Why are people with diabetes more prone to developing cardiovascular disease?

Why People with Diabetes Develop Heart Problems

Diabetes dramatically increases cardiovascular disease risk through multiple interconnected mechanisms: the diabetic metabolic state itself directly damages blood vessels, while simultaneously clustering with other major cardiovascular risk factors including hypertension, dyslipidemia, and obesity—creating what is now recognized as cardiorenal metabolic disease. 1

The Magnitude of Risk

• People with diabetes face a 2-3 times higher risk of coronary artery disease compared to those without diabetes, with women experiencing an even greater relative risk increase of 3-5 times. 1
• Heart failure is at least twofold more prevalent in people with diabetes and represents a major cause of morbidity and mortality. 1
• Cardiovascular disease is the most common cause of death in adults with diabetes. 1

Direct Metabolic Damage Mechanisms

The diabetic state causes cardiovascular damage through several direct pathophysiologic pathways:

• Chronic hyperglycemia independently damages blood vessels through oxidative stress, formation of advanced glycation end products, activation of inflammatory pathways, and decreased nitric oxide production. 2
• The relationship between hyperglycemia and cardiovascular disease exists on a continuum—even glucose levels above normal but below the diabetes threshold (pre-diabetes) substantially increase cardiovascular risk. 1
• Post-prandial (after-meal) glucose elevations provide better prediction of future cardiovascular risk than fasting glucose levels alone. 1

The Clustering Effect: Cardiorenal Metabolic Disease

Diabetes rarely exists in isolation and typically clusters with other cardiovascular risk factors:

• The combination of metabolic risk factors—frequently driven by obesity—leads to a triad of atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease, collectively termed cardiorenal metabolic disease. 1
• The incidence of all three conditions rises progressively with increasing hemoglobin A1C levels. 1
• Common comorbidities include hypertension (present in 80% of diabetic patients in major trials), dyslipidemia, and excess body weight. 1, 3

Insulin Resistance as a Central Driver

• Insulin resistance, common to both type 1 and type 2 diabetes, is a major independent risk factor for cardiovascular events. 4
• The association of hyperglycemia with insulin resistance further amplifies cardiovascular and heart failure risk beyond either factor alone. 4
• Insulin resistance contributes to endothelial dysfunction, altered platelet activity, and microalbuminuria—all of which independently increase coronary heart disease risk. 5

Heart Failure: A Unique Diabetic Complication

Diabetes causes heart failure through distinct mechanisms:

• People with diabetes can develop structural heart disease and heart failure with reduced ejection fraction even without obstructive coronary artery disease. 1
• Excess body weight and hypertension often precede heart failure with preserved ejection fraction (HFpEF) and are implicated in its pathophysiology in diabetic patients. 1
• Coronary artery disease and prior myocardial infarction remain major causes of heart failure with reduced ejection fraction (HFrEF) in this population. 1

Why Traditional Risk Factors Don't Explain Everything

A critical clinical point:

• The increased cardiovascular risk in diabetes is only partly explained by concomitant traditional risk factors like hypertension, obesity, dyslipidemia, and smoking—the diabetic state itself and hyperglycemia's direct consequences are independently responsible for substantial cardiovascular risk. 1
• The total cardiovascular disease risk in type 2 diabetes cannot be explained by traditional risk factors alone; specific metabolic changes significantly contribute. 4

Clinical Implications

• Diabetic patients require aggressive management of multiple risk factors simultaneously, not just glucose control. 5
• Treatment with SGLT2 inhibitors and/or GLP-1 receptor agonists that have demonstrated cardiovascular and renal benefits is now considered fundamental for risk reduction beyond traditional glucose, blood pressure, and lipid management. 1
• The atherosclerotic risk is greatest in poorly controlled patients, possibly due to associated hypercholesterolemia and hypertriglyceridemia. 5