The importance of beta-cell management in type 2 diabetes.
Despite intervention with effective oral glucose-lowering agents, most patients with type 2 diabetes will experience a gradual loss of glycaemic control. Irrespective of underlying levels of insulin resistance, the progressive failure and loss of beta-cells are ultimately responsible for the onset of frank type 2 diabetes. The mechanisms responsible for loss of beta-cell function are likely to be multifactorial, but may involve toxicity because of elevated glucose and/or lipid levels, increased secretory demand because of insulin resistance, amyloid deposition and altered levels of cytokines. Preservation of beta-cell function is now gaining recognition as a critical target in the management of type 2 diabetes. For patients with frank type 2 diabetes, preservation of beta-cell function has the potential to reduce or stabilise the progression of type 2 diabetes and to decrease the need for additional oral glucose-lowering agents and/or insulin therapy. There is a growing body of animal/preclinical evidence for improved and preserved beta-cell function with current glucose-lowering agents, such as the thiazolidinediones, metformin and the glucagon-like peptide-1 analogue, exenatide. Clinical studies incorporating indirect measures of beta-cell function also support a protective effect with some agents. A number of novel therapies that are currently under investigation may also offer beta-cell structural and functional protection, including dipeptidyl peptidase IV inhibitors and cannabinoid receptor type 1 blockers. Emerging evidence from interventional trials suggests that both intensive lifestyle changes and pharmacotherapy can delay or possibly prevent the onset of type 2 diabetes in high-risk individuals. For patients newly diagnosed with type 2 diabetes, early and aggressive intervention strategies that combine maximal glucose-lowering efficacy alongside potential beta-cell preserving properties may provide an opportunity to delay or prevent progression of the disease.
Standl
E
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Munich Institute of Diabetes Research and Medical Department, Krankenhaus Munchen-Schwabing, Munich, Germany. eberhard.standl@lrz.uni-muenchen.de
D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D019317:Evidence-Based Medicine; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents