Sital Moorjani

Hyperinsulinemia as an independent risk factor for ischemic heart disease.

BACKGROUND Prospective studies suggest that hyperinsulinemia may be an important risk factor for ischemic heart disease. However, it has not been determined whether plasma insulin levels are independently related to ischemic heart disease after adjustment for other risk factors, including plasma lipoprotein levels. METHODS In 1985 we collected blood samples from 2103 men from suburbs of Quebec City, Canada, who were 45 to 76 years of age and who did not have ischemic heart disease. A first ischemic event (angina pectoris, acute myocardial infarction or death from coronary heart disease) occurred in 114 men (case patients) between 1985 and 1990. Each case patient was matched for age, body-mass index, smoking habits, and alcohol consumption with a control selected from among the 1989 men who remained free of ischemic heart disease during follow-up. After excluding men with diabetes, we compared fasting plasma insulin and lipoprotein concentrations at base line in 91 case patients and 105 controls. RESULTS Fasting insulin concentrations at base line were 18 percent higher in the case patients than in the controls (P<0.001). Logistic-regression analysis showed that the insulin concentration remained associated with ischemic heart disease (odds ratio for ischemic heart disease with each increase of 1 SD in the insulin concentration, 1.7; 95 percent confidence interval, 1.3 to 2.4) after adjustment for systolic blood pressure, use of medications, and family history of ischemic heart disease. Further adjustment by multivariate analysis for plasma triglyceride, apolipoprotein B, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations did not significantly diminish the association between the insulin concentration and the risk of ischemic heart disease (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3). CONCLUSIONS High fasting insulin concentrations appear to be an independent predictor of ischemic heart disease in men.

Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease.

Several epidemiological studies have reported that the regional distribution of body fat is a significant and independent risk factor for cardiovascular disease (CVD) and related mortality. Although these associations are well established, the causal mechanisms are not fully understood. Numerous studies have, however, shown that specific topographic features of adipose tissue are associated with metabolic complications that are considered as risk factors for CVD such as insulin resistance, hyperinsulinemia, glucose intolerance and type II diabetes mellitus, hypertension, and changes in the concentration of plasma lipids and lipoproteins. The present article summarizes the evidence on the metabolic correlates of body fat distribution. Potential mechanisms for the association between body fat distribution, metabolic complications, and CVD are reviewed, with an emphasis on plasma lipoprotein levels and plasma lipid transport. From the evidence available, it seems likely that subjects with visceral obesity represent the subgroup of obese individuals with the highest risk for CVD. Although body fat distribution is now considered as a more significant risk factor for CVD and related death rate than obesity per se, further research is clearly needed to identify the determinants of body fat distribution and the causal mechanisms involved in the metabolic alterations. It appears certain, however, that an altered plasma lipid transport is a significant component of the relation between body fat distribution and CVD.

The response to long-term overfeeding in identical twins.

We undertook this study to determine whether there are differences in the responses of different persons to long-term overfeeding and to assess the possibility that genotypes are involved in such differences. After a two-week base-line period, 12 pairs of young adult male monozygotic twins were overfed by 4.2 MJ (1000 kcal) per day, 6 days a week, for a total of 84 days during a 100-day period. The total excess amount each man consumed was 353 MJ (84,000 kcal). During overfeeding, individual changes in body composition and topography of fat deposition varied considerably. The mean weight gain was 8.1 kg, but the range was 4.3 to 13.3 kg. The similarity within each pair in the response to overfeeding was significant (P less than 0.05) with respect to body weight, percentage of fat, fat mass, and estimated subcutaneous fat, with about three times more variance among pairs than within pairs (r approximately 0.5). After adjustment for the gains in fat mass, the within-pair similarity was particularly evident with respect to the changes in regional fat distribution and amount of abdominal visceral fat (P less than 0.01), with about six times as much variance among pairs as within pairs (r approximately 0.7). We conclude that the most likely explanation for the intrapair similarity in the adaptation to long-term overfeeding and for the variations in weight gain and fat distribution among the pairs of twins is that genetic factors are involved. These may govern the tendency to store energy as either fat or lean tissue and the various determinants of the resting expenditure of energy.

Small, Dense Low-Density Lipoprotein Particles as a Predictor of the Risk of Ischemic Heart Disease in Men Prospective Results From the Que´bec Cardiovascular Study

BACKGROUND Case-control studies have reported that patients with ischemic heart disease (IHD) have a higher proportion of small, dense LDL particles than do healthy control subjects. The extent to which the risk attributed to small LDL particles may be independent of concomitant variations in plasma lipoprotein-lipid concentrations remains to be clearly determined, however, particularly through prospective studies. METHODS AND RESULTS Baseline characteristics were obtained in 2103 men initially free of IHD, among whom 114 developed IHD during a 5-year follow-up period. These 114 case patients were matched with healthy control subjects for age, body mass index, smoking habits, and alcohol intake. LDL peak particle diameter (PPD) was measured a posteriori in 103 case-control pairs by nondenaturing gradient gel electrophoresis of whole plasma. Conditional logistic regression analysis of the case-control status revealed that men in the first tertile of the control LDL-PPD distribution (LDL-PPD < or = 25.64 nm) had a 3.6-fold increase in the risk of IHD (95% CI, 1.5 to 8.8) compared with those in the third tertile (LDL-PPD > 26.05 nm). Statistical adjustment for concomitant variations in LDL cholesterol, triglycerides, HDL cholesterol, and apolipoprotein B concentrations had virtually no impact on the relationship between small LDL particles and the risk of IHD. CONCLUSIONS These results represent the first prospective evidence suggesting that the presence of small, dense LDL particles may be associated with an increased risk of subsequently developing IHD in men. Results also suggest that the risk attributed to small LDL particles may be partly independent of the concomitant variation in plasma lipoprotein-lipid concentrations.

Visceral Obesity in Men: Associations With Glucose Tolerance, Plasma Insulin, and Lipoprotein Levels

The relations of regional adipose tissue (AT) distribution measured by computed tomography (CT) to plasma insulin-glucose homeostasis and lipoprotein-lipid levels were studied in 58 obese and 29 lean control men. In the group of obese men, the visceral AT area measured by CT was positively correlated with fasting plasma triglyceride and insulin levels and with glucose and insulin areas under the curves measured during a 75-g oral glucose tolerance test. Visceral AT area was also negatively associated with plasma high-density lipoprotein (HDL) and HDL2 cholesterol levels. The relative accumulation of abdominal fat, estimated by the ratio of abdominal to femoral AT areas obtained by CT, was also a significant correlate of indices of carbohydrate metabolism and was the best univariate correlate of plasma lipoprotein levels. No significant associations were observed between the visceral AT area, the ratio of abdominal to femoral AT areas, and indices of carbohydrate and lipoprotein metabolism in the group of lean men. On the other hand, the subcutaneous abdominal AT area was a significant correlate of the glucose area under the curve in both groups of men, but this association was not independent from the percentage of total body fat. No relationship was observed between the femoral AT area and indices of carbohydrate metabolism in either lean or obese groups. In obese men, however, the femoral AT area was negatively correlated with plasma triglyceride concentration and positively correlated with plasma HDL and HDL2 cholesterol levels. Comparison between two subgroups of equally obese men showing either low or high levels of visceral AT and a group of lean men generally revealed that only obese men with high levels of visceral AT showed significant metabolic alterations compared with lean men. These results demonstrate that the amount of visceral AT and the ratio of abdominal to femoral AT measured by CT are important correlates of the alterations in carbohydrate and lipoprotein metabolism observed in obese men. In addition, our results suggest that obesity is required to observe significant associations between body fat distribution measured by CT and metabolic variables. Finally, we suggest that, in men, a high accumulation of femoral fat may be protective against the adverse effects of obesity, particularly abdominal obesity, on plasma lipoprotein levels.

Role of Deep Abdominal Fat in the Association Between Regional Adipose Tissue Distribution and Glucose Tolerance in Obese Women

Computed tomography (CT) was used to study the association between adipose tissue localization and glucose tolerance in a sample of 52 premenopausal obese women aged 35.7 ± 5.5 yr (mean ± SD) and with a body fat of 45.9 ± 5.5%. Body-fat mass and the body mass index (BMI) were significantly correlated with plasma glucose, insulin, and connecting peptide (C-peptide) areas after glucose (75 g) ingestion (.40 ≥ r ≤ .51, P < .01). Trunk-fat accumulation and the size of fat cells in the abdomen displayed highly significant correlations with postglucose insulin levels. The C-peptide area was also positively correlated with abdominal fat cell size (r = .76, P < .01) and was more closely associated with the sum of trunk skin folds (r = .59, P <.001) than with the extremity skin folds (r = .29, P < .05). Subcutaneous and deep-abdominal-fat areas measured by CT displayed comparable associations with the plasma insulin area (r = .44 and .49, respectively; P < .001) but marked differences in the associations with glucose tolerance. Indeed, subcutaneous abdominal fat was not significantly correlated with the glucose area, whereas deep abdominal fat showed a significant correlation (r = .57, P < .001) with the glucose area. Midthigh fat deposition measured by CT was not, however, correlated with plasma glucose, insulin, or C-peptide areas. Partial correlation analyses indicated that the effect of accumulation of deep abdominal fat on glucose tolerance was independent from total adiposity and that no association was observed between total adiposity and glucose tolerance after control for accumulation of deep abdominal fat. These results emphasize the importance of deep abdominal fat as an independent correlate of glucose tolerance in obese women.

Assessment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements

1. Abdominal obesity is associated with numerous metabolic complications. Deep abdominal adipose tissue is critical in the association between the level of abdominal obesity and cardiovascular risk factors. 2. Adipose tissue localization was assessed by computed axial tomography (CAT), and its association with body density and anthropometric measurements was investigated in a sample of fifty-one obese women (percentage body fat 45.9 (SD 5.6)) aged 35.7 (SD 5.5) years. The CAT scans were performed at three levels: lower chest, abdomen and mid-thigh. 3. The total adipose tissue volume computed from these three scans was highly correlated with body fat mass (r 0.94, P less than 0.001). The proportion of deep abdominal fat as measured by the ratio of deep: total adipose tissue areas at the abdominal level was not significantly correlated with body fat mass, but it was moderately associated with the ratio of waist: hip circumferences (WHR) (r 0.49, P less than 0.001). The absolute amount of deep abdominal fat was, however, significantly correlated with body fat mass (r 0.72, P less than 0.001). 4. The subscapular (r 0.38) and the abdominal (r 0.38) skinfolds were the only two skinfolds that were significantly associated with the proportion of deep abdominal fat (P less than 0.01). These skinfolds were also those which showed the highest correlation with the absolute amount of deep abdominal fat (r 0.65, P less than 0.001, for both skinfolds). 5. A three-site CAT-scan procedure can be used for the estimation of body fat mass in premenopausal obese women. 6. In these obese women, there was no significant association between total adiposity and the proportion of deep adipose tissue at the abdominal level. 7. In premenopausal obese women, the absolute amount of deep abdominal fat can be predicted from anthropometric measurements with more accuracy than the relative amount of deep abdominal fat.

The dense LDL phenotype : Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men

OBJECTIVE To investigate the potential relationship between the cluster of metabolic abnormalities found in visceral obesity and the small dense LDL phenotype. RESEARCH DESIGN AND METHODS We have estimated LDL peak particle size by nondenaturing 2–16% gradient gel electrophoresis in a sample of 79 men. Glucose tolerance and fasting plasma insulin and lipoprotein levels were also measured. RESULTS The LDL particle score, calculated from migration, distances and relative band intensities and reflecting the proportion of small dense LDL particles, was positively correlated with plasma triglyceride (TG) (r = 0.60, P < 0.0001) and negatively correlated with HDL cholesterol (r = −0.56, P < 0.0001) levels. Although the LDL particle score was not associated with variations in plasma LDL cholesterol or LDL apolipoprotein (apo) B concentrations, it was significantly correlated with the LDL apo B–to–LDL cholesterol ratio (r = 0.60, P < 0.0001). Fasting plasma insulin and visceral adipose tissue (AT) areas measured by computed tomography were weakly but significantly correlated with the LDL particle score (r = 0.23 and 0.29, respectively, P < 0.05). LDL peak particle size showed similar but inverse correlations with anthropometric and metabolic variables. Subjects classified as having small dense LDL particles (by comparing subjects in the highest tertile versus those in the lowest tertile of the LDL particle score distribution) were characterized by increased plasma TG, reduced HDL cholesterol, higher fasting insulin levels, and elevated visceral AT accumulation. However, multiple regression analyses revealed that visceral AT accumulation was not an independent predictor of the dense LDL phenotype after inclusion of TG and HDL cholesterol levels and lipoprotein ratios in the model. CONCLUSIONS It thus appears that the high TG–low HDL cholesterol dyslipidemia frequently found in visceral obesity and in a hyperinsulinemic state is a strong correlate of the small dense LDL phenotype. Although associated with the dense LDL phenotype, visceral obesity and hyperinsulinemia were not independent predictors of an increased proportion of small dense LDL particles after controlling for TG and HDL cholesterol levels.

Adipose tissue distribution and plasma lipoprotein levels in obese women. Importance of intra-abdominal fat.

Prospective studies have shown that excess abdominal fat Is associated with an Increased risk of coronary heart disease and related death. We used computed axial tomography (CAT) to assess the association between deep and subcutaneous abdominal adipose tissue and plasma lipoprotein levels In a sample of 52 premenopausal obese women aged 35.7±5.5 years (mean±SD). Whereas the plasma lipoprotein concentrations were not significantly correlated with fat mass, the data obtained by CAT Indicated that the absolute amount of deep abdominal fat was negatively correlated with high density lipoprotein cholesterol (HDL-CHOL) levels (r=−0.35, /x 0.01), as well as with HDL-CHOL/low density lipoprotein (LDL)-CHOL, HDL- apoprotein-(apo) A-l/LDL-apo B, and HDL2-CHOL/HDL,-CHOL ratios (−0.32srs-0.40, 0.05>p<0.01). Adipose tissue deposition at the mid-thigh region determined by CAT did not show any significant relationship with plasma lipoprotein levels. When subgroups of women with comparable ages and adiposity but with high and low Intra-abdominal fat accumulation were compared, women with a high accumulation of Intra-abdominal fat displayed significantly lower HDL-CHOL (p<0.001), HDLj- CHOL (p<0.001), HDL3-CHOL (p<0.01), and HDL-apo A-l (p<0.05) levels, as well as reduced HDL-CHOL/LDL-CHOL (p<0.01), HDL-apo A-l/LDL-apo B (p<0.05), and HDL2-CHOL/HDL4-CHOL ratios (p<0.05) in comparison with obese women with low accumulations of Intra-abdominal fat These data Indicate that, in a sample of obese women, body fat distribution, especially Intra-abdominal fat accumulation, is a significant correlate of plasma lipoprotein levels Independent of total fatness.

Increase in plasma high-density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma

There is evidence that endogenous estrogens have a positive effect on plasma high density lipoprotein (HDL) concentration, whereas the relation between HDL and male sex hormones is unclear, since both positive and negative effects have been reported. This study examined the effects of LHRH agonist in combination with an antiandrogen on plasma lipids and lipoproteins in 17 elderly men with prostatic carcinoma. Subjects were examined prior to and after therapy at 4-week intervals up to 16 weeks. Prior to therapy, their lipid and lipoprotein profiles were not significantly different from a control group composed of individuals of similar age and living in the same community area. Following therapy plasma levels of testosterone and dihydrotestosterone were markedly decreased (above 90%) and their residual activity neutralized through effective use of an antiandrogen. Plasma estradiol decreased between 65% and 85% and the concentration of cortisol was unaffected. The very low density lipoprotein (VLDL) apo-B decreased and low density lipoprotein (LDL) apo-B increased; thus, no change was observed in the total plasma apo-B levels. Total plasma cholesterol increased by 6% (baseline v peak values, mg/dL, mean +/- SEM; 219 +/- 9 v 233 +/- 9, P less than 0.05) due to a significant rise in HDL cholesterol concentration (45.5 +/- 2.8 v 56.5 +/- 3.6, P less than 0.01). Both VLDL and LDL cholesterol levels remained unchanged. The mean elevation of 21% in HDL cholesterol was accompanied by a significant rise in HDL apo-A concentration (161 +/- 6 v 193 +/- 10, P less than 0.01), thus suggesting an increase in HDL mass and/or particle number.(ABSTRACT TRUNCATED AT 250 WORDS)