High-density lipoprotein composition in obesity: interrelationships with plasma insulin levels and body weight

Hyperinsulinism may play a role in the development of atherosclerosis. In this study we analyzed the interrelationships between plasma glucose, insulin, body weight and high-density lipoproteins (HDL) in a group of obese women and faced the question of what is the effect of obesity on insulin, glucose and HDL relationships. HDL cholesterol was significantly lower, while HDL triglycerides resulted significantly higher in the obese women than in the controls. The two groups did not show any difference in the serum concentration of HDL apoprotein A-I and apoprotein A-II. There was an inverse correlation between fasting plasma glucose and summated means of glucose and insulin levels after an oral glucose tolerance test and HDL cholesterol in the two groups; on the contrary a positive relationship between the same parameters and HDL triglyceride occurred. HDL cholesterol was inversely related also to the weight index, while HDL triglyceride concentration was directly correlated with this parameter in the two groups. Partial correlation analysis demonstrates that, when exposed to similar plasma insulin and glucose levels, HDL cholesterol and triglyceride concentrations were no longer correlated with the weight index, and therefore that the significant correlations between these variables are likely to be due to the significant correlations of each of them with plasma glucose and insulin levels. Further studies clarifying the role of glucose and insulin in determining HDL composition would appear important.     

Metabolic and adipose risk factors for NIDDM and coronary disease in third- generation Japanese-American men and women with impaired glucose tolerance

Summary Since second-generation (Nisei) Japanese Americans are prone to develop the insulin resistance syndrome, younger third-generation (Sansei) Japanese Americans from a cross-sectional 10 % volunteer sample of Sansei men (n=115) and women (n=115) 34 years or older in King County, Washington with normal glucose tolerance or IGT were examined for metabolic and adipose risk factors associated with this syndrome. After an overnight 10-h fast, blood samples were taken for measurement of glucose, insulin, C-peptide, lipids, and lipoproteins, followed by a 3-h 75-g oral glucose tolerance test with blood samples taken for glucose, insulin, and C-peptide measurement. BMI (kg/m²), skinfolds, and body fat areas (by computed tomography) were measured. IGT was diagnosed in 19 % of the men and 31 % of the women. Men with IGT had more adiposity, both overall and in thoracic and visceral sites, had higher fasting plasma insulin and C-peptide, and tended to have higher fasting triglyceride and lower HDL cholesterol than men with normal glucose tolerance. Women with IGT had more thoracic subcutaneous fat and intra-abdominal fat and lower fasting HDL cholesterol than women with normal glucose tolerance, and tended to have higher fasting triglyceride and LDL cholesterol. Women with IGT also had higher fasting plasma insulin than women with normal glucose tolerance but tended to be less hyperinsulinaemic than men. Differences in fasting insulin, C-peptide, and lipids were best predicted by intra-abdominal fat. Thus metabolic (higher fasting insulin and a tendency to higher triglyceride and lower HDL cholesterol) and adipose (visceral adiposity) risk factors associated with the insulin resistance syndrome are identifiable among Sansei men and women with IGT, who may therefore be at increased risk of future development of NIDDM and CHD. [Diabetologia (1994) 37: 524–532] Received: 9 July 1993 and in revised form: 14 December 1993     

Relation among the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio, insulin resistance, and associated cardio-metabolic risk factors in men and women

Results of recent studies using the ratio of plasma triglyceride (TG) to high-density lipoprotein (HDL) cholesterol concentration to identify insulin-resistant patients at increased cardiometabolic risk have emphasized that the cut point used for this purpose will vary with race. Because TG and HDL cholesterol concentrations vary with gender, this analysis was initiated to define gender-specific plasma TG/HDL cholesterol concentration ratios that best identified high-risk subjects among women (n = 1,102) and men (n = 464) of primarily European ancestry. Insulin resistance was defined as the 25% of the population with the highest values for fasting plasma insulin concentration and homeostasis model assessment of insulin resistance. Using TG/HDL concentration ratios >2.5 in women and >3.5 in men identified subgroups of men and women that were comparable in terms of insulin resistance and associated cardiometabolic risk, with significantly higher values for fasting plasma insulin, homeostasis model assessment of insulin resistance, blood pressure, body mass index, waist circumference, and glucose and TG concentrations and lower HDL cholesterol concentrations than in women and men below these cut points. The sensitivity and specificity of these gender-specific cut points to identify insulin-resistant subjects were about 40% and about 80%, respectively. In conclusion, the plasma TG/HDL cholesterol concentration ratio that identifies patients who are insulin resistant and at significantly greater cardiometabolic risk varies between men and women.     

Association of obesity and distribution of obesity with glucose tolerance and cardiovascular risk factors in the elderly.

The association of obesity and fat distribution with glucose tolerance and cardiovascular risk factor levels were investigated in a population-based study in East Finland including 396 non-diabetic men and 673 women aged from 65 to 74 years. Obese men and women (BMI greater than 27 kg/m2) had higher levels (P less than 0.001) of fasting and 2 h plasma glucose and insulin as well as total triglycerides and diastolic blood pressure, and lower levels of HDL cholesterol than normal weight men and women. Central fat distribution (the highest vs. the lowest tertile of waist-hip ratio) was associated independently of obesity with high fasting glucose (5.7 vs. 5.5 mmol/l in non-obese subjects, 5.9 vs. 5.7 mmol/l in obese subjects, P less than 0.05) and insulin levels (13.7 vs. 10.6 mU/l in non-obese subjects, 18.4 vs. 15.6 mU/l in obese subjects, P less than 0.01) and with adverse changes (P less than 0.05) in lipid and lipoprotein levels (triglycerides: 1.59 vs. 1.41 mmol/l in non-obese subjects, 1.92 vs. 1.69 mmol/l in obese subjects; HDL cholesterol: 1.33 vs. 1.43 mmol/l in non-obese subjects, 1.20 vs. 1.32 mmol/l in obese subjects). There were no marked differences in metabolic aberrations related to obesity between men and women. However, the association between waist-hip ratio and risk factors was non-linear in men whereas it was linear in women. In conclusion, obesity per se rather than its distribution was a more significant determinant of glucose and insulin as well as total triglyceride and HDL cholesterol levels in elderly subjects.     

A relationship between serum ferritin and the insulin resistance syndrome is present in non-diabetic women but not in non-diabetic men

BACKGROUND: Previous studies have suggested that serum ferritin is one of the components of the insulin resistance syndrome in Caucasians. Because serum ferritin levels differ significantly between men and women, variation in the role of ferritin in insulin resistance between the sexes, particularly in Asian populations, is still unknown. OBJECTIVE: To examine whether the association between serum ferritin and insulin resistance differs between men and women in randomly selected non-diabetic Chinese subjects. DESIGN: A retrospective study. PATIENTS: Four hundred and seventeen non-diabetic Chinese subjects (140 men and 277 women) were studied. MEASUREMENTS: Fasting plasma glucose, insulin, lipoproteins and serum ferritin concentrations, as well as plasma glucose and insulin responses to a 75-g oral glucose test (n = 219), were determined. RESULTS: Fasting serum ferritin concentrations (mean +/- SEM) were significantly higher in men than in women (504 +/- 33 vs. 242 +/- 18 pmol/l, P < 0.001). In women, fasting serum ferritin concentrations correlated significantly with age, body mass index (BMI), amount of body fat, fasting plasma glucose, insulin, cholesterol, triglyceride concentrations, glucose response to an oral glucose load, and homeostasis model assessment (HOMA) of insulin resistance but not with blood pressure, high density lipoprotein (HDL) cholesterol levels and insulin response to oral glucose. On the contrary, none of the above anthropometric and metabolic variables was related to fasting serum ferritin levels in men. HOMA insulin resistance increased progressively across three different tertiles for measured serum ferritin concentrations in women (P < 0.003). In men, HOMA insulin resistance levels were not different among three differing measured serum ferritin levels (P = 0.424). Adjustment for age, BMI and menopause status did not change the significant relationship between HOMA insulin resistance and serum ferritin in women. CONCLUSIONS: We observed that a relationship between serum ferritin levels and insulin resistance exists in women but not in men. This sexual dimorphism merits further investigation.     

Plasma tumor necrosis factor alpha levels and insulin sensitivity in hypertensive subjects

Recent studies have shown that tumor necrosis factor-alpha (TNFalpha), secreted by macrophage, adipocyte and muscle cells, are associated with insulin resistance syndrome i.e., hyperinsulinemia, hypertriglyceridemia and decreased high density lipoprotein (HDL) cholesterol levels. However, it is unclear whether plasma TNFalpha levels relate to insulin resistance syndrome in subjects with essential hypertension who are also characterized by an insulin resistance state. We recruited 85 nondiabetic subjects (45 men and 40 women) with essential hypertension and 85 nondiabetic subjects who were matched for age, sex and body mass index (BMI) to determine their fasting plasma glucose, insulin and lipoprotein concentrations, their glucose and insulin responses to an oral glucose challenge, and their degrees of insulin resistance. Fasting plasma leptin and TNFalpha levels were measured by radioimmunoassay and chemiluminescent enzyme immunometric assay respectively. Total body fat mass was assessed by the bioelectrical impedance method. The results showed that fasting plasma leptin levels were similar between hypertensive and normotensive subjects (7.9 +/- 0.6 vs 7.4 +/- 0.7 ng/ml, p=0.190). Fasting plasma TNFalpha concentrations were not different between subjects with hypertension and normotension (10.5 +/- 0.5 vs 9.8 +/- 0.4 pg/ml, p=0.360). Fasting plasma TNFalpha concentrations were not different across three subgroups of the insulin resistance both in hypertensive patients (8.4 +/- 0.4 vs. 10.9 +/- 1.6 vs. 9.9 +/- 1.0 pg/ml, p=0.297) and normotensive subjects (9.2 +/- 0.7 vs. 9.3 +/- 0.9 vs. 9.7 +/- 0.9 pg/ml, p=0.875). Fasting plasma TNFalpha values showed significantly positive correlations with triglyceride concentrations (p<0.03) but negative correlation with HDL cholesterol concentrations (p<0.04) in normotensive but not in hypertensive individuals. These relations persisted even after adjustment for BMI and total fat mass. In conclusion, our data indicated that circulating levels of TNFalpha did not differ between hypertensive subjects and normotensive controls. Plasma TNFalpha concentrations correlated positively with fasting plasma triglyceride levels and negatively with HDL cholesterol concentrations in normotensive but not in hypertensive subjects. The influence of TNFalpha on carbohydrate and lipoprotein metabolism in hypertensive patients deserves further investigations.     

Relationship between plasma insulin levels and high density lipoprotein cholesterol levels in healthy men

Summary Insulin and high density lipoproteins are considered to play a role in the development of atherosclerosis. In order to study whether there was a relationship between endogenous plasma insulin response and high density lipoproteins, an acute intravenous glucose tolerance test (0.5 g glucose/kg body weight) was performed in 94 healthy men, aged 20–49 years. Cholesterol and triglyceride levels were measured in very low density lipoproteins, low density lipoproteins and high density lipoproteins isolated from fasting serum by preparative ultracentrifugation. The subjects were divided into quartiles according to their fasting and post-glucose load plasma insulin and high density lipoprotein cholesterol levels. The results obtained in the subjects of the upper quartiles were compared with the results obtained in the subjects of the lower quartiles. The mean glucose disappearance rates were within the normal range and did not differ between the upper and lower quartiles. Subjects with high fasting plasma insulin had lower high density lipoprotein cholesterol levels (1.11±0.34 mmol/l, p=0.01) than men with low fasting plasma insulin (1.40±0.37 mmol/l). Higher mean post-glucose plasma insulin was associated with lower high density lipoprotein cholesterol levels (1.18±0.32 mmol/l, p<0.05) and increased high density lipoprotein triglyceride levels (0.14±0.07 mmol/l, p<0.01) when compared with the men with low post-glucose plasma insulin (1.40±0.36 mmol/l and 0.09±0.03 mmol/l respectively). These observations reflect the close relationship between endogenous insulin and lipoprotein metabolism.     

PLASMA TUMOR NECROSIS FACTOR α LEVELS AND INSULIN SENSITIVITY IN HYPERTENSIVE SUBJECTS

Recent studies have shown that tumor necrosis factor-alpha (TNFα), secreted by macrophage, adipocyte and muscle cells, are associated with insulin resistance syndrome i.e., hyperinsulinemia, hypertriglyceridemia and decreased high density lipoprotein (HDL) cholesterol levels. However, it is unclear whether plasma TNFα levels relate to insulin resistance syndrome in subjects with essential hypertension who are also characterized by an insulin resistance state. We recruited 85 nondiabetic subjects (45 men and 40 women) with essential hypertension and 85 nondiabetic subjects who were matched for age, sex and body mass index (BMI) to determine their fasting plasma glucose, insulin and lipoprotein concentrations, their glucose and insulin responses to an oral glucose challenge, and their degrees of insulin resistance. Fasting plasma leptin and TNFα levels were measured by radioimmunoassay and chemiluminescent enzyme immunometric assay respectively. Total body fat mass was assessed by the bioelectrical impedance method. The results showed that fasting plasma leptin levels were similar between hypertensive and normotensive subjects (7.9±0.6 vs 7.4±0.7 ng/ml, p=0.190). Fasting plasma TNFα concentrations were not different between subjects with hypertension and normotension (10.5±0.5 vs 9.8±0.4 pg/ml, p=0.360). Fasting plasma TNFα concentrations were not different across three subgroups of the insulin resistance both in hypertensive patients (8.4±0.4 vs. 10.9±1.6 vs. 9.9±1.0 pg/ml, p=0.297) and normotensive subjects (9.2±0.7 vs. 9.3±0.9 vs. 9.7±0.9 pg/ml, p=0.875). Fasting plasma TNFα values showed significantly positive correlations with triglyceride concentrations (p<0.03) but negative correlation with HDL cholesterol concentrations (p<0.04) in normotensive but not in hypertensive individuals. These relations persisted even after adjustment for BMI and total fat mass. In conclusion, our data indicated that circulating levels of TNFα did not differ between hypertensive subjects and normotensive controls. Plasma TNFα concentrations correlated positively with fasting plasma triglyceride levels and negatively with HDL cholesterol concentrations in normotensive but not in hypertensive subjects. The influence of TNFα on carbohydrate and lipoprotein metabolism in hypertensive patients deserves further investigations.     

The relationship between uric acid and metabolic syndrome in normal glucose tolerance and normal fasting glucose subjects

Elevated serum uric acid (SUA) concentrations have been suggested to associate with metabolic syndrome (MetS) and its components. However, limited information is available regarding the relationship between SUA and MetS in subjects with normal glucose levels. A total of 501 subjects with normal fasting glucose and normal glucose tolerance were included in the study. Anthropometrical and biochemical parameters were examined using standard methods. The updated NECP criteria were used to define the MetS. Values of SUA above the sex-specific percentile 75 were used to define hyperuricemia. The prevalence of general and abdominal obesity, hypertension, hypertriglyceridemia, low-HDL, smokers, MetS and insulin resistance was significantly greater in the fourth SUA quartile. Multiple regression indicated that SUA was independently predicted by BMI, triglyceride and 2 h glucose in women, and BMI, triglyceride, 2 h glucose and cholesterol in men. Logistic regression analysis showed that the obesity, hypertriglyceridemia, MetS and insulin resistance were independent determinants of hyperuricemia in women. In men, hyperuricemia was associated with the obesity, hypertriglyceridemia and hypercholesterolemia. Factor analysis yielded three factors interpreted as weight/waist, blood pressure and lipid/glucose. Including SUA in the model did not affect total variance of factor analysis. Our results indicate that SUA is associated with MetS and its components even in subjects with normal glucose levels. General obesity was the major determinant of hyperuricemia in this population. The data from this study do not show the contribution of SUA as an additional component of the MetS.     

Triglyceride and glucose intolerance as a risk factor for coronary heart disease

The electrophoresis of plasma lipoproteins frequently showed midbands between beta- and pre-beta-lipoproteins in survivors of myocardial infarction. There were increases in intermediate-density-lipoprotein (IDL) cholesterol and triglycerides with an increase in IDL cholesterol/triglycerides in the very-low-density-lipoprotein fraction, even if the increase in cholesterol was not so significant. Impaired glucose tolerance (IGT) was also frequently found in these patients. Among the patients with an apparently normal glucose tolerance, the coronary atherosclerosis scores judged by the American Heart Association reporting system on coronary angiography increased as the total insulin area by 75 g oral glucose tolerance test increased. The correlation between the atherosclerosis score and the insulin area was still significant even after adjustment for body mass index and plasma triglyceride level. Our data suggest that hypertriglyceridemia, IGT, and hyperinsulinemia may become independent risk factors for atherosclerosis in addition to cholesterol. Another study showed that the morbidity of coronary heart disease increased with an elevation of plasma triglyceride levels among patients with familial hypercholesterolemia.     

Metabolic heterogeneity underlying postprandial lipemia among men with low fasting high density lipoprotein cholesterol concentrations

The high triglyceride (TG) and low high density lipoprotein (HDL) cholesterol dyslipidemia has been associated with increased postprandial lipemia. Although fasting TG is a powerful predictor of postprandial hyperlipidemia, the role of hypoalphalipoproteinemia in postprandial TG metabolism is uncertain. We have studied postprandial lipemia among 63 men with low fasting plasma HDL cholesterol concentrations (<0.9 mmol/L), but with either low (<2.0 mmol/L) or high (>2.0 mmol/L) fasting plasma TG levels. A significant relationship was noted between postprandial TG response and fasting HDL cholesterol concentration (r = -0.43; P: < 0.0005). We also found that men with high TG/low HDL dyslipidemia (high TG and low HDL cholesterol; n = 16) were characterized by abdominal obesity as well as increased visceral adipose tissue accumulation, whereas normolipidemic controls (low TG and high HDL cholesterol; n = 26) and men with isolated low HDL cholesterol concentrations (low TG and low HDL cholesterol; n = 17) were not characterized by features of the insulin resistance syndrome (visceral obesity, hyperinsulinemia, and hypertriglyceridemia). Although controls and men with isolated low HDL cholesterol levels had similar postprandial lipemic responses, men with the high TG/low HDL dyslipidemia had a marked increase in their postprandial TG responses to the fat load compared with the other subgroups (P: < 0. 001). Men with the high TG/low HDL dyslipidemia were also characterized by higher concentrations of apolipoprotein (apo) B-48 and B-100 particles (chylomicron remnants and very low density lipoproteins, respectively) before and during the postprandial period compared with the other subjects. These results suggest that low HDL cholesterol concentration is a heterogeneous metabolic phenotype that it is not associated with postprandial hyperlipidemia unless accompanied by other features of the insulin resistance syndrome.     

Effect of aging on the relationship between multiple risk factors and waist circumference

OBJECTIVE: To examine the relationship between various coronary risk factors and the different levels of fat distribution in younger (<65 years) and older (> or = 65 years) men and women, using the classifications proposed by the National Heart, Lung and Blood Institute (NHLBI) and the World Health Organization (WHO). DESIGN: Cross-sectional study of subjects enrolled in the Baltimore Longitudinal Study of Aging. MEASUREMENTS: Systolic blood pressure, diastolic blood pressure, fasting glucose, 2-hour glucose, fasting insulin, homeostasis model assessment insulin resistance (HOMAIR), triglyceride, total cholesterol, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol were measured as risk factors. The proportion of subjects with abnormal risk factor levels by waist circumference classifications was determined in the age and gender subgroups. RESULTS: There were significant adverse effects of age per se on all risk factors with the exception of fasting insulin and HOMAIR in both men and women, total cholesterol in men, and diastolic blood pressure in women. HDL-cholesterol was higher in older subjects. There were significant correlations between waist circumference and all of the risk factors in the younger group. Waist circumference did not have a significant correlation with total cholesterol in older men, or with total cholesterol and LDL-cholesterol in older women. The proportion of subjects with an abnormal risk factor level increased with increasing waist circumference for most risk factors in both younger and older subjects, but proportions of subjects in each individual waist group were higher in older than in younger groups for systolic blood pressure, diastolic blood pressure, fasting glucose, and 2-hour glucose in men, and for systolic blood pressure, fasting glucose, 2-hour glucose, total and LDL-cholesterol, and triglyceride in women. CONCLUSIONS: Our data indicate that the waist circumference cutpoints proposed by NHLBI and WHO standards are useful for the prediction of cardiovascular disease risk factors in older as well as in younger men and women.     

A preponderance of small dense LDL is associated with specific insulin,proinsulin and the components of the insulin resistance syndrome in non-diabetic subjects

Summary Recently, the presence of small dense low density lipoprotein (LDL) has been postulated to be a stronger risk factor for coronary heart disease than large LDL. While small dense LDL has been associated with individual components of the insulin resistance syndrome such as hypertension, high triglyceride level, low high density (HDL) cholesterol, and diabetess mellitus, there has been little work exploring whether LDL size is decreased in subjects with multiple metabolic disorders. We examined the association of LDL size and pattern to specific insulin (which does not cross-react with proinsulin), proinsulin, increased triglyceride, decreased HDL, hypertension and impaired glucose tolerance in 488 non-diabetic subjects from the San Antonio Heart Study. LDL size was significantly related to specific insulin, proinsulin and the fasting proinsulin/insulin ratio. Small dense LDL was significantly associated with high triglyceride level, decreased HDL cholesterol, hypertension and impaired glucose tolerance. LDL size (å) decreased in a stepwise fashion with increasing number of the metabolic disorders described above (zero 262.6±9.4; one 257.0±9.3; two 256.4±9.4; three 249.0±9.1; and four 244.9±9.0). These results were similar in men and women and in non-Hispanic whites and Mexican Americans. The association between LDL size and the number of metabolic disorders remained statistically significant even after adjustment for obesity, body fat distribution, gender, ethnicity, proinsulin and insulin concentrations. Furthermore, decreases in LDL size are also significantly associated with both a selective beta-cell defect (as estimated by the fasting proinsulin/insulin ratio) and insulin resistance (as estimated by the fasting insulin concentrations) although the association was some-what stronger for the latter. We conclude that small dense LDL may form part of the insulin resistance syndrome in non-diabetic subjects.Abbreviations BMI Body mass index - LDL low density lipoprotein - HDL high density lipoprotein - IGT impaired glucose tolerance - NIDDM non-insulin-dependent diabetes mellitus - WHR waist-hip ratio     

Coronary artery disease risk predicted by insulin resistance, plasma lipids, and hypertension in people without diabetes

BACKGROUND: It has been shown that insulin resistance syndrome, including glucose intolerance, dyslipidemia, and hypertension, is frequently associated with coronary artery disease (CAD). However, their relative contributions and predictive power in the development of CAD are still unclear, particularly in persons without diabetes. METHOD: We examined these risk factors between 96 patients without diabetes but with angiographically documented CAD and 96 age-, sex-, and body mass index-matched healthy control subjects. Fasting plasma lipoprotein, glucose, and insulin concentrations in response to a 75-g oral glucose tolerance test were determined, and insulin sensitivity was measured by the insulin suppression test. RESULTS: Patients with CAD had significantly higher values of fasting glucose, glucose and insulin responses to oral glucose tolerance test, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride and decreased high-density lipoprotein (HDL) cholesterol concentrations compared with those of healthy people (P < 0.02-0.001). Although the steady-state plasma insulin values were similar in both groups, the steady-state plasma glucose (SSPG) concentrations were significantly higher in patients with CAD (12.2+/-0.4 versus 8.1+/-0.4 mmol/L, P < 0.001) compared with healthy subjects. When HDL < 0.9 mmol/L, LDL cholesterol > or = 4.1 mmol/L, triglyceride > or = 2.3 mmol/L, SSPG > or = 10.5 mmol/L, and presence of hypertension were defined as separate risk factors for CAD, significantly higher odds-ratio values were observed in patients with CAD compared with healthy people. From logistic multiple regression analysis, SSPG was the strongest risk, followed by lowered HDL cholesterol, elevated triglyceride and LDL cholesterol, and hypertension, to predict CAD. These 5 factors accounted for 36% of total risk for development of CAD in persons without diabetes. CONCLUSIONS: Patients without diabetes with CAD have abnormal glucose metabolism, hyperinsulinemia, and insulin resistance. Degree of insulin resistance (SSPG values), plasma lipid values, and history of hypertension together accounted for one third of all risk for CAD, although degree of insulin resistance was the strongest risk factor.     

Relationship between lipoprotein levels and in vivo insulin action in normal young white men

In epidemiologic studies, hyperinsulinemia has been found to be an independent risk factor for coronary heart disease (CHD). However, the mechanisms responsible for its role in atherogenesis remain unclear. We studied the relationship of in vivo insulin action and plasma lipids and lipoproteins in 44 normotriglyceridemic white men (aged 18 to 34 years). The euglycemic, hyperinsulinemic glucose clamp technique was used to quantitate insulin-mediated glucose disposal (M/I value) at a plasma insulin concentration of approximately 100 microU/mL. The M/I value correlated negatively with plasma triglycerides (r = -0.553, P less than .0001), as well as with fasting plasma insulin levels (r = -0.483, P less than .001), independent of age, body mass index, and fasting plasma glucose levels. A negative correlation of the M/I value was also observed with very low density lipoprotein (VLDL)-cholesterol (r = -0.347, P less than .05), VLDL-triglycerides (r = -0.474, P less than 0.005), and total cholesterol/high density lipoprotein (HDL)-cholesterol ratio (r = -0.431, P less than .01). The relationship between the M/I value and the total cholesterol/HDL-cholesterol ratio was independent of VLDL-cholesterol and VLDL-triglycerides, however, not independent of plasma triglycerides. No relationship was observed between insulin-mediated glucose uptake and total cholesterol, low density lipoprotein (LDL)-cholesterol, and HDL-cholesterol values. Individual differences in plasma triglycerides, fasting insulin concentration, and the total cholesterol/HDL-cholesterol ratio accounted for about half the variance observed in the M/I value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development and progression of atherosclerotic disease in relation to insulin resistance and hyperinsulinemia.

It is unclear whether the role of insulin resistance in the development of atherosclerotic cardiovascular disease is similar in populations in which the incidence of atherosclerotic diseases significantly differs from that in Western countries. The aim of this study was to determine the relationship between insulin resistance and the development of cardiovascular disease in the Japanese population. We conducted 75 g-oral glucose tolerance tests (OGTTs) on 1,928 inhabitants of two towns in Hokkaido, Japan. Subjects using antihypertensive agents and known diabetic patients were excluded from the study. Data from the remaining 1,227 subjects (540 males and 687 females; mean age 56.0 +/- 10.8 years) were used for the analysis, and 1,051 subjects were seen in a follow-up care setting for a period of 8 years. The presence of insulin resistance was defined according to the guidelines reported our previous study: insulin levels of 64.0 mU/l or higher 2 h after the 75 g-OGTT. The insulin-resistant (IR) group had several risk factors such as hypertension, diabetes, treated or untreated hypercholesterolemia, hypertriglyceridemia, low high-density-lipoprotein (HDL) cholesterol levels, and obesity. During the follow-up period of 8 years, the incidence of coronary artery disease, which was adjusted for age, body mass index, sex, systolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, and HDL cholesterol was significantly (3.2 times) higher in the IR group than in the insulin non-resistant group. The results suggested that insulin resistance is an independent risk factor for coronary artery disease in Japanese subjects, as has also been demonstrated in the case of individuals in Europe and USA.     

Gender differences in relation to leptin concentration and insulin sensitivity in nondiabetic Chinese subjects.

OBJECTIVE: To investigate the relationship between fasting plasma leptin concentrations and insulin resistance in Chinese men and women. DESIGN: Cross-sectional study design. SUBJECTS: Ninety-six nondiabetic Chinese (51 men and 45 women) with body mass index (BMI) between 18.4-35.8 kg/m2 were studied. MEASUREMENTS: Plasma glucose and insulin concentrations were measured every 30 min for 2 h after a 75 g oral glucose load. The degree of insulin resistance was assessed using a modified insulin suppression test. Plasma leptin values were determined by radioimmunoassay. RESULTS: Fasting plasma glucose, glucose areas, fasting insulin, insulin areas, most of the lipoprotein concentrations and steady state plasma glucose (SSPG) concentrations were relatively similar between men and women. Despite the fact that men had higher BMI values (26.1 +/- 0.5 vs 24.7 +/- 0.5 kg/m2, P < 0.05), fasting plasma leptin concentrations were significantly lower in men than in women (4.9 +/- 0.5 vs 9.0 +/- 0.8 ng/ml, P < 0.001). Fasting leptin values were positively related to SSPG concentrations by simple correlation analysis in both sexes. However, this relationship persisted in men (r = 0.513, P < 0.01) but not in women (r = 0.119, P = NS) after adjustment for BMI. Multiple regression analysis showed that SSPG concentrations, BMI, glucose and insulin responses together accounted for 62.5% and 52.2% of the variation in plasma leptin concentrations in Chinese men and women respectively. CONCLUSION: Fasting plasma leptin concentrations were lower in Chinese men than in Chinese women despite the higher BMI observed in men. After adjustment for BMI, plasma leptin values correlated with the degree of insulin resistance in men but not in women.     

Effect of contraceptive steroids on arginine-stimulated glucagon and insulin secretion in women. III. Medroxyprogesterone acetate

The effect of medroxyprogesterone acetate (MPA) on basal circulating lipids, arginine-stimulated glucagon and insulin secretion, and glucose tolerance was studied in normal women. After 5 days of oral MPA treatment (10 mg/day), there was a small but significant decline in basal circulating triglycerides. No changes were observed in fasting plasma concentrations of cholesterol, free fatty acids, glucagon, insulin, or glucose; in the plasma glucagon, insulin, or glucose responses during L-arginine infusion; or in the plasma insulin or glucose responses during oral glucose tolerance tests. There was no correlation of any of these parameters with the observed decline in fasting plasma triglyceride concentrations. These results confirm previous reports of no consistent changes in lipid or glucose homeostasis in women using derivatives of 17α-acetoxyprogesterone derivatives for contraceptive purposes, and suggest that MPA may be a suitable alternative for those women who develop hyperlipemia or glucose intolerance when they use contraceptive agents which contain derivatives of ethinyl estradiol and nortestosterone.     

高血压病合并脂肪肝发病的危险因素分析

目的探讨高血压病合并脂肪肝发病的危险因素。方法选择进行了肝脏B超检查的住院高血压病患者,根据超声影像的诊断结果分为高血压合并脂肪肝组(98例)和高血压未合并脂肪肝组(102例),分析体重指数(BMI)、收缩压(SBP)、舒张压(DBP)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)、胰岛素抵抗指数(HO-MA-IR)、糖耐量试验各时段的血糖水平、胰岛素释放试验的胰岛素水平与脂肪肝之间的关系。结果(1)Logistic回归分析的结果表明空腹血糖升高、肥胖、糖负荷后3小时胰岛素水平升高、高甘油三酯血症是高血压患者脂肪肝形成的独立危险因素;(2)高血压合并脂肪肝组的HOMA-IR、TG、空腹和糖负荷后2、3小时的血糖和胰岛素水平高于对照组(均P<0.05)。校正两组BMI后,上述差异仍然存在。结论(1)高血压病患者脂肪肝发病的独立危险因素是空腹血糖升高、肥胖、糖负荷后3小时胰岛素水平升高、高甘油三酯血症,随着这些危险因素的聚集,脂肪肝的检出率增加。(2)脂肪肝是高血压病患者胰岛素抵抗的“重要标志”,脂肪肝是代谢综合征的一种表现。     

Abnormal glucose tolerance in young male patients with nonalcoholic fatty liver disease

Objective: The association of nonalcoholic fatty liver disease (NAFLD) with insulin resistance and metabolic syndrome has been documented for obese men and middle‐aged men. This study was designed to determine the relationship between NAFLD and the oral glucose tolerance test (OGTT) to predict preclinical diabetes in nondiabetic young male patients (<30 years old). Methods: A total of 75 male patients who had elevated liver enzymes and who were diagnosed with NAFLD were enrolled in this study. A standard 75 g OGTT was carried out on all patients. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined as a fasting plasma glucose (FPG) level ≥100 mg/dl but <126 mg/dl, and a 2‐h post‐load glucose on the OGTT of ≥140 mg/dl, but <200 mg/dl respectively. Results: According to the OGTT results, 24 (32%) patients were diagnosed as having IGT and 12 (16%) patients were diagnosed as having diabetes. Among the 48 patients with normal fasting glucose, 18 (37.6%) patients showed abnormal glucose tolerance (15 had IGT and three had diabetes). The NAFLD patients with abnormal glucose tolerance showed significant differences in age, weight, body mass index, waist–hip ratio, alanine aminotransferase, total bilirubin, total cholesterol, low‐density lipoprotein cholesterol, triglyceride, insulin, FPG and homeostasis model for insulin resistance (HOMA‐IR). Multiple regression analysis showed that age, FPG and HOMA‐IR were independent predictors of abnormal glucose tolerance. Conclusions: Although the patients were young men, an OGTT should be recommended for NAFLD patients with elevated liver enzymes and IFG to predict the risk of type 2 diabetes.