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.

A single LAT treatment of solid nodules results in significant and persistent volume reduction and local symptom improvement, in the absence of thyroid function changes.

Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low.

The present studies were performed to test the hypothesis that the liver, by increasing the synthesis of specific plasma proteins during the absorption of an amino acid meal, may play an important role in the temporary "storage" of ingested essential amino acids and to explore the effects of glucocorticosteroids and recombinant human growth hormone (rhGH) on these processes. The fractional synthetic rates of albumin and fibrinogen were determined using simultaneous infusions of intravenous [1-14C]leucine and intraduodenal [4,5-3H]leucine after 22 h fasting and during absorption of glucose and amino acids in four groups of normal subjects treated for 1 wk with placebo, prednisone (0.8 mg.kg-1.day-1), rhGH (0.1 mg.kg-1.day-1), or combined treatment. When compared with the fasted state and independent of the route of tracer delivery and hormonal treatment, albumin, but not fibrinogen, synthesis increased (P < 0.0001) during absorption of a mixed glucose amino acid meal in all groups. This increase in albumin synthesis accounted for 28% of the increase in whole body protein synthesis associated with feeding and for 24, 22, and 14% in the prednisone, rhGH, and combined treatment groups, respectively. These data suggest that the stimulation of albumin synthesis observed during feeding prevents irreversible oxidative losses of a significant fraction of ingested essential amino acids and may serve as a vehicle to capture excess dietary amino acids and transport them to peripheral tissues to sustain local protein synthesis.

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...

Insulin deficiency decreases tissue protein synthesis, albumin mRNA concentration, and albumin synthesis in rats. In contrast, insulin deficiency does not change, or, paradoxically, increases estimates of whole body protein synthesis in humans.To determine if such estimates of whole body protein synthesis could obscure potential differential effects of insulin on the synthetic rates of individual proteins, we determined whole body protein synthesis and albumin and fibrinogen fractional synthetic rates using 5-h simultaneous infusions of [14Cjleucine and I13C]bicarbonate, in six type 1 diabetics during a continuous i.v.insulin infusion (to maintain euglycemia) and after short-term insulin withdrawal (12±2 h).Insulin withdrawal increased (P < 0.03) whole body proteolysis by 35% and leucine oxidation by -100%, but did not change 3CO2 recovery from NaH13CO3 or estimates of whole body protein synthesis (P = 0.21). Insulin deficiency was associated with a 29% decrease (P < 0.03) in the albumin fractional synthetic rate but a 50% increase (P < 0.03) in that of fibrinogen.These data provide strong evidence that albumin synthesis in humans is an insulin-sensitive process, a conclusion consistent with observations in rats. The increase in fibrinogen synthesis during insulin deficiency most likely reflects an acute phase protein response due to metabolic stress. These data suggest that the absence of changes in whole body protein synthesis after insulin withdrawal is the result ofthe summation of differential effects of insulin deficiency on the synthesis of specific body proteins. (J. Clin. Invest. 1991. 88:833-840.)