Fat distribution and glucose metabolism in older, obese men and women

BACKGROUND: Previous studies have identified relationships between subcutaneous abdominal fat (SAF), visceral fat (VF), and insulin resistance. In addition, lower muscle attenuation and decreased adiponectin have also been associated with insulin resistance. METHODS: In order to define these relationships within a group of older, obese adults, we studied 48 individuals (20 men; 71+/-1 years and 28 women; 65+/-1 years) who underwent a single, hyperinsulinemic, euglycemic clamp procedure, computed tomography scan at the L4-L5 level, and whole-body plethysmography or dual energy x-ray absorptiometry. Endogenous glucose production (basal glucose R(a)) was also measured at baseline and during the clamp procedure using an infusion of [6,6(2)H(2)] glucose. RESULTS: Mean body mass index (BMI; 31+/-1 kg/m(2)) and glycosylated hemoglobin A1c (HbA1c; 5.7+/-0.1%) levels were not significantly different between men and women. In men, there was an inverse relationship between SAF and insulin-stimulated glucose disposal (ISGD) (r= -.60, p=.01). In addition, there was a trend between thigh muscle attenuation and ISGD in men (r=.41, p=.07). Adiponectin was associated with ISGD in men (r=.46, p=.04) and women (r=.48, p =.01). There were no significant relationships between body fat distribution and basal glucose R(a) in men or women, and no relationships between triglycerides and glucose metabolism. CONCLUSIONS: Our results indicate that (i) SAF was negatively associated with ISGD in men, (ii) thigh muscle attenuation demonstrated a trend toward ISGD in men, and (iii) adiponectin was associated with ISGD in men and women.     

Fat distribution and plasminogen activator inhibitor activity in nondiabetic obese women

Epidemiologic data strongly suggest that upper distribution of body fat and high plasminogen activator inhibitor (PAI) activity are risk factors for cardiovascular disease. Therefore, a link between these two parameters was evaluated by studying 51 menstrually active nondiabetic obese women. In this group positive correlations were observed between body mass index (BMI), waist to hip circumference ratio (W/H ratio, which estimates body fat distribution), plasma insulin, and PAI activity. In addition, plasma triglycerides were related to the W/H ratio and insulin and PAI activity. Partial correlations revealed that BMI was independently and solely related to W/H ratio, which was also independently related to plasma insulin, which in turn related to PAI activity. These results suggest that upper body fat distribution acts as a risk factor of cardiovascular disease through its association with high PAI activity.     

Fat distribution and end-expiratory lung volume in lean and obese men and women

BACKGROUND: Although obesity significantly reduces end-expiratory lung volume (EELV), the relationship between EELV and detailed measures of fat distribution has not been studied in obese men and women. To investigate, EELV and chest wall fat distribution (ie, rib cage, anterior subcutaneous abdominal fat, posterior subcutaneous fat, and visceral fat) were measured in lean men and women (ie, < 25% body fat) and obese men and women (ie, > 30% body fat). METHODS: All subjects underwent pulmonary function testing, hydrostatic weighing, and MRI scans. Data were analyzed for the men and women separately by independent t test, and the relationships between variables were determined by regression analysis. RESULTS: All body composition measurements were significantly different among the lean and obese men and women (p < 0.001). However, with only a few exceptions, fat distribution was similar among the lean and obese men and women (p > 0.05). The mean EELV was significantly lower in the obese men (39 +/- 6% vs 46 +/- 4% total lung capacity [TLC], respectively; p < 0.0005) and women (40 +/- 4% vs 53 +/- 4% TLC, respectively; p < 0.0001) compared with lean control subjects. Many estimates of body fat were significantly correlated with EELV for both men and women. CONCLUSIONS: In both men and women, the decrease in EELV with obesity appears to be related to the cumulative effect of increased chest wall fat rather than to any specific regional chest wall fat distribution. Also, with only a few exceptions, relative fat distribution is markedly similar between lean and obese subjects.     

Regional body fat distribution and metabolic profile in postmenopausal women

The aim of the study was to examine how body fat distribution variables were associated with metabolic parameters in a sample of 113 postmenopausal women not receiving hormone therapy (56.9 ± 4.4 years, 28.4 ± 5.1 kg/m²). Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT, and total midthigh AT) were measured using computed tomography; body fat mass was assessed by hydrostatic weighing; insulin sensitivity was determined with the euglycemic-hyperinsulinemic clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) concentrations were measured by a 75-g oral glucose load; and (high-sensitivity) C-reactive protein (hs-CRP) was measured using a highly sensitive assay. After controlling for fat mass, visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated with insulin sensitivity. Stepwise multiple regression analyses including abdominal visceral AT, subcutaneous AT and total midthigh AT as independent variables showed that abdominal visceral AT best predicted the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak particle size, hs-CRP, FPG, 2hPG, and insulin sensitivity. Abdominal subcutaneous AT was a significant predictor of only insulin sensitivity, whereas total midthigh AT predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal visceral AT and subcutaneous AT were unfavorably related. These results confirmed that abdominal visceral fat is a critical correlate of metabolic parameters in postmenopausal women. In addition, a higher proportion of AT located in the total midthigh depot is associated with a favorable metabolic profile.     

Body composition, fat distribution and metabolic characteristics in lean and obese women with polycystic ovary syndrome

The polycystic ovary syndrome (PCOS), characterized by chronic anovulation and hyperandrogenism, has many features of metabolic syndrome and can be considered a metabolic disease. Approximately 50% of patients with PCOS are overweight or obese with abdominal fat accumulation. Some metabolic alterations and abdominal fat distribution have also been reported in lean women with PCOS. The aim of this study was to evaluate the effect, if any, of obesity on metabolic features, body composition and fat distribution in patients with PCOS. Body composition and abdominal fat distribution (evaluated by DEXA), waist circumference, blood pressure, lipid profile, glucose tolerance and homeostasis model assessment index were determined in 23 lean [mean age 23 +/- 5 yr, mean body mass index (BMI) 22 +/- 2 kg/m2] and 27 overweight-obese (mean age 21 +/- 5 yr, mean BMI 32 +/- 5 kg/m2) patients with PCOS and in 20 age- and weight-matched eumenorrhoic women. Patients exhibited slight but non-significant differences in metabolic parameters, waist circumference, blood pressure and total and abdominal fat content compared with weight-matched controls. None of the lean subjects suffered from metabolic syndrome according to the National Cholesterol Education Program--Adult Treatment Panel III (NCEP-ATPIII) criteria as opposed to 10 overweight-obese patients and three overweight-obese control subjects (37% and 33.3% of each subgroup, respectively). Our data do not show significant metabolic alterations in lean PCOS women. Results indicate that obesity seems to underpin the metabolic alterations exhibited by the overweight-obese patients. However, since women with PCOS are at increased cardiovascular risk, further studies are needed to evaluate metabolic alterations and body composition in these patients.     

Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables

OBJECTIVE Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not Invariably so when the degree of obesity is taken into account. We have therefore Investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN Cross-sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight-matched controls. PATIENTS Twenty-four obese (Pob, mean BMI ± SD 30·6±3·3kg/m²) and 25 non-obese (Pnob, 22·2 ±2·3kg/m²) women with PCOS. Twenty obese (Cob, 30·2 ± 3·5 kg/m²) and 20 non-obese (Cnob, 21·4 ± 1·5 kg/m²) controls. MEASUREMENTS Fasting concentrations of plasma free fatty acids, serum cholesterol and triglycerides in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) In relation to insulin sensitivity index (M/I; assessed with the euglycaemic insulin clamp), glucose tolerance (k-value; intravenous glucose tolerance test), basal serum hormone concentrations, and body fat distribution (skinfolds and waist hip ratio). RESULTS Plasma concentrations of free fatty acids were markedly higher in Pob than in the other groups (all P < 0 001). The lipoprotein lipids did not differ between Pob and Cob, or between the non-obese groups, whereas both obese groups had higher serum concentrations of triglycerides, totally and in VLDL, and lower HDL-cholesterol than their non-obese counterparts. Pob also had higher serum levels of total and LDL-cholesterol than Pnob. Pob had a more pronounced subcutaneous truncal-abdominal adiposity, higher fasting insulin levels and lower M/I than the other groups, and a lower k-value than Cob. Cob had higher levels of fasting insulin than Cnob. Free fatty acid levels correlated with the k-value (inversely) in both women with PCOS and controls, and with M/I (inversely), age and testosterone levels in PCOS. Step-wise regression analysis for the total population, comparing endocrine, anthropometric and metabolic explanatory variables, showed that the serum levels of HDL-cholesterol and triglycerides were mainly correlated with body fat distribution (both) and fasting insulin levels (triglycerides), and levels of total and LDL-cholesterol with BMI and age. CONCLUSIONS Plasma free fatty acid correlations were markedly increased In obese women with PCOS, closely associated with the lower insulin sensitivity and lower glucose tolerance in these women. In spite of these profound metabolic aberrations, the lipoprotein lipid profile was not significantly more abnormal in obese women with PCOS than in their weight-matched controls.     

Fat distribution and steroid hormones in women with alcohol abuse

Anthropometric, hormonal and liver function parameters were examined in 18 premenopausal women with a history of early alcohol abuse, and compared with the data for randomly selected controls of the same age. The alcoholic women showed slightly elevated levels of transaminases, but no clinical or laboratory signs of advanced liver damage. These women were characterized by an increased waist-to-hip ratio, due to enlarged waist circumference. Several endocrine abnormalities were found, including irregular or absent menses as well as low oestrogen, progesterone and delta-4-androstendione levels. The concentration of free testosterone was high and that of sex-hormone-binding globulin was low. These data suggest abdominal distribution of body fat, as well as hyperandrogenicity in alcoholic, premenopausal women. It is postulated that the endocrine abnormalities might be responsible for the abdominal fat distribution.     

Metabolic profile in obese women with the polycystic ovary syndrome

Nine obese women with oligo- or ameno-rrhoea, all with clinical and endocrinological signs of polycystic ovary syndrome (PCO) were submitted to metabolic studies. Their mean weight was 96 kg and their mean plasma testosterone concentration was 3.5 nmol/l. A group of nine obese, regularly menstruating women of similar age and degree of obesity (mean body weight 102 kg) served as controls. Their mean testosterone concentration was 1.9 nmol/l. The high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations in plasma were significantly lower in women with PCO than in control women. Furthermore, in the whole group the testosterone level showed significant inverse relationships to HDL-cholesterol (r = -0.64; P less than 0.01) and apo A-I (r = -0.59; P less than 0.01). The lipoprotein lipase activity (LPLA) in adipose tissue was lower in the women with PCO than in the control group with levels similar to those found in adipose tissue in men. There was an inverse relationship between the testosterone concentration in plasma and LPLA in adipose tissue (r = -0.51; P less than 0.05). The fat cells were of similar size at different regions in the women with PCO but showed marked differences in the control subjects who had much larger cells at the femoral than the abdominal site. The results show that the hyperandrogenism in PCO affects adipose tissue LPLA which could explain the lower HDL cholesterol values in women with PCO.     

Analysis of weight loss outcomes using VLCD in black and white overweight and obese women with and without metabolic syndrome

OBJECTIVE: To evaluate the efficacy of very low calorie diet (VLCD) in black and white obese women. Changes in weight, metabolic profile, and body composition are assessed. METHOD: Patients are enrolled in a self-paid, university-based, outpatient weight loss program. All are prescribed VLCD (500-800 Cal/day), an exercise regimen, and group behavioral counseling. Black and white patients are matched for age, weight, body mass index, and by metabolic syndrome (MS) status. RESULTS: A total of 304 black and white women (152 in each group) were included the analysis. Approximately 40% of patients had MS (white women: 39.5%; black women: 41.2%). Mean baseline weights were similar. After 12 weeks, weight reduction of 9.97% was seen in white women and 9.02% drop was seen in black women (both P<0.0001). However, the degree of weight change was not different between the groups (P = 0.244). Marked improvements in fasting glucose, total cholesterol, LDL, triglyceride, and blood pressures (BP) were observed (all P<0.01); however, no difference between cohorts were seen. Patients with MS had higher baseline weight, BP, glucose and triglyceride levels when compared to patients without MS (all P<0.01). Significant reductions in % body fat were seen in white and black patients, independent of MS status. CONCLUSION: Obese patients, independent of race, were able to achieve significant weight loss when enrolled in a structured outpatient program. Weight loss significantly correlated with all aspects of MS. Our results suggest that differences seen in past studies may be influenced by socioeconomic and behavioral factors rather than differences in physiological response to dieting.     

Resting metabolic rate in obese and normal weight women

The relationship between resting metabolic rate and different parameters of body size was investigated among 28 female volunteers in the age group of 20--30 years. The resting metabolic rate of the subjects was determined indirectly by measuring the oxygen consumption in a closed circuit, in which the oxygen concentration was stabilised. The fat percentage of the body was determined by densitometry. The population was divided into two groups: the obese, with an average fat percentage of 33.6 and the normal-weight with an average fat percentage of 20.4. Mean values for the resting metabolic rate were 1550 kcal/24 h (6.488 MJ/24 h) for the obese and 1421 kcal/24 h (5.948 MJ/24 h) for the normal-weight group. The resting metabolic rate per kg body weight was lower in the obese than in the normal-weight persons. However, expressed per kg fat-free body mass, energy expenditure under resting conditions in the obese was higher than in the normal-weight. No single body parameter seems to be suitable in the explantation of RMR in women with substantially different fat content. The best prediction of resting metabolic rate in this population of obese and normal-weight women is obtained when both fat-free mass and fat mass are used as independent variables in a linear regression equation.     

Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline

OBJECTIVE: Our objective was to develop clinical practice guidelines for the evaluation and treatment of hirsutism in premenopausal women. PARTICIPANTS: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, two methodologists, and a medical writer. The Task Force received no corporate funding or remuneration. EVIDENCE: Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations, and "suggest" for weak recommendations. CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and e-mail communications. The drafts prepared by the Task Force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Core Committee (CACC), and Council. The version approved by the CGS and CACC was placed on The Endocrine Society's Web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. CONCLUSIONS: We suggest testing for elevated androgen levels in women with moderate or severe hirsutism or hirsutism of any degree when it is sudden in onset, rapidly progressive, or associated with other abnormalities such as menstrual dysfunction, obesity, or clitoromegaly. For women with patient-important hirsutism despite cosmetic measures, we suggest either pharmacological therapy or direct hair removal methods. For pharmacological therapy, we suggest oral contraceptives for the majority of women, adding an antiandrogen after 6 months if the response is suboptimal. We recommend against antiandrogen monotherapy unless adequate contraception is used. We suggest against using insulin-lowering drugs. For women who choose hair removal therapy, we suggest laser/photoepilation.     

Resting metabolic rate, weight, surface area and body composition in obese women

Resting metabolic rate was measured in 22 women with varying degrees of obesity. Body composition was estimated from total body potassium and from total body water, and creatinine excretion in urine was measured over a period of three weeks while the patients were on a creatinine and creatine-free reducing diet. Resting metabolic rate was highly significantly correlated with body weight, surface area, creatinine excretion and lean body mass calculated either from potassium or water measurements (P less than 0.001). Correlation with adipose tissue was less strong, and when multiple regression of both fat and lean on metabolic rate was performed, the relationship was seen to depend mostly on the mass of lean rather than adipose tissue. In obese people the water content of fat-free tissue is greater than that in normal subjects, so it is not valid to assume that fat content can be calculated accurately from a measurement of total body water.     

Association of obesity with leukocyte count in obese individuals without metabolic syndrome

AimsInflammation in obesity is associated to insulin resistance (IR), hyperglycemia, hypertension and hyperlipidemia. Leukocytes play an important role in obesity associated inflammation. The initial factors that generate the inflammatory events in the obesity remain unclear. Therefore, the aim of this study was to determine the association of circulating leukocytes with clinical and biochemical parameters in obese individuals with clinical and biochemical parameters in normal range and with or without IR.MethodsNineteen obese non-diabetic and 9 lean subjects were studied for serum levels of insulin, lipids, glycated hemoglobin, glycemia, for clinical parameters as HOMA-IR, arterial pressure and anthropometric parameters, and for leukocyte counts. Neutrophil/lymphocyte ratio (N/L) was calculated using the log_e of leukocyte counts. Association between leukocytes and studied parameters was determined by Pearson's correlation.ResultsTwo groups of obese individuals were observed: with high levels of insulin (with IR) and with normal levels (without IR). Positive correlations were observed between leukocyte and lymphocyte counts with body mass index and HOMA-IR and negative correlation with decreased HDL levels. Lymphocytes correlated with increased levels of insulin. Leukocytes and neutrophils correlated positively with increased visceral fat and liver steatosis. These associations were absent in the obese group without IR. N/L ratio did not show correlations with studied parameters. The leukocyte associations were mainly observed in obese individuals with IR.ConclusionsThese data may represent initial leukocyte associations with morbidity features and define two different obese individuals that may evolve to the chronic inflammation observed in the obesity.     

Evidence for metabolic endotoxemia in obese and diabetic Gambian women

Objective:

Emerging evidence from animal models suggests that translocation of bacterial debris across a leaky gut may trigger low-grade inflammation, which in turn drives insulin resistance. The current study set out to investigate this phenomenon, termed ‘metabolic endotoxemia'', in Gambian women.

Methods:

In a cross-sectional study, we recruited 93 age-matched middle-aged urban Gambian women into three groups: lean (body mass index (BMI): 18.5–22.9 kg m⁻²), obese non-diabetic (BMI: ⩾30.0 kg m⁻²) and obese diabetic (BMI: ⩾30.0 kg m⁻² and attending a diabetic clinic). We measured serum bacterial lipopolysaccharide (LPS) and endotoxin-core IgM and IgG antibodies (EndoCAb) as measures of endotoxin exposure and interleukin-6 (IL-6) as a marker of inflammation.

Results:

Inflammation (IL-6) was independently and positively associated with both obesity and diabetes (F=12.7, P<0.001). LPS levels were highest in the obese-diabetic group compared with the other two groups (F=4.4, P<0.02). IgM EndoCAb (but not total IgM) was highly significantly reduced in the obese (55% of lean value) and obese diabetic women (30% of lean; F=21.7, P<0.0001 for trend) compared with lean women.

Conclusion:

These data support the hypothesis that gut-derived inflammatory products are associated with obesity and diabetes. Confirmation of these findings and elucidation of the role of the microbiota, gut damage and the pathways for translocation of bacterial debris, could open new avenues for prevention and treatment of type 2 diabetes.