The number of individuals with prediabetes is expected to grow substantially and estimated 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 recognizing 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.

Highlights A 1-hour plasma glucose (1-h PG) threshold >155 mg/dl (8.6 mmol/L) during an oral glucose tolerance test (OGTT) may be a suitable biomarker for identifying normal glucose tolerant (NGT) individuals at risk for future type 2 diabetes (T2D). A one-hour, non-fasting, 50g Glucose Challenge Test (GCT) performed during a routine health care visit has potential for practical screening of glucose disorders. The shape of the glucose curve reflects the cumulative effect of insulin sensitivity and response on glucose concentrations with prospective studies warranted to evaluate its prognostic utility. The continuous glucose monitor (CGM) has facilitated insight into the pathophysiology of prediabetes and phenotypes of T2D and holds promise for detecting glycemic disorders. Metabolomic profiling including amino acids, lipids, carbohydrates and other metabolites may be useful for early diagnosis of glycemic disorders. Non-classical markers for assessing glycemic disorders including fructosamine, glycated albumin, and 1,5-anhydroglucitol that evaluate shorter periods of glucose exposure than HbA1c have potential use as adjunctive tools.

For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1-h PG. Measurement of the 1-h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic ß-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2-h OGTT making it more acceptable in the clinical setting.

Identifying the earliest moment for intervention to avert progression to prediabetes and diabetes in high-risk individuals is a substantial challenge. As β-cell function is already compromised in prediabetes, attention should therefore be focused on identifying high-risk individuals earlier in the so-called pre-prediabetes stage. Biomarkers to monitor progression and identify the time point at which β-cell dysfunction occurs are therefore critically needed. Large-scale population studies have consistently shown that the 1-h plasma glucose (1-h PG) ≥ 155 mg/dl (8.6 mmol/l) during the oral glucose tolerance test detected incident type 2 diabetes and associated complications earlier than fasting plasma glucose or 2-h plasma glucose levels. An elevated 1-h PG level appears to be a better alternative to HbA1c [5.7-6.4% (37-47 mmol/mol)] or traditional glucose criteria for identifying high-risk individuals at a stage when ß-cell function is substantially more intact than in prediabetes. Diagnosing high-risk individuals earlier proffers the opportunity for potentially reducing progression to diabetes, development of microvascular complications and mortality, thereby advancing benefit beyond that which has been demonstrated in global diabetes prevention programs.

Abstract Many health care providers screen high-risk individuals exclusively with an HbA1c despite its insensitivity for detecting dysglycemia. The 2 cases presented describe the inherent caveats of interpreting HbA1c without performing an oral glucose tolerance test (OGTT). The first case reflects the risk of overdiagnosing type 2 diabetes (T2D) in an older African American male in whom HbA1c levels, although variable, were primarily in the mid-prediabetes range (5.7-6.4% [39-46 mmol/mol]) for many years although the initial OGTT demonstrated borderline impaired fasting glucose with a fasting plasma glucose of 102 mg/dL [5.7 mmol/L]) without evidence for impaired glucose tolerance (2-hour glucose ≥140-199 mg/dl ([7.8-11.1 mmol/L]). Because subsequent HbA1c levels were diagnostic of T2D (6.5%-6.6% [48-49 mmol/mol]), a second OGTT performed was normal. The second case illustrates the risk of underdiagnosing T2D in a male with HIV having normal HbA1c levels over many years who underwent an OGTT when mild prediabetes (HbA1c = 5.7% [39 mmol/mol]) developed that was diagnostic of T2D. To avoid inadvertent mistreatment, it is therefore essential to perform an OGTT, despite its limitations, in high-risk individuals, particularly when glucose or fructosamine and HbA1c values are discordant. Innate differences in the relationship between fructosamine or fasting glucose to HbA1c are demonstrated by the glycation gap or hemoglobin glycation index.

Introduction: Sodium-glucose cotransporter-2 [SGLT2] inhibitors reduce cardiovascular events and mortality in patients with diabetes, particularly patients with established cardiovascular disease. Euglycemic diabetic ketoacidosis [euDKA], a complication of SGLT2 therapy, can be exacerbated by a low carbohydrate diet. Case Report: A 61-year-old man with a history of type 2 diabetes, taking a SGLT2 inhibitor empagliflozin 10 mg orally daily, presented to the emergency room with a 2-day history of nausea and chest pain. A week prior to presentation, he had started a ketogenic diet. He was initially admitted with a diagnosis of acute coronary syndrome. On initial assessment in the emergency room, his cardiac enzymes were normal and there were no ischemic changes in his ECG. As there was concern for unstable angina, he underwent cardiac catheterization, which showed a known total occlusion with collaterals and arteries with non-obstructive disease without evidence of acute plaque rupture. His baseline laboratory assessments revealed an elevated anion gap of 17, increased urinary and plasma ketones, and metabolic acidosis. His plasma glucose level was 84 mg/dL. The diagnosis of euDKA was made, and treatment with intravenous fluids and insulin was initiated. His chest pain and nausea subsequently resolved. Conclusion: We present a case of euDKA triggered by a ketogenic diet while on SGLT2 inhibitor therapy presenting as chest pain. The recognition of euDKA is important in the context of increased SGLT2 use for management of cardiovascular risk for patients with diabetes.

Significant glycemic reduction in subjects with poorly controlled diabetes led to reduced circulating WBC counts and inflammatory gene expression.

Objective: The purpose of this study was to assess and compare the readability of type 2 diabetes online patient education materials from academic institutions in the northeast USA and the American Diabetes Association. Many US residents utilise the Internet to obtain health information. Studies have shown that online patient education materials are often written above the recommended fifth grade reading level, and this may pertain to diabetes health information as well. As diabetes is the seventh leading cause of death in the USA and glycaemic control is related to health literacy, the readability of diabetic health information is pertinent. Methods: Many academic institutions provide type 2 diabetes online health information. A readability analysis was conducted of materials on the websites of academic institutions or affiliate hospitals with endocrinology fellowships in the northeast USA, and from the American Diabetes Association, using 10 quantitative scales: the Flesch Reading Ease Score, the Flesch–Kincaid Grade Level, the Simple Measure of Gobbledygook, the Gunning Frequency of Gobbledygook, the New Dale–Chall Test, the Coleman–Liau Index, the New Fog Count, the Raygor Readability Estimate, the FORCAST test and the Fry Graph. Results: On average, northeast US academic institutions prepared their online diabetes patient education materials at above a 10th grade reading level. Conclusion: The readability of type 2 diabetes patient health information from academic websites is too difficult. It may benefit people with diabetes for future patient education materials to be prepared at lower reading grade levels.