OBJECTIVE—There is enough evidence that physical activity is an effective therapeutic tool in the management of type 2 diabetes. The present study was designed to validate a counseling strategy that could be used by physicians in their daily outpatient practice to promote the adoption and maintenance of physical activity by type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—The long-term (2-year) efficacy of the behavioral approach (n = 182) was compared with usual care treatment (n = 158) in two matched, randomized groups of patients with type 2 diabetes who had been referred to our Outpatient Diabetes Center. The outcome of the intervention was consistent patient achievement of an energy expenditure of >10 metabolic equivalents (METs)-h/week through voluntary physical activity. RESULTS—After 2 years, 69% of the patients in the intervention group (27.1 ± 2.0 METs × h/week) and 18% of the control group (4.1 ± 0.8 METs × h/week) achieved the target (P < 0.001) with significant (P < 0.001) improvements in BMI (intervention group 28.9 ± 0.2 versus control group 30.4 ± 0.3 kg/m2) and HbA1c (intervention group 7.0 ± 0.1 versus control group 7.6 ± 0.1%). CONCLUSIONS—This randomized, controlled study shows that physicians can motivate most patients with type 2 diabetes to exercise long-term and emphasizes the value of individual behavioral approaches in daily practice.

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...

Whole-body vibration is reported to increase muscle performance, bone mineral density and stimulate the secretion of lipolytic and protein anabolic hormones, such as GH and testosterone, that might be used for the treatment of obesity. To date, as no controlled trial has examined the effects of vibration exercise on the human endocrine system, we performed a randomized controlled study, to establish whether the circulating concentrations of glucose and hormones (insulin, glucagon, cortisol, epinephrine, norepinephrine, GH, IGF-1, free and total testosterone) are affected by vibration in 10 healthy men [age 39 +/- 3, body mass index (BMI) of 23.5 +/- 0.5 kg/m2, mean +/- SEM]. Volunteers were studied on two occasions before and after standing for 25 min on a ground plate in the absence (control) or in the presence (vibration) of 30 Hz whole body vibration. Vibration slightly reduced plasma glucose (30 min: vibration 4.59 +/- 0.21, control 4.74 +/- 0.22 mM, p=0.049) and increased plasma norepinephrine concentrations (60 min: vibration 1.29 +/- 0.18, control 1.01 +/- 0.07 nM, p=0.038), but did not change the circulating concentrations of other hormones. These results demonstrate that vibration exercise transiently reduces plasma glucose, possibly by increasing glucose utilization by contracting muscles. Since hormonal responses, with the exception of norepinephrine, are not affected by acute vibration exposure, this type of exercise is not expected to reduce fat mass in obese subjects.

Ghrelin is a novel enteric hormone that stimulates growth hormone (GH), ACTH, and epinephrine; augments plasma glucose; and increases food intake by inducing the feeling of hunger. These characteristics make ghrelin a potential counterregulatory hormone. At present, it is not known whether ghrelin increases in response to insulin-induced hypoglycemia. To answer this question, we compared plasma ghrelin concentrations after a short-term insulin infusion that was allowed or not (euglycemic clamp) to cause hypoglycemia (2.7 ؎ 0.2 mmol/l at 30 min) in five healthy volunteers. In both studies, plasma ghrelin concentrations decreased (P < 0.01) after insulin infusion (hypoglycemia by 14%, euglycemia by 22%), reached a nadir at 30 min, and returned to baseline at 60 min, without differences between the hypoglycemia and the euglycemia studies. Glucagon, cortisol, and GH increased in response to hypoglycemia despite the decreased ghrelin. There was a strong correlation (R 2 ‫؍‬ 0.91, P < 0.002) between the insulin sensitivity of the subjects and the percentage suppression of ghrelin from baseline. These data demonstrate that ghrelin is not required for the hormonal defenses against insulin-induced hypoglycemia and that insulin can suppress ghrelin levels in healthy humans. These results raise the possibility that postprandial hyperinsulinemia is responsible for the reduction of plasma ghrelin that occurs during meal intake. Diabetes 51:2911-2914, 2002 G hrelin, a 28 -amino acid hormone, was recently identified in the stomach as the endogenous ligand for the growth hormone (GH) secretagogue receptor (1). Ghrelin is a potent stimulator of GH secretion (2); promotes ACTH, cortisol (2,3), and epinephrine (3) release; increases food intake, possibly by augmenting hypothalamic mRNA levels of neuropeptide Y and agouti gene-related protein (4); and increases plasma glucose in normal subjects (5). Recently, it was shown in humans that circulating ghrelin levels rise shortly before and fall shortly after every meal (6,7) and that ghrelin administration increases subjective hunger and voluntary food intake (8). All of these data suggest that ghrelin works as a hormone signaling the need to conserve energy (9). Therefore, ghrelin secretion might be triggered by an acute decrease of plasma glucose concentrations. The hypoglycemia alarm symptom of hunger and the responses of GH and cortisol play an important role in the defense against insulin-induced hypoglycemia (10,11). Ghrelin might act, at least in part, as a physiological mediator of these protective mechanisms. In addition, ghrelin could directly contribute to glucose counterregulation by stimulating hepatic glucose production. The prompt increase of plasma glucose after an intravenous bolus of ghrelin in healthy humans suggests a direct glycogenolytic activity (5), whereas recent data show that ghrelin upregulates markers of gluconeogenesis and downregulates markers of glycogen synthesis in hepatoma cells (12).For demonstrating that ghrelin is required for glucose counterregul...

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...