The burden of diabetes is expected to rise from 415 million individuals in 2015 to 642 million individuals by 2040. Most individuals pass through a phase of prediabetes before developing full-blown diabetes. Insulin resistance, impaired incretin action, and insulin hypersecretion are central to the pathophysiology of prediabetes. Individuals older than 40 years of age and other high-risk individuals should be screened for diabetes with fasting plasma glucose and/or hemoglobin A1c. For those diagnosed with prediabetes, the goal of treatment should be restoring euglycemia, because there are data showing that restoring normoglycemia during prediabetes and early diabetes can produce lasting remission. The preferred approach for this is intensive lifestyle intervention, which besides reducing progression to diabetes, has also been shown to reduce all-cause mortality in a long-term follow-up study. The best evidence for a pharmacological approach is with metformin. Other drugs that have shown efficacy include thiazolidinediones, alpha-glucosidase inhibitors, orlistat, basal insulin, and valsartan. However, except for metformin, none of these drugs are currently recommended for this purpose. Newer agents such as glucagon-like peptide-1 agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors also have considerable promise in this area. Bariatric surgery can be offered to patients with metabolic syndrome and body mass index of 30-35.
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