Insulin resistance, hyperinsulinemia primary drivers of atherosclerotic CVD
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Underlying insulin resistance and hyperinsulinemia work together as “bad actors” to drive atherosclerotic CVD long before a person is diagnosed with type 2 diabetes, and early treatment is needed to slow the process, according to a speaker.
“What really kills our [diabetes] patients are macrovascular complications, like heart attacks and strokes,” Ralph A. DeFronzo, MD, professor of medicine and chief of the diabetes division at the University of Texas Health Science Center at San Antonio, said during a presentation at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “This accounts for 80% of the mortality in our diabetic patients.”
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Obesity, diabetes, hypertension and dyslipidemia are individually major independent risk factors for CVD; however, the underlying insulin resistance, as well as the compensatory hyperinsulinemia, play a “critical role” in directly promoting the atherogenic process, DeFronzo said.
Early data from insulin clamp studies measuring insulin sensitivity suggest that a people with type 2 diabetes, whether overweight or lean, are severely insulin resistant with defects observed in the glucose storage pathway. Similarly, adults with essential hypertension and hypertriglyceridemia are also severely insulin resistant even without underlying obesity or dyslipidemia, DeFronzo said.
“If you look at people with prediabetes, you can see this disease starts long before you develop diabetes and, in fact, even if you look at people with normal glucose tolerance, you can show these people are already significantly insulin resistant,” DeFronzo said. “The data are really quite consistent.”
DeFronzo said data from the Insulin Resistance Intervention after Stroke (IRIS) trial show that early intervention with the thiazolidinedione pioglitazone can “reverse” the development of atherosclerotic CVD in adults with prediabetes or normal glucose tolerance, giving clinicians an opportunity to intervene early. Data from IRIS show a 30% reduction in recurrent CV events for participants assigned pioglitazone during follow-up compared with placebo, regardless of HbA1c, he said.
“If we want to reduce this residual risk, we have to think about different ways of approaching it to reverse this molecular defect which, in my opinion, is contributing in a major way to underlying atherosclerosis,” DeFronzo said.
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DeFronzo RA. Session 1: 20th WCIRDC Celebration – A Tribute to Gerald Reaven. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 1-3, 2022; Universal City, California (hybrid meeting).
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