Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo. F...

This study shows the importance of medical nutritional therapy on glycaemic control in Type 1 diabetic subjects.

OBJECTIVES: To investigate the activity of the hypothalamic ± pituitary ± adrenal (HPA) axis in male obesity and its relationship with several prominent parameters of the metabolic syndrome. DESIGN: A cross-sectional clinical study of the activity of the HPA axis in groups of obese males and normal-weight controls. SUBJECTS: Seventeen obese non-diabetic males with a body mass index (BMI) b 28 and eight normal-weight controls were examined. MEASUREMENTS: Fat free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance, and the waistto-hip circumference ratio (WHR) was calculated in all subjects. Baseline samples were taken for sex hormone and lipid determination, and an oral glucose tolerance test (OGTT) was performed for glucose and insulin determination. The activity of the HPA axis was determined by the combined administration of human corticotropin releasing hormone (CRH) (100 m mg) and arginine vasopressin (AVP) (0.3 IU). RESULTS: As expected, FFM and FM and the WHR were higher in obese men than in controls, as were fasting insulin and stimulated (as area under the curve (AUC)) glucose and insulin concentrations. Baseline adrenocorticotropin (ACTH) and cortisol concentrations were similar in both groups, but stimulated (as AUC), ACTH was higher (P`0.05) in obese subjects than in controls, whereas no signi®cant difference in cortisol AUC was present. Since the main differences between obese subjects and controls were present during the early 30 min of the test, the correlation coef®cients between total and incremental ACTH AUC 0 ± 30 min and cortisol AUC 0 ± 30 min and all other variables were analyzed. A signi®cant correlation coef®cient was present between them and all anthropometric parameters, fasting insulin and insulin AUC , but not with androgens and gonadotrophins. In addition, a signi®cant correlation was present between total and incremental ACTH AUC 0 ± 30 min and triglyceride concentrations. However, after adjusting for BMI or FM values, all correlation coef®cients became non-signi®cant, except the one between incremental ACTH AUC 0 ± 30 min and insulin AUC (P`0.05). CONCLUSION: These ®ndings indicate that obese men may also have an altered pituitary response to combined CRHaAVP stimulation, which appears to be predominantly related to body size and total body fat. ACTH hyperresponsiveness after CRHaAVP stimulation also appears to be related to hyperinsulinaemia, but underlying mechanisms of this relationship remain to be elucidated.

OBJECTIVE: To investigate the effects of weight loss on sex hormone-binding globulin (SHBG) in massively obese males and whether normal SHBG concentrations could be obtained regardless or not of the achievement of normal body weight values. DESIGN AND SUBJECTS: Sera were collected for SHBG determination from 63 massively obese men, partly before they underwent biliopancreatic diversion (pre-op group 11) and partly during the post-surgical follow up (post-op group 52), and twenty normal weight healthy control men. MEASUREMENTS: Serum SHBG was measured using a noncompetitive liquid-phase immunoradiometric assay. RESULTS: Baseline general characteristics were similar in both obese groups. Obese patients in the post-op group had lost 46.4 AE 2.9 kg since they had undergone operation, namely during a mean period of 14.9 AE 13.8 (range 1±58) months follow up. Obese groups had signi®cantly lower SHBG than normal weight controls (66.2 AE 18.6 nmol/l). However, preop obese (19.9 AE 5.5 nmol/l) had signi®cantly lower values than post-op obese subjects (45.5 AE 24.8 nmol/l; P`0.001). There were a highly signi®cant correlation between SHBG and individual BMI values (r 7 0.629; P`0.001). Moreover, the post-op obese with BMI values lower or equal to 28 had signi®cantly higher SHBG concentrations than those with BMI greater than 28 (62.8 AE 22.2 nmol/l vs 32.1 AE 19.6 nmol/l; P`0.001), but not signi®cantly different with respect to normal weight controls. CONCLUSIONS: Massively obese men weight loss can completely reverse SHBG abnormalities, which can be restored to the normal range when near-normal body weight is achieved. Since reduced SHBG concentrations can be an independent risk factor for the development of diabetes and cardiovascular disease, this represents an additional bene®t of weight loss program in massively obese individuals.