Nonalcoholic fatty liver disease (NAFLD) has been associated with the insulin-resistance syndrome, at present defined as the metabolic syndrome, whose limits were recently set. We assessed the prevalence of the metabolic syndrome in 304 consecutive NAFLD patients without overt diabetes, on the basis of 3 or more criteria out of 5 defined by the U.S. National Institutes of Health (waist circumference, glucose, high-density lipoprotein [HDL]-cholesterol, triglycerides, and arterial pressure). The prevalence of the metabolic syndrome increased with increasing body mass index, from 18% in normal-weight subjects to 67% in obesity. Insulin resistance (Homeostasis Model Assessment method) was significantly associated with the metabolic syndrome (odds ratio [OR], 2.5; 95% CI, 1.5-4.2; P < .001). Liver biopsy was available in 163 cases (54%). A total of 120 patients (73.6%) were classified as having nonalcoholic steatohepatitis (NASH); 88% of them had a metabolic syndrome (vs. 53% of patients with pure fatty liver; P < .0001). Logistic regression analysis confirmed that the presence of metabolic syndrome carried a high risk of NASH among NAFLD subjects (OR, 3.2; 95% CI, 1.2-8.9; P ‫؍‬ .026) after correction for sex, age, and body mass. In particular, the syndrome was associated with a high risk of severe fibrosis (OR, 3.5; 95% CI, 1.1-11.2; P ‫؍‬ .032). In conclusion, the presence of multiple metabolic disorders is associated with a potentially progressive, severe liver disease. The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension, and ultimately the metabolic syndrome puts a very large population at risk of forthcoming liver failure in the next decades. (HEPATOLOGY 2003;37:917-923.)

Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU ⅐ m ؊2 ⅐ min ؊1) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m 2 . Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (؊69% in NAFLD vs. ؊84% in control subjects; P ‫؍‬ 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-2 H 2 ]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P ‫؍‬ 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulinmediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance. Diabetes

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We studied a group of obese hyperandrogenic amenorrheic women to determine the effects of weight loss on anthropometry, hormonal status, menstrual cycles, ovulation, and fertility. Fourteen women had polycystic ovaries, two the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, one hirsutism of adrenal origin, and three idiopathic chronic anovulation. The duration of amenorrhea before the study ranged from 3-17 months [mean, 8.6 +/- 4.5 (+/- SD)]. All women ate a hypocaloric diet for a period of 8.0 +/- 2.4 months. Weight loss ranged from 4.8 to 15.2 kg (mean, 9.7 +/- 3.1 kg; 1.35 +/- 0.56 kg/month) and the waist to hip ratio, which was used as a measurement of body fat distribution, decreased from 0.86 +/- 0.1 to 0.81 +/- 0.06 (P less than 0.0001). The women's mean plasma testosterone and LH concentrations decreased significantly (P less than 0.001 and P less than 0.005, respectively). A significant positive correlation was found between the decreases in plasma testosterone levels and the decreases in glucose-stimulated insulin levels. Moreover, the decreases in the waist to hip ratio correlated positively with the decreases in glucose-stimulated insulin levels and inversely with the decreases in plasma 17 beta-estradiol. No relationships were found between weight loss and the changes in plasma insulin, steroid, and gonadotropin concentrations. The responsiveness to the weight reduction program was evaluated by comparing the number of menstrual cycles during the study period with the number reported before it. Eight women had significantly improved menstrual cyclicity (responders), while 12 did not (nonresponders). The clinical characteristics and hormone values were similar in responder and nonresponder women. In the group as a whole, 33% of the menstrual cycles during the study were ovulatory, and 4 pregnancies occurred. Hirsutism improved significantly in more than half of the women, as did acanthosis nigricans when present. We conclude that weight loss is beneficial in all obese hyperandrogenic women regardless of the presence of polycystic ovaries, the degree of hyperandrogenism, and the degree and distribution of obesity.

Interventions. An initial intensive treatment period (3-6 months) was followed by a less intensive continuous care (a follow-up control every 2-4 months).Main outcome measures. Attrition, reasons for treatment interruption and BMI change. Data were recorded by telephone interview in dropouts. Results. Only 157 patients (15.7%) were in continuous treatment at 36 months. The main reasons of attrition were logistics, unsatisfactory results and lack of motivation. The only basal predictor for continuous care was lower Expected One-Year BMI Loss (P ¼ 0.016). The probability of dropout increased systematically for any 5% expected BMI loss (Hazard ratio, 1.05; 96% confidence interval, 1.01-1.09). The mean percentage weight loss was greater in continuers (5.2% vs. 3.0% in dropouts; P ¼ 0.016). However, the dropouts satisfied with the results or confident to lose additional weight without professional help reported a mean weight loss of 9.6% and 6.5% respectively. Discussion. Continuous care produces long-term weight loss only in a subgroup of obese patients seeking treatment in medical centres. The finding that subgroups of dropouts report long-term weight loss has implication for the treatment of obesity.

Minimum criteria for the metabolic syndrome are met in most patients with Type 2 diabetes. Correct identification of the syndrome is important for an integrated approach to reduce the high costs and the associated disabilities. The ATPIII proposal more clearly identifies the burden of coronary heart disease associated with the metabolic syndrome.

DALLE GRAVE, RICCARDO, SIMONA CALUGI, FLAVIA MAGRI, MASSIMO CUZZOLARO, ELISABETTA DALL'AGLIO, LUCIO LUCCHIN, NAZARIO MEL-CHIONDA, GIULIO MARCHESINI, AND THE QUO-VADIS STUDY GROUP. Weight loss expectations in obese patients seeking treatment at medical centers. Obes Res. 2004;12:2005-2012. Objective: To investigate weight loss expectations (expected 1-year BMI loss, dream BMI, and maximum acceptable BMI) in obese patients seeking treatment and to examine whether expectations differ by sex, weight, diet and weight history, age, psychological factors, and primary motivations for weight loss. Research Methods and Procedures: 1891 obese patients seeking treatment in 25 Italian medical centers (1473 women; age, 44.7 Ϯ 11.0 years; BMI, 38.2 Ϯ 6.5 kg/m 2 ) were evaluated. Diet and weight history, weight loss expectations, and primary motivation for seeking treatment (health or improving appearance) were systematically recorded. Psychiatric distress, binge eating, and body image dissatisfaction were tested by self-administered questionnaires (Symptom CheckList-90, Binge Eating Scale, and Body Uneasiness Test). Results: In 1011 cases (53.4%), 1-year expected BMI loss was Ն9 kg/m 2 , dream BMI was 26.0 Ϯ 3.4 kg/m 2 (corresponding to a 32% loss), and maximum acceptable BMI was 29.3 Ϯ 4.4 kg/m 2 (Ϫ23%). BMI and age were the strongest predictors of weight goals. Weight loss necessary to reach the desired targets was largely in excess of weight loss observed during previous dieting. Psychiatric distress, body dissatisfaction, and binge eating did not predict weight loss expectations. The primary motivation for weight loss was concern for future or present health; women seeking treatment to improve appearance had a lower grade of obesity, were younger, and had first attempted weight loss at a younger age. Discussion: Obese Italian patients had unrealistic weight loss expectations. There were significant disparities between patients' perceptions and physicians' weight loss recommendations of desirable treatment outcome.