OBJECTIVE:To study the relation of fibrinogen and C-reactive protein (CRP) to various measures of body fat and body fat distribution and to investigate whether these relations were explained by differences in insulin sensitivity. DESIGN AND SUBJECTS: Cross-sectional analysis of the IRAS (Insulin Resistance Atherosclerosis Study), a large (n ¼ 1559) triethnic population (non-Hispanic whites, African-Americans and Mexican-Americans) across different states of glucose tolerance. MEASUREMENTS: Glucose tolerance (oral glucose tolerance test), insulin sensitivity (frequently sampled intravenous glucose tolerance test and minimal model analysis), assessment of body fat mass and distribution (weight, girths, bioelectrical impedance), subclinical atherosclerosis (B-mode ultrasonography of carotid artery intima-media thickness, IMT), CRP (highly sensitive immunoassay), fibrinogen (standard assay). RESULTS: Both CRP and fibrinogen were related to all measures of body fat. Strong correlations (correlation coefficient r ! 0.35) were found between CRP and body mass index (BMI), waist circumference and adipose body mass, respectively. The associations were consistent in non-diabetic and type-2 diabetic subjects, were generally stronger in women, and were only moderately attenuated by the prevailing insulin sensitivity (S I ). In a multivariate linear regression model waist circumference explained 14.5% of the variability of circulating CRP levels (P ¼ 0.0001), BMI 0.4% (P ¼ 0.0067), and S I 1.7% (P ¼ 0.0001). Common carotid artery IMT was related to CRP and fibrinogen in men, but not in women, and was attenuated after adjusting for BMI or waist. CONCLUSION: Our findings show that measures of body fat are strongly associated with circulating levels of CRP and fibrinogen. These associations were not explained by lower S I in obese subjects. Chronic, subclinical inflammation may be one pathophysiological mechanism explaining the increased risk of atherosclerotic disease associated with adiposity.

We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes.

Patients with NIDDM are at increased risk for coronary heart disease (CHD). However, information on the predictive value of cardiovascular risk factors and the degree of hyperglycemia with respect to the risk for CHD in diabetic patients is still limited. Therefore, we carried out a prospective study on risk factors for CHD, including a large number of NIDDM patients. At baseline, risk factor levels of CHD were determined in 1,059 NIDDM patients (581 men and 478 women), aged from 45 to 64 years. These patients were followed up to 7 years with respect to CHD events. Altogether, 158 NIDDM patients (97 men [16.7%] and 61 women [12.8%]) died of CHD and 256 NIDDM patients (156 men [26.8%] and 100 women [20.9%]) had a serious CHD event (death from CHD or nonfatal myocardial infarction). A previous history of myocardial infarction, low HDL cholesterol level (<1.0 mmol/l), high non-HDL cholesterol (> or =5.2 mmol/l), high total triglyceride level (>2.3 mmol/l), and high fasting plasma glucose (>13.4 mmol/l) were associated with a twofold increase in the risk of CHD mortality or morbidity, independently of other cardiovascular risk factors. High calculated LDL cholesterol level (> or =4.1 mmol/l) was significantly associated with all CHD events. The simultaneous presence of high fasting glucose (>13.4 mmol/l) with low HDL cholesterol, low HDL-to-total cholesterol ratio, or high total triglycerides further increased the risk for CHD events up to threefold. Our 7-year follow-up study provides evidence that dyslipidemia and poor glycemic control predict CHD mortality and morbidity in patients with NIDDM.

The relative importance of insulin resistance and abnormal insulin secretion as risk factors for the development of impaired glucose tolerance (IGT) is controversial. Few prospective data are available on metabolic precursors of IGT. We examined the relation of fasting serum insulin level (as a marker of insulin resistance) and change in insulin/glucose ratio (delta I30/ delta G30) over the first 30 min after glucose ingestion (as a marker of insulin secretion) as predictors of the 7-year development of IGT in 839 Mexican Americans and non-Hispanic whites with normal glucose tolerance at baseline from the San Antonio Heart Study. IGT eventually developed in 148 subjects. When modelled separately, fasting serum insulin (odds ratio (OR) = 2.60, 95% confidence interval (CI) = 1.58, 4.28, p < 0.005), but not delta I30/ delta G30 (OR = 0.80, 95% CI = 0.50, 1.27, p = 0.339) predicted the development of IGT. However, when both variables were included in the same logistic regression model, fasting serum insulin (OR = 3.50, 95% CI = 1.97, 6.21, p < 0.001) and low delta I30/ delta G30 (OR = 0.48, 95% CI = 0.28, 0.82, p = 0.008) both predicted IGT. These results were basically unchanged after further adjustment for obesity, body fat distribution and fasting plasma glucose level. We conclude that both decreased insulin secretion (as assessed by low delta I30/ delta G30) and increased insulin resistance (as assessed by fasting serum insulin) predict the development of IGT and are thus early precursors of non-insulin-dependent diabetes mellitus; further studies of insulin secretion should take into account the level of basal insulin resistance.

No abstract

OBJECTIVE: Leptin is a hormone regulating weight in the mouse. Leptin regulates food intake and appetite. Leptin concentrations are increased in obese individuals suggesting resistance to its effect. However, there is considerable variability in leptin levels at each level of adiposity suggesting that environmental and genetic factors may regulate leptin concentrations. We examined whether subjects with decreased insulin sensitivity have increased leptin levels. METHODS: We used a radioimmunoassay to measure serum leptin levels and the hyperinsulinemic euglycemic clamp (with indirect calorimetry) to measure insulin sensitivity in 87 normoglycemic relatively lean men. RESULTS: Leptin levels were signi®cantly correlated with fasting insulin (r 0.58), insulin area (r 0.45), overall (r 70.57), non-oxidative (r 70.51) and oxidative (r 70.51) whole body glucose disposal (all P-values`0.001). After adjustment for body mass index, leptin levels remained signi®cantly correlated with fasting insulin (r 0.44), insulin area (r 0.40), overall (r 70.40), non-oxidative (r 70.28) and oxidative (r 70.33) whole body glucose disposal although the magnitude of the associations was considerably decreased. Leptin levels were signi®cantly related to insulin sensitivity in both less obese and more obese subjects. CONCLUSIONS: We conclude that leptin concentrations are related to insulin resistance and insulin concentrations in relatively lean normoglycemic men and these associations are to some extent independent of body mass index. Thus, subjects with insulin resistance may be relatively resistant to the effects of leptin.

Diabetes mellitus is associated with a marked increase in coronary heart disease (CHD) [1,2]. In many [1,[3][4][5][6][7] but not all [8][9][10][11] studies this excess risk of CHD is relatively higher for female diabetic subjects than for male diabetic subjects. The reasons for the excess risk of CHD in diabetic subjects are multifactorial but include dyslipidaemia, hypertension, and insulin resistance. In some cases, the increase in these risk factors may be relatively greater in female diabetic subjects than in male diabetic subjects. For example, diabetic women have a relatively worse pattern of dyslipidaemia (especially increased low density lipoprotein (LDL) cholesterol and decreased high density lipoprotein (HDL) cholesterol) than diabetic men [12][13][14][15].However, the relatively greater increase in CHD risk for diabetic women than for diabetic men may not depend solely upon greater risk factors for CHD after the development of non-insulin-dependent diabetes mellitus (NIDDM). While the degree and duration of hyperglycaemia are major risk factors for microvascular complications [16,17], several studies have suggested that these risk factors are not related Diabetologia (1997) 40: 711-717 Relatively more atherogenic coronary heart disease risk factors in prediabetic women than in prediabetic men

BACKGROUND: Leptin, a hormone which is produced by adipose tissue, has been shown to inhibit food intake and increase energy expenditure. In humans, leptin levels are correlated with body fat. In addition, leptin levels decline in subjects who lose weight. Yet few data exist on whether leptin levels predict weight change, except for a recent report suggesting that low leptin levels predict weight gain in very obese middle-aged Pima Indians. METHODS: We have examined the association between baseline leptin levels and subsequent weight gain over 3.25 y in 180 non-diabetic participants in the Mexico City Diabetes Study. RESULTS: At baseline, the correlation between leptin levels and body mass index (BMI) was 0.712 in men and 0.691 in women (both P`0.001). Subjects were matched on age (AE 2 y), gender and BMI (AE 2 kgam 2 ) at baseline. Baseline BMI was 25.3 kgam 2 in men and 27.2 kgam 2 in women. Baseline leptin levels (ngaml) did not predict weight gain in either men (weight gainers: 4.3; weight stable: 5.8; and weight losers: 5.2) or women (weight gainers: 17.4; weight stable: 17.7; and weight losers: 17.4). CONCLUSIONS: We conclude that baseline leptin levels did not predict weight change in moderately obese individuals.