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Revised QUICKI provides a strong surrogate estimate of insulin sensitivity when compared with the minimal model.

OBJECTIVE: To compare insulin sensitivity (Si) from a frequently sampled intravenous glucose tolerance test (FSIGT) and subsequent minimal model analyses with surrogate measures of insulin sensitivity and resistance and to compare features of the metabolic syndrome between Caucasians and Indian Asians living in the UK. SUBJECTS: In all, 27 healthy male volunteers (14 UK Caucasians and 13 UK Indian Asians), with a mean age of 51.2+/-1.5 y, BMI of 25.8+/-0.6 kg/m(2) and Si of 2.85+/-0.37. MEASUREMENTS: Si was determined from an FSIGT with subsequent minimal model analysis. The concentrations of insulin, glucose and nonesterified fatty acids (NEFA) were analysed in fasting plasma and used to calculate surrogate measure of insulin sensitivity (quantitative insulin sensitivity check index (QUICKI), revised QUICKI) and resistance (homeostasis for insulin resistance (HOMA IR), fasting insulin resistance index (FIRI), Bennetts index, fasting insulin, insulin-to-glucose ratio). Plasma concentrations of triacylglycerol (TAG), total cholesterol, high density cholesterol, (HDL-C) and low density cholesterol, (LDL-C) were also measured in the fasted state. Anthropometric measurements were conducted to determine body-fat distribution. RESULTS: Correlation analysis identified the strongest relationship between Si and the revised QUICKI (r=0.67; P=0.000). Significant associations were also observed between Si and QUICKI (r=0.51; P=0.007), HOMA IR (r=-0.50; P=0.009), FIRI and fasting insulin. The Indian Asian group had lower HDL-C (P=0.001), a higher waist-hip ratio (P=0.01) and were significantly less insulin sensitive (Si) than the Caucasian group (P=0.02). CONCLUSION: The revised QUICKI demonstrated a statistically strong relationship with the minimal model. However, it was unable to differentiate between insulin-sensitive and -resistant groups in this study. Future larger studies in population groups with varying degrees of insulin sensitivity are recommended to investigate the general applicability of the revised QUICKI surrogate technique.

Adult↗

Gastric emptying is accelerated in obese type 2 diabetic patients without autonomic neuropathy.

OBJECTIVE: To clarify the impact of type 2 diabetes mellitus on the gastric emptying rate. MATERIAL AND METHODS: Using a double-isotope scintigraphic technique, we assessed the gastric emptying of a standard liquid-solid meal in 13 obese type 2 diabetic patients without autonomic neuropathy (age: 47.4 +/- 8.6 yr, body mass index: 33.9 +/- 4.8 kg/m(2), glycaemia: 9.1 +/- 2.6 mmol/l) and in 7 controls with similar sex ratio, age, BMI and body fat distribution. RESULTS: The half gastric emptying time for the liquid phase was not significantly different between diabetic patients and controls (respectively: 52.7 +/- 14.5 min and 63.1 +/- 15.2 min). However, the half gastric emptying time for the solid phase was significantly shortened in diabetic patients versus controls (respectively 88.8 +/- 23.2 min in diabetic patients and 113.6 +/- 26.9 min in controls; p<0.04). Furthermore, a negative relationship was highlighted between the half gastric emptying time for the solid phase and basal glycaemia (r=-0.65, p<0.02) in diabetic patients. No significant relationship was found between gastric emptying parameters and cardiac autonomic nerve function, insulin or gastrin levels. CONCLUSION: Solid gastric emptying is accelerated in obese type 2 diabetic patients without patent autonomic neuropathy when compared to obese non diabetic patients.

Adult↗

[Nutritional status and body composition of a group of non-institutionalized elderly in the State of Zulia, Venezuela].

To assess the nutritional status and body composition of an elderly free-living population from the State of Zulia, Venezuela, ninety-four persons (47 male and 47 female), ages ranging from 60 to 88 years (mean age 69.55 +/- 6.60) (X +/- SD) were studied. Anthropometric measurements, and a dietary study by means of 24-hour recall and a Food Frequency were performed. Significant statistical differences (p < 0.001, and p < 0.05) were observed among female and male groups in all measures and indices except weight, waist, arm area, and arm muscle area. Significant differences (p < 0.05) were also observed among age groups in weight, Quetelet index, percentage ideal weight (% IW), and triceps skinfold thickness. The means of anthropometric measures and nutritional indicators were higher than the results obtained in other studies. The percentage of elderly obese with Quetelet greater than 30 kg/m < or = was 42.6% (females) and 6.4% (males). In contrast, when utilizing % IW it was observed that 4.3% of the men and 48.9% of the women were obese. Body fat distribution index (waist/hip) shows abdominal fat distribution in 21.3% males and 68.1% females. We found sex-based significant differences in dietary intake of energy, total fat, carbohydrates, iron, vitamin A, and thiamin. The results indicate that the intake of protein, total fat, calcium, phosphorus, iron, thiamin, and niacin is high among males y females, when compared with the present Recommended Dietary Allowance (RDA) values of Venezuela. The intake of carbohydrate, fiber, vitamin A, riboflavin, zinc, and copper is low among males and females according RDA values, as well as the intake of riboflavin in males. The study indicates a high frequency of men and women obese, and with overweight among females as a consequence of the inadequacy of dietary intake. The present findings emphasizes the need to study in depth the different factors that affect nutritional status of elderly individuals in our country.

Aged↗

A pathogenic role of visceral fat beta 3-adrenoceptors in obesity.

Increased release of free fatty acids (FFA) from visceral fat cells to the portal venous system may cause several metabolic disturbances in obesity. However, this hypothesis and the underlying mechanism remain to be demonstrated. In this study catecholamine-induced lipid mobilization through lipolysis in omental adipose tissue was investigated in vitro in 25 markedly obese subjects (body mass index range 35-56 kg/m2) undergoing weight reduction surgery and in 19 nonobese subjects (body mass index range 20-28 kg/m2) undergoing cholecystectomy. Release of FFA and glycerol, induced by norepinephrine or adrenergic receptor subtype-specific agonists, were determined in isolated omental fat cells. The obese subjects had higher fat cell volume, blood pressure, plasma insulin levels, blood glucose, plasma triglycerides, and plasma cholesterol than the controls. There was evidence of upper-body fat distribution in the obese group. The rate of FFA and glycerol response to norepinephrine was increased twofold in the cells of obese subjects; no significant reutilization of FFA during catecholamine-induced lipolysis was observed in any of the groups (glycerol/FFA ratio near 1:3). There were no differences in the lipolytic sensitivity to beta 3- or beta 2-adrenoceptor specific agonists between the two groups. However, beta 3-adrenoceptor sensitivity was approximately 50 times enhanced (P = 0.0001), and the coupling efficiency of these receptors was increased from 37 to 56% (P = 0.01) in obesity. Furthermore, the obese subjects demonstrated a sixfold lower alpha 2-adrenoceptor sensitivity (P = 0.04). beta 3-Adrenoceptor sensitivity, but not alpha 2-, beta 1-, or beta 2-adrenoceptor sensitivity, correlated with norepinephrine-induced lipolysis (r = -0.67, P = 0.0001) and fat cell volume (r = -0.71, P = 0.0001). In conclusion, catecholamine-induced rate of FFA mobilization from omental fat cells is accelerated due to elevated rate of lipolysis in obesity, mainly because of an increased beta 3-adrenoceptor function, but partly also because of a decreased alpha 2-adrenoceptor function. This promotes an increased release of FFA to the portal system, which may contribute to the parallel metabolic disturbances observed in upper-body obesity.

Adipose Tissue↗

Selective effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome.

BACKGROUND: To investigate the effectiveness and safety of pioglitazone (45 mg/day) on clinical and endocrine-metabolic features of polycystic ovary syndrome (PCOS), we studied 18 obese PCOS patients, classified as normoinsulinaemic (N-PCOS, n = 6) and hyperinsulinaemic (H-PCOS, n = 12) according to their insulin secretion. METHODS: Evaluation of clinical signs, hormonal and lipid profile assays, oral glucose tolerance tests and euglycaemic hyperinsulinaemic clamps were performed at baseline and after 2 (visit 2), 4 (visit 3) and 6 (visit 4) months of treatment. RESULTS: Body weight, body fat distribution and blood pressure remained stable throughout the treatment; hirsutism and acne significantly improved (P < 0.001 for visits 3 and 4 versus baseline) in both groups. A restoration of menstrual cyclicity was observed at visit 4 in 83% (P < 0.001) of H-PCOS and in 33% of N-PCOS. A decrease in LH, LH/FSH ratio, androstenedione and 17-hydroxy-progesterone was observed in both groups, attaining statistical significance in H-PCOS. A significant amelioration of insulin secretion, sensitivity and clearance was obtained in H-PCOS. A trend towards improvement was observed in lipid assessment of both groups. Therapy was well-tolerated. CONCLUSIONS: Present data suggest that there is a selective effect, partially independent of insulin secretion, of pioglitazone on the clinical and hormonal disturbances of PCOS.

17-alpha-Hydroxyprogesterone↗

Visceral adiposity is associated with increased lipid oxidation in obese, postmenopausal women.

Lipolysis is increased in upper-body obese individuals but it is unclear whether body fat distribution is associated with differences in resting metabolic rate (RMR) and/or substrate oxidation in older women. This study determined whether RMR and lipid oxidation are higher in postmenopausal women with visceral obesity. A single-slice computed tomography scan was taken midway between L4 and L5 in 29 women aged 52-72 y with a fat mass of 29.2-68.8 kg. RMR and lipid oxidation rates were measured by using indirect calorimetry. RMR was related to waist circumference (r = 0.45, P < 0.05), but not to waist-hip ratio (WHR; r = 0.23) or intraabdominal fat area (r = 0.26). However, there was a strong, positive relation between lipid oxidation and intraabdominal fat area (r = 0.57, P < 0.01), waist circumference (r = 0.54, P < 0.01), and WHR (r = 0.42, P < 0.05). These correlations remained significant after statistical adjustment for total fat and fat-free mass. These results suggest that in postmenopausal women higher amounts of intraabdominal fat are associated with an enhanced rate of lipid oxidation independent of total adiposity, but not with alterations in RMR.

Adipose Tissue↗

Surrogate indexes vs. euglycaemic-hyperinsulinemic clamp as an indicator of insulin resistance and cardiovascular risk factors in overweight and obese postmenopausal women.

BACKGROUND: There is considerable interest in validating the most convenient method to estimate insulin sensitivity in clinical research protocols that could best indicate cardiovascular risk factors. To address this issue we examined the interrelationships of several cardiovascular risk factors with surrogate indexes such as fasting insulin, the homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI) and the revised QUICKI vs the euglycaemic-hyperinsulinemic (EH) clamp in a non-diabetic overweight or obese postmenopausal female population. DESIGN: Cross-sectional study involving 88 obese postmenopausal women (age: 57.5+/-5.0 yrs; body mass index: 32.52+/-4.4 kg/m2; percent body fat: 46.35+/-4.9%). METHODS: Insulin sensitivity was determined by the EH clamp technique as well as by surrogate indexes such as fasting insulin, HOMA, log HOMA, QUICKI and revised QUICKI. Body composition and body fat distribution were measured using dual energy x-ray absorptiometry and computed tomography, respectively. RESULTS: Correlations between insulin resistance indexes (fasting insulin, revised QUICKI, QUICKI, log HOMA, HOMA) vs glucose disposal were similar (range of r's=0.40 to 0.49), suggesting that no index was superior to another with respect to its relationship with the EH clamp. Correlations between the insulin resistance indexes with plasma lipids were comparable among all indexes, however, systolic blood pressure, visceral fat and C-reactive protein were moderately superior with index vs the EH clamp. CONCLUSION: Surrogate measures of insulin resistance, in particular fasting insulin, are simple tools appropriate for epidemiological studies that can be used as substitutes for the EH clamp to estimate glucose disposal and cardiovascular risk factors in overweight and obese postmenopausal women.

Adipose Tissue↗

Hepatic steatosis in Cushing's syndrome: a radiological assessment using computed tomography.

OBJECTIVE: Hepatic steatosis may occur in association with insulin resistance and obesity, two features commonly seen in Cushing's syndrome (CS). The aim of this report is to assess the prevalence of hepatic steatosis in patients with active CS using computed tomography (CT) and to identify any associations between hepatic steatosis, endocrine and biochemical variables and body fat distribution. PATIENTS AND MEASUREMENTS: We identified 50 patients with active CS in whom appropriate CT was available to allow measurement of liver and spleen attenuation. In 26 patients, abdominal fat measurements were also available. Serum markers of CS and liver function tests were recorded. RESULTS: Ten of 50 patients had a liver-to-spleen CT attenuation ratio (L/S) of less than 1, indicating hepatic steatosis. There was a significant negative correlation between both liver attenuation and L/S ratio with total abdominal fat area, visceral fat area, the percentage of visceral fat and the visceral to subcutaneous fat ratio; the strongest negative correlation was found between visceral fat area and L/S ratio (r=-0.638, P<0.001, n=26). L/S ratio positively correlated with alkaline phosphatase levels (r=+0.423, P=0.044, n=23) but with no other serum marker of CS activity or liver enzyme. CONCLUSIONS: We have demonstrated hepatic steatosis on CT in 20% of patients with active CS. The presence of hepatic steatosis was significantly correlated with total abdominal fat area and visceral fat area.

Adipose Tissue↗

Decreased hepatic insulin extraction in upper body obesity: relationship to unbound androgens and sex hormone binding globulin.

Hyperinsulinemia is a well-recognized entity of simple obesity. It is demonstrated that hyperinsulinemia is associated with upper body fat and fat cell hypertrophy. Androgen excess and lower levels of sex hormone binding globulin (SHBG) may produce fat cell hypertrophy and hyperinsulinemia as well. We measured serum insulin and C-peptide levels during an OGTT in two groups of obese premenopausal women to determine whether the hyperinsulinemia is due to hypersecretion or due to a diminished hepatic extraction of insulin. In this study, we found no correlation between the insulin and C-peptide levels or their ratio and the degree of obesity. However, a significant correlation was found between the waist-to-hip circumference ratio (WHR), used as an index of body fat distribution, and the areas of insulin (r = 0.55; P less than 0.001) and C-peptide (r = 0.51; P less than 0.001). SHBG and free androgen index (FAI) were also significantly related to these areas. The peripheral C-peptide/insulin molar ratio has been assumed to reflect changes in hepatic insulin extraction while the corrected C-peptide response reflects beta-cell function. WHR was negatively related to this ratio (r = -0.44; P less than 0.005) and SHBG showed a positive correlation (r = 0.34; P less than 0.05). Stepwise multiple regression analysis revealed that the 2-h insulin and C-peptide values and both curve areas can be explained up to 40-80% by sex hormones and anthropometric variables. Also the C-peptide/insulin molar ratio is dependent in a first step on WHR (r2 = 0.23; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Leptin and the hypothalamic-pituitary-adrenal axis activity in women with different obesity phenotypes.

OBJECTIVE: Women with visceral obesity may have hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Since glucocorticoids are involved in the expression of the ob gene, this study was carried out to investigate the relationship between serum leptin and the activity of the HPA axis in women with different obesity phenotypes. DESIGN: Cross sectional clinical study. SUBJECTS: Fifteen obese (Body Mass Index BM128 kg/m2) women and ten normal weight control women (BM126 kg/m2) were included in the study. MEASUREMENTS: Body fat distribution was defined by CT scan at the L4-L5 level. Baseline blood samples were obtained for hormone concentrations. The activity of the HPA axis was evaluated by measuring ACTH and cortisol blood levels after combined iv administration of corticotropin releasing factor (100 microg) + arginine-vasopressin (0.3 IU). RESULTS: Baseline cortisol, ACTH, and androgen levels were similar in all groups, whereas leptin levels were significantly higher in the obese groups than in normal weight controls, without any significant difference between women with different obesity phenotypes. Incremental areas of ACTH and cortisol were significantly higher in women with visceral obesity than in those with subcutaneous obesity and controls. No significant correlation was found between the activity of the HPA axis and leptin concentrations. Leptin showed a highly significant correlation with BMI and subcutaneous fat and a weak but significant correlation with visceral fat and the visceral-to-subcutaneous fat ratio. CONCLUSION: Women with different obesity phenotypes had similar serum leptin concentrations but different HPA axis activity, and there was no correlation between them.

Adrenocorticotropic Hormone↗

Adaptive significance of female physical attractiveness: role of waist-to-hip ratio.

Evidence is presented showing that body fat distribution as measured by waist-to-hip ratio (WHR) is correlated with youthfulness, reproductive endocrinologic status, and long-term health risk in women. Three studies show that men judge women with low WHR as attractive. Study 1 documents that minor changes in WHRs of Miss America winners and Playboy playmates have occurred over the past 30-60 years. Study 2 shows that college-age men find female figures with low WHR more attractive, healthier, and of greater reproductive value than figures with a higher WHR. In Study 3, 25- to 85-year-old men were found to prefer female figures with lower WHR and assign them higher ratings of attractiveness and reproductive potential. It is suggested that WHR represents an important bodily feature associated with physical attractiveness as well as with health and reproductive potential. A hypothesis is proposed to explain how WHR influences female attractiveness and its role in mate selection.

Adipose Tissue↗

Body composition and fuel metabolism after kidney grafting.

Kidney transplant patients display decreased muscle mass and increased fat mass. Whether this altered body composition is due to glucocorticoid induced altered fuel metabolism is unclear. To answer this question, 16 kidney transplant patients were examined immediately after kidney transplantation (12 +/- 4 days, mean +/- SEM) and then during months 2, 5, 11 and 16, respectively, by whole body dual energy X-ray absorptiometry (Hologic QDR 1000W) and indirect calorimetry. Results were compared with those of 16 age, sex and body mass index matched healthy volunteers examined only once. All patients received dietary counselling with a step 1 diet of the American Heart Association and were advised to restrict their caloric intake to the resting energy expenditure plus 30%. Immediately after transplantation, lean mass of the trunk was higher by 7 +/- 1% (P < 0.05) and that of the limbs was lower by more than 10% (P < 0.01) in patients than in controls. In contrast, no difference in fat mass and resting energy expenditure could be detected between patients and controls. During the 16 months of observation, total fat mass increased in male (+4.9 +/- 1.5 kg), but not in female patients (0.1 +/- 0.8 kg). The change in fat mass observed in men was due to an increase in all subregions of the body analysed (trunk, arms+legs as well as head+neck), whereas in women only an increase in head+neck by 9 +/- 2% (P = 0.05) was detected. Body fat distribution remained unchanged in both sexes over the 16 months of observation. Lean mass of the trunk mainly decreased between days 11 and 42 (P < 0.01) and remained stable thereafter. After day 42, lean mass of arms and legs (mostly striated muscle) and head+neck progressively increased over the 14 months of observation by 1.6 +/- 0.6 kg (P < 0.05) and 0.4 +/- 0.1 kg (P < 0.01), respectively. Resting energy expenditure was similar in controls and patients at 42 days (30.0 +/- 0.7 vs. 31.0 +/- 0.9 kcal kg-1 lean mass) and did not change during the following 15 months of observation. However, composition of fuel used to sustain resting energy expenditure in the fasting state was altered in patients when compared with normal subjects, i.e. glucose oxidation was higher by more than 45% in patients (P < 0.01) during the second month after grafting, but gradually declined (P < 0.01) over the following 15 months to values similar to those observed in controls. Protein oxidation was elevated in renal transplant patients on prednisone at first measurement, a difference which tended to decline over the study period. In contrast to glucose and protein oxidation, fat oxidation was lower in patients 42 days after grafting (P < 0.01), but increased by more than 100% reaching values similar to those observed in controls after 16 months of study. Mean daily dose of prednisone per kg body weight correlated with the three components of fuel oxidation (r > 0.93, P < 0.01), i.e. protein, glucose and fat oxidation. These results indicate that in prednisone treated renal transplant patients fuel metabolism is regulated in a dose-dependent manner. Moreover, dietary measures, such as caloric and fat intake restriction as well as increase of protein intake, can prevent muscle wasting as well as part of the usually observed fat accumulation. Furthermore, the concept of preferential upper body fat accumulation as consequence of prednisone therapy in renal transplant patients has to be revised.

Adipose Tissue↗

Family history of diabetes in relation to different types of obesity and change of obesity during 12-yr period. Results from prospective population study of women in Göteborg, Sweden.

OBJECTIVE--To assess the relationship between family history and different types of obesity and change in obesity in a longitudinal population study. RESEARCH DESIGN AND METHODS--A longitudinal population study of 1462 randomly selected women (38-60 yr old) was conducted in Göteborg, Sweden, in 1968-69. The women were restudied after 12 yr. RESULTS--A family history of diabetes in mothers but not fathers showed, in univariate analysis, a significant positive association with obesity expressed as BMI. A family history of diabetes in the mothers was inversely related to body fat distribution expressed as WHR. No other association was observed between family history of diabetes and WHR. The association with BMI was independent of age, WHR, smoking habits, blood glucose, systolic blood pressure, serum cholesterol, serum triglycerides, maternal obesity, and the incidence of diabetes during the 12-yr follow-up period. Twelve years later, in 1980-1981, an independent association still existed between family history for diabetes and BMI measured at that examination, whereas there was no relationship with WHR. Women who had a family history of diabetes increased their BMI significantly more during the 12-yr follow-up compared with the women without a family history of diabetes, whereas there was no difference for the change of WHR. Family history of coronary heart disease and family history of cancer did not correlate to any kind of obesity. CONCLUSIONS--These findings indicate that family history of diabetes is related to overall obesity but not to abdominal adiposity per se.

Adipose Tissue↗

[Waist-to-hip ratio in Dutch women and its relationship with self-reported diabetes mellitus, hypertension and cholecystectomy].

The waist-to-hip circumference ratio is recognized as a measure of body fat distribution and as a risk indicator of premature mortality. The distribution of waist-to-hip ratio values in 12,000 Dutch women aged between 40 and 75 years is presented. In addition, the statistical associations between the waist-to-hip ratio and the degree of overweight as well as the prevalence of self-reported diabetes mellitus, hypertension, and cholecystectomy are described. The odds ratios for the prevalence of these disorders increased progressively with increasing waist-to-hip ratio. The age-adjusted odds ratios for women with a waist-to-hip ratio greater than 0.85 in comparison to those with a waist-to-hip ratio less than 0.70 were 4.8, 4.6 and 5.8 for diabetes mellitus, hypertension, and cholecystectomy respectively. The presented data on waist-to-hip ratio can, in combination with Quetelet's index, serve as a guide in the interpretation of measured waist-to-hip ratios in women between 40 and 75 years of age.

Adult↗

The relationship between waist-to-hip ratio and occupational status and life-style factors among middle-aged male and female Japanese workers.

As a marker of body fat distribution and therefore level of obesity, the waist-to-hip ratio (W:H) is a good indicator of coronary heart disease risk status. The present study investigated the association between occupational status and life-style factors, and W:H of middle-aged Japanese male (n = 2,550) and female (n = 1,283) workers in a metal-products factory. A higher W:H was observed in the management level males as compared with the other male workers and we suggest this was promoted by the sedentary aspect of their work, as well as their higher levels of alcohol consumption and lower levels of leisure-time physical activity. In contrast, a higher W:H was recorded in female labourers, whose work was typically less sedentary as compared with female managers. Life-style factors included in the study were not related to this observation. We conclude that other unmeasured psychosocial factors may be important in promoting higher W:H in female labourers.

Adult↗

Elevated plasma levels of alpha-melanocyte stimulating hormone (alpha-MSH) are correlated with insulin resistance in obese men.

OBJECTIVE: The role of alpha-melanocyte stimulating hormone (MSH) in obesity has been well-documented. However, circulating alpha-MSH concentrations in obese men and their relationship with clinical indicators of obesity and glucose metabolism have not as yet been evaluated. METHODS: We measured the plasma concentrations of alpha-MSH in 15 obese and 15 non-obese male subjects. The relationship of the plasma concentrations of alpha-MSH with body mass index (BMI), body fat mass (measured by bioelectric impedance), body fat distribution (measured by computed tomography), insulin levels, insulin resistance (assessed by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study) and with the serum concentrations of leptin and TNF-alpha were also evaluated. RESULTS: In obese men, the plasma alpha-MSH concentrations were significantly increased compared with those in non-obese men (P< 0.02). The plasma levels of alpha-MSH were positively correlated with BMI (r= 0.560, P< 0.05), fasting insulin levels (r=0.528, P< 0.05) and with visceral fat area (r=0.716, P<0.01), but negatively correlated with GIR (r= -0.625, P< 0.02) in obese male subjects. There were significant correlations between plasma concentrations of alpha-MSH and visceral fat area (r=0.631, P< 0.02), and GIR (r = -0.549, P< 0.05) in non-obese male subjects. Circulating concentrations of alpha-MSH were not significantly correlated with the serum concentrations of leptin and TNF-alpha in both obese and non-obese men. CONCLUSION: Circulating concentrations of alpha-MSH are significantly increased and correlated with insulin resistance in obese men.

Adult↗

Leptin secretion from subcutaneous and visceral adipose tissue in women.

Upper body obesity is a risk factor for type 2 diabetes. Little is known about the regulation of body fat distribution, but leptin may be involved. This study examined the secretion of leptin in subcutaneous and omental fat tissue in 15 obese and 8 nonobese women. Leptin secretion rates were two to three times higher in subcutaneous than in omental fat tissue in both obese and nonobese women (P < 0.0001 and P < 0.001, respectively). There was a positive correlation between BMI and leptin secretion rates in both subcutaneous (r = 0.87, P < 0.0001) and omental (r = 0.74, P < 0.0001) fat tissue. Furthermore, leptin secretion rates in subcutaneous and omental fat tissue correlated well with serum leptin levels (r = 0.84, P < 0.0001 and r = 0.73, P = 0.001, respectively), although in multivariate analysis, the subcutaneous leptin secretion rate was the major regressor for serum leptin (F = 42). Subcutaneous fat cells were approximately 50% larger than omental fat cells, and there was a positive correlation between fat cell size and leptin secretion rate in both fat depots (r = 0.8, P < 0.01). Leptin (but not gamma-actin) mRNA levels were twofold higher in subcutaneous than in omental fat tissue (P < 0.05). Thus the subcutaneous fat depot is the major source of leptin in women owing to the combination of a mass effect (subcutaneous fat being the major depot) and a higher secretion rate in the subcutaneous than in the visceral region, which in turn could be due to increased cell size and leptin gene expression.

Adipose Tissue↗

The role of abdominal adiposity and insulin resistance in dyslipidemia of chronic renal failure.

The atherogenic profile of high triglyceride, reduced high-density lipoprotein (HDL) cholesterol, and small low-density lipoprotein particle size found in patients on chronic hemodialysis is known to be associated with insulin resistance and abdominal obesity in the general population. To assess the influence of insulin resistance and abdominal adiposity on the lipid profile in subjects on hemodialysis, intravenous glucose tolerance test and dual-energy x-ray absorptiometry were performed in 26 nondiabetic subjects on hemodialysis and compared with 22 nondiabetic control subjects matched for age, sex, and body mass index. Subjects on hemodialysis were found to have higher triglyceride (133 mg/dL [95% confidence interval, 115 to 159 mg/dL] v 97 mg/dL [95% confidence interval, 80 to 124 mg/dL]; P < 0.05), lower HDL cholesterol (36 +/- 3 mg/dL v 51 +/- 4 mg/dL [mean +/- SEM]; P < 0.01), enhanced insulin response to glucose (2.72 +/- 0.28 mUL(-1) min per mg dL(-1) v 1.67 +/- 0.22 mUL(-1) min per mg dL(-1); P < 0.01), and reduced sensitivity to the action of insulin (2.24 min(-1) per mUL(-1) min [95% confidence interval, 1.86 to 2.75 min(-1) per mUL(-1) min] v 4.17 min(-1) mUL(-1) min [95% confidence interval, 2.95 to 5.9 min(-1) per mUL(-1) min]; P < 0.01) than the control subjects. Abdominal adiposity measured by dual-energy x-ray absorptiometry (2,004 +/- 210 g v 2,163 +/- 198 g [mean +/- SEM]; P = NS) and percentage of body fat distributed to the abdomen (10.5% +/- 0.3% v 9.7% +/- 0.5% [mean +/- SEM]; P = NS) did not differ between the two groups. Subjects on hemodialysis were insulin resistant, but unlike control subjects, their lipid profile was not predicted by their insulin sensitivity. Abdominal adiposity was associated with a deteriorating lipid profile and insulin resistance in subjects on hemodialysis, as it was in control subjects. The presence of renal failure resulted in additional insulin resistance and a higher triglyceride level in the leaner subjects on hemodialysis compared with control subjects with similar levels of abdominal fat. In the more obese subjects, insulin sensitivity and triglyceride level did not differ between the two groups of subjects, although HDL cholesterol level remained low in subjects on hemodialysis. In conclusion, insulin resistance in subjects on hemodialysis did not directly account for their abnormal lipid profile. The negative impact of abdominal adiposity on the metabolic profile was preserved in subjects on hemodialysis, but the presence of renal failure itself resulted in insulin resistance in the leaner subjects and dyslipidemia in all subjects on hemodialysis compared with control subjects of comparable abdominal adiposity.

Abdomen↗