LAUSR

According to the Centers for Disease Prevention and Control, prediabetes affects 81 million adults in the United States (US), yet 90% of those with prediabetes are not aware of it. Prediabetes is defined by the American Diabetes Association (ADA) as a fasting blood glucose of 100-125 mg/dL, a 2-hour postprandial glucose of 140-199 mg/dL, or glycosylated hemoglobin (HbA1c) between 5.7% and 6.4%. Criteria for screening patients include those who are overweight or obese as well as those with other risk factors, such as family history of type 2 diabetes mellitus (DM) or gestational DM. An online test (http://www.diabetes.org/are-you-at-risk/diabetes-risk-test/) that can be easily implemented in clinical practice is also available. The consequences of prediabetes are significant. The rates of progression from prediabetes to DM can be as high as 5%-10% per year. Most importantly, prediabetes increases the risk of atherosclerotic cardiovascular disease (ASCVD). A meta-analysis of 52 prospective cohort studies involving more than 1.6 million adults showed prediabetes was associated with a 13% relative risk (RR) increase of ASCVD, as well as a 13% RR increase of all-cause mortality. Additional data from the Atherosclerosis Risk in Communities Study found a 40% RR increase of incident heart failure in adults without a history of DM and a baseline HbA1c of 6%-6.4%. These data suggest that prediabetes must be taken seriously by patients and clinicians alike as it is associated with significantly increased overall cardiovascular risk. Recently, the American College of Cardiology and American Heart Association released guidelines for the primary prevention of ASCVD. This guideline included lifestyle recommendations and highlighted key recommendations from practice guidelines for the management of major ASCVD risk factors, including hypertension, dyslipidemia, and DM. Despite the comprehensive nature of the guideline, there was little to no mention of DM prevention. While the primordial prevention of other risk factors (eg, hypertension) was not mentioned in the guideline either, we feel the omission of prediabetes is different given that prediabetes is considered, itself, a disease by some and it increases the risk for additional established risk factors, increasing the cardiovascular risk even further. Therefore, we feel it is imperative to encourage clinicians to appropriately screen patients for prediabetes, promote evidence-based lifestyle modification interventions, and when attempts to improve lifestyle have been exhausted, consider initiating medications shown to prevent the development of DM (Figure 1). Lifestyle interventions remain the cornerstone for the prevention of DM. In the Diabetes Prevention Program (DPP) and Finnish Diabetes Prevention Study (FDPS), an intensive lifestyle intervention comprised of increased physical activity and exercise combined with tailored dietary interventions including caloric restriction and diet quality improvement strategies, reduced the risk of developing DM by nearly 60%. This magnitude of DM prevention is similar to what can be only achieved with a dual or triple combination pharmacologic strategy. Although the implementation of such intensive lifestyle interventions in routine clinical practice remains challenging, even less intensive lifestyle interventions provide significant benefits in reducing the risk of DM. Of note, while both DPP and FDPS were associated with significant weight loss, which may partially explain the preventive effects of the interventions, changes in diet quality may also confer similar benefits, independent of changes in body weight. For instance, in the PREDIMED trial, a Mediterranean diet supplemented with four tablespoons per day of extra-virgin olive oil or 30 g per day of mixed nuts, food rich in unsaturated fatty acids, was associated with >50% RR reduction in the likelihood of developing DM in those with prediabetes. The PREDIMED-plus trial is currently investigating whether a dietary intervention combining both strategies of caloric restriction and diet quality improvements may be more beneficial than diet quality improvement alone to prevent DM. Although lifestyle interventions are recommended in all patients with prediabetes, several antihyperglycemic medications have also been found to prevent DM, including metformin, thiazolidinediones (TZDs), alpha-glucosidase inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1RA), used individually or in combination. Received: 5 November 2019 Revised: 30 January 2020 Accepted: 18 March 2020