Insulin resistance correlates with blood vessel damage leading to heart attack and stroke

PLOS ONEThere is a wealth of evidence showing the relationship between insulin resistance (diminished ability of cells to take up and metabolize glucose in response to insulin) and cardiovascular disease. Carotid intima–media thickness (thickening of the lining of the carotid artery) is a particularly strong risk factor indicator heart attack and stroke. A study just published in PLOS ONE (Public Library of Science) shows a strong association of insulin resistance with the blood vessel damage resulting in increased carotid intima–media thickness. The authors observe:

Insulin resistance (IR) is considered an important risk factor for both atherosclerotic cardiovascular disease, and type 2 diabetes, and a key determinant of cardiovascular risk factors, including visceral obesity, atherogenic dyslipidemia, and hypertension, clustering within the metabolic syndrome. Accumulating evidence suggests an association between hyperinsulinemia and/or IR and cardiovascular diseases.”

Furthermore, insulin resistance appears to carry more weight than hyperinsulinemia:

“Importantly, it has been shown that IR…rather than hyperinsulinemia, was independently associated with early vascular atherosclerosis.”

But insulin resistance is notoriously difficult to measure:

“…methods to directly measure IR are complex, time-consuming, expensive, and unsuitable for large scale epidemiological studies. Therefore, surrogate indexes of insulin sensitivity have been developed using fasting insulin and/or glucose levels alone or in combination with insulin and glucose levels during an oral glucose tolerance test (OGTT) as well as with other metabolic variables. Since IR occurs in multiple tissues, these indexes reflects predominantly either hepatic or muscle IR.”

So it had not yet been made clear if these IR indexes are specifically associated with vascular atherosclerosis. They decided to investigate using carotid artery intima–media thickness because:

Intima–media thickness (IMT) of common carotid artery is a well-recognized index of vascular damage, and is widely utilized as a surrogate marker for cardiovascular disease.”


“The aim of this study was to examine the relationship between different indexes of insulin resistance and common carotid IMT in a cohort of nondiabetic Caucasian individuals.”

They performed a 75 gram oral glucose tolerance test on 847 non-diabetic subjects and computed a variety of indexes of insulin. IMT was measured by ultrasound method. There was an outstanding feature in their data:

The Stumvoll ISIOGTT index was correlated with IMT more strongly than the other indexes of IR. The IR indexes correlated significantly with all cardiovascular risk factors examined. The Stumvoll ISIOGTT index was correlated with waist circumference and high sensitivity C-reactive protein more strongly than the other indexes of IR. The area under the ROC curve (AUC), used to evaluate the accuracy of the IR indexes in identifying individuals with vascular damage defined as IMT >0.9 mm, for the Stumvoll ISIOGTT index was significantly higher as compared with the AUCs of Matsuda, OGIS, HOMA and Liver IR indexes. In a logistic regression model adjusted for age and gender, subjects in the lowest tertile of the Stumvoll ISIOGTT index had the highest risk of having vascular damage as compared to the corresponding tertiles of the other surrogate indexes.”

In other words, the Stumvoll ISIOGTT index as a metric for insulin resistance outperformed the others in correlating with blood vessel damage manifested by carotid intima-media thickening. Practitioners, and all other readers, should bear in mind that this cardiovascular damage happens before diabetes. The authors reiterate the significance of insulin resistance in these matters:

 “IR is also a key feature of a spectrum of metabolic abnormalities such as obesity and glucose intolerance, and is associated with multiple cardiovascular risk factors (visceral adiposity, hypertension, atherogenic dyslipidemia), a clinical constellation that has been referred to as metabolic syndrome. IR is a predictor of atherosclerotic cardiovascular disease, and this association has vast social implications, and calls for intensive investigation of the causes of the disease, to optimize its treatment and to possibly prevent its onset.”

I think it can be fairly said that managing insulin resistance is a crucial core element of cardiovascular disease treatment and prevention.The authors conclude:

“In conclusion, in the present study we demonstrated that, among the different validated surrogates indexes of IR, the Stumvoll ISIOGTT index correlates better with vascular damage, as assessed by IMT of common carotid artery, in a large cohort of non-diabetic individuals. Thus, the Stumvoll ISIOGTT index might be a significant indicator of vascular damage with an important clinical significance.”

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