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 HbA_1c (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.

Among the numerous functions of melatonin, the control of survival and differentiation of mesenchymal stem cells (MSCs) has been recently proposed. MSCs are a heterogeneous population of multipotent elements resident in tissues such as bone marrow, muscle, and adipose tissue, which are primarily involved in developmental and regeneration processes, gaining thus increasing interest for tissue repair and restoration therapeutic protocols. Receptor‐dependent and receptor‐independent responses to melatonin are suggested to occur in these cells. These involve antioxidant or redox‐dependent functions of this indolamine as well as secondary effects resulting from autocrine and paracrine responses. Inflammatory cytokines and adipokines, proangiogenic/mitogenic stimuli, and other mediators that influence the differentiation processes may affect the survival and functional integrity of these mesenchymal precursor cells. In this scenario, melatonin seems to regulate signaling pathways that drive commitment and differentiation of MSC into osteogenic, chondrogenic, adipogenic, or myogenic lineages. Common pathways suggested to be involved as master regulators of these processes are the Wnt/β‐catenin pathway, the MAPKs and the, TGF‐β signaling. In this respect melatonin emerges a novel and potential modulator of MSC lineage commitment and adipogenic differentiation. These and other aspects of the physiological and pharmacological effects of melatonin as regulator of MSC are discussed in this review.

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 $393 in group 0, did not significantly change in group 1–10 ($206, P = 0.09), and decreased in group 11–20 (−$196, P = 0.01), group 21–30 (−$593, P = 0.009), group 31–40 (−$660, P = 0.003), and group >40 (−$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.

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.