Insulin Resistance Portends Congestive Heart Failure



By Neil Osterweil , MedPage Today Staff Writer - Reviewed by Rubeen K. Israni, M.D., Fellow, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine



MedPage Today Action Points
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Advise patients that impaired glucose tolerance/insulin sensitivity puts them at risk for future congestive heart failure.
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Explain the importance of strict glucose management in preventing future complications, including cardiovascular disease, renal disease, retinopathies and neuropathies.
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Counsel obese patients and those with high waist circumferences about diet, exercise, and overall weight management strategies.

UPPSALA, Sweden, July 19-Insulin resistance is an important risk factor for congestive heart failure independent of diabetes, reported researchers here.

In a study of nearly 1,200 elderly men who were free of congestive heart failure (CHF) or valvular heart disease at baseline, investigators at Uppsala University found that even when controlling for other causes of CHF, insulin resistance remained an independent risk factor. The controlled variables included previous myocardial infarction, hypertension, diabetes, or smoking.

The finding also points to a likely role for insulin resistance in the development of CHF associated with obesity, Erik Ingelsson, M.D., and colleagues reported in the July 20 issue of the Journal of the American Medical Association.

The link between diabetes and CHF was first described by Framingham Heart Study researchers in the mid 1970s. More recently obesity has been fingered as a major risk factor for CHF as well. The two largest risk factors for CHF are hypertension and coronary heart disease, as well as metabolic and lifestyle factors.

"In recent years, associations between diabetes or impaired glucose regulation and altered left ventricular geometry and function have been reported," the authors wrote. "Furthermore, in patients who manifest CHF, insulin resistance is associated with more severe disease and a worse prognosis, but insulin resistance has not been investigated as a predictor of CHF."

To test their hypothesis that insulin resistance may predict CHF and could be the agent for CHF in obesity, the investigaors followed a cohort of 1,187 men 70-years-old and older who were free of both CHF and valvular disease at baseline. The men were followed from 1990-95 to 2002 (median follow-up, 8.9 years).

The investigators analyzed variables reflecting insulin sensitivity and obesity together with established risk factors for CHF, which include prior MI, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and serum cholesterol level.

Insulin sensitivity and other glucose metabolic parameters were measured by euglycemic clamp glucose disposal rate (mg/kg body weight per min), fasting plasma glucose, two-hour oral glucose tolerance test (OGTT) fasting insulin and proinsulin, fasting 32-33 split proinsulin and HOMA insulin resistance index.

During the study, 104 men developed CHF, an incidence rate of 10.5 per 1,000 person-years at risk. In unadjusted Cox proportional hazards analyses, all of the variables indicating impaired glucose regulation and obesity significantly predicted CHF.

When the presence of diabetes at baseline was accounted for, most of the variables related to insulin resistance remained as significant predictors of CHF, including clamp glucose disposal rate, OGTT, fasting insulin, proinsulin, and 32-33 split proinsulin, body mass index (BMI), and waist circumference.

Further adjustment for other baseline risk factors failed to eliminate the insulin sensitivity measures clamp glucose disposal rate, OGTT, fasting proinsulin, the obesity measures BMI and waist-circumference, indicating that both insulin sensitivity and obesity are independent risk factors for CHF.

They also found a strong correlation between variables indicating impaired glucose tolerance and obesity (Pearson r=-0.60, P < .001 for clamp glucose disposal rate versus both BMI and waist circumference).

Noting the established link between diabetes and CHF, the authors acknowledged that incipient diabetes, as indicated by impaired glucose tolerance at baseline, could account for some of the cases of CHF observed.

"Still, we show that impaired glucose regulation in healthy participants without diabetes or obesity at baseline is a strong predictor of subsequent CHF, independent of established risk factors," they wrote. "Our observations may indicate that the risk for CHF is already increased in the long subclinical phase of impaired glucose regulation that precedes clinically manifest diabetes."

They speculated that insulin resistance either precedes obesity in a causal pathway to CHF, "or simply that the relation of obesity to CHF is circumstantial and that obesity in this case may be regarded as an indicator of the more important trait, insulin resistance."

Primary source: JAMA - Source reference: JAMA. 2005;294:334-341

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