Nazario Melchionda

Metformin in non-alcoholic steatohepatitis

There is no established treatment for steatohepatitis in patients who are not alcoholics. This disease is a potentially progressive liver disease associated with hepatic insulin resistance. Only a weight-reducing diet in overweight patients has proved effective. We treated 20 patients who had steatohepatitis but were not alcoholics with metformin (500 mg three times a day for 4 months), an agent that improves hepatic insulin sensitivity. When compared with the six individuals not complying with treatment, long-term metformin significantly reduced mean transaminase concentrations, which returned to normal in 50% of actively-treated patients. Also, insulin sensitivity improved significantly and liver volume decreased by 20%. Similar data have been reported in insulin-resistant ob/ob mice with fatty liver. A randomised-controlled study is needed.

WHO and ATPIII proposals for the definition of the metabolic syndrome in patients with Type 2 diabetes

Aims  Different criteria have been proposed by the World Health Organization (WHO) and by the Third Report of the National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) for the diagnosis of the metabolic syndrome. Its identification is of particular importance for coronary risk assessment.

Effect of weight loss and antiandrogenic therapy on sex hormone blood levels and insulin resistance in obese patients with polycystic ovaries

This study was performed in two randomly defined groups of obese patients with polycystic ovaries to investigate the overall effects of hypocaloric diet combined (group 2) or not combined (group 1) with an antiandrogenic therapy (cyproterone acetate, 50 mg/day, plus ethinyl estradiol, 0.05 mg/day) on sex hormone plasma levels, insulin secretion and resistance, and body weight loss and on their reciprocal interrelationships. All obese patients with polycystic ovaries showed elevated luteinizing hormone and androgen levels, hyperinsulinemia, and marked insulin resistance. After an average period of 3 months both groups showed a similar weight loss and a similar reduction in the insulin-resistant state. During treatment in group 1 three patients had a greater frequency of menstrual bleeding, and in one of them an ovulatory cycle was documented. Whereas, no changes in gonadotropin and sex steroid levels were found in group 1, a significant fall was observed in group 2. No relationships were observed between these changes and those which occurred on insulin levels. We conclude that hyperandrogenism in obese patients with polycystic ovaries does not appear to be a primary factor leading to the insulin-resistant state.

Cardiovascular disease in cirrhosis--a point-prevalence study in relation to glucose tolerance.

OBJECTIVE:Impaired glucose tolerance or diabetes are frequently observed in cirrhosis. Overt diabetes was reported to affect long term survival of cirrhotic patients by increasing the risk of hepatocellular failure, without increasing the risk of diabetes-associated cardiovascular events.METHODS:We evaluated the prevalence of cardiovascular disease in 122 patients with cirrhosis, subdivided according to their glucose tolerance. The following parameters were considered: arterial pressure, peripheral vascular disease (ankle to brachial pressure ratio), ischemic heart disease, microalbuminuria, retinopathy. The prevalence of abnormal findings was compared with that observed in 60 randomly selected patients with non–insulin-dependent diabetes and in 40 controls.RESULTS:Noninsulin-dependent diabetic patients and patients with cirrhosis and diabetes were comparable for age, metabolic control, and smoking habits; the duration of diabetes was 5 yr longer for noninsulin-dependent diabetes. In cirrhosis, the prevalence of micro- and peripheral macroangiopathy, as well as coronary heart disease, was not different in relation to glucose tolerance, it was comparable to that of controls, and significantly lower than that observed in noninsulin-dependent diabetes.CONCLUSIONS:Cirrhotic patients, even in the presence of overt diabetes, are at low risk of cardiovascular disease. The low prevalence may be related to shorter duration of diabetic disease, also in relation to reduced life expectancy, as well as to liver disease-induced abnormalities protecting the cardiovascular system from atherosclerosis.

Metabolic syndrome, psychological status and quality of life in obesity: The QUOVADIS Study

Objective:We aimed to investigate the association of the clinical variables of the metabolic syndrome (MS) and psychological parameters on health-related quality of life (HRQL) in obesity. In particular, our aim was to investigate the relative impact of physical symptoms, somatic diseases and psychological distress on both the physical and the mental domains of HRQL.Design:Cross-sectional study.Subjects:A cohort of 1822 obese outpatients seeking treatment in medical centers.Measurements:HRQL was measured by the standardized summary scores for physical (PCS) and mental (MCS) components of the Short Form 36 Health Survey (SF-36). Patients were grouped according to tertiles of PCS and MCS. Metabolic and psychological profiles of PCS and MCS tertiles were compared by discriminant analysis.Results:The profile of metabolic and psychological variables was tertile-specific in 62.4 and 68.3% of patients in the lowest and highest tertiles of PCS, respectively, while concordance was low in the mid-tertile (32.8%). Concordance was very high in the lowest (74.4%) and in the highest (75.5%) tertiles of MCS, and was fair in the mid-tertile (53.2%). The main correlates of PCS were obesity-specific and general psychological well-being, BMI, body uneasiness, binge eating, gender and psychiatric distress. Only hypertension and hyperglycemia qualified as correlates among the components of MS. The components of MS did not define MCS.Conclusions:Psychological well-being is the most important correlate of HRQL in obesity, both in the physical and in the mental domains, whereas the features of MS correlate only to some extent with the physical domain of HRQL.

Continuous care in the treatment of obesity: an observational multicentre study

Objectives.  To investigate weight loss and reasons for attrition in obese patients on long‐term continuous care.

Weight cycling in treatment-seeking obese persons: data from the QUOVADIS study

OBJECTIVE: To determine parameters of weight history useful for the assessment of weight cycling and their association with psychological distress and binge eating.DESIGN: Cross-sectional.SUBJECTS: A total of 1889 treatment-seeking obese subjects, enrolled by 25 Italian centers (78% female subject), aged 20–65 y (median 45); 1691 reported previous efforts to lose weight (median age of first dieting, 30 y).MEASUREMENTS: The number of yearly attempts to lose weight, weight gain since age 20 y, cumulative weight loss and gain were checked by a predefined structured interview. Psychological distress was tested by means of Symptom Check-List 90 (SCL-90), Binge Eating Scale (BES) and Three Factor Eating Questionnaire (TFEQ).RESULTS: Differences in anthropometric, clinical and psychological parameters were observed in relation to previous attempts to lose weight. Patients in the upper quartile of parameters of weight history were considered weight cyclers. In multivariate logistic regression analysis, after correction for age, sex and BMI, a high BES score was the only factor systematically associated with a high frequency of dieting (OR, 1.70; 95% confidence interval, 1.22–2.36; P=0.022), with higher cumulative weight loss (1.42; 1.12–1.80; P=0.003) and cumulative weight gain (1.38; 1.06–1.79; P=0.017). However, the sensitivity, specificity and positive predictive value of a high BES score were very low to detect cyclers. Weight cycling did not carry a higher risk of complicating diseases.CONCLUSIONS: Weight cycling is associated with psychological distress, and binge eating independently increases the risk, but cannot be used to predict cycling. Also, obese patients who do not experience overeating as a loss of control discontinue treatment or regain weight following therapy.

Effects of cognitive–behavioural therapy on health-related quality of life in obese subjects with and without binge eating disorder

OBJECTIVE: To measure the effects of cognitive–behavioural therapy on health-related quality of life (HRQL) in obese patients, in relation to binge eating disorder.DESIGN: Longitudinal, clinical intervention study consisting of structured sessions of cognitive–behavioural therapy, preceded by sessions chaired by a psychologist in subjects with binge eating.SUBJECTS: Two groups of obese patients (92 treated by cognitive–behavioural therapy (77 females); 76 untreated controls (67 female), selected from the waiting list (control group)). Of 92 treated patients, 46 had a binge eating disorder at psychometric testing and structured clinical interview.MEASUREMENTS: Health-related quality of life by means of Short-Form 36 questionnaire at baseline and after 3–5 months.RESULTS: Cognitive–behavioural treatment produced an average weight loss of 9.4±7.5 kg, corresponding to a BMI reduction of 3.48±2.70 kg/m2. No changes were observed in the control group. All scales of HRQL improved in treated subjects (by 5–19%). In obese subjects with binge eating weight loss was lower in comparison to non-bingers (7.7±8.1 vs 11.1±6.6; P=0.034). However, the improvement in HRQL was on average larger, and significantly so for Role Limitation—Physical (P=0.006), Role Limitation—Emotional (P=0.002), Vitality (P=0.003), Mental Health (P=0.032) and Social Functioning (P=0.034). Bodily Pain was the sole scale whose changes paralleled changes in body weight.CONCLUSIONS: The positive effects of cognitive–behavioural therapy, mainly in subjects with binge eating, largely outweigh the effects on body weight, resulting in a significant change in self-perceived health status.

A physical activity program to reinforce weight maintenance following a behavior program in overweight/obese subjects

Objective:To investigate the effects of a specific program to implement physical activity (fitness program) on weight loss maintenance, activity level and resting energy expenditure (REE).Design:Observational study of subjects completing a behavioral program.Subjects:In total, 200 overweight/obese subjects (36 males, aged 20–66 years; average BMI, 35.2 kg/m2).Program and measurements:The fitness program consisted of 12 bimonthly sessions, chaired by doctors and dietitians, involving groups of 8–12 subjects. Patients entered the program approximately 9 months after the end of behavioral treatment, during a weight loss maintenance period. The goal was set at a light-to-moderate daily physical activity (brisk walking), quantitatively measured by a pedometer; REE was measured before and after the fitness program by indirect calorimetry in a subset of patients.Results:The fitness program restarted the process of weight loss in over 60% of subjects. At the end of the study, 84% of patients walked at least 5000 steps per day, compared with 24% at the beginning of the study. The probability of losing from 5 to 10% of initial body weight increased by 20% for any 1000 steps/day (OR, 1.20; 95% CI (confidence interval), 1.07–1.35), and that of losing more than 10% by over 30% (OR, 1.33; 95% CI, 1.19–1.49). REE increased significantly by 100 kcal/day (+7.5%), in spite of further weight loss (−1.8%).Conclusion:A specific fitness program in the weight maintenance phase after a behavioral program may significantly improve the long-term control of obesity.

The relative contribution of androgens and insulin in determining abdominal body fat distribution in premenopausal women

To investigate the relative contribution of insulin and sex hormones in determining the abdominal pattern of fat distribution in premenopausal women, five groups of age-matched subjects were examined: Group 1 consisted of 14 normal weight eumenorrheic women (NO); Group 2 of 9 obese eumenorrheic women (OB); Group 3 of 14 normal weight hyperandrogenic women with polycystic ovary syndrome (NO-HA); Group 4 of 10 obese hyperandrogenic women with polycystic ovary syndrome (OB-HA) and, finally, Group 5 of 10 obese hyperandrogenic women with polycystic ovary syndrome and acanthosis nigricans (OB-HA-AN). Both the two normal weight groups and the three obese groups were matched for body mass index values. Sex hormone pattern showed significantly higher LH and testosterone levels in hyperandrogenic women with respect to NO and OB women but obese hyperandrogenic groups (OB-HA and OB-HA-AN) presented significantly lower LH concentrations than NO-HA. Fasting and glucose-stimulated insulin levels were significantly higher in OB than NO, in OB-HA and OB-HA-AN than in OB and NO-HA, and in OB-HA-AN than in OB-HA, without any significant difference between OB and NO-HA. Body fat distribution, expressed by the waist to hip ratio (WHR), showed progressively higher values (p < 0.01) from NO to OB, NO-HA, OB-HA and, particularly, OB-HA-AN women. Determination coefficients r2 obtained from simple regression analysis showed that the sum of insulin values during the glucose tolerance test and testosterone levels had a more significant power in determining WHR variability. Multiple regression analysis showed that more than 30 percent (r2 = 0.322, p < 0.01) of the total variance accounting for WHR was explained by these two variables. Therefore we suggest that hyperinsulinemia and androgens probably represent important factors in determining predominant localization of body fat in the abdominal sites in premenopausal women, since they can explain more than 30 percent of the total variability of WHR.