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Insulin resistance appears to be highly heritable among Mexican Americans: expressed via syndrome X. (Clinical Rounds).

SAN DIEGO -- Insulin resistance appears to be highly heritable and expressed via syndrome X in Mexican Americans, results from a novel study suggest.

Concurrent high heritabilities of insulin resistance, lipid levels, blood pressure values, and fasting glucose levels are consistent with the definition of syndrome X--a precursor to type 2 diabetes--and imply common biologic mechanisms, Dr. Claudia Mikail reported at the annual meeting of the American College of Preventive Medicine.

"Our results suggest that distinct genetic loci regulate the interactions between insulin resistance and each component of syndrome X," commented Dr. Mikail, a National Institutes of Health fellow in medical genetics at Cedars-Sinai Medical Center, Los Angeles. "Eventually, localizing the responsible genes may enable us to better predict who will develop dyslipidemia, hypertension, and/or glucose intolerance in relatives of patients with type 2 diabetes or syndrome X."

High heritability for insulin resistance alone has been shown in other populations, such as Pima Indians, but she said that this is the first study to report subclinical correlations between heritabilities of direct measures of insulin resistance, type 2 diabetes, and syndrome X traits.

In the study, 304 nondiabetic offspring in 69 Mexican American families were located through type 2 diabetes probands. Average age of the offspring was 32 years.

Dr. Mikail and her associates measured traits associated with insulin resistance (as measured by glucose infusion rate, or GINF), including body mass index (BMI), lipid levels, blood pressure values, and fasting glucose levels. For each trait, the investigators calculated heritabilities using the quantitative trait disequilibrium test, with adjustment for age, sex, and BMI. Multivariate analyses were used to evaluate the relative roles of the syndrome X components in insulin resistance.

Heritability of GINF was highly statistically significant among offspring. Heritability also was statistically significant for lipid levels, blood pressure values, and fasting glucose levels.

GINF heritability was decreased by adjustment for lipid levels, blood pressure values, and fasting glucose levels. "This means that these traits are correlated with each other," Dr. Mikail explained. "When you apply covariance, you can explain part of the genetic variance of GINF by these other traits, implying that they are coinherited."

After adjustment for all of the syndrome X traits simultaneously, GINF heritability fell to zero, suggesting that all of the heritability of insulin resistance manifests in lipid levels, blood pressure values, and/or fasting glucose levels. The study design allowed the investigators to detect associations between traits but not the causal relationships between them.

The findings emphasize the importance of family history in determining potential risks for insulin resistance, syndrome X, and type 2 diabetes, Dr. Mikail said.

"It reinforces the concept that individuals are not just at increased risk for the specific disease that has occurred in a relative, but for all of the syndrome X--associated disorders," coinvestigator Dr. Leslie Raffel told this newspaper.

Dr. Mikail added that the finding favors the use of preventive measures by at-risk individuals. Before symptom onset, relatives of diabetics might benefit from lifestyle modifications, along with closer monitoring for dyslipidemia, hypertension, and glucose intolerance.

The National Heart, Lung, and Blood Institute and the Juvenile Diabetes Foundation supported the study.
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Author:Brunk, Doug
Publication:Internal Medicine News
Date:Apr 1, 2003
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