A new predictive equation for evaluating women body fat percentage and obesity-related cardiovascular disease risk.

BACKGROUND: Obesity represents a global public health problem due to its association with cardiovascular diseases and reduced lifespan. The most widely used classification of obesity is expressed as Body Mass Index (BMI); however, this formula is an imprecise adiposity measurement that ignores several important factors involved. Body Adiposity Index (BAI) was more recently proposed as an indirect evaluation of percentage body fat (PBF). PBF is a direct measure of person's relative body fat and a better predictor of obesity-related risk diseases than BMI and BAI. Since obesity and consequent diseases are considered epidemic, new accurate formulas for epidemiological studies are of interest to the scientific community. Because direct measurement of body composition could be quite expensive, the aims of our work were to analyse the distributions of PBF by Dual X-ray absorptiometry, and the creation of new predictive equation using only anthropometric measures that could be helpful to clinicians to assess easily body fat of female patients. METHODS/RESULTS: A sample of 1,031 Caucasian Italian women was recruited and BMI, BAI and PBF were evaluated. With the aim of developing a predictive model of PBF a multivariate regression model was fitted to observed data. CONCLUSIONS: The definition of universally recognized PBF by gender and age could have public health implications. In this study, we developed a new predictive PBF equation that does not require the use of medical instruments or skilled measurement techniques and that may be easily applicable to Italian women.

Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes.

AIMS/HYPOTHESIS: Recent evidence suggests that reduced synthesis of nitric oxide in endothelial cells, i.e. endothelial dysfunction, contributes to the impaired action of insulin in the vasculature of patients with type 2 diabetes. We investigated whether selective inhibition of phosphodiesterase-5 by tadalafil has beneficial effects on peripheral microcirculation and glucose uptake in these patients. METHODS: We enrolled seven postmenopausal women with type 2 diabetes and ten age-matched healthy women as controls in a placebo-controlled study to evaluate the acute metabolic effects of tadalafil. We performed microdialysis and blood flow measurements in muscle, and sampled arterial and deep venous blood before and after a single dose of tadalafil 20 mg or placebo. Circulating glucose and insulin levels, muscle capillary recruitment as reflected by permeability surface area for glucose (PS(glu)) and forearm glucose uptake were measured. RESULTS: In women with type 2 diabetes, but not in the control group, tadalafil induced increases in the incremental AUC for PS(glu) (tadalafil vs placebo 41 +/- 11 vs 4 +/- 2 ml [100 g](-1) min(-1), p < 0.05) and forearm glucose uptake (46 +/- 9 vs 8 +/- 4 micromol [100 g](-1) min(-1), p < 0.05). The variable that best predicted forearm glucose uptake was PS(glu), which explained 70% of its variance. However, fasting glucose and insulin concentrations were similar following treatment with placebo or tadalafil in the two groups. CONCLUSIONS/INTERPRETATION: This study suggests that tadalafil evokes positive metabolic effects in insulin-resistant women with type 2 diabetes.

Insulin differentially modulates the peripheral endocannabinoid system in human subcutaneous abdominal adipose tissue from lean and obese individuals.

Human obesity has been associated with a dysregulation of the peripheral and adipose tissue (AT) endocannabinoid system (ES). The aim of this study was to elucidate the acute in vivo effects of insulin on gene expression of the cannabinoid type 1 (CB-1) and type 2 (CB-2) receptors, as well as of the fatty acid amide hydrolase (FAAH) in the sc abdominal adipose tissue (SCAAT). Nine lean (L) and 9 obese (OB), but otherwise healthy males were studied in the fasting state and during a euglycemic hyperinsulinemic clamp (40 mU/m2 * min(-1)). SCAAT biopsies were obtained at baseline and after 270 min of i.v. maintained hyperinsulinemia. The basal SCAAT gene expression pattern revealed an upregulation of the FAAH in the OB (p=0.03 vs L), whereas similar CB-1 and CB-2 mRNA levels were seen. Following hyperinsulinemia, the FAAH mRNA levels significantly increased approximately 2-fold in the L (p=0.01 vs baseline) but not in the OB. In contrast, insulin failed to significantly change both the adipose CB-1 and CB-2 gene expression. Finally, the FAAH gene expression positively correlated with the fasting serum insulin concentration (r 0.66; p=0.01), whereas an inverse association with the whole-body glucose disposal (r -0.58; p<0.05) was seen. Taken together, these first time observations demonstrate that the ES-related genes in the SCAAT differentially respond to hyperinsulinemia in lean/insulin-sensitive and in obese/insulin-resistant individuals. We suggest that insulin may play a key role in the obesity-linked dysregulation of the adipose ES at the gene level.

Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients.

AIM: The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese hypertensive patients, with a specific attention to cardiovascular effects and to side effects because of this treatment. METHODS: Patients were enrolled, evaluated and followed at three Italian Centres of Internal Medicine. We evaluated 115 obese and hypertensive patients. (55 males and 60 females; 26 males and 29 females, aged 50 +/- 4 with orlistat; 28 males and 30 females, aged 51 +/- 5 with sibutramine). All patients took antihypertensive therapy for at least 6 months before the study. We administered orlistat or sibutramine in a randomized, controlled, double-blind clinical study. We evaluated anthropometric variables, blood pressure and heart rate (HR) during 12 months of this treatment. RESULTS: A total of 113 completed the 4 weeks with controlled energy diet and were randomized to double-blind treatment with orlistat (n = 55) or sibutramine (n = 58). Significant body mass index (BMI) improvement was present after 6 (p < 0.05), 9 (p < 0.02), and 12 (p < 0.01) months in both groups, and body weight (BW) improvement was obtained after 9 (p < 0.05) and 12 (p < 0.02) months in both groups. Significant waist circumference (WC), hip circumference (HC) and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p < 0.05, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05) was present in orlistat group after 12 months. Lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides] reduction (p < 0.05, respectively) was observed in orlistat group and triglyceride reduction (p < 0.05) in sibutramine group after 12 months. No significant change was observed in sibutramine group during the study. No significant HR variation was obtained during the study in both groups. Of the 109 patients who completed the study, 48.1% of patients in the orlistat group and 17.5% of patients in the sibutramine group had side effects (p < 0.05 vs. orlistat group). Side-effect profiles were different in the two treatment groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pressure (both SBP and DBP) in two patients, but it has been controlled by antihypertensive treatment. The vitamin changes were small and all mean vitamin and beta-carotene values stayed within reference ranges. No patients required vitamin supplementation. CONCLUSIONS: Both orlistat and sibutramine are effective on anthropometric variables during the 12-month treatment; in our sample, orlistat has been associated to a mild reduction in blood pressure, while sibutramine assumption has not be associated to any cardiovascular effect and was generically better tolerated than orlistat.

Comparison of metabolic effects of orlistat and sibutramine treatment in Type 2 diabetic obese patients.

AIM: The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese diabetic patients of both sexes, with specific attention to metabolic pattern-induced changes and cardiovascular effects. METHODS: Patients were enrolled, evaluated, and followed in 3 Italian Centres of Internal Medicine. We evaluated 144 obese diabetic patients. All were required to have been diagnosed as being diabetic for at least 6 months, and had glycaemic control with diet alone or diet and oral hypoglycaemic agents. We administered orlistat (360 mg/d) or sibutramine (10 mg/d) in a randomized, controlled, double-blind clinical study, and evaluated anthropometric variables, glycaemic control, blood pressure and heart rate (HR) during 12 months of this treatment. RESULTS: A total of 141 (69 males and 72 females; 35 males and 36 females, aged 53 +/- 5 yr with orlistat; 34 males and 36 females, aged 51 +/- 4 yr with sibutramine) completed the 4 weeks on controlled-energy diet and were randomized to double-blind treatment with orlistat (n=71) or sibutramine (n=70). Significant body mass index (BMI) improvement was present after 6 (p<0.05), 9 (p<0.02), and 12 (p<0.01) months in both groups. Significant waist circumference (WC), hip circumference (HC), and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p<0.05, respectively) in both groups. Significant HbA1c decrease was obtained after 6 (p<0.05), 9 (p<0.02), and 12 (p<0.01) months in both groups. After 9 and 12 months, mean fasting plasma glucose (FPG) and post-prandial plasma glucose (PPG) levels were significantly decreased in both groups (p<0.05 andp<0.02, respectively). Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p<0.05) was present in the orlistat group after 12 months. No significant change in blood pressure measurements was observed in the sibutramine group during the study. No significant HR variation was obtained during the study in either group. Of the 133 patients who completed the study, 33.8% of patients in the orlistat group and 13.2% of patients in the sibutramine group had side effects (p<0.05 vs orlistat group). Side effect profiles were different in the two treatmen groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pres sure (both SBP and DBP) in one patient, but it was controlled by anti-hypertensive treatment. The vita min changes were small and all mean vitamin and beta-carotene values stayed within reference ranges. No patients required vitamin supplementation. CONCLUSIONS: Both orlistat and sibutramine were effective on anthropometric variables and on metabolic pattern during the 12-month treatment; in our sample, orlistat appears to be slightly more efficacious as an anti-obesity drug, while sibutramine intake was not associated to any cardiovascular effect and was generally better tolerated than orlistat.

Acute effects of lyophilised red wine on total antioxidant capacity in healthy volunteers.

This is an open, cross-over study to examine the acute effects of lyophilised red wine (LYOW) on total antioxidant capacity and some metabolic variables in 10 healthy subjects (age 27.7 +/- 3.9 yr) following a light meal. Each subject was studied on two occasions for a 360-min period, after consumption of a 1.22 MJ (291 kcal) meal; on one occasion without and on another occasion with intake of LYOW with high antioxidant activity [15.4 mM trolox equivalent (eq)]. Plasma oxygen radical absorbance capacity (ORAC) values decreased significantly after meal alone from 4.97 +/- 0.499 to 4.39 +/- 0.383 mM trolox eq. (mean +/- SD; p < 0.05) and remained lower until 360 min compared to basal values (p < 0.05). In contrast, ORAC values after meal with LYOW increased significantly from a baseline of 4.79 +/- 0.356 to the highest value of 6.39 +/- 0.570 mM trolox eq at 90 min; then, it decreased to a plateau of 4.99 +/- 0.316 mM trolox eq (p < 0.05), whose values were still higher than baseline ones until 360 min and also significantly different from the values obtained without LYOW from 90 to 360 min (p < 0.05). No correlations were observed between dietary antioxidant vitamin, fruit and vegetable intakes and plasma antioxidant capacity. No differences were found in plasma insulin and glucose values after meal between the two occasions. We conclude that moderate drinking of red wine (350 ml) with high antioxidant capacity increased and sustained for 360 min plasma antioxidant level of 10 healthy subjects after a meal.

Expression of endocrine autoantibodies in chronic hepatitis C, before and after interferon-alpha therapy.

Interferon-alpha (IFN-alpha) treatment for chronic hepatitis C (CHC) has been associated with thyroid autoimmunity and/or dysfunction. Only a few data concerning the prevalence of islet-cell or adrenal cortex autoantibodies in IFN-alpha-treated subjects are currently available. The aims of our study were to evaluate in CHC, 1) the prevalence and association of thyroid, islet-cell and adrenal autoantibodies, and 2) the appearance of endocrine dysfunction, before and after a 6 month IFN-alpha treatment. We analyzed serum samples from 203 adult patients at the time of clinical diagnosis of CHC and showed that the prevalence of thyroperoxidase (TPOAb), thyroglobulin (TGAb), TSH-receptor (TRAb), glutamic acid decarboxylase (GAD65Ab), IA-2/ICA512 (IA-2/ICA512Ab) and 21-hydroxylase (21OHAb) autoantibodies was similar to that observed among healthy control subjects of similar age and sex distribution. Among 99 patients with follow-up serum samples, 83 accepted and 16 refused IFN-alpha treatment. The IFN-alpha treatment was associated with increase of TPOAb levels in 3 subjects already positive at baseline, with progression to overt hypothyroidism in 2 of them. The de novo appearance of autoantibodies was observed in 5/80 (6%) cases for TPOAb, 1/81 (1.2%) for GAD65Ab and 2/81 (2.5%) for IA-2/ICA512Ab. Clinical or subclinical signs of either hyperthyroidism or hypothyroidism were demonstrated in 3/5 cases with de novo appearance of TPOAb. Four subjects, initially positive for either GAD65Ab or IA2/ICA512Ab, were all found negative after IFN-alpha-treatment. No subjects showed positivity for 21OHAb either at baseline or after the follow-up period. Our study suggests that, in CHC untreated patients, the prevalence of endocrine autoantibodies is similar to that observed in the general population. Furthermore, we demonstrate that IFN-alpha treatment is associated with the induction or enhancement of thyroid, but not of islet-cell or adrenal cortex autoimmunity.

Increased risk for endocrine autoimmunity in Italian type 2 diabetic patients with GAD65 autoantibodies.

OBJECTIVE: Glutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) in type 2 diabetic subjects with secondary failure to sulphonylurea treatment identify the so-called latent autoimmune diabetes of the adult (LADA). The aim of our study was to estimate the risk for endocrine autoimmunity in type 2 diabetic subjects with GAD65Ab. DESIGN AND PATIENTS: We analysed serum samples from 600 adult subjects with a clinical diagnosis of type 2 diabetes mellitus for the presence and levels of GAD65Ab and antibodies directed against the islet autoantigen IA-2/ICA512 (IA-2/ICA512Ab). All the patients had been treated initially with hypoglycaemic agents and/or diet for at least 1 year. GAD65Ab+ subjects were studied for the presence of thyroid peroxidase autoantibodies (TPOAb), 21 hydroxylase autoantibodies (21OHAb) and frequency of HLA class II haplotypes. RESULTS: GAD65Ab were found in 67/600 (11%) and IA-2/ICA512Ab in 12/600 (2%) subjects (P < 0.0001). The presence of GAD65Ab, but not that of IA-2/ICA512Ab, was significantly associated with insulin therapy, low BMI (P < 0.0001) and low basal C-peptide (P < 0.01). Islet-cell antibodies (ICA) were detected in 43/67 (64%) GAD65Ab+ and in 10/12 (83%) IA-2/ICA512Ab + subjects. TPOAb occurred more frequently in GAD65Ab+ (16/67, 24%) than in GAD65Ab-subjects (9/174, 5%) (P < 0.0001). 21OHAb were detected only in GAD65Ab+ subjects (3/67, 4.5%) (P = 0.03 vs. GAD65Ab-subjects). None of the 21OHAb+ subjects had metabolic or clinical signs of adrenal dysfunction. HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent in GAD65Ab+ subjects than in healthy controls (OR = 5.42, corrected P < 0.0026). The presence of TPOAb was significantly associated with DR3-DQ2 (P = 0.024). CONCLUSIONS: Our study demonstrates that the presence of GAD65Ab identifies a subgroup of type 2 diabetic patients with high risk for thyroid and adrenal autoimmunity, and that both GAD65Ab and TPOAb are associated with the presence of HLA-DR3-DQ2, in these patients.

Meal intake similarly reduces circulating concentrations of octanoyl and total ghrelin in humans.

UNLABELLED: ABSTRACT. Several data show that meal intake and nutritional status regulate circulating ghrelin concentrations in humans. Ghrelin mainly circulates in two different forms: octanoyl and des-octanoyl ghrelin. Most circulating ghrelin is des-octanoyl ghrelin which is considered inactive because it lacks endocrine activity. However, recent evidence suggests that des-octanoyl ghrelin exerts biological activity such as stimulation of adipogenesis, cardiovascular effects and control of cell growth. In healthy humans, although the total ghrelin concentration is known to peak before meals and to be reduced by food intake, no data are available about the octanoyl ghrelin response in the absorptive state. Therefore, after an overnight fast, we compared the effects of a mixed meal ingestion (meal study) or of additional 240 min fasting (control study) on plasma concentrations of octanoyl and total ghrelin in 6 healthy subjects (body mass index: 23 +/- 0.7). At baseline, octanoyl-ghrelin accounted for 3.15 +/- 0.2% of total circulating ghrelin without differences between the two sessions. A similar ratio was maintained in the absorptive state with no differences between the studies and basal values. Compared with control, meal intake significantly suppressed (nadir at 90 min) octanoyl and total ghrelin by 38 +/- 3 and 40 +/- 3% of basal values, respectively. In the meal study, multivariate analysis of variance showed that serum insulin best predicted plasma octanoyl-ghrelin concentrations accounting for 97% of its variation (r2 = -0.97,p = 0.0016). IN CONCLUSION: in healthy humans, octanoyl-ghrelin represents about 3-4% of total circula-ting ghrelin and this ratio is closely maintained in post-absorptive and absorptive states.

Metabolic response to exercise.

At the beginning, the survival of humans was strictly related to their physical capacity. There was the need to resist predators and to provide food and water for life. Achieving these goals required a prompt and efficient energy system capable of sustaining either high intensity or maintaining prolonged physical activity. Energy for skeletal muscle contraction is supplied by anaerobic and aerobic metabolic pathways. The former can allow short bursts of intense physical activity (60-90 sec) and utilizes as energetic source the phosphocreatine shuttle and anaerobic glycolysis. The aerobic system is the most efficient ATP source for skeletal muscle. The oxidative phosporylation of carbohydrates, fats and, to a minor extent, proteins, can sustain physical activity for many hours. Carbohydrates are the most efficient fuel for working muscle and their contribution to total fuel oxidation is positively related to the intensity of exercise. The first metabolic pathways of carbohydrate metabolism to be involved are skeletal muscle glycogenolysis and glycolysis. Later circulating glucose, formed through activated gluconeogenesis, becomes an important energetic source. Among glucose metabolites, lactate plays a primary role as either direct or indirect (gluconeogenesis) energy source for contracting skeletal muscle. Fat oxidation plays a primary role during either low-moderate intensity exercise or protracted physical activity (over 90-120 min). Severe muscle glycogen depletion results in increased rates of muscle proteolysis and branched chain amino acid oxidation. Endurance training ameliorates physical performance by improving cardiopulmonary efficiency and optimizing skeletal muscle supply and oxidation of substrates.

Diabetes and exercise.

Physical activity has acute and chronic effects on glucose, lipid and protein metabolism. Long-term effects of regular exercise are particularly advantageous for Type 2 diabetic patients. Regular aerobic exercise reduces visceral fat mass and body weight without decreasing lean body mass, ameliorates insulin sensitivity, glucose and BP control, lipid profile and reduces the cardiovascular risk. For these reasons, regular aerobic physical activity must be considered as an essential component of the cure of Type 2 diabetes mellitus. In this regard, individual behavioral strategies have been documented to be effective in motivating sedentary Type 2 diabetic subjects to the adoption and the maintenance of regular physical activity. In Type 1 diabetic subjects, the lack of the physiological inhibition of insulin secretion during exercise results in a potential risk of hypoglycemia. On the other hand, exercise-induced activation of counter-regulatory hormones might trigger an acute metabolic derangement in severe insulin-deficient subjects. Thus, diabetic patients, before starting exercise sessions, must be carefully educated about the consequences of physical activity on their blood glucose and the appropriate modifications of diet and insulin therapy.

Circulating ghrelin levels of visceral obese men are not modified by a short-term treatment with very low doses of GH replacement.

Ghrelin, the endogenous ligand for the GH secretagogue-receptor (GHS-R), in addition to its GH-releasing action, has orexigenic and adipogenic properties. These characteristics make ghrelin a potential hormone involved in the pathogenesis of obesity. Ghrelin levels are decreased in obese humans and it is unknown whether this decrease is responsible for the blunted GH secretion reported in visceral obesity. Since only few data are available on the potential feedback regulation by GH on systemic ghrelin concentrations, it remains to be established whether the correction of circulating GH concentrations in obese individuals affects ghrelin concentrations. To answer this question, we measured plasma ghrelin levels after a week of administration of low doses of recombinant human GH (rhGH) in a randomized, double-blind, placebo (PL)-controlled trial. This study was originally designed to evaluate the effects of GH replacement on lipid kinetics in visceral obese men. Six adult men with abdominal/visceral obesity (age 42+/-3 yr, body weight 107 +/- 10 kg, BMI 33 +/- 1 kg/m2, waist circumference 111 +/- 3 cm, mean +/- SE) were evaluated in the basal state (BS) and after one week of treatment with subcutaneous bedtime injections of either PL, 2.5 (GH2.5) or 3.3 (GH3.3) pg/kg/die of rhGH. In comparison to BS either PL, GH2.5 or GH3.3 did not significantly modify circulating ghrelin concentrations (p = 0.77). In contrast, a significant increase of serum GH (p = 0.0028), IGF-I (p = 0.0033) and whole body rate of lipolysis (p = 0.038, GH2.5; p = 0.009, GH3.3) occurred, in comparison to BS or PL, after GH2.5 and GH3.3, without differences between the two treatments. These data demonstrate that in abdominal/visceral obese men a short-term treatment with very low doses of rhGH replacement, sufficient to augment the rate of lipolysis, do not modify circulating ghrelin levels.

Effects of whole-body vibration exercise on the endocrine system of healthy men.

Whole-body vibration is reported to increase muscle performance, bone mineral density and stimulate the secretion of lipolytic and protein anabolic hormones, such as GH and testosterone, that might be used for the treatment of obesity. To date, as no controlled trial has examined the effects of vibration exercise on the human endocrine system, we performed a randomized controlled study, to establish whether the circulating concentrations of glucose and hormones (insulin, glucagon, cortisol, epinephrine, norepinephrine, GH, IGF-1, free and total testosterone) are affected by vibration in 10 healthy men [age 39 +/- 3, body mass index (BMI) of 23.5 +/- 0.5 kg/m2, mean +/- SEM]. Volunteers were studied on two occasions before and after standing for 25 min on a ground plate in the absence (control) or in the presence (vibration) of 30 Hz whole body vibration. Vibration slightly reduced plasma glucose (30 min: vibration 4.59 +/- 0.21, control 4.74 +/- 0.22 mM, p=0.049) and increased plasma norepinephrine concentrations (60 min: vibration 1.29 +/- 0.18, control 1.01 +/- 0.07 nM, p=0.038), but did not change the circulating concentrations of other hormones. These results demonstrate that vibration exercise transiently reduces plasma glucose, possibly by increasing glucose utilization by contracting muscles. Since hormonal responses, with the exception of norepinephrine, are not affected by acute vibration exposure, this type of exercise is not expected to reduce fat mass in obese subjects.