T2D were associated with ASCVD, CKD, and heart failure, but a substantial gradient of risk was observed across HbA1c levels below the threshold for diabetes. These findings highlight the need to design risk-reduction strategies across the glycemic spectrum.

Keywords: atherosclerotic cardiovascular disease; heart failure; prediabetes; prevention; type 2 diabetes.

Publication types

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

MeSH terms

  • Aged
  • Biological Specimen Banks
  • Blood Glucose / analysis*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Female
  • Humans
  • Kidney Diseases / blood*
  • Kidney Diseases / epidemiology
  • Kidney Diseases / etiology
  • Male
  • Middle Aged
  • Prediabetic State / blood
  • Prediabetic State / complications
  • United Kingdom

Substances

  • Blood Glucose