Improving care for patients with type 2 diabetes: applying management guidelines and algorithms, and a review of new evidence for incretin agents and lifestyle intervention
ABSTRACT Diabetes affects an estimated 25.8 million US adults, or 8.3% of the population. By 2050, the prevalence of type 2 diabetes mellitus (T2DM) in the United States may be as high as 1 in 3 adults. This paper summarizes key national treatment goals, guidelines, and algorithms for T2DM management in a way that clarifies their similarities and areas of disparity, for use by managed care organizations and other healthcare professionals. In addition, the role of long-standing and newer classes of antihyperglycemic agents, including incretin-related agents, bromocriptine, and colesevelam, will be reviewed, as will emerging research on the role of lifestyle intervention in T2DM and prediabetes. Lastly, comparative and long-term clinical efficacy data on incretin therapy, reported at the American Diabetes Association's 2011 71st Scientific Sessions, will be summarized. Although the treatment landscape for T2DM has increased substantially in complexity, major guidelines have similar goals. While established, relatively inexpensive, and thoroughly investigated antihyperglycemic agents maintain popularity, incretin-based agents offer glycemic efficacy along with other benefits relative to weight loss or neutrality and low rates of hypoglycemia. In addition, the feasibility of matching patients to appropriate lifestyle intervention, for both diabetes and diabetes prevention, is increasing.
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- "For the time being, appropriate lifestyle management in type 2 diabetic patients has a strong evidence class I, level A recommendation in most guidelines [8, 10–12, 23]. "
ABSTRACT: Some 30% of contemporary cardiology patients have coexisting known diabetes, and another 40% have either undiagnosed diabetes or prediabetes. There is still no final conclusive evidence of cardiovascular benefit by good glycemic control in type 2 diabetes, although studies like the United Kingdom Prospective Diabetes Study (UKPDS) and the Prospective Pioglitazone Clinical Trial in Macrovascular Events, and meta-analyses based on these and other randomized controlled trials of blood glucose-lowering therapies have been encouraging. On the other hand, microvascular disease is clearly reduced by good glycemic control. Structured education has remained a mandatory prerequisite of any successful treatment. Not only is appropriate weight management by diet and exercise able to revert new onset diabetes to normal, but it is also the foundation of any successful pharmacotherapy of diabetes. Aiming at normal fasting plasma glucose concentrations of 5.3 mmol/L or 95 mg/dL appears to be safe since publication of the long-term outcome results of the Outcome Reduction with an Initial Glargine INtervention trial. Individualized target glycosylated hemoglobin levels as near to normal as safely possible (i.e., <7% and avoiding hypoglycaemia) are the goal for glycemic control. Hypoglycemia seems to emerge as a real concern in cardiology patients. Based on the findings of UKPDS, including the “legacy” study, metformin is the most widely recommended first-line drug therapy in type 2 diabetes, also in terms of preventing cardiovascular complications. An alternate first-line option in some parts of the world, especially Asian countries, is the class of alpha-glucosidase inhibitors. In most patients, combination therapies with two or three classes of drugs are warranted. Early combination are the golden strategy as type 2 diabetes is a multi-causal disease; the various classes of drugs have distinct and synergistic modes of action, and the blood glucose-lowering efficacy of these drugs is more or less fully maintained in combination. The recent joint American Diabetes Association/European Association for the Study of Diabetes position statement mentions five options as step two of the treatment algorithm for combination with metformin: sulfonylureas, pioglitazone, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, and basal insulin.06/2013; 2(1). DOI:10.1007/s40119-012-0007-7
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ABSTRACT: There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1alpha). In diabetes, HIF-1alpha function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1alpha transactivation. We examined whether local enhancement of HIF-1alpha activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1alpha activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1alpha transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.Proceedings of the National Academy of Sciences 01/2015; 112(1):94-99. DOI:10.1073/pnas.1413445112 · 9.81 Impact Factor