Thresholds of various glycemic measures for diagnosing diabetes based on prevalence of retinopathy in community-dwelling Japanese subjects: the Hisayama Study

Abstract

BackgroundThere has been controversy over the diagnostic thresholds of hemoglobin A1c (HbA1c) for diabetes. In addition, no study has examined the thresholds of glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) for diagnosing diabetes using the presence of diabetic retinopathy (DR). We examined the optimal thresholds of various glycemic measures for diagnosing diabetes based on the prevalence of DR in community-dwelling Japanese subjects.MethodsA total of 2,681 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test, measurement of HbA1c, GA, and 1,5-AG, and an ophthalmic examination in 2007-2008. The associations of glycemic measures with DR status were examined cross-sectionally. DR was assessed by an examination of the fundus photograph of each eye and graded according to the International Clinical Diabetic Retinopathy Disease Severity Scale. We divided the values of glycemic measures into ten groups on the basis of deciles. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold of each glycemic measure for detecting the presence of DR.ResultsOf the subjects, 52 had DR. The prevalence of DR increased steeply above the ninth decile for fasting plasma glucose (FPG) (6.2-6.8 mmol/l), for 2-hour postload glucose (PG) (9.2-12.4 mmol/l), for HbA1c (5.9-6.2% [41-44 mmol/mol]), and for GA (16.2-17.5%), and below the second decile for 1,5-AG (9.6-13.5 μg/mL). The ROC curve analysis showed that the optimal thresholds for DR were 6.5 mmol/l for FPG, 11.5 mmol/l for 2-hour PG, 6.1% (43 mmol/mol) for HbA1c, 17.0% for GA, and 12.1 μg/mL for 1,5-AG. The area under the ROC curve (AUC) for 2-hour PG (0.947) was significantly larger than that for FPG (0.908), GA (0.906), and 1,5-AG (0.881), and was marginally significantly higher than that for HbA1c (0.919). The AUCs for FPG, HbA1c, GA, and 1,5-AG were not significantly different.ConclusionsOur findings suggest that the FPG and HbA1c thresholds for diagnosing diabetes in the Japanese population are lower than the current diagnostic criterion, while the 2-hour PG threshold is comparable with the diagnostic criterion. 2-hour PG had the highest discriminative ability, whereas FPG, HbA1c, GA, and 1,5-AG were similar in their ability.

The Association of Retinopathy and Plasma Glucose and HbA1c: A Validation of Diabetes Diagnostic Criteria in a Chinese Population

“…Particularly, the cutoff of FPG by deciles in the Chinese population (7.03–7.2 mmol/L) was much higher than those in other Asian populations (6.2–6.5 mmol/L) [13, 15, 16, 23, 24]. However, in our study, the optimal FPG, determined using ROC curve analysis (6.52 mmol/L), was close to that in the previous Asian studies.…”

Metrics Beyond Hemoglobin A1C in Diabetes Management: Time in Range, Hypoglycemia, and Other Parameters

“…1,5-AG reflects glucose control over the previous 48 h to 2 weeks, its concentration is mainly useful in detecting postprandial glucose (PPG), where lower levels result from glucose peaks above the renal threshold and particularly useful in patients with A1C <8%. 49 1,5-AG was found to be negatively associated with longterm risk of microvascular outcomes, 14,50,51 and an increased risk of CV disease [52][53][54] and mortality in DM. 53 The concentrations of 1,5-AG decrease as pregnancy progresses in both nondiabetic and diabetic subjects 55 ; nonetheless, 1,5-AG has been found to be a useful marker in pregnancy complicated by DM, associated with mean glycemia, glycemic variability (GV), and glycemic exposure in females with T1D1 in whom glycemic control was assessed by a continuous glucose monitoring (CGM) system.…”

“…FA refers to several proteins, with albumin accounting for *90%; GA refers exclusively to albumin. 12 Glycated proteins have been associated with micro- [13][14][15] and macrovascular complications [16][17][18][19][20][21] and mortality in people with DM. 22 Several prospective studies have shown their utility for patients at risk of developing micro-and macrovascular complications.…”

Beyond HbA1c and Glucose: the Role of Nontraditional Glycemic Markers in Diabetes Diagnosis, Prognosis, and Management

“…29 In a Japanese cohort of more than 2,500 participants, the performance of glycated albumin and 1,5-AG to identify cases of retinopathy—as measured by the C-statistic—was shown to be comparable to fasting glucose and HbA1c. 38 In a study of 1,575 Japanese adults without diagnosed diabetes, glycated albumin was associated with carotid artery intima-media thickness, a measure of subclinical atherosclerosis. 39 Glycated albumin has been associated with prevalent kidney outcomes, 40–42 and cardiovascular disease.…”