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Cardiovascular and Kidney Outcomes in Diabetes and Prediabetes
Quick Takes
- In this prospective cohort study of 336,709 individuals in the UK, prediabetes was independently associated with atherosclerotic cardiovascular disease, chronic kidney disease, and heart failure (adjusted hazard ratio, ~1.1 for each).
- After full covariate adjustment, risks of clinical endpoints were increased above the following hemoglobin A1c thresholds: atherosclerotic cardiovascular disease, >5.4%; chronic kidney disease, >6.2%; heart failure, 7.0%.
Study Questions:
Among patients with normoglycemia, prediabetes, and type 2 diabetes (T2D), what are the risks of atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and heart failure (HF)?
Methods:
This prospective cohort study from the UK Biobank included patients with hemoglobin A1c (HbA1c) <15% and no prevalent type 1 diabetes, ASCVD, CKD, or HF at baseline. The primary study exposure was T2D (defined as self-reported T2D, HbA1c ≥6.5%, or use of insulin) versus prediabetes (defined as absence of self-reported T2D with HbA1c ≥5.7% and <6.5%) versus normoglycemia. HbA1c, treated as a continuous variable, was a secondary exposure. The coprimary outcomes were ASCVD (coronary artery disease, ischemic stroke, and peripheral arterial disease), CKD, and HF. All-cause mortality was a secondary outcome. Absolute incidence rates and rate differences for outcomes were calculated for 1,000 person-years of follow-up. Multivariable-adjusted Cox proportional hazard models tested the association of glycemic status with cardiometabolic outcomes.
Results:
Among 336,709 individuals (mean age 56.3 ± 8.1 years, 55.4% female), 82.3% had normoglycemia, 13.9% had prediabetes, and 3.8% had T2D at baseline. Compared with normoglycemic individuals, those with T2D and prediabetes were more commonly non-White, current or former smokers, and of lower socioeconomic status. T2D and prediabetes were associated with higher body mass index, higher systolic blood pressure, lower high-density lipoprotein cholesterol, higher triglycerides, and microalbuminuria.
Over a median follow-up period of 11.1 years, ≥1 primary outcome occurred in 7.9% of normoglycemic individuals, 13.8% of those with prediabetes, and 23.7% of those with T2D. Prediabetes and T2D were independently associated with ASCVD (prediabetes: adjusted hazard ratio [aHR], 1.11; T2D: aHR, 1.44; p < 0.001 for both), CKD (prediabetes: aHR, 1.08; T2D: aHR, 1.57; p < 0.001 for both), and HF (prediabetes: aHR, 1.07; p = 0.03; T2D: aHR, 1.25; p < 0.001). After full covariate adjustment, risks of the primary endpoints were increased above the following HbA1c thresholds: ASCVD, >5.4%; CKD, >6.2%; HF, 7.0%. Death occurred in 4.4% of normoglycemic individuals, 7.2% of those with prediabetes, and 10.4% of those with T2D. Prediabetes was independently associated with all-cause mortality (HR, 1.10; p < 0.001). After full covariate adjustment, all-cause mortality risk increased with HbA1c >6.2%.
Conclusions:
Prediabetes and T2D are independently associated with incident ASCVD, CKD, and HF, as well as all-cause mortality. Particularly for ASCVD, risk begins to increase at the lower end of the glycemic spectrum.
Perspective:
These findings suggest that in addition to careful glycemic control and monitoring for progression to T2D, patients with prediabetes may benefit from ASCVD screening and primary prevention strategies (such as coronary calcium scoring and statin therapy) and screening for albuminuria. Patient education regarding all aspects of cardiometabolic health, including blood pressure control and weight management, is critically important in this vulnerable population. Collaborative relationships among cardiologists, endocrinologists, and primary care physicians are helpful in optimizing risk management. Ongoing trials are examining use of metformin and the GLP-1RA semaglutide for secondary ASCVD prevention in the context of prediabetes.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Acute Heart Failure, Smoking
Keywords: Albuminuria, Atherosclerosis, Blood Pressure, Body Mass Index, Brain Ischemia, Cholesterol, HDL, Coronary Artery Disease, Diabetes Mellitus, Type 2, Dyslipidemias, Glycated Hemoglobin A, Heart Failure, Insulin, Kidney Diseases, Metabolic Syndrome, Myocardial Ischemia, Peripheral Arterial Disease, Prediabetic State, Primary Prevention, Renal Insufficiency, Chronic, Risk, Smoking, Stroke, Triglycerides, Vascular Diseases
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