G. Forlani

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.

Moderate alcohol use and health: a consensus document.

AIMS The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. DATA SYNTHESIS In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. CONCLUSIONS The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.

Insulin-dependent metabolism of branched-chain amino acids in obesity

The effect of euglycemic hyperinsulinism on branched-chain amino acids (BCAA; valine, isoleucine and leucine) was evaluated in five obese subjects and five controls. A continuous intravenous insulin infusion raised plasma insulin to a steady-state level. An artificial endocrine pancrease that infused glucose was used to sustain euglycemia. Basal and steady-state insulin levels were significantly higher in the obese subjects than in the controls. The amount of glucose infused to maintain euglycemia and its ratio to steady-state insulin levels was significantly lower in the obese subjects, suggesting an impaired insulin action on glucose metabolism. Basal BCAA levels were similar in the two groups of subjects. During insulin infusion the decremental areas of BCAA below basal levels were significantly lower in the obese patients (63 +/- 5 nmol/mL X min v 143 +/- 8 nmol/mL X min, P less than 0.001), as was the ratio of the decremental areas of BCAA to the incremental areas of insulin (1.11 +/- 0.05 nmol/microU v 3.30 +/- 0.24 nmol/microU, P less than 0.001). Our data suggest that insulin resistance in obesity reduces hormonal effects on glucose as well as on BCAA metabolism.

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 Direct Economic Cost of Pharmacologically-Treated Diabetes in Italy-2006. The ARNO Observatory

AIMS/HYPOTHESIS To estimate the prevalence and the direct cost of pharmacologically-treated diabetes in Italy. METHODS The ARNO observatory database, containing the 20-year medical prescriptions of over 10 million Italian people, was used. Ten-year longitudinal data were available in 22 Local Health Districts (LHD). Subjects were classified as having diabetes when prescribed glucose-lowering drugs (oral agents or insulin) (311,979 individuals in 2006). The direct cost was calculated as the sum of drug use, financial compensation by LHD for the inpatient (hospital DRG) and outpatient activities (consultations, laboratory tests, radiology, etc.), all regulated by government contracts. Individuals with diabetes were compared with pharmacologically-treated subjects without diabetes, pair-matched for age, sex and general practitioner. RESULTS In the 10-year period, the prevalence of pharmacologically-treated diabetes increased from 3.08% to 4.45% (P for trend, <0.001). The average pro capita cost totaled €2,589 in 2006 (95% confidence interval (CI), 2,584-2,594), corresponding to a rate ratio vs. no-diabetes of 1.54 (95% CI, 1.50-1.56). The cost of drugs was € 827 (rate ratio, 1.80 vs. no-diabetes; 95% CI, 1.79-1.82), that of service use, € 488 (rate ratio, 1.07 (0.93-1.25). Only 20% of the pharmaceutical cost was due to glucose-lowering drugs, a percentage stable through the years. The cost of any hospital admission, as defined by DRGs, was independent of diabetes, but the overall cost was much higher in diabetes due to much higher admission rates. Cardiovascular complications and renal failure accounted for the large majority of excess hospital cost. CONCLUSION The direct economic burden of pharmacologically-treated diabetes on the National Health System is very high, due to the growing prevalence of disease and the cost of complications.

Prevalence of elevated liver enzymes in Type 2 diabetes mellitus and its association with the metabolic syndrome

The occurrence of liver disease and raised liver enzymes is common in Type 2 diabetes, and may be multifactorial in origin. Very few studies are available on the exact prevalence of the phenomenon, however. We carried out an observational point-prevalence study of elevated liver enzymes in eight hospital-based Italian diabetes units. Data of 9621 consecutive Type 2 diabetes patients (males, 52.4%; median age, 65 yr) were analyzed, and alanine and aspartate aminotransferase (ALT, AST) and γ-glutamyltransferase (GGT) levels were related to body mass index (BMI), metabolic control and the presence of the metabolic syndrome. ALT, AST, and GGT levels exceeding the upper limit of normal were present in 16.0%, 8.8%, 23.1%, respectively, the prevalence being higher in males, increasing with obesity class and poor metabolic control, and decreasing with age. Elevated enzymes were systematically associated with most parameters of the metabolic syndrome. After correction for age, gender, BMI, and differences across centers, elevated triglyceride levels/fibrate treatment [odds ratio (OR), 1.57; 95% confidence interval (CI), 1.34–1.84] and an enlarged waist circumference (OR, 1.47; 95% CI, 1.17–1.85) were the only parameters independently associated with high ALT. In a separate analysis, the presence of metabolic syndrome (Adult Treatment Panel III criteria) was highly predictive of raised liver enzymes. After exclusion of hepatitis B and C positive cases, tested in 2 centers, the prevalence of raised enzymes decreased by approximately 4%, but the association with the metabolic syndrome did not change significantly. In conclusion, the high prevalence of elevated liver enzymes in Type 2 diabetes is in keeping with the well-demonstrated risk of progressive liver disease. A large amount of diabetes patients may require a thorough clinical, laboratory and histological investigation.

Branched-chain amino acids and alanine as indices of the metabolic control in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients

SummaryAlterations in plasma branched-chain amino acids (valine, isoleucine and leucine) and alanine have been described in patients with insulin-dependent diabetes mellitus who have poor metabolic control. To assess the relevance of these abnormalities as indices of metabolic control, we sequentially evaluated plasma amino acids in 14 poorly controlled diabetics (seven Type 1 (insulin-dependent) and seven Type 2 (non-insulin-dependent) patients) until good control was achieved. The sum of branched-chain amino acids in both groups of uncontrolled diabetic patients was significantly increased compared with the values for the same subjects in good metabolic control. No statistically significant differences were present between ketotic and non-ketotic uncontrolled patients. The amelioration of the diabetic state with either insulin treatment or oral hypoglycaemic agents, reduced progressively branched-chain amino acids. The sum of valine, isoleucine and leucine strictly correlated with daily urinary glucose (r=0.73), but less well with fasting blood glucose (r=0.43), nonesterified fatty acids (r=0.46) and glycosylated haemoglobin (r=0.38). Alanine did not show any statistically significant differences at various stages of diabetic control. Branched-chain amino acids, but not alanine, may be used as indices of short-term diabetic control.

WHO and ADA criteria for the diagnosis of diabetes mellitus in relation to body mass index. Insulin sensitivity and secretion in resulting subcategories of glucose tolerance.

OBJECTIVE: To determine the influence of body mass index (BMI) on agreement between the American Diabetes Association (ADA) and the new World Health Organization diagnostic criteria for the diagnosis of diabetes mellitus and to investigate the metabolic profile of the resulting subcategories.DESIGN: Cross-sectional studySUBJECTS: A total of 3018 subjects with no previous history of diabetes and fasting glucose <7.8 mmol/l, with a wide range of BMIs.MEASUREMENTS: (1) Prevalence of impaired glucose regulation (IGR) and diabetes (DM) according to ADA and WHO diagnostic criteria; (2) basal and post-load insulin sensitivity and secretion, calculated on the basis of data derived from an oral glucose tolerance test (OGTT).RESULTS: The diagnosis according to the two classifications was concordant in 2490 subjects, discordant in 528 (452 were identified as impaired glucose tolerance (IGT) and 76 as DM only by means of OGTT). The disagreement increased with increasing BMI, being as high as 25.3% in subjects with BMI ≥35 kg/m2. Subjects with isolated fasting hyperglycaemia were mainly characterised by reduced insulin sensitivity and secretion in the basal state, but normal first-phase insulin secretion and moderately reduced insulin sensitivity after glucose challenge. Subjects with isolated 2 h hyperglycaemia were mainly characterised by normal basal insulin secretion and by a marked insulin resistance associated with a blunted first-phase insulin secretion after the glucose load.CONCLUSIONS: The disagreement between ADA and WHO classifications is particularly relevant in obesity, making OGTT mandatory in these subjects. Different pathogenic mechanisms are involved in isolated fasting or post-load hyperglycaemia, possibly related to a different site of insulin resistance (hepatic vs peripheral), and/or to a different disregulation of insulin secretion (basal vs post-load). A correct identification of the underlying mechanism(s) is the rationale for future studies to detect the effectiveness of different pharmacological or behavioural approaches.

NUTRITIONAL EFFECTS OF ORAL ZINC SUPPLEMENTATION IN CIRRHOSIS

Abstract Poor zinc status is common in cirrhosis. Experimental studies proved that zinc supplementation produces metabolic effects, and trends towards improved liver function and nutritional status have previously been reported. We measured liver function by means of dynamic, quantitative tests and biochemical indices of nutrition in response to zinc treatment in patients with cirrhosis. Fifteen patients with advanced cirrhosis were studied before and after long-term oral zinc-sulfate supplementation (200 mg t.i.d. for 2–3 months). Liver function was measured by routine biochemistry, galactose elimination capacity and antipyrine clearance; nutritional assessment included the measurement of daily urinary creatinine excretion, and albumin, prealbumin, retinol-binding protein and insulin-like growth factor-1 (IGF-1) serum or plasma concentrations. In 10 patients data were correlated with the parameters of glucose metabolism obtained during a frequently-sampled i.v. glucose tolerance test. At baseline, serum zinc was low normal or reduced, and returned to normal range in all patients after supplementation. Liver function improved significantly. All nutritional indices improved as well, but remained on average below normal. IGF-1 increased on average by 30%, but was in the normal range in only 2 cases. Changes in IGF-1 correlated with improved glucose tolerance after i.v. glucose load, namely with the increased non-insulin-mediated glucose uptake. The study confirms that oral zinc produces metabolic effects in zinc-deficient patients with cirrhosis. Improved liver function and nutritional status may increase glucose disposal via increased IGF-1, responsible for the non-insulin-dependent fraction of glucose disappearance.