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. Diabetes 52:2923-2927, 2003 G hrelin, an endogenous ligand for the growth hormone secretagogue receptor (1,2), appears to play a key role in regulating food intake and energy homeostasis (3-5). Hormonal and nutritional factors might both affect ghrelin production. In lean subjects, plasma ghrelin levels rise progressively before meals and fall to a nadir within 1 h of eating, a pattern mirroring that of insulin (6). Ghrelin concentrations are decreased by oral or intravenous administration of glucose (7) but not by filling the stomach with an equal volume of water (4,7). Potentially, one or more dietary nutrients could directly suppress ghrelin production or they could act indirectly by stimulating insulin secretion. The inverse temporal relationship between circulating concentrations of plasma ghrelin and insulin (6) suggests that postprandial hyperinsulinemia might inhibit ghrelin secretion during meal absorption.At present, the effect of physiologic hyperinsulinemia on plasma ghrelin concentrations in healthy humans is controversial (8 -14) and the contribution of postprandial hyperinsulinemia to plasma ghrelin suppression is unknown. In particular, it remains to be established whether a short-lived insulin peak or sustained hyperinsulinemia is required to induce plasma ghrelin decrease. Caixà s et al. (8) reported that, unlike food intake, a subcutaneous injection of a short-acting insulin analo...

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 Ϯ 1 years [mean Ϯ 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 ϭ 28), group 1-10 (6.8 Ϯ 0.3, n ϭ 27), group 11-20 (17.1 Ϯ 0.4, n ϭ 31), group 21-30 (27.0 Ϯ 0.5, n ϭ 27), group 31-40 (37.5 Ϯ 0.5, n ϭ 32), and group Ͼ40 (58.3 Ϯ 1.8, n ϭ 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][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] and Ͼ40, HbA 1c , blood pressure, total serum cholesterol, triglycerides, and estimated percent of 10-year coronary heart disease risk improved (P Ͻ 0.05). In group 21-30, 31-40, and Ͼ40, body weight, waist circumference, heart rate, fasting plasma glucose, serum LDL and HDL cholesterol also improved (P Ͻ 0.05). METs per hour per week correlated positively with changes of HDL cholesterol and negatively with those of other parameters (P Ͻ 0.001). After 2 years, per capita yearly costs of medications increased (P ϭ 0.008) by $393 in group 0, did not significantly change in group 1-10 ($206, P ϭ 0.09), and decreased in group 11-20 (Ϫ$196, P ϭ 0.01), group 21-30 (Ϫ$593, P ϭ 0.009), group 31-40 (Ϫ$660, P ϭ 0.003), and group Ͼ40 (Ϫ$579, P ϭ 0.001). CONCLUSIONS -Energy expenditure Ͼ10METs ⅐ h Ϫ1 ⅐ week Ϫ1 obtained through aerobic leisure time physical activity is sufficient to achieve health and financial advantages, but full benefits are achieved with energy expenditure Ͼ20 METs ⅐ h Ϫ1 ⅐ week Ϫ1 . Diabetes Care 28:1295-1302, 2005W estern and developing countries face two serious health problems: the rising prevalence of obesity and diabetes and the fact that people no longer need to be physically active in their daily lives (1-4). Many studies have shown that regular physical activity improves quality of life, reduces the risk of mortality from all causes (1-4), and is particularly advantageous in subjects with impaired glucose tolerance (5,6) or type 2 diabetes (7-12). Physical activity counseling can motivate most diabetic subjects to increase their levels of voluntary energy expenditure (9 -11), but, at present, the relationship between amounts of physical activity and longterm beneficial effects in type 2 diabetes care is unknown. The American Diabetes Association emphasizes the benefits of regular physical activity in the prevention and treatment of type 2 diabetes, referring to proposals given to the general population by...

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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 (6.5 ml; 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.