Heart in Diabetes

Heart in Diabetes

July 14, 2017
2 min read

Insulin resistance underlies CV risk factors

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Ralph DeFronzo
Ralph A. Defronzo

PHILADELPHIA — Insulin resistance is a major factor by which patients with diabetes are at elevated risk for cardiovascular disease, according to a speaker at the Heart in Diabetes Conference.

As much as 80% of mortality in patients with diabetes is accounted for by macrovascular diseases such as myocardial infarction, stroke and peripheral vascular disease, Ralph A. DeFronzo, MD, professor of medicine and chief of the diabetes division at the University of Texas Health Science Center, San Antonio, said. This begs the question of the role of hyperglycemia in the pathogenesis of atherosclerosis, he said.

Epidemiological studies have determined that a 1% reduction in HbA1c confers a 14% decreased risk for MI and a 12% decreased risk for stroke, but the magnitude of effect for these diseases is much less than that for others such as retinopathy, according to DeFronzo.

“Hyperglycemia is a risk factor for CVD, but it’s an extremely weak risk factor compared to how much of a risk factor it is for eye, kidney and nerve damage,” DeFronzo said. “If hyperglycemia is not the major risk factor for CVD, then what is?”

The answer, he said, is “Insulin Resistance Syndrome,” a term he said he prefers to metabolic syndrome. A number of risk factors to which insulin resistance contributes are connected to the development of atherosclerosis, he said.

“Every single one of these disorders is not only an insulin-resistant state, but insulin resistance is promoting the actual pathophysiology,” DeFronzo said.

Obesity and diabetes have insulin resistance in common, he said, noting that “normal-weight diabetics and people with obesity but not diabetes are equally insulin-resistant.”

Patients with hypertension have a similar degree of insulin resistance, and patients with dyslipidemia show “exactly the same thing,” he said.

The parallel extends to patients with coronary artery disease, who have been found to have a similar severity of insulin resistance to patients with diabetes, obesity, hypertension and hypertriglyceridemia, according to DeFronzo.

“All of these important factors that are part of the metabolic syndrome are characterized by insulin resistance,” he said.

Epidemiological studies have consistently shown that insulin resistance predicts CVD and diabetes. “These studies have shown that if you are insulin-resistant, compared to insulin-sensitive, you are at elevated risk for getting a coronary event,” he said.

In one study of 2,569 people without diabetes, patients in the highest quintile of insulin resistance had 2.5 times the odds of CVD onset over 8 years compared with the lowest quintile, he said. This finding persisted after adjustment for age, sex, blood pressure, low-density lipoprotein, high-density lipoprotein, triglycerides, smoking, exercise and waist circumference.

“CV risk factors are all intimately related to insulin resistance, and if you simply get rid of the insulin resistance, you would correct most or all of what we consider to be CV risk factors,” DeFronzo said. He also noted that a number of mechanistic studies have shown how insulin resistance contributes to the development of atherosclerosis and how amelioration of insulin resistance can inhibit the development of atherosclerosis and redice CV events. – by Erik Swain


DeFronzo RA. Prevalence and Pathophysiology of CVD and Diabetes. Presented at: Heart in Diabetes Clinical Education Conference; July 14-16, 2017; Philadelphia.

Disclosure: DeFronzo reports serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Ecelyx, Intarcia, Janssen and Novo Nordisk; speaking for AstraZeneca and Novo Nordisk; and receiving research grant support from AstraZeneca, Boehringer Ingelheim, Janssen and Takeda.