Background and aims: It is unknown whether lifestyle change is effective in people with type 2 diabetes with inadequate glucose control. The aim of this study was to asses, in a group of people with type 2 diabetes, the impact of baseline values of glycosylated haemoglobin (HbA1c) on the effects of an intensive lifestyle intervention on metabolic, clinical and strength parameters.Methods and results: 222 people with type 2 diabetes with mean +/- standard deviation baseline HBA1c of 7.50% +/- 1.27 (range 5.1-12.7%), were enrolled in a 3-month structured multidisciplinary lifestyle intervention. Anthropometric, biochemical, clinical and fitness measurements were collected at baseline, at the end of the lifestyle intervention program and at two-year follow-up visit. Significant improvements in glycometabolic control (HbA1c: p <= 0.0001); anthropometric parameters (BMI p <= 0.0001; waist circumference: p <= 0.0001); and systemic blood pressure (p <= 0.0001) were observed both at the end of the three month intensive lifestyle program and at the two-year follow up visit. In addition, defined daily doses of hypoglycaemic treatment significantly decreased (p = 0.001).Fitness measures exhibited significant increments in the whole sample at the end of the intensive intervention program (p <= 0.0001). When patients were divided into tertiles considering the baseline value of HbA1c, the most marked improvements in HbA1c, blood glucose and triglycerides were observed in the group with inadequate glucose control (Hba1c >= 7.71%), both at the three-month and two-year follow-ups.Conclusion: These results demonstrate that an intensive lifestyle intervention should be recommended for people with type 2 diabetes, particularly those with the most inadequate glycaemic control. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Background and aims: To be successful, lifestyle intervention in obesity must take into account patients' views. The aim of the present study, conducted using a narrative-autobiographical approach, was to report on the perception of disease, food and physical exercise in a group of 80 obese patients during a structured multidisciplinary lifestyle intervention.Methods and Results: Patients underwent lifestyle intervention, of three months' duration, structured in the following steps: 1) an initial medical examination; 2) an interview by a psychologist; 3) an assessment by a dietician, 4) a physical examination by a specialist in sports medicine; 5) an individualized program consisting of 24 sessions (two per week) of structured indoor exercise 6) eight sessions of group therapeutic education; 7) Nordic walking activity combined with walking excursions during weekends. All the narrative autobiographic texts obtained during the lifestyle intervention were submitted for content analysis; data were analysed according to the "grounded theory'' method.According to patients' descriptions at the end of the intervention, lifestyle intervention resulted in enhanced self-efficacy and a reduction in their dependency on food and people; their fear of change was also diminished because, by undergoing intervention, they had experienced change.Conclusion: The findings made in the present qualitative analysis suggest that whenever multidisciplinary lifestyle intervention is planned for patients with obesity, it is of the utmost importance to tailor the approach while taking the following key aspects into account: motivation, barriers and/or facilitators in lifestyle change, patients' perceptions of obesity and relationship with food, diet and exercise. (C) 2011 Elsevier B.V. All rights reserved.

Aim: To describe the multidisciplinary lifestyle intervention model used in an experimental CURIAMO (Centro Universitario Ricerca Interdipartimentale Attività Motoria) project designed to validate the short- and long-term efficacy of the model in obesity and Type 2 diabetes. Research design and methods: Over a 3-yr period, about 1000 adults (70% diabetes-free and overweight or obese; 30% with Type 2 diabetes and overweight or obese). Inclusion criteria: Age range 18–80 yr, body mass index >27 kg/m 2 with or without Type 2 diabetes mellitus; participants will be divided into three age groups (18–45, 45–65, 65–80 yr). The study duration will be from 5 to 6 yr: 1 yr of intervention followed by a mean follow-up period of 4 yr. In the first years, after a 4-month intensive lifestyle intervention, subjects will follow a maintenance programme. The intervention, which includes seven steps, involves the following experts: endocrinologists, sport medicine doctors or cardiologists, psychologists, dietitians, educators, nurses, exercise physiologists, and promoters of outdoor activities. Results: The main endpoint of the study is to measure the efficacy of the lifestyle improvement intervention, defined as a loss of at least 7% of body weight combined with an increase of at least 10 MET/h −1 week −1 of energy expenditure by physical activity, after 1 yr and during the follow-up. A cost/utility analysis of the model will be made in participants with diabetes. Conclusions: We expect that the CURIAMO model will be highly effective, and that the aim of the intervention will be achieved in more than 70% of cases.

This study was performed to establish whether only 2 sessions per week of combined aerobic and resistance exercise are enough to reduce glycated hemoglobin (HbA1c) and to induce changes in skeletal muscle gene expression in Type 2 diabetes mellitus (DM2) subjects with metabolic syndrome. Eight DM2 subjects underwent a 1-yr exercise program consisting of 2 weekly sessions of 140 min that combined aerobic [at 55–70% of maximal oxygen uptake (VO2max)] and resistance circuit training [at 60–80% of 1 repetition maximum (RM)]. The training significantly improved VO2max) (from 33.5±3.8 ml/kg/min to 38.2±3.5 ml/kg/min, p=0.0085) and muscle strength (p<0.05). Changes over baseline were significant for HbA1c, reduced by 0.45% (p=0.0084), fasting blood glucose (from 8.8±1.5 to 6.9±2.2 mmol/l, p=0.0132), waist circumference (from 98.9±4.8 to 95.9±4.6 cm, p=0.0054), body weight (from 87.5±10.7 to 85.7±10.1 kg, p=0.0375), systolic blood pressure (from 137±15 to 126±8 mmHg, p=0.0455), total cholesterol (from 220±24 to 184±13 mg/dl, p=0.0057), and LDL-cholesterol (from 150±16 to 105±15 mg/dl, p=0.0004). Mitochondrial DNA/nuclear DNA ratio at 6 and 12 months did not change. There was a significant increase of mRNA of peroxisome proliferator-activated receptor (PPAR)-γ after 6 months of training(p=0.024); PPARα mRNA levels were significantly increased at 6 (p=0.035) and 12 months (p=0.044). The mRNA quantification of other genes measured [mitochondrially encoded cytochrome c oxidase subunit II (MTCO2), cytochrome c oxidase subunit Vb (COX5b), PPARγ coactivator 1α (PGC-1α), glucose transporter 4 (GLUT 4), forkhead transcription factor BOX O1 (FOXO-1), carnitine palmitoyltransferase 1 (CPT-1), lipoprotein lipase (LPL), and insulin receptor substrate 1 (IRS-1)] did not show significant changes at 6 and 12 months. This study suggests that a twice-per-week frequency of exercise is sufficient to improve glucose control and the expression of skeletal muscle PPARγ and PPARα in DM2 subjects with metabolic syndrome.

This randomized controlled study was designed to test the efficacy and safety of percutaneous ultrasound (US)-guided laser photocoagulation (PLP) for treatment of subjects with compressive symptoms due to benign thyroid nodules and/or at high surgical risk. Twenty six subjects were randomized to the intervention (no. 13, age 68±3 yr, mean±SEM) or observation (no. 13, age 71±2 yr) groups. In the control group, the volume of nodules did not significantly change over the 30 week period of observation. In the intervention group, median nodule volume at baseline was 8.2 ml (range 2.8–26.9) and was not significantly different from that of the control group. Nodules decreased significantly ( p <0.0001) by 22% after 2 weeks (6.5ml; range 2.4–16.7) and by 44% after 30 weeks (4.6 ml; range 0.69–14.2). Energy given was correlated ( p <0.05) with the reduction of thyroid nodule volume. All patients tolerated the treatment well and reported relief from compressive and cosmetic complaints ( p <0.05). At the time of enrolment 7/13 (54%) and 6/13 (46%) of patients in the intervention and control groups, respectively, had sub clinical hyperthyroidism. PLP normalized thyroid function at 6 and 30 weeks after treatment. In conclusion, PLP is a promising safe and effective procedure for treatment of benign thyroid nodules in patients at high surgical risk.

This brief review will focus on indicators of metabolic control alternative to glucose, ketone body and lactate measurements, specifically reviewed in other articles of this issue. The effects of insulin on protein metabolism are summarized and, the potential clinical relevance of monitoring energy expenditure in diabetic subjects is discussed. Many studies have shown that maintaining a regular physical activity regimen improves quality of life, reduces the risk of mortality from all causes, prevents type 2 diabetes mellitus in subjects with impaired glucose tolerance, and enhances glucose control in subjects affected by type 2 diabetes mellitus. Monitoring energy expenditure is a novel approach to implement the non-pharmacological treatment of subjects with diabetes mellitus.

OBJECTIVE:To establish the impact of different amounts of increased energy expenditure on type 2 diabetes care. RESEARCH DESIGN AND METHODS:Post hoc analysis of long-term effects of different amounts of increased energy expenditure (metabolic equivalents [METS] per hour per week) through voluntary aerobic physical activity was performed in 179 type 2 diabetic subjects (age 62 +/- 1 years [mean +/- SE]) randomized to a physical activity counseling intervention. Subjects were followed for 2 years and divided into six groups based on their increments in METs per hour per week: group 0 (no activity, n = 28), group 1-10 (6.8 +/- 0.3, n = 27), group 11-20 (17.1 +/- 0.4, n = 31), group 21-30 (27.0 +/- 0.5, n = 27), group 31-40 (37.5 +/- 0.5, n = 32), and group >40 (58.3 +/- 1.8, n = 34). RESULTS:At baseline, the six groups did not differ for energy expenditure, age, sex, diabetes duration, and all parameters measured. After 2 years, in group 0 and in group 1-10, no parameter changed; in groups 11-20, 21-30, 31-40, and >40, HbA(1c), blood pressure, total serum cholesterol, triglycerides, and estimated percent of 10-year coronary heart disease risk improved (P < 0.05). In group 21-30, 31-40, and >40, body weight, waist circumference, heart rate, fasting plasma glucose, serum LDL and HDL cholesterol also improved (P < 0.05). METs per hour per week correlated positively with changes of HDL cholesterol and negatively with those of other parameters (P < 0.001). After 2 years, per capita yearly costs of medications increased (P = 0.008) by USD393 in group 0, did not significantly change in group 1-10 (USD 206, P = 0.09), and decreased in group 11-20 (USD -196, P = 0.01), group 21-30 (USD -593, P = 0.009), group 31-40 (USD -660, P = 0.003), and group >40 (USD -579, P = 0.001). CONCLUSIONS:Energy expenditure >10 METs . h(-1) . week(-1) obtained through aerobic leisure time physical activity is sufficient to achieve health and financial advantages, but full benefits are achieved with energy expenditure >20 METs . h(-1) . week(-1).

Background: Growing evidence indicates that the administration of large amounts of ghrelin to humans increases circulating concentrations of several pituitary and adrenal hormones, induces hyperglycemia and reduces serum insulin concentrations. At present, it is not known whether physiological increments in plasma ghrelin concentrations affect glucose kinetics or hormone concentrations in humans.Methods and results: We compared the effects of two- and three-fold increments in plasma ghrelin concentrations in eight healthy subjects during a 2 h intravenous infusion of 7.5 (GHRE7.5), 15 (GHRE15) pmol kg(-1) min(-1) acylated human ghrelin or placebo (PL), in a randomized double-blind study. Compared with PL (146 +/- 24 pM) plasma ghrelin concentrations increased at 120 min (p < 0.001) about two-fold after GHRE7.5 (300 +/- 35 pM) and three-fold after GHRE15 (494 +/- 30 pM). GHRE15 significantly increased circulating concentrations of NEFA, GH, ACTH, epinephrine, and protactin (p < 0.01). GHRELIN7.5 significantly (p < 0.01) increased only serum GH concentrations. Neither ghrelin infusions changed glucose flux or circulating concentrations of glucose, insulin, C-peptide, glucagon, IGF-1, cortisol and norepinephrine.Conclusions: GH secretion is the only response that is stimulated by physiological increments in plasma ghrelin concentrations; about three-fold increases in plasma ghrelin concentrations are required to elicit the responses of epinephrine, prolactin, ACTH and NEFA. (c) 2005 Elsevier B.V. All rights reserved.

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 (r 2 =−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.

Accumulating evidence indicates that ghrelin plays a role in regulating food intake and energy homeostasis. In normal subjects, circulating ghrelin concentrations decrease after meal ingestion and increase progressively before meals. At present, it is not clear whether nutrients suppress the plasma ghrelin concentration directly or indirectly by stimulating insulin secretion. To test the hypothesis that insulin regulates postprandial plasma ghrelin concentrations in humans, we compared the effects of meal ingestion on plasma ghrelin levels in six C-peptide-negative subjects with type 1 diabetes and in six healthy subjects matched for age, sex, and BMI. Diabetic subjects were studied during absence of insulin (insulin withdrawal study), with intravenous infusion of basal insulin (basal insulin study) and subcutaneous administration of a prandial insulin dose (prandial insulin study). Meal intake suppressed plasma ghrelin concentrations (nadir at 105 min) by 32 +/- 4% in normal control subjects, 57 +/- 3% in diabetic patients during the prandial insulin study (P < 0.002 vs. control subjects), and 38 +/- 8% during basal insulin study (P = 0.0016 vs. hyperinsulinemia; P = NS vs. control subjects) but did not have any effect in the insulin withdrawal study (P < 0.001 vs. other studies). In conclusion, 1). insulin is essential for meal-induced plasma ghrelin suppression, 2). basal insulin availability is sufficient for postprandial ghrelin suppression in type 1 diabetic subjects, and 3). lack of meal-induced ghrelin suppression caused by severe insulin deficiency may explain hyperphagia of uncontrolled type 1 diabetic subjects.