Prediabetes deserves more attention: A review

Abstract

Evidence increasingly demonstrates that prediabetes is a toxic state, as well as a risk factor for diabetes, and is associated with pathophysiological changes in several tissues and organs. Unfortunately, use of available evidence-based treatments for prediabetes is low. This review seeks to explain why prediabetes must be viewed and treated as a serious pathological entity in its own right. It offers an overview of the pathophysiology and complications of prediabetes and describes how this condition can be reversed if all treatment avenues are deployed early in its course. Prediabetes is defined as a state of abnormal glucose homeostasis in which blood glucose levels are elevated above those considered normal, but not high enough to meet the criteria required for a diagnosis of diabetes (1,2). It is characterized by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Evidence increasingly demonstrates that prediabetes is a toxic state, in addition to being a risk factor for diabetes (3). Emerging evidence suggests that prediabetes is associated with pathophysiological changes in several tissues and organs, which would support its recognition as a distinct pathological entity. The recent inclusion of prediabetes and associated billable conditions in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems gives credence to this position (1). The frequency of prediabetes is increasing as the prevalence of obesity rises worldwide (1). The pathophysiologic defects underlying prediabetes include insulin resistance, β-cell dysfunction, increased lipolysis, inflammation, suboptimal incretin effect, and hepatic glucose overproduction (3). These metabolic derangements associated with concomitant obesity cause endothelial vasodilator and fibrinolytic dysfunction, leading to increased risk of macrovascular and microvascular complications (2-6). Prediabetes has also been associated with increased risks of cancer and dementia (4). Recent studies have demonstrated that patients with prediabetes can suffer from coronary artery disease and diastolic heart failure even before progressing to overt diabetes (5). Macrovascular complications are the greatest contributor to diabetes-related health care expenditures, and prediabetes contributes substantially to these costs (7,8). Lifestyle interventions, including diet and exercise, are first-line treatments. Medications can also play a role; randomized controlled trials of biguanides (metformin), α-glucosidase inhibitors (acarbose), inhibitors of pancreatic lipase (orlistat), peroxisome proliferator-activated receptor-γ agonists (rosiglitazone and pioglitazone), meglitinides (nateglinide), and glucagon-like peptide 1 receptor agonists (liraglutide) have all shown benefits. Bariatric surgery is another efficacious means of treating prediabetes and type 2 diabetes (9). Unfortunately, despite the availability of evidence-based treatment options, and especially the pharmacological and surgical means, they are not being fully exploited by clinicians to tackle prediabetes. This underutilization most probably stems from the mindset that prediabetes is just a risk factor and not a serious pathological entity in its own right. Likewise, people with prediabetes are often reluctant to accept antidiabetic prescriptions because they do not have diabetes, aggravating clinicians' own hesitance to initiate drug treatment for prediabetes. The hesitant predisposition of clinicians and patients alike motivated the authors to write this review, which seeks to add to the growing voice aimed at enlightening practitioners and patients worldwide that prediabetes must be viewed and treated as a serious pathological entity, although it is less severe than diabetes. This review provides insight into the pathophysiology and complications of prediabetes and how they compare with the enormous problems associated with diabetes. By pointing out that prediabetes can be reversed if all treatment avenues are deployed early on in its course (9,10), the authors seek to convince practitioners that prediabetes deserves more attention than it is presently being given. Literature sources included in this review were obtained from searches of databases, including PubMed, PubMed Central, and Google Scholar. Search terms used were "pathophysiology of prediabetes and/or impaired fasting glucose and/or impaired glucose tolerance,""complications of prediabetes,""complications of impaired fasting glucose,"and "complications of impaired glucose tolerance."