Novel biomarkers for prediabetes, diabetes, and associated complications

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Dovepress open access to scientific and medical research Review Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy downloaded from https://www.dovepress.com/ by 220.72.33.45 on 11-Jul-2020 For personal use only. Open Access Full Text Article Novel biomarkers for prediabetes, diabetes, and associated complications This article was published in the following Dove Press journal: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 14 August 2017 Number of times this article has been viewed Brenda Dorcely 1 Karin Katz 1 Ram Jagannathan 2 Stephanie S Chiang 1 Babajide Oluwadare 1 Ira J Goldberg 1 Michael Bergman 1 1 New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY, 2 Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA Correspondence: Michael Bergman New York University School of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, 550 1st Avenue, Suite 5E, New York, NY 10016, USA Tel +1 212 481 1350 Fax +1 212 481 1355 Email Introduction Prediabetes is defined as an intermediate state with plasma glucose levels ranging between normoglycemia and diabetes. The Centers for Disease Control estimated that in 2012 about 86 million, or one out of three, adults had prediabetes in the US.1 However, 90% of these individuals were unaware of their diagnosis. In 2015, the International Diabetes Federation estimated that the worldwide prevalence of impaired glucose tolerance (IGT) in adults was 318 million and expected to reach 482 million by 2040.2 The annual progression rate to diabetes is 5–10%,3 with older individuals, those with severe insulin resistance (IR), low insulin secretion, and other diabetes risk factors even more likely to progress.4 How can we identify patients with prediabetes and what can we do to prevent progression to diabetes? Lifestyle and pharmacological interventions have been most effective in preventing progression to diabetes and associated complications. Preservation of β-cell function and reduction in IR and diabetes complications such as retinopathy, cardiovascular disease (CVD), and all-cause mortality were observed subsequent to lifestyle modifica tion.5,6 The Da Qing Diabetes Study in China,6 the Finnish Diabetes Prevention Study,7,8 and the U.S. Diabetes Prevention Program3,9 have shown that changes in dietary habits, weight loss, and increased physical activity reduced the risk of progression to diabetes. Bariatric surgery promotes weight loss and is beneficial in prediabetes.10 Identification of risk and diagnosis of prediabetes Development of prediabetes involves multiple factors including genetics, peripheral IR, defects in insulin secretion, glucotoxicity, lipotoxicity, impaired incretin release, 345 submit your manuscript | www.dovepress.com Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2017:10 345–361 Dovepress © 2017 Dorcely et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/DMSO.S100074 Powered by TCPDF (www.tcpdf.org) Abstract: The number of individuals with prediabetes is expected to grow substantially and esti mated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recogni zing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. Keywords: prediabetes, biomarkers, inflammatory markers, diabetes, diabetes complications Dovepress Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy downloaded from https://www.dovepress.com/ by 220.72.33.45 on 11-Jul-2020 For personal use only. Dorcely et al amylin accumulation, inflammation, oxidative stress, and decreased β-cell mass leading to β-cell dysfunction.11–13 Prediabetes is classified as isolated impaired fasting glucose (IFG) or IGT.14 Glucose and glycated hemoglobin (HbA1c) criteria for diagnosing dysglycemic states are controversial as there are differing thresholds recommended by the American Diabetes Association (ADA) and the World Health Organiza tion.15,16 We will review several additional biomarkers used to predict the risk of progression to diabetes. Diagnostic biomarkers and their clinical utility Hemoglobin A1c HbA1c is the most commonly used biomarker to diagnose prediabetes and diabetes. HbA1c forms when glucose attaches to the amino-terminal group of the β subunit of hemoglobin.17 HbA1c reflects chronic glycemia rather than glucose levels at a single time point. Currently, the ADA criteria for diabetes are HbA1c ≥6.5% (48 mmol/mol) and 5.7–6.4% (39–46 mmol/mol) for prediabetes.14 Increased HbA1c levels are associated with increased morbidity and mortality. In the Norfolk prospective study, higher HbA1c levels were also associated with increased CVD, cancer, and all-cause mortality.18 Long-term prospective studies, includ ing the Diabetes Control and Complications Trial, the UK Prospective Diabetes Study Group, and the Epidemiology of Diabetes Interventions and Complications study have shown that diabetic complications are directly related to the mean HbA1c, with a level ≥6.5% (48 mmol/mol) associated with retinopathy.19–21 Additionally, HbA1c was more strongly cor related with retinopathy than fasting plasma glucose (FPG). Thus, HbA1c may be a better predictor of microvascular complications than FPG.22 HbA1c has several advantages versus FPG and oral glu cose tolerance test (OGTT) including greater convenience as fasting is not required, greater pre-analytical stability, and less day-to-day perturbation during periods of stress and ill ness.23 Since HbA1c r (...truncated)