Coronary Heart Disease Risk Factors in Morbidly ... - Diabetes Care

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Coronary Heart Disease Risk Factors in Morbidly Obese Women With Normal Glucose Tolerance HlSHAM A . BARAKAT, PHD

PRABHAKER G. KHAZANI, PHD

NiTIN MOONEY, MD

WALTER PORIES, MD

KEVIN O'BRIEN, PHD

JOSE F. CARO, MD

STUART LONG, BS

OBJECTIVE— To examine if the risk for CHD increases progressively with increases in the BMI of normoglycemic, hyperinsulinemic, morbidly obese women (BMI > 35 kg/m2). RESEARCH DESIGN AND METHODS— Insulin sensitivity was evaluated by calculating an ISI following an OGTT. There was a significant linear relationship between ISI and BMI fitted by two straight lines intersecting at a point corresponding to a BMI of 29.7 ± 1.5 kg/m2. Significant linear relationships between insulin sensitivity and BMI were obtained below and above this breakpoint. Similarly, a breakpoint for the relation between dBP and BMI corresponding to a BMI >33.7 ± 3.4 kg/m2 was obtained. Significant linear relationships between BMI and plasma fasting glucose, triglyceride, cholesterol, HDL cholesterol, sBP, or dBP were not observed in the women with a BMI >35 kg/m2.

tudies have shown that elevations in plasma total cholesterol, LDL cholesterol, and triglyceride levels and decreases in the concentration of HDL cholesterol may contribute to an increased risk of developing CHD (1-5). In addition, conditions associated with decreased insulin sensitivity have been reported to predispose individuals to a higher CHD risk (6-8). Recently, Zavaroni et al. (9) examined CHD risk factors in a group of lean normoglycemic, but insulin-resistant men, versus age- and sex-matched insulin-sensitive control subjects. They reported that fasting triglyceride levels were higher, but HDLcholesterol concentrations were lower in the insulin-resistant group compared with the insulin-sensitive control subjects. In addition, both sBP and dBP were elevated in the insulin-resistant group.

The predisposition of obese individuals to a higher CHD risk may be related to the tendency of those individuals to have high plasma insulin levels, high plasma triglycerides, and low HDL concentrations. Recently, Manson et al. RESULTS— Compared with lean (BMI 29 kg/ 2 which insulin sensitivity is associated with CHD risk. Above this threshold, there m , it is not possible from that study to does not appear to be a progressive increase in the risk factors for CHD with increases determine the effects of a BMI > 3 5 kg/m2 on risk for CHD. Because we at in BMI. East Carolina University School of Medicine are a tertiary referral center undertaking prospective studies of morbid FROM THE DEPARTMENTS OF BIOCHEMISTRY, MEDICINE, BIOSTATISTICS AND EPIDEMIOLOGY, AND SURGERY, obesity, we sought to determine the efSCHOOL OF MEDICINE, EAST CAROLINA UNIVERSITY, GREENVILLE, NORTH CAROLINA. fects of a BMI >35 kg/m2 on the three ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO H.A. BARAKAT, PHD, DEPARTMENT OF BIOCHEMprincipal risk factors for CHD, namely, ISTRY, EAST CAROLINA UNIVERSITY, SCHOOL OF MEDICINE, GREENVILLE, NC 2 7 8 5 8 - 4 3 5 4 . insulin sensitivity, BP, and plasma lipid RECEIVED FOR PUBLICATION 2 JANUARY 1992 AND ACCEPTED IN REVISED FORM 12 AUGUST 1992. levels. C H D , CORONARY HEART DISEASE; B M I , BODY MASS INDEX; H D L , HIGH-DENSITY LIPOPROTEIN; L D L , LOW-DENSITY LIPOPROTEIN; SBP, SYSTOLIC BLOOD PRESSURE; DBP, DIASTOLIC BLOOD PRESSURE; B P , BLOOD PRESSURE; OGTT, ORAL GLUCOSE TOLERANCE TEST; APO A-I, APOLIPOPROTEIN A-I; APOB, APOLIPOPROTEIN B; I S I , INSULIN SENSITIVITY INDEX; C l , CONFIDENCE INTERVAL.

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Our hypothesis was that increasing BMI >35 kg/m2 would be associated with a progressive increase in these risk factors. We report herein ourfindingsof

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the evaluation of CHD risk in morbidly obese women (BMI > 35 kg/m2) compared with lean control subjects (BMI 35 kg/ m2.

64 pM, the mean insulin concentration of the lean group (Table 1). All the obese subjects had an 1SI 35 kg/m2. Reaven et al. (37) described Syndrome X, where the risk of CHD was higher in hyperinsulinemic, nonobese normoglycemic subjects than age- and sexmatched control subjects. This study showed that this correlation between CHD and insulin resistance does not seem to apply to morbidly obese subjects. Our results indicated that our hypothesis was not correct in that with increases in BMI >35 kg/m2, the coronary risk status does not increase progressively with increasing BMI. These results lead us to postulate that a threshold of body weight may exist up to which insulin sensitivity is associated with a high CHD risk, and which defines the population of individuals with Syndrome X. Above this threshold, there does not appear to be substantial additional risk that would further compound CHD. Our findings suggest that this threshold point corresponds to a BMI = 31 kg/m2. Acknowledgments—This study was supported, in part, by National Institutes of Health Grant P01-DK36296. We would like to thank Dr. Richard H. Jones from the University of Colorado Health Sciences Center for supplying us with the

computer program for the determination of breakpoints.

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