Cardiovascular and Kidney Outcomes Across the Glycemic Spectrum

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 HbA_1c levels below the threshold for diabetes. These findings highlight the need to design risk-reduction strategies across the glycemic spectrum.