Obesity worsens cardiovascular risk profiles independently of hyperinsulinaemia.

OBJECTIVE: To investigate whether human obesity is characterized by a worse cardiovascular risk profile (than no obesity) even in the absence of hyperinsulinaemia. SUBJECTS AND DESIGN: A total of 367 healthy subjects (247 nonobese and 120 obese) with normal glucose tolerance and without family history of diabetes mellitus. INTERVENTIONS: A 75-g oral glucose tolerance test was performed in all participants. MAIN OUTCOME MEASURES: Anthropometry, blood pressure, fasting plasma lipids and urate, plasma glucose and insulin concentrations at fasting, 1 h and 2 h after oral glucose load. RESULTS: In a multivariate linear regression analysis, body mass index was strongly related to all cardiovascular risk factors, independently of sex, age and plasma insulin. When risk factors were compared in 37 normoinsulinaemic obese subjects (plasma insulin within one standard deviation of the mean values observed in the 247 nonobese subjects), and in 37 sex- and age-matched normoinsulinaemic nonobese subjects, we found that plasma glucose levels were similar in the two groups, whereas plasma triglyceride (1.50 +/- 0.13 vs. 1.13 +/- 0.08 mmol L-1; mean +/- SE), low-density lipoprotein cholesterol (3.42 +/- 0.25 vs. 2.77 +/- 0.18 mmol L-1) and urate (290 +/- 12 vs. 255 +/- 12 mumol L-1) levels were significantly higher, and plasma high-density lipoprotein cholesterol concentrations were lower (1.27 +/- 0.04 vs. 1.46 +/- 0.06 mmol L-1) in obese than in nonobese subjects with normal plasma insulin levels (P < 0.01). Also systolic (132 +/- 2 vs. 124 +/- 2 mmHg) and diastolic (86 +/- 1 vs. 81 +/- 1 mmHg) blood pressure values were significantly higher in normoinsulinaemic obese subjects than in normoinsulinaemic nonobese individuals (P < 0.001). CONCLUSIONS: These results suggest that in human obesity a worse cardiovascular risk profile is found (than in the nonobese) independently of the presence of hyperinsulinaemia.

Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study.

The associations between fasting plasma insulin concentration and risk factors for cardiovascular disease were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)-total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol, concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F = 7.1; P < 0.001). However, systolic blood pressure and uric acid were close to statistical significance (P = 0.06-0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e, three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F = 4.0; P < 0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides.

Serum uric acid and related factors in 500 hospitalized subjects.

The study purpose was to determine the following in a large sample of hospitalized patients: (1) the prevalence of hyperuricemia, (2) the association of hyperuricemia with other metabolic disorders, and (3) the factors independently predicting hyperuricemia. Five hundred adult patients (250 men and 250 women) were randomly selected from those admitted as inpatients over a period of 5 months. In all patients, body mass index (BMI), blood pressure, and serum glucose, lipid, creatinine, urea nitrogen, and urate concentrations were measured. The presence of diseases or use of medications known to affect serum urate levels were recorded. The mean level of serum urate was 5.6 mg/dL in the whole sample, 6.0 mg/dL in men and 5.3 mg/dL in women (P = .003, men v women). The prevalence of hyperuricemia was 27.6% (28.8% and 26.4% in men v women, P = nonsignificant). A definite or probable secondary hyperuricemia was found in 87.7% of the subjects. Hyperuricemia was rarely isolated (21%), whereas it was frequently associated with hypertension (60.1%), hyperlipidemia (31.2%), diabetes (28.3%), and obesity (21.7%). In 26.8% of the subjects, hyperuricemia was associated with two metabolic disorders, in 13.8% with three, and in 2.9% with four. Multiple metabolic disorders (three to four) were found in 16.7% of subjects with hyperuricemia. Serum urate levels progressively increased across a range of subjects from those without diabetes, hyperlipidemia, hypertension, or obesity to those with one, two, or a greater number of associated metabolic abnormalities. Multiple stepwise regression analysis showed that 43% of serum urate variability was explained by urea nitrogen levels, triglyceride levels, diuretic therapy, the inverse of creatinine (as an index linearly related to creatinine clearance), and BMI. These results indicate that in hospitalized subjects, hyperuricemia is (1) frequent, (2) a secondary phenomenon in most cases, and (3) frequently associated with other metabolic disorders. The major predictors of high serum urate levels are BMI, triglycerides, parameters of renal function, and use of diuretics. These variables explain a large proportion of serum urate variability.

Relationship of uric acid concentration to cardiovascular risk factors in young men. Role of obesity and central fat distribution. The Verona Young Men Atherosclerosis Risk Factors Study.

OBJECTIVE: To examine the relationships of serum uric acid concentration with several risk factors of cardiovascular diseases (CVD). SUBJECTS: 957 men 18 y old participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. MEASUREMENTS: Body mass index (BMI), waist/hip ratio (WHR), serum uric acid, serum lipids, blood pressure, fasting insulin and behavioural variables. RESULTS: Serum uric acid concentration showed positive associations with BMI (r = 0.24; P < 0.0001), WHR (r = 0.19; P < 0.0001) and serum triglyceride levels (r = 0.19; P < 0.0001); it was also significantly correlated to systolic (r = 0.08; P < 0.01) and diastolic (r = 0.11; P < 0.001) blood pressure, fasting insulin (r = 0.11; P < 0.001), total (r = 0.12; P < 0.001) and LDL cholesterol (r = 0.10; P < 0.01) plasma concentrations. Life-style characteristics, such as smoking and physical activity did not show any significant association, while daily alcohol intake was positively associated with uric acid concentration (r = 0.09; P < 0.01). While the adjustment for fasting insulin did not substantially change these results, the magnitude of the correlations between uric acid and CVD risk factors markedly decreased when allowance was made for BMI and WHR. Only triglycerides maintained an independent correlation with uric acid levels (r = 0.17; P < 0.0001). In multivariate regression analysis, serum triglycerides, BMI and WHR (at borderline significance) were independent positive predictors of uric acid (R2 of the model 0.122, P < 0.001), while fasting insulin concentration did not give any independent contribution to explain the variability uric acid levels. CONCLUSIONS: These data indicate that, already in young, essentially health subjects, hyperuricaemia associates with several components of the so-called insulin resistance syndrome, thus suggesting that increased levels of uric acid might be another member of this syndrome. In addition, these data suggest that obesity and central body fat distribution, rather than hyperinsulinaemia/insulin resistance, play a major role in linking hyperuricaemia with CVD risk factors clustering in the insulin resistance syndrome. Nevertheless, hypertrigliceridemia is related to hyperuricemia independently of obesity and central body fat distribution.

Cardiovascular risk profile in 38-year and 18-year-old men. Contribution of body fat content and regional fat distribution.

OBJECTIVE: To evaluate whether young and middle-age men differ in blood pressure and serum lipid profiles and, if so, to what extent these differences are dependent on total body fat, regional fat distribution, plasma insulin and behavioural variables. SUBJECTS: Random samples of 94 young (18 year-old) and 94 middle-age (38 year-old) healthy men matched for body mass index (BMI). MEASUREMENTS: BMI, total body fat (by bioelectrical impedance), regional fat distribution (by anthropometry), serum lipids, blood pressure, fasting insulin and some behavioural variables. RESULTS: Total body fat was similar in the two groups (mean +/- s.e.: 16.6 +/- 0.5 vs 16.0 +/- 0.6 kg and 20.8 +/- 0.5 vs 20 +/- 0.5%), while waist/hip circumference ratio (WHR) was significantly higher in middle-age as compared to young men (0.96 +/- 0.001 vs 0.92 +/- 0.003, P < 0.0001). The former also had significantly higher serum concentrations of total cholesterol (6.21 +/- 0.13 vs 4.10 +/- 0.10 mmol/l; P < 0.0001). LDL-cholesterol (4.24 +/- 0.11 vs 2.34 +/- 0.10 mmol/l; P < 0.0001), triglycerides 1.40 +/- 0.09 vs 1.02 +/- 0.06 mmol/l; P < 0.01) as well as higher systolic (134.0 +/- 1.6 vs 126.3 +/- 1.4 mmHg; P < 0.0001) and diastolic (86.8 +/- 0.9 vs 82.0 +/- 1.1 mmHg; P < 0.001) blood pressure values. HDL-cholesterol and fasting insulin concentrations were similar in the two groups (1.33 +/- 0.03 vs 1.28 +/- 0.03 mmol/l and 13.7 +/- 0.6 vs 14.7 +/- 0.7 mU/l, respectively). Significant differences in the two groups also were found in daily alcohol consumption (49.6 +/- 5.7 vs 20.0 +/- 3.4 g/day; P < 0.0001), whereas no significant differences were found in smoking and physical activity level. The comparison of subgroups (n = 41) of young and middle-age men matched for both BMI and WHR showed virtually unchanged differences in serum lipids and blood pressure. When age, BMI, WHR, fasting insulin and behavioural variables were included as independent variables in a multiple linear regression analysis in which subjects of the two groups were pooled, age was a significant predictor of total and LDL cholesterol, triglycerides and systolic blood pressure, insulin predicted HDL cholesterol and systolic blood pressure, BMI predicted triglycerides and diastolic blood pressure and WHR was not an independent predictor of any risk factor. CONCLUSIONS: These results indicate that middle-age men have a cardiovascular risk profile less favourable than young men, which is largely independent of differences in total body fat content, regional fat distribution and behavioural variables.

Influence of body fat and its regional localization on risk factors for atherosclerosis in young men.

A study was carried out in 1988 in Verona, Italy, to examine the relation of body fat and its localization to several risk factors for atherosclerosis in young men. Total body fat (bioelectrical impedance), waist and hip circumferences, and waist/hip circumference ratio were measured in 1,293 18-year-old men. Fasting serum levels of total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, and insulin, as well as systolic and diastolic blood pressure, were also measured. Significant differences were found in all metabolic and hemodynamic variables among quartiles of total body fat. Most of these differences remained significant after the authors controlled for the independent effect of fat localization and behavioral factors such as smoking, alcohol intake, and physical activity. Triglycerides, insulin, and blood pressure were significantly different among quartiles of waist/hip ratio, but these differences disappeared after the authors controlled for the independent effect of total body fat. These results indicate that in young men, irrespective of its regional localization, an excess of body fat is associated with a poor profile of risk for atherosclerosis. On the other hand, the prevalent localization of fat in the central part of the body is not independently associated with any risk factor.