Preserved insulin sensitivity and {beta}-cell activity, but decreased glucose effectiveness in normal-weight women with the polycystic ovary syndrome.

Insulin resistance and hyperinsulinemia are often considered intrinsic features of the polycystic ovary syndrome (PCOS). Nevertheless, conflicting results of insulin sensitivity and secretion have been obtained in the subgroup of normal-weight women with PCOS. Differences in body composition, ethnicity, and diet composition and a family history of metabolic diseases may act as confounding variables in women with PCOS. In the present study, insulin sensitivity and secretion were estimated by an iv glucose tolerance test (IVGTT), analyzed by minimal models, in 20 normal-weight healthy women with PCOS and no family history of type 2 diabetes mellitus and in 20 normally ovulating women, matched for age and body mass index. Insulin sensitivity [mean (95% confidence intervals); PCOS 4.0 (2.8-5.1) vs. controls 4.5 (3.5-5.4) 10(-4) min(-1)/microU.ml], and insulin secretion, expressed as the acute insulin response to glucose [PCOS 3.7 (3.3-4.2) vs. controls 3.7 (3.4-4.0) microU/ml] were similar in the two groups. The women with PCOS showed an increased proportion of total body fat (PCOS 29% vs. controls 27.2%; P < 0.01). They also showed decreased glucose effectiveness, i.e. the proportion of glucose uptake independent from insulin activity [PCOS 2.6 (2.1-3.0) vs. controls 3.8 (3.0-4.6) mg x 100 min(-1); P = 0.01]. The levels of insulin sensitivity and of glucose effectiveness did not correlate in either group. Whether the isolated finding of decreased glucose effectiveness could reflect an early stage in the development of the metabolic aberrations often associated with the syndrome remains to be clarified.

Snoring, hypertension and Type 2 diabetes in obesity. Protection by physical activity.

Sleep-related breathing disorders are recognized as major health problems in obesity. They are involved in both hypertension and Type 2 diabetes, through mechanisms possibly related to increased sympathetic tone. We studied the association of habitual snoring with diabetes, hypertension, weight cycling and physical activity in a large Italian database of treatment-seeking obese subjects. Clinical and behavioral data were assessed by standardized questionnaires. Consecutive data of 1890 obese patients were analyzed [average body mass index (BMI), 38.2 kg/m2, median age: 46 yr, 78% females], from 25 obesity Italian centers, with low prevalence of clinical manifestations of cardiovascular disease. Habitual snoring was reported in 56% of the cases, and was associated with day-time sleepiness. The prevalence increased with obesity class and waist circumference, and was positively associated with weight cycling and weight gain since the age of 20, and smoking. Regular physical activity had a protective effect. Snoring was associated with diabetes and hypertension at univariate analysis, but in multivariate analysis an independent effect was only observed for hypertension. After adjustment for age, gender and BMI, physical activity maintained an independent, protective effect on both snoring (odds ratio 0.65, 95% confidence interval 0.49-0.84; p=0.001), diabetes (0.50, 0.30-0.86; p=0.011) and hypertension (0.71, 0.53-0.95; p=0.023). We conclude that in treatment-seeking, obese subjects with low prevalence of cardiovascular disease, snoring independently increases the risk of hypertension, whereas physical activity exerts a protection on both snoring and complications. These data underline the importance of lifestyle interventions to limit the burden of obesity and associated diseases.

Atrial fibrillation and mitral prolapse in a subject affected by Refetoff syndrome.

Inappropriate secretion of TSH (IST) refers to a heterogeneous group of syndromes in which patients show unsuppressed TSH levels in spite of high serum free thyroid hormone concentrations. It has been recognised that IST can be due to both thyroid hormone resistance (RTH) and pituitary TSH-secreting tumours. The former can be generalised (GRTH) or pituitary (PRTH) if the resistance is more severe in the pituitary than in the remaining tissues. This case report describes a peculiar coexistence of atrial fibrillation and mitral valve prolapse in a patient affected by generalized resistance to thyroid hormone. This finding is suggestive for a major and almost physiological sensitivity of the myocardium to the thyroid hormones activity which in the course of years may determine the modifications responsible for the pathologies described.

[Management of overweight and obese patient. New acquisition]. / Management del paziente in sovrappeso e obeso. Recenti acquisizioni.

Obesity is a chronic disease and prevalence and incidence are progressively increasing. Treatment of obesity is important to reduce mortality and associated diseases, like diabetes mellitus, hypertension, abnormal blood lipid levels, coronary heart disease, thromboembolic disease, cancer (endometrial, gallbladder, cervical, ovarian, breast, prostate and colorectal), polycystic ovary syndrome (PCOS), gallbladder disease, respiratory disease, arthritis, gout. Most of these pathologies profits by a modest weight loss (5-10%). A correct management of obesity should include integration of therapeutic strategies, that we have actually at disposal: diet, physical training, behaviour therapy, pharmacologic therapy and surgery. We should get together low-calorie and low-fat diet with behaviour change and physical training. Physical training induces a significant weight loss and reduces cardiovascular risks and insulin resistance. Orlistat, that reduces up to 30% lipid adsorption, is a valid remedy if with an adequate diet. A new drug, sibutramine, shows efficacy: it increases satiety and energy expenditure caused by thermogenesis in brown adipose tissue. Surgical approaches including some procedures, are indicated for great obesity (BMI >40).

[Management of obese patients: surgical therapy]. / Management del paziente obeso. Terapia chirurgica.

At present, the management of obesity includes integration of therapeutic strategies such as diet, physical training, behaviour therapy and pharmacologic therapy. An increased number of selected patients with morbid obesity, where medical therapy was ineffective, have been surgically treated in the last years due to less invasive surgical techniques, such as laparoscopic surgery. Main operations include gastroplasty, adjustable gastric banding, gastric bypass, bilio-pancreatic diversion. A less invasive procedure is intragastric balloon, i.e. a temporary device which is removed after few months. Surgery shows efficacy to induce weight loss and duration in time. All obese patients can't be treated by the same operation. Available surgical techniques are different and have to be chosen in each case according to the patient's clinical conditions.

In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance.

BACKGROUND: Circulating lymphocytes of obese individuals with and without type 2 diabetes have derangements of pyruvate dehydrogenase (PDH) that are described as reflecting a disorder underlying systemic insulin resistance, namely basal activity below normal and, in vitro, unresponsiveness to insulin at 33 pmol/l and activation at 330 pmol/l instead of activation and inhibition as in controls. OBJECTIVE: To explore whether the above enzyme derangements are overcome in obese individuals on dexfenfluramine treatment, known to improve poor peripheral insulin sensitivity. METHODS: Fifteen obese diabetic patients and 15 age-matched euglycaemic obese subjects with normal glucose tolerance were enrolled for a trial composed of two 21-day periods; in the first (D-21-D0), participants received a placebo, and in the second (D0-D21), dexfenfluramine (30 mg/day). At D-21, D0 and D21 participants were evaluated for weight, BMI, fasting glycaemia (FG), fasting insulinaemia (FI), fasting insulin resistance index (FIRI), area under the glycaemic (G-AUC) and insulinaemic (I-AUC) curves from an OGT test, and for PDH activity assayed in their circulating lymphocytes before (basal activity) and after incubation with 33 or 330 pmol/l insulin. At D2, basal PDH activity and clinical parameters were assayed. RESULTS: In both groups of participants at D0 all parameters tested were constant with respect to D-21; at D2, only basal PDH activity rose significantly; at D21, basal and insulin stimulated PDH activities were normalized and weight decreased significantly, as did FG, FI, FIRI and G-AUC in the diabetic, and FI, FIRI, G-AUC and I-AUC in the non-diabetic participants. CONCLUSION: In obese, non-diabetic and diabetic individuals on dexfenfluramine treatment, amelioration of clinical parameters and indexes of poor insulin sensitivity of blood glucose homeostasis are preceded by correction, in their circulating lymphocytes, of PDH derangements described as reflecting a disorder underlying insulin resistance.

Abnormally high TSH in subject with thyrotoxicosis affected by congenital hypothyroidism. Case report.

Inappropriate secretion of TSH (IST) refers to a heterogeneous group of syndromes in which patients show unsuppressed TSH levels in spite of high serum free thyroid hormone concentrations. It has been recognised that IST can be due to both thyroid hormone resistance (RTH) and pituitary TSH-secreting tumours. The former can be generalised (GRTH) or pituitary (PRTH) if the resistance is more severe in the pituitary than in the rest of the tissues. This case report points out the persistence of this patient's TSH resistance to the inhibition of high concentrations of circulating thyroid hormones with clear symptoms of thyrotoxicosis even after many years of replacement therapy; it also suggests that in this case FT4 is the parameter to evaluate the therapy's effectiveness.

[Increased body mass index increase and insulin resistance parameters in dyslipidemia. Risk and positive correlation in essential obesity]. / Aumento del BMI e parametri di insulino-resistenza e di dislipidemia. Riscontro di correlazioni positive nell'obesità essenziale.

BACKGROUND: Obesity is frequently characterized by hyperinsulinemia with insulin-resistance, tendency to impaired glucose tolerance and by impaired lipidic picture. The relationship existing between some obesity parameters i.e. BMI and weight excess (EP) regarding ideal weight calculated according Lorenz's formula and main parameters both of insulin-resistance and lipidic picture can be interesting. METHODS: 58 obese subject (10 M e 48 F) age 38 +/- 6.2 years (mean +/- DS) with BMI 34.3 +/- 5.3 and EP 33.7 +/- 15; they didn't suffer from hypertension and diabetes; they was subjected to an OGTT and evaluation of glycemia and insulinemia after 0', 60', 90', 120', 150', 180'. Moreover an assessment of lipidic state (cholesterol, triglyceride, HDL, LDL) was carried out. Glycemia and insulinemia with respective areas under curve (AUC glyc. e AUC ins.) and increases (AUCI glyc. e AUCI ins.) were compared with BMI and EP for searching relationship. The same was done for lipidic state. RESULTS: BMI was found positively related with glycemia after 0' (r = 0.3043, p < 0.05) 60' (r = 0.3465, p < 0.05) 120' (r = 0.2895, p < 0.05) with AUC glyc. (r = 0411, p < 0.01) and AUCI glyc. (r = 0.276, p < 0.05), with insulinemia after 0' (r = 0.365, p < 0.01) 60' (r = 0.350, p < 0.01) and with AUC ins. (r = 0.272, p < 0.05). HDL is negatively (r = -0.307, p < 0.05) instead of triglyceride positive related (r = 0.338, p < 0.05) with BMI. EP is positively related with glycemia after 0' (r = 0.376, p < 0.01), 60' (r = 0.362, p < 0.01), 120' (r = 0.290, p < 0.05), with AUC glyc. (r = 0.422, p < 0.01), with insulinemia after 0' (r = 0.512, p < 0.01), 60' (r = 0.473, p < 0.01) with AUC ins. (r = 0.420, p < 0.01) and AUCI ins. (r = 0.354, p < 0.01). Triglyceride was positively related (r = 0.365 p < 0.01) with EP. CONCLUSIONS: These relationships suggest that BMI and EP can be considered as indicators not only of obesity degree, but also of hyperinsulinemia and, to a lesser extent, dyslipidemia severity.

Insulin resistance in obese subjects and newly diagnosed NIDDM patients and derangements of pyruvate dehydrogenase in their circulating lymphocytes.

BACKGROUND: In circulating lymphocytes of individuals with insulin resistance and overt hyperglycaemia (NIDDM patients), alterations, affecting pyruvate dehydrogenase (PDH), the key enzyme in glucose oxidative breakdown, have been observed. They include below normal enzyme activity and, in vitro, no enzyme response to insulin at low physiological levels (5 microU/ml) as well as activation up to the basal values of controls with insulin at high physiological levels (50 microU/ml), instead of activation and inhibition respectively, as in controls. OBJECTIVE: To investigate whether these alterations characterize circulating lymphocytes of individuals with insulin resistance in whom derangements of glucose homeostasis are absent (obese subjects with normal glucose tolerance), or present but still controllable (nonobese and obese newly diagnosed NIDDM patients on an appropriate diet). SUBJECTS: Thirty obese subjects (BMI 36 +/- 3) responding normally to an oral glucose tolerance (OGT) test; 60 newly diagnosed NIDDM patients (30 nonobese, BMI 22 +/- 4 and 30 obese, BMI 38 +/- 2); 30 nonobese (BMI 21 +/- 5) and nondiabetic subjects, with no family history for NIDDM, served as controls. METHODS: Evaluation of PDH activity in circulating lymphocytes before and after exposure to insulin at 5 and 50 microU/ml, and of clinical parameters before and during an OGT test. RESULTS: 1) in circulating lymphocytes of obese nondiabetic subjects as well as obese and nonobese newly diagnosed NIDDM patients, PDH activity was significantly below normal. In vitro, enzyme response to insulin at 5 microU/ml was reduced in nonobese NIDDM patients with respect to controls, and absent in obese nondiabetic subjects and obese NIDDM patients. Enzyme response to insulin at 50 microU/ml was reversed in all individuals, which allowed enzyme activity to recover up to the basal level of controls. 2) In NIDDM patients and obese nondiabetic subjects, undergoing an OGT test, the area under the glycaemic curve (g-AUC) was as expected; the area under the insulinaemic curve (i-AUC) was increased in both groups with respect to controls, but significantly only in the latter. CONCLUSION: In individuals with insulin resistance PDH activity in their circulating lymphocytes rises up to basal levels of controls, only if these cells are exposed to insulin at high physiological concentrations, and g-AUC is normal only in those subjects who have significantly increased i-AUC. This suggests that with insulin at sufficiently high concentrations both parameters can be corrected. We conclude that the derangements responsible for the alterations of the two parameters share common features and thus the described PDH alterations in circulating lymphocytes reflect systemic insulin resistance whether accompanied by hyperglycaemia or not.

Clinical and genetic variability in XX sex-reversed patients.

Three 46, XX hypogonadal subjects are described who exhibited different clinical and genetic characteristics. Two patients, with complete sex-reversal, are sterile males with hypogonadal features; the third patient, with partial sex-reversal, presented with a eunuchoid appearance and with ambiguous genitalia. Polymerase chain reaction (PCR) amplification of DNA from these patients showed the presence of a translocation of the sex-determining region of the Y chromosome (Sry) only in the first two patients described.

[Essential obesity: an unresolved clinical problem. Considerations on central appetite stimulants and inhibitors]. / L'obesità essenziale: problema clinico non ancora risolto. Considerazioni sugli stimolatori ed inibitori centrali dell'appetito.

The recent theories on the etiology of obesity have attributed more importance to the mechanisms of feeding control. The amount of calories taken daily seems to be under the control of a group of substances which stimulate or inhibit the appetite at the hypothalamic level. The hypothalamus is particularly rich in neurotransmitters or neurohormones which are biologically active and represent the connexion between the cells of the upper centers and the hypothalamus and they interfere in the regulation of feeding. The authors pass in review the more recent literature data regarding the main appetite stimulators as well as their site and their mechanism of action.

[The role of opioid antagonists in the treatment of obesity. Results of a clinical trial with naltrexone]. / Il ruolo degli antagonisti oppioidi nel trattamento dell'obesità. Risultati di una sperimentazione clinica con naltrexone.

On the basis of literature data relative to the alteration of beta-endorphin tone in obese subjects, we conducted a clinical trial employing Naltrexone (a receptorial antagonist of endogen opioids) in order to evaluate its efficacy in increasing the compliance of these subjects on dietary treatment. The drug dosage was 50 mg/daily (100 mg/die). The clinical study was carried out following the double-blind crossover method for a period of 4 months in a group of 17 obese subjects who also underwent to psychodiagnostic interviews. Significant weight reduction was observed in the 9 patients who carried out the treatment by assuming Naltrexone (kg 4.00 +/- 3.97) rather than with placebo (kg 0.96 +/- 4.95). The drug was subjectively well tolerated and it did not alter the endocrine, metabolic, psychometric, and cardiovascular monitored parameters. The insulin secretion during OGTT did not show significant alterations. Our data emphasize the Naltrexone efficacy in improving the compliance of the obese subjects during dietary treatment.

[Psychometric evaluations in a group of obese patients]. / Valutazioni psicometriche in un gruppo di pazienti obesi.

Several reported cases point out significant alterations in the psychologic profile of obese subjects and the utility of a psychotherapeutic support to the dietetic or pharmacological therapy. Each patient underwent a psychodiagnostic interview and the following rating-scales were applied: QPF (Psychophysiological Test); STAI X-1 and X-2 (State and Trait Anxiety Inventory); Hamilton-D (Depression); ZUNG (Self-administered Depression Test); TSR (Reaction Schemes Test). We observed an increase in the answer of the blocked projection (in the 40% of subjects), of negation (26.6%), of guilt (13.3%), a decrease in the projection answer (33.3%), high scores of QPF (21%). The STAI, the Hamilton, and the Zung were altered in the 10% of the examined subjects. Our data emphasize the importance of an individual psychotherapeutic support in a subgroup of obese subjects.

[Sipple's syndrome. Review of the literature and personal case load]. / La sindrome di Sipple. Revisione della letteratura e casistica personale.

A family with Sipple's syndrome was studied over three generations. The syndrome is transmitted as a dominant autosomic hereditary trait with high penetrance and varying expressiveness. Our series include 13 patients of three generations: 1) husband and wife who were 1st degree cousins; 2) 4 sisters and 1 brother; 3) 5 sisters and 1 brother. In the first generation we did not find any sign that could be related to the syndrome, in the second generation 2 thyroid carcinomas and a pheochromocytoma were present, and in the third one 2 sisters had these neoplasias, one pheochromocytoma and the other thyroid cancer, another one had marfanoid habitus and the fourth one had pheochromocytoma. This series includes 11 subjects of the second and third generation; the Sipple's syndrome was present in 7 females. The incidence of the syndrome was 63.8% and present only in female subjects. The high incidence rate could be caused by the strict relation between the grandparents. The diffusion of this pathology may be related to the high penetrance of the gene(s) involved whereas the clinical variations may be interpreted to the variable expressiveness and, even more so, as evidence that the other manifestations of the syndrome may occur later in time.

Reductions of body weight and blood pressure in obese hypertensive patients treated by diet. A retrospective study.

A retrospective survey was carried out in a group of 39 previously obese and hypertensive subjects to evaluate: the rate of blood pressure reductions achieved by dietary treatment, the smallest weight reduction accompanied by a significant decrease in blood pressure, and the mean weight reduction associated with normalization of pressure. Significant decrease in weight, systolic and diastolic pressures were observed after 15 days of treatment in 21 patients who had never assumed antihypertensive drugs and 9 who were on medication. Blood pressure normalization was achieved in 19 of the former with a weight reduction of 7.63 +/- 4.29% kg and in 7 of the latter after losing 8.63 +/- 2.20% kg; in 3 patients the medication was reduced and in 1 was withdrawn. In 4 patients weight but not pressure had decreased and in 5 neither did. Reduction, often normalization, of blood pressure can be obtained through relatively minor weight loss in most obese hypertensive patients.

Antiandrogenic properties of spironolactone. Clinical trial in the management of female hirsutism.

The effect of spironolactone on female hirsutism was studied in 18 patients. The drug was administered at the dose of 400 mg for the first ten days and 300-200 mg later on in a first group of women (Group A); a second group (Group B) was given 200 mg spironolactone for the whole length of therapy. A significant decrease of the index of Ferriman and Gallwey (p = 0.01) was noted from the 100th day of treatment; acne and seborrhoea improved concomitantly. Plasma total testosterone values fell from 0.64 +/- 0.24 ng/ml to 0.32 +/- 0.12 ng/ml (p = 0.002) during the first 5 days only in the patients of Group A; in the other patients no significant changes were observed. PRL did not significantly change from pretreatment values; FSH and LH values at the 5th, 10th, and 15th day of therapy did not show a uniform course in both groups. On the basis of these results spironolactone administration appears promising in the therapy of female hirsutism.

Effect of sulpiride on plasma prolactin levels in women with puerperal or pathological hyperprolactinaemia.

The effect of 100 mg im sulpiride on plasma Prl levels was studied in 10 normal females, 21 patients with galactorrhoea and normal plasma Prl, 10 women with puerperal hyperprolactinaemia and 27 patients with amenorrhoea-galactorrhoea and high plasma Prl levels. The response to sulpiride in patients with galactorrhoea but normal PRL was slightly higher (P < 0.05) than that observed in normal women, but only if expressed in per cent. Women with puerperal hyperprolactinaemia respond to the drug with a marked increase in Prl (mean +/- SEM: 563.0 +/- 142.8%), even though their baseline values are already very high (mean +/- SEM: 133.6 +/- 23.8 ng/ml). By contrast, there is a lower or no response to sulpiride in 13 women with pituitary tumour. The same was true in 11 patients with hyperprolactinaemia of uncertain aetiology but also 10 of these subjects presented signs suggestive of a tumour. In the last 3 patients with pathological hyperprolactinaemia in whom a consistent Prl increase after sulpiride was observed, hyperprolactinaemia was probably not of tumourous origin. On the basis of these results, the sulpiride test appears promising for discriminating between organic and 'functional' cases of enhanced Prl secretion.