Clinical study: obesity, diabetes, and heart disease
.
Abstract
Objectives
The study goals were to: 1) define the relationship between body mass index (BMI) and insulin resistance in 314 nondiabetic, normotensive, healthy volunteers; and 2) determine the relationship between each of these two variables and coronary heart disease (CHD) risk factors.
Background
The importance of obesity as a risk factor for type 2 diabetes and hypertension is well-recognized, but its role as a CHD risk factor in nondiabetic, normotensive individuals is less well established.
Methods
Insulin resistance was quantified by determining the steady-state plasma glucose (SSPG) concentration during the last 30 min of a 180-min infusion of octreotide, glucose, and insulin. In addition, nine CHD risk factors: age, systolic blood pressure, diastolic blood pressure (DBP), total cholesterol, triglycerides (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein cholesterol concentrations, and glucose and insulin responses to a 75-g oral glucose load were measured in the volunteers.
Results
The BMI and the SSPG concentration were significantly related (r = 0.465, p < 0.001). The BMI and SSPG were both independently associated with each of the nine risk factors. In multiple regression analysis, SSPG concentration added modest to substantial power to BMI with regard to the prediction of DBP, HDL cholesterol and TG concentrations, and the glucose and insulin responses.
Conclusions
Obesity and insulin resistance are both powerful predictors of CHD risk, and insulin resistance at any given degree of obesity accentuates the risk of CHD and type 2 diabetes.
Abbreviations: BMI, body mass index; CHD, coronary heart disease; DBP, diastolic blood pressure; EGIR, European Group for the Study of Insulin Resistance; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NHANES, National Health and Nutrition Examination Survey; SBP, systolic blood pressure; SSPG, steady-state plasma glucose; SSPI, steady-state plasma insulin; TG, triglycerides
Article Outline
Results of the Third National Health and Nutrition Examination Survey (NHANES III) have documented the fact that obesity has become a national epidemic (1). The importance of obesity as a risk factor for type 2 diabetes (2) and hypertension (3) has been well recognized, but its role as a coronary heart disease (CHD) risk factor in nondiabetic, normotensive individuals has been less well established. In this context, two issues seemed worthy of inves- tigation in order to define more clearly the relationship between obesity and CHD. Although insulin resistance is often considered to be the link between obesity and type 2 diabetes, hypertension, and CHD risk, there is evidence that obese and overweight individuals can also be insulin-sensitive [4] , [5] and [6] . Thus, the first goal of this study was to define the relationship between resistance to insulin-mediated glucose disposal and body mass index (BMI) in a large group of healthy, nondiabetic volunteers.
Our second goal was to clarify the relative impact of obesity, per se, as distinguished from insulin resistance, on CHD risk factors. Given the difficulty in achieving success in weight control programs (7), it would be helpful to identify a subset of obese individuals who would benefit the most from weight loss and, therefore, be given the highest priority in weight loss programs.
The present report describes the relationship between BMI and insulin resistance in 314 nondiabetic, normotensive, healthy volunteers and defines the association of conventional CHD risk factors with obesity and insulin resistance.
Methods
The data to be analyzed represent information gathered on 314 volunteer subjects, 186 women and 128 men, who had participated in our research studies from 1990 to 1998. Subjects included in the evaluation had no history of diabetes, CHD, or hypertension. In addition, they had normal findings upon physical examination and routine laboratory tests and were nondiabetic (8). The majority of participants were Caucasian (77%), with a small percentage of individuals of Asian (12%), Hispanic (10%), and African ancestries (1%). The volunteers had a mean ± SD age of 46 ± 13 years (range, 19 to 79) and BMI of 25.2 ± 3.8 kg/m2 (range, 18.5 to 34.6).
Subjects were weighed on an electronic scale to the nearest 0.01 kg in hospital garments, height was measured to the nearest 0.01 cm without shoes, and BMI was calculated by dividing weight in kilograms by the square of the height in meters. Fasting plasma glucose and insulin concentrations were measured before and 30, 60, 120, and 180 min after the ingestion of a 75-g oral glucose challenge. The total integrated glucose and insulin responses were quantified by calculating the glucose and insulin area under the curve by use of the trapezoidal method. The analytical methods used for determining plasma glucose and insulin concentrations were similar over the duration of the study, as were those used for the determination of fasting concentrations of total cholesterol, triglycerides (TG), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol [9] , [10] and [11] . Insulin-mediated glucose disposal was estimated by a modification of the insulin suppression test (12) as introduced and validated by our research group (13). After an overnight fast, an intravenous catheter was placed in each arm of the patient. One arm was used for the administration of a 180-min infusion of octreotide, insulin, and glucose, and the other arm was used for collecting blood samples. Blood was sampled every 30 min initially and then at 10-min intervals from 150 to 180 min of the infusion to determine the steady-state plasma insulin (SSPI) and glucose concentrations for each individual. Because SSPI concentrations are similar for all subjects, the steady-state plasma glucose (SSPG) concentration provides a direct measure of the ability of insulin to mediate disposal of an infused glucose load; the higher the SSPG, the more insulin-resistant is the individual.
The population was divided into three categories of BMI as proposed by the National Institutes of Health (14): normal weight (18.5 to 24.9 kg/m2); overweight (25.0 to 29.9 kg/m2); and obesity class I (30.0 to 34.9 kg/m2). When this was done, our study population closely resembled the distribution of BMI in NHANES III, containing 52.5%, 32.1%, and 15.3% of individuals defined as being normal weight, overweight, and obese (15), compared with values of 43.6%, 32.6%, and 14.3%, respectively, for the same groups in NHANES III 1 and [15] .
Data are expressed as mean ± SE. In each of the three BMI categories, means of BMI, SSPG, and the nine CHD risk factors (age, systolic blood pressure [SBP], diastolic blood pressure [DBP], total cholesterol, TG, HDL cholesterol, LDL cholesterol, glucose response, and insulin response) were compared using one-way analysis of variance.
The relationship between BMI and SSPG concentration was depicted in the form of a scatter plot, and Pearson and Spearman correlation coefficients were calculated. Individuals were defined as insulin-sensitive and insulin-resistant if they were in the lower (SSPG <4.66 mmol/l) and upper (SSPG >8.38 mmol/l) SSPG tertiles of the sample, respectively.
Simple and partial (adjusting for sex) correlation coefficients were calculated, first between each of the nine CHD risk factors and BMI, and then between each of the nine CHD risk factors and SSPG.
Multiple regression analyses were performed to evaluate whether the prediction of each of the nine CHD risk factors from the level of BMI would be modified if the degree of insulin resistance (SSPG) and an interaction between obesity (BMI) and insulin resistance (SSPG) were known in addition to the BMI. Two regression models were employed to evaluate these relationships. In model A, each risk factor was regressed on BMI and SSPG jointly. In model B, each risk factor was regressed on BMI, SSPG, and an interaction term. The interaction term was calculated by multiplying BMI and SSPG for each individual. Furthermore, using the results of regression model B, each of the nine CHD risk factors and BMI were graphed as continuous variables, while holding SSPG constant at three levels, namely, the means of the lower (insulin-sensitive), intermediate, and upper (insulin-resistant) SSPG tertiles of the sample.
ليست هناك تعليقات:
إرسال تعليق