Impaired glucose tolerance is a well documented consequence of absolute bedrest in man. Previous studies have shown a decrease in forearm glucose uptake during intravenous glucose infusion after fourteen days of bedrest. Bedrest is associated not only with physical inactivity but with a change in gravitational vector. This study was designed to examine the individual contributions of these factors to the glucose intolerance of bedrest. Thus, glucose tolerance tests were carried out in exercising subjects at bedrest and in rhesus monkeys immobilized in the vertical plane. Exercise in man improved glucose tolerance during bedrest, and vertically immobilized monkeys demonstrated significant glucose intolerance. It is concluded that the glucose intolerance of bedrest is a function of the decrease in physical activity.

A B S T R A C T Five patients with fasting and(or) postprandial hypoglycemia were found to have insulin antibodies in the absence of previously documented immunization. Studies on the equilibrium-binding of insulin to the autoantibodies revealed two classes of binding sites with association constants and binding capacities analogous to those of insulin antibodies from insulin-treated diabetic patients. Similarly, no consistent differences in these parameters were found in both groups of patients with insulins ofbovine, porcine, and human origin. Proinsulin (C-segment directed) antibodies capable ofbinding bovine or porcine proinsulin were present in 10 of 10 and 9 of 10 insulin-treated diabetics serving as controls, respectively, and, when present, provide incontrovertible evidence of exogenous insulin administration. No such antibodies could be detected in the hypoglycemic patients with autoimmune insulin antibodies.The kinetics of dissociation of the insulin-antibody complexes were consistent with the existence of two classes of antibody sites. The corresponding dissociation rate constants were large enough to predict that significant amounts of free hormone may be generated by this mechanism and provide a plausible pathogenesis for the hypoglycemia in these patients.

Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305).

Thiazolidinediones (TZDs) are insulin-sensitizing antidiabetes agents that act through the peroxisome proliferator-activated receptor-γ to cause a durable improvement in glycemic control in patients with type 2 diabetes mellitus. Although less well recognized, TZDs also exert a protective effect on β-cell function. In addition to their beneficial effects on glucose homeostasis, TZDs-especially pioglitazone-exert a number of other pleiotropic effects that make them ideal agents as monotherapy or in combination with other oral agents, glucagon-like peptide-1 analogs, or insulin. Pioglitazone improves endothelial dysfunction, reduces blood pressure, corrects diabetic dyslipidemia, and reduces circulating levels of inflammatory cytokines and prothrombotic factors. Pioglitazone also redistributes fat and toxic lipid metabolites in muscle, liver, β cells, and arteries, and deposits the fat in subcutaneous adipocytes where it cannot exert its lipotoxic effects. Consistent with these antiatherogenic effects, pioglitazone reduced major adverse cardiac event endpoints (ie, mortality, myocardial infarction, and stroke) in the Prospective Pioglitazone Clinical Trial in Macrovascular Events and in a meta-analysis of all other published pioglitazone trials. Pioglitazone also mobilizes fat out of the liver, improving liver function and histologic abnormalities in patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Pioglitazone also reduces proteinuria, all-cause mortality, and cardiovascular events in patients with type 2 diabetes mellitus with a reduced glomerular filtration rate. These benefits must be weighed against the side effects of the drug, including weight gain, fluid retention, atypical fractures, and, possibly, bladder cancer. When low doses of pioglitazone are used (eg, 7.5-30 mg/d) with gradual titration, and physician recognition of the potential side effects are applied, the risk-to-benefit ratio is very favorable. Despite having similar effects on glycemic control, pioglitazone and rosiglitazone appear to have different effects on cardiovascular outcomes. Rosiglitazone has been associated with an increased risk of myocardial infarction, and its use in the United States is restricted because of cardiovascular safety concerns.

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