Review of methods for detecting glycemic disorders

Abstract

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity.

Keywords: Biomarkers; Cardiovascular disease; Continuous glucose monitoring; Glycemic variability; HbA1c; Metabolomics; Oral glucose tolerance test; Prediabetes; Type 2 diabetes.

Fig. 1 –

Classification of glucose curve shape. (A) Simple analysis of curve shape: monophasic (red), biphasic (green) and unclassified (purple) and (B) Latent mixed class trajectory modeling of curve shape: Class 1 (green), Class 2 (blue), Class 3 (orange), Class 4 (red) (adapted from [151].

Fig. 2 –

Illustration of the continuum in the deterioration of glucose homeostasis throughout the natural history of T2D. HbA1c = 5.7–6.4% (39–46 mmol/mol): dawn phenomenon. HbA1c = 6.5–6.9% (48–52 mmol/mol): dawn phenomenon plus postprandial hyperglycemia. HbA1c ≥ 7% (53 mmol/mol): progressive increment of basal hyperglycemia. The respective contributions of postprandial and basal hyperglycemia can be depicted as follows: postprandial > basal when HbA1c = 7.0–7.4% (53–57 mmol/mol), equal when HbA1c = 7.5–7.9% (58–63 mmol/mol) and basal ≥ postprandial when HbA1c > 8.0% (64 mmol/mol). Total hyperglycemia is determined by the sum of the black (AUCbasal) and shaded areas (AUCpostprandial).

Fig. 3 –

Overview of Methods for Detecting Glycemic Disorders.