Hormonal influences on the relationships between body fatness, body fat distribution, lipids, lipoproteins, glucose and blood pressure in French working women

The independent associations between overall obesity, body fat distribution, lipids, lipoproteins, glucose, blood pressure and some hormonal factors (sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG) and fasting insulin) were cross-sectionally examined in 205 French working women. After adjustment for age, overall adiposity assessed by body mass index (BMI) was significantly associated with most metabolic parameters, whereas regional adiposity assessed by the waist-hip ratio (WHR) was significantly associated only with triglyceride, systolic and diastolic blood pressure. Blood pressure, glucose but not triglyceride, were also negatively and significantly correlated with SHBG and positively with fasting insulin. Negative independent associations were found between SHBG and both BMI and WHR, whereas CBG was positively associated only with WHR. Fasting insulin was no longer related to WHR after adjustment for BMI. After controlling for the effect of SHBG or insulin, the associations between triglyceride, blood pressure and both BMI and WHR were not substantially modified. After adjustment for BMI and WHR, fasting insulin was independently associated with both HDL cholesterol and diastolic blood pressure. In conclusion, in these French women, hormonal factors under study appeared to have little influence on the relationships between body fatness, body fat distribution, metabolic variables and blood pressure.     

Increased visceral adipose tissue is associated with increased circulating insulin and decreased sex hormone binding globulin levels in massively obese adolescent girls.

The current study was designed to examine the relationship between body fat distribution, as evaluated by anthropometry and magnetic resonance imaging (MRI), and circulating insulin, sex hormone and SHBG levels in obese adolescent girls. Twenty-nine obese adolescent girls, aged 12.6-16.9 years with a mean BMI of 30.51+/-1.86 participated in this study. All girls had breast stage B4-5 and pubic hair stage P4-5. Percent obesity and BMI as indices of being overweight were calculated; the waist-to-hip ratio (WHR) and the waist-to-thigh ratio (WTR) were calculated to obtain two anthropometric indices for the pattern of body fat distribution. The areas of visceral (VAT) and subcutaneous adipose tissue (SAT) were evaluated by MRI at the L4-L5 level. Serum concentrations of total T, DHEAS, 17beta-estradiol, progesterone and SHBG were measured. Plasma glucose and insulin concentrations were evaluated during an oral glucose tolerance test. WHR was the only anthropometric parameter that was significantly associated with the area of VAT. Insulin level showed correlation with both WHR and the area of VAT; no correlation was found between insulin levels and WTR. Both WHR and VAT were negatively correlated with serum DHEAS level and positively correlated with T level. There were strong negative correlations between serum SHBG level and the area of VAT and WHR. Inverse correlation was found between serum SHBG level and insulin. Serum 17beta-estradiol and progesterone levels showed no significant correlation with all the patterns of body fat distribution. SAT was not significantly correlated with both anthropometric parameters and any of the sex hormones evaluated. We can draw two main conclusions. Firstly, in massively obese adolescent girls, the WHR seems to be a good indicator for the accumulation of VAT, and abdominal obesity, rather than adiposity per se, appears to be related to biochemical complications. Secondly, increased upper body adiposity and, in particular, the intra-abdominal fat area are associated with increased insulin levels in massively obese adolescent girls. The associated reductions in SHBG and DHEAS levels represent an early general risk factor for the development of metabolic and cardiovascular diseases in this population, as previously described for obese adult women.     

Associations between regional body fat distribution, fasting plasma free fatty acid levels and glucose tolerance in premenopausal women

The associations between total adiposity, body fat distribution measured by computed tomography (CT) and estimated by the waist-to-hip ratio (WHR), regional fat cell morphology, fasting plasma free fatty acid (FFA) levels and glucose tolerance were studied in a sample of 37 premenopausal women aged 35.3 +/- 4.6 years (mean +/- s.d.). Body fat mass, CT-derived abdominal and femoral fat areas, as well as the abdominal fat cell weight were all significantly associated with fasting plasma FFA levels (0.34 less than r less than 0.49, 0.005 less than P less than 0.05), and with the glucose and insulin areas during the oral glucose tolerance test (OGTT) (0.36 less than r less than 0.70, 0.0001 less than P less than 0.05). No associations were found between the WHR, the femoral fat cell weight and fasting plasma FFA levels or glucose area during the OGTT. However, the WHR and the femoral fat cell weight were positively associated with insulin area. Plasma FFA levels were positively correlated with the glucose area during the OGTT, whereas no association was found between plasma FFA levels and the insulin area. Covariance analysis indicated that this effect of plasma FFA levels on the magnitude of glucose response to OGTT was independent from that of total adiposity or regional body fat distribution variables. These results emphasize the importance of plasma FFA levels as a correlate of glucose tolerance and suggest that the associations previously reported between obesity, regional body fat distribution, fat cell size and glucose tolerance are, at least partly, mediated by variations in plasma FFA levels.     

Relationship of body fat distribution to the metabolic clearance of insulin in premenopausal women

The effects of body fat distribution on the metabolic clearance rate of insulin (MCR) and its relationship to peripheral insulin sensitivity (M/I) and androgenic activity were assessed in six nonobese and 20 obese premenopausal women with varying waist-to-hip girth ratio (WHR). As an index of androgenic activity, plasma levels of the sex hormone binding globulin (SHBG) and percentage free testosterone (%FT) were determined. The mean MCR in the obese and nonobese groups were similar (571 +/- 29 vs 578 +/- 31 ml/min/m2). Within the obese group, MCR varied between 401 and 822 ml/min/m2 and was inversely correlated with the WHR (r = -0.50, P less than 0.05). The reduction in MCR with upper body fat localization was observed at both sub- and supra-maximal plasma insulin levels. MCR correlated negatively with fasting and postglucose challenge plasma insulin levels and positively with M/I. MCR also correlated with plasma SHBG and %FT levels. We conclude that upper body fat localization is associated with diminished insulin clearance. This diminution is closely aligned with the degree of peripheral insulinemia and insulin sensitivity. The increase in androgenic activity may contribute to the aberrant insulin clearance observed in upper body obese subjects.     

Muscle tissue in obesity with different distribution of adipose tissue. Effects of physical training

Obese men and women with the same body fat mass, as well as obese women in another study, were divided into groups with male or female type of body fat distribution, but again with similar body fat mass. The participants were examined with measurements of body composition, including muscle fiber distribution, as well as circulatory and metabolic variables before and after physical training under controlled conditions. Obese men had higher lean body mass, blood pressure, blood glucose and plasma insulin, C-peptide, cholesterol and triglyceride concentrations than age- and body fat-matched obese women. Obese women with male type of adipose tissue distribution showed the same differences (except cholesterol) in comparisons with women with female type of adipose tissue distribution. The women with male type obesity were also more insulin resistant in glucose clamp measurements, and had male type of muscle fiber distribution. Physical training in the group of obese men resulted in a decrease of body fat, a further increase of lean body mass, an increase of fast twitch, aerobic type, muscle fibres as well as lower plasma insulin, cholesterol and triglyceride concentrations and lower blood pressure. Obese women with male type distribution of adipose tissue responded to physical training essentially like men. The insulin sensitivity was improved to the same level as in obese women with female type of adipose tissue distribution. In contrast, the latter women showed an increase of body fat and no metabolic improvements after training. These results show that obese women with male type of body fat distribution also have male characteristics of muscle mass, morphology and function. It is suggested that the obesity complications associated with this condition are improved by physical training because of an adaptation to a negative energy balance, in combination with an improvement of insulin sensitivity of the muscle mass. In contrast, the failure of obese women with female type of adipose tissue distribution to adapt to a negative energy balance during physical training is probably explaining their failure to decrease body fat and to improve metabolism during physical training.     

Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women

The relationship of body fat distribution to metabolic profiles was determined in 80 healthy premenopausal white women of a wide range of obesity levels [percentage of ideal body weight (% IBW) 92-251]. Distribution of fat between the upper and lower body was assessed from the waist/hips girth ratio (WHR), which varied from 0.64 to 1.02. In 23 women, in vivo insulin sensitivity was also determined from the steady-state plasma glucose (SSPG) level at comparable insulin levels of approximately 100 microU/mL attained by the intravenous infusion of somatostatin, glucose, and insulin. Increasing WHR was accompanied by progressively increasing fasting plasma insulin levels (r = 0.47, P less than 0.001), insulin and glucose areas after glucose challenge (r = 0.53, P less than 0.001; r = 0.50, P less than 0.001, respectively) and fasting plasma triglyceride concentrations (r = 0.48, P less than 0.001). Obesity level was similarly correlated with these metabolic indices. Partial and multiple regression analysis and analysis of variance with a linear contrast model revealed that the effects of body fat topography were independent of, and additive to, those of obesity level. Within obese subjects alone (%IBW: 130), %IBW had no predictive value, but WHR remained a significant predictor of plasma glucose, insulin, and triglyceride concentrations. The WHR also correlated with the plasma cholesterol level, but this association was largely dependent on its relationship to %IBW. Both WHR and %IBW correlated with the insulin resistance index, SSPG (r = 0.60, P less than 0.01; r = 0.61, P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01). This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.     

SHBG levels correlate with insulin resistance in postmenopausal women

BackgroundOverweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance and has been identified as a target for new therapeutic strategies, including early change in lifestyle. Early biochemical markers for identifying at-risk patients will be useful for prevention studies. The aim of this study is to investigate whether or not SHBG level is a useful index of hyperinsulinemia and/or insulin resistance in pre- and postmenopausal obese women. At the same time, the relationship between SHBG concentrations and features of the metabolic syndrome were evaluated.Methods229 women were eligible for this study. MetS was defined by using a modification of the ATP III guidelines. All patients were euthyroid, obese and overweight, 25 to 69 years of age. Subjects were divided into groups of premenopausal women (n = 125) and postmenopausal women (n = 104). Various fatness and fat distribution parameters, SHBG, sex hormones, FSH, LH, thyroid hormones, serum levels of fasting and postprandial glucose, lipid profile, uric acid and serum insulin, and blood pressure were measured.ResultsNo significant difference was found in mean SHBG levels between pre- and postmenopausal obese women in this study (p = 0.866).In premenopausal obese women, SHBG correlated negatively with BMI, waist circumference, fasting glucose, uric acid levels and FAI.In postmenopausal obese women, SHBG correlated negatively with fasting glucose, postprandial plasma glucose, fasting insulin, HOMA-IR and FAI and positively with HDL.SHBG had a significant inverse association with MetS parameters only in postmenopausal women, also after adjusting for BMI, age and estradiol.ConclusionsObesity may influence the levels of endogenous sex steroid, especially after menopause. SHBG concentrations are correlated with features of the metabolic syndrome, particularly in postmenopausal obese women.These results suggest that SHBG may be an index of insulin resistance in postmenopausal obese women.     

Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1

Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHR), is associated with increased cardiovascular morbidity and mortality. The present study examines components of the fibrinolytic system in obese and lean middle-aged women with a high and low WHR. Ten women in each group were carefully matched with respect to age, body weight, lean body mass, and body fat. Fibrinogen and endothelial type of plasminogen activator inhibitor -1 (PAI-1) were significantly elevated in the obese women with a high WHR compared with the obese women with a low WHR or with both groups of lean women. In addition, obese women with a high WHR exhibited a greater metabolic risk profile (elevated glucose, insulin, and triglyceride levels). When all subjects were pooled for the analyses, both fibrinogen and PAI-1 levels correlated positively with glucose and insulin levels. PAI-1 was also negatively related to degree of insulin sensitivity measured with the euglycemic clamp technique. In the obese groups, WHR but not body mass index (BMI), correlated with PAI-1 levels. No such correlations were seen in the lean groups. In conclusion, the data show that a high WHR in obese, but not lean middle-aged women, is associated with an impaired fibrinolytic activity. This perturbation becomes enhanced when it is associated with hyperinsulinemia and insulin resistance, which is a typical feature of abdominal obesity.     

The effect of weight loss on change in waist-to-hip ratio in patients with type II diabetes.

This study sought to determine whether weight loss would alter body fat distribution in obese men and women with type II diabetes. Subjects were 60 women and 33 men who participated in a year-long weight loss program. Weight losses of women and men, respectively, averaged 13.4 kg and 16.8 kg at six months and 11.2 kg and 13.1 kg at one year. WHR decreased significantly in both genders: for women, WHR decreased from 0.95 at baseline to 0.93 at six months and 0.94 at one year; for men WHR decreased from 0.99 at baseline to 0.96 at six months and 0.96 at one year. Subjects with greater upper body obesity at baseline did not lose more weight than subjects with less upper body obesity, but they did have greater reductions in WHR at six months in both genders and at one year in men. The magnitude of WHR reduction was strongly related to the amount of weight lost in men, but was not related to weight loss in women. Improvements in fasting glucose, fasting insulin, and HbA1 were significantly related to weight loss, but not to reductions in WHR. Thus, participation in a weight loss program had beneficial effects on body fat distribution in patients with type II diabetes, but these changes in WHR were not independently associated with improvements in glycemic control.     

High saturated fat and low starch and fibre are associated with hyperinsulinaemia in a non-diabetic population: The San Luis Valley Diabetes Study

Summary A geographically based sample of 1069 Hispanic and non-Hispanic white persons aged 20–74 years, living in southern Colorado and who tested normal on an oral glucose tolerance test (World Health Organization criteria) were evaluated to determine associations of dietary factors with fasting serum insulin concentrations. Subjects were seen for up to three visits from 1984 to 1992. A 24-h diet recall and fasting insulin concentrations were collected at all visits. In longitudinal data analysis, lower age, female gender, Hispanic ethnicity, higher body mass index, higher waist circumference, and no vigorous activity were significantly related to higher fasting insulin concentrations. High total and saturated fat intake were associated with higher fasting insulin concentrations after adjusting for age, sex, ethnicity, body mass index, waist circumference, total energy intake and physical activity. Dietary fibre and starch intake were inversely associated with fasting insulin concentrations. No associations with fasting insulin concentrations were observed for monounsaturated fat, polyunsaturated fat, sucrose, glucose and fructose intake. Associations were similar in men and women and for active and inactive subjects, though associations of fibre and starch intake with insulin concentrations were strongest in lean subjects. These findings support animal studies and a limited number of human population studies which have suggested that increased saturated and total fat intake and decreased fibre and starch intake increase fasting insulin concentrations and may also increase insulin resistance. These findings, which relate habitual macronutrient consumption to hyperinsulinaemia in a large population, may have implications for studies attempting primary prevention of non-insulin-dependent diabetes mellitus. [Diabetologia (1997) 40: 430–438] Received: 6 August 1996 and in revised form: 17 December 1996     

Effect of obesity and body fat distribution on sex hormones and insulin in men

To investigate the relationship between body fat distribution, sex hormones, and hyperinsulinemia in male obesity, we examined 52 obese men (body mass index [BMI], 35.0 +/- 6.1, mean +/- SD) and 20 normal-weight controls. Their waist to hip circumference ratio (WHR), which was used as an index of fat distribution, was 0.985 +/- 0.052 and 0.913 +/- 0.061 (P less than .005), respectively. Compared with controls, obese men presented significantly lower levels of total (357 +/- 132 v 498 +/- 142 ng/dL; P less than .005) and free testosterone (14.2 +/- 2.9 v 17.1 +/- 2.6 pg/mL; P less than .05) and sex hormone-binding globulin (SHBG; 41.7 +/- 31.9 v 66.2 +/- 18.6 nmol/L; P less than .001) without any significant difference on the other sex steroid or on gonadotropin concentrations. Fasting and glucose-stimulated insulin and C-peptide levels were significantly higher in obese than in controls, and in obese with the WHR value greater than 0.97 (corresponding to the distribution median) than in those with WHR lower or equal to 0.97. BMI was negatively correlated with testosterone (P less than .005), free testosterone (P less than .01), and SHBG (P less than .001) and positively with fasting (P less than .001) and glucose-stimulated (P less than .005) C-peptide concentrations, whereas no relationship was found between these variables and WHR values. On the contrary, WHR was significantly correlated with fasting and post-glucose insulin levels (P less than .05), but not with those of sex steroids.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

The counterregulatory response to hypoglycaemia in women with the polycystic ovary syndrome

OBJECTIVE The pathogenetic mechanisms behind insulin resistance in polycystic ovary syndrome (PCOS) are far from fully elucidated. Aberrant counterregulatory responses to hypoglycaemia have been reported in patients with insulin resistance, and recent reports suggest that plasma glucose may be regulated at lower levels in women with PCOS. In this study we investigated the complete hormonal counterregulatory response to hypoglycaemia in women with PCOS. DESIGN Prospective cross-sectional study. PATIENTS Eight obese (BMI 25) and 10 non-obese (BMI < 25) women with PCOS, diagnosed by means of ultrasonography and clinical signs of chronic anovulation. Eight obese and 9 non-obese controls. MEASUREMENTS Hypoglycaemia was induced by an intravenous bolus of soluble insulin (0.15 IU/kg body weight). The counterregulatory responses of cortisol, GH, catecholamines, glucagon, chromogranin A (CGA), and neuropeptide Y (NPY) were studied together with symptoms of hypoglycaemia. RESULTS The obese women with PCOS had a more pronounced truncal-abdominal body fat distribution (waist hip ratio, WHR) and were hyperinsulinaemic, compared with the obese controls. All the women exhibited blood glucose levels (< 2 mmol/l) well below the threshold for the hormonal counterregulatory response and for the appearance of clinical symptoms. The non-obese women with PCOS showed a greater increase in serum concentrations of GH than the lean controls. The obese women with PCOS exhibited blunted responses of noradrenaline and NPY, but similar increases of adrenaline and CGA, compared with the obese controls. They also showed a lower symptom score during hypoglycaemia. The response of noradrenaline to hypoglycaemia correlated inversely with fasting insulin levels in the women with PCOS. Among all the obese women (PCOS and controls pooled) basal levels of noradrenaline correlated inversely with the WHR. CONCLUSIONS All the women with PCOS, independent of BMI, body fat distribution and insulin levels, showed preserved counterregulatory responses to hypoglycaemia. The reduced plasma levels of noradrenaline and the lower perception of hypoglycaemic symptoms in the obese women with PCOS could both reflect a lower activation of the sympathetic nervous system. This aberration seems related to truncal-abdominal obesity and hyperinsulinaemia. The finding of an increased response of GH in the lean women with PCOS could support previous suggestions of an altered activity of the GH/IGF-I system in these women.     

Racial disparities in metabolism, central obesity, and sex hormone-binding globulin in postmenopausal women

Increased total and intraabdominal fat (IAF) obesity as well as other metabolic conditions associated with the insulin resistance syndrome (IRS) are related to low levels of sex hormone-binding globulin (SHBG) in young and older Caucasian (CAU) and young African-American (AA) women. We examined whether postmenopausal AA women, a population with a high incidence of obesity and IRS despite low IAF, would have higher levels of circulating SHBG compared with CAU women, and whether there would be negative relationships between indexes of obesity and risk factors associated with IRS and SHBG levels. We measured body composition, SHBG, free testosterone, leptin, glucose tolerance, insulin, and lipoprotein lipids in 55 CAU (mean +/- SD, 59 +/- 7 yr) and 35 AA (57 +/- 6 yr) sedentary women of comparable obesity (48% body fat, by dual energy x-ray absorptiometry). Compared with CAU women, AA women had larger waist (101 vs. 96 cm), larger fat mass (44.9 +/- 8.8 vs. 39.9 +/- 8.1 kg), larger sc fat area (552 +/- 109 vs. 452 +/- 109 cm(2)), and lower IAF/SC ratio (0.28 +/- 0.12 vs. 0.38 +/- 0.15; P < 0.01), but similar waist to hip ratio (0.83). Both groups had similar SHBG (117 vs. 124 nmol/L) and free testosterone (3.7 vs. 3.4 pmol/L) levels, but AA women had a 35% higher leptin, 34% higher fasting insulin, and 39% greater insulin response to a glucose load (P < 0.05) compared with CAU women. In CAU, but not AA, women SHBG correlated negatively with body mass index (r = -0.28; P < 0.05), waist (r = -0.36; P = 0.01), IAF (r = -0.34; P = 0.01), and insulin response to oral glucose (r = -0.37; P < 0.05) and positively with high density lipoprotein cholesterol (r = 0.30; P = 0.03). The relationship between insulin area and SHBG in CAU women disappeared after adjusting for IAF, whereas the relationship between high density lipoprotein cholesterol and SHBG persisted after adjusting for IAF, but not for fat mass. Leptin was positively related to fat mass (P < 0.05) in both groups, but it was related to insulin only in the Caucasian women (P< 0.01). There was a racial difference in the slopes (P< 0.05) of the relationships of leptin to fat mass (P < 0.05). Racial differences in leptin disappeared after adjustment for fasting insulin. These results suggest that the metabolic relationships between total and regional obesity, glucose, and lipid metabolism with SHBG in CAU women are different from those in postmenopausal obese AA women.     

Effects of luteinizing hormone, insulin, insulin-like growth factor-I and insulin-like growth factor small binding protein 1 in the polycystic ovary syndrome.

This study explores the clinical and endocrine implications of hyperinsulinaemia in the polycystic ovary syndrome (PCOS). Oral glucose tolerance tests were performed on 34 lean and 19 obese women with PCOS and on 13 lean women with normal ovaries. Insulin measurements were compared with basal gonadotrophins, androgens, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein 1 (IGFBP-1). Unselected lean women with PCOS were found to have fasting hyperinsulinaemia and the raised serum insulin concentrations were associated with menstrual disturbance and hyperandrogenaemia. In addition, serum insulin concentrations in lean women with PCOS correlated positively with serum IGF-I and negatively with serum IGFBP-1 concentrations. Ovarian stimulation by insulin appears to be independent of luteinizing hormone (LH) and is an important feature in 30% of lean women with PCOS.     

The role of the opioid peptides in the development of hyperinsulinemia in obese women with abdominal body fat distribution.

In this study, we investigated the hypothesis that increased opioid activity may be involved in the development of hyperinsulinemia in women with obesity and abdominal body fat distribution. Two groups of nine obese body (body mass index [BMI], 30 to 40 kg/m2) women with abdominal (A-ob) (waist to hip ratio [WHR] greater than 0.85) or gluteo-femoral (F-ob) (WHR greater than or equal to 0.80) fat distribution were examined and compared with eight normal-weight controls. Basal beta-endorphin levels were higher in the A-ob group than in the other groups. Each woman underwent two oral glucose tolerance tests (OGTT, 75 g glucose). A bolus of naloxone (0.8 mg) followed by a constant infusion of naloxone (0.04 mg/kg/h) or saline was also administered during the glucose challenge in random order, and blood samples for glucose, insulin, and C-peptide were collected at regular times after glucose administration. No difference was observed in basal or stimulated glucose concentrations between the three groups, nor between the saline or naloxone study. However, basal and stimulated insulin levels were significantly higher in obese women (particularly in the A-ob group) than in controls. Naloxone administration, however, did not significantly modify insulin and C-peptide glucose-stimulated concentrations in controls and in the F-ob group, whereas it significantly reduced (by approximately 47%) insulin levels in the A-ob group. Partial correlation coefficients showed a significant negative correlation between percent variation of glucose-stimulated insulin incremental areas during the naloxone study and the WHR in all women considered together (r = .544, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fat oxidation, body composition and insulin sensitivity in diabetic and normoglycaemic obese adults 5 years after weight loss

OBJECTIVE: To investigate whether normal glucose-tolerant and type II diabetic overweight adults differ in response to weight regain with regard to substrate oxidation and metabolic parameters. METHODS: A total of 15 overweight-obese subjects: seven normal glucose tolerant (NGT) and eight with type II diabetes (DM) were restudied 5 y after significant weight loss. Prediet, after 28 days calorie restriction and at 5 y, subjects were characterised for weight, height, waist-to-hip ratio (WHR) and body composition by dual-energy X-ray absorptiometry. Fasting glucose, insulin, leptin and lipid levels were measured and subjects underwent euglycaemic-hyperinsulinaemic clamp (insulin 0.25 U/kg/h for 150 min). Indirect calorimetry was performed resting and in the final 30 min of the clamp. Dietary assessment was by 4-day diet-diary. RESULTS: Both NGT and DM groups regained weight at 5 y and were not different to prediet. Total body fat (%) and WHR were higher at 5 y compared to prediet in both groups. Fasting glucose was increased in NGT subjects at 5 y, and fasting insulin was higher in both groups at 5 y compared to prediet. Insulin sensitivity (GIR) was similar at 5 y compared to prediet, but at 5 y DM subjects were more insulin resistant than NGT subjects. At 5 y, both DM and NGT groups had significantly reduced basal fat oxidation and no significant suppression of fat oxidation with insulin. Clamp respiratory quotient levels at 5 y were significantly higher in NGT compared to DM subjects. CONCLUSION: Reduced basal fat oxidation, and reduced variation in substrate oxidation in response to insulin develop with fat regain and fasting hyperinsulinaemia in both NGT and DM obese adults.     

The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis

While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone‐binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment‐insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total‐cholesterol and low‐density lipoprotein‐cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.     

Interrelationships between body weight, body fat distribution and insulin in obese women before and after hypocaloric feeding and weight loss

The effects were investigated of weight loss on the relationship between hyperinsulinemia, body weight and body fat distribution in two groups of women with central-type obesity (CTO) (waist-to-hip ratio WHR greater than 0.85) or peripheral-type obesity (PTO) (WHR less than 0.85). An oral glucose tolerance test was carried out before and after a hypocaloric nutritional treatment lasting 4 months. Both groups were matched for age, body mass index and amount of body fat. At the basal condition, group CTO had fasting and glucose-stimulated insulin levels significantly higher than group PTO; fasting (but not stimulated) C peptide levels were also higher in CTO compared with PTO. Weight and fat loss were significantly higher in CTO than in PTO women. Moreover, unlike PTO, CTO subjects significantly reduced their WHR values. In both groups weight loss led to a significant drop in fasting and glucose-stimulated insulin and C peptide levels. However, PTO women reduced their C peptide levels significantly less than CTO. In conclusion, weight loss only modified body fat distribution in women with CTO, who appeared to be prone to a greater weight loss than the PTO women. Compared to PTO, CTO women were characterized by higher insulin levels and peripheral insulin resistance, which improved during hypocaloric feeding probably due to the combined effect of weight loss and the change in body fat distribution.