Association of 1,5-Anhydroglucitol with Diabetes and Microvascular Conditions

Abstract

Background 1,5-anhydroglucitol (1,5-AG) is inversely related to hyperglycemia and may be a useful indicator of short-term (1-2 week) hyperglycemia and glycemic excursions but its prognostic value is unclear. We sought to evaluate the associations of 1,5-AG with risk of diabetes and microvascular disease. Methods We measured 1,5-AG in blood samples from over 10,000 participants in the ARIC Study (baseline, 1990-1992) and characterized the independent associations with prevalent retinopathy, and with incident chronic kidney disease and incident diabetes during approximately 20 years of follow-up. Results We found that 1,5-AG was associated with prevalent retinopathy, driven primarily by the strong association in persons with diagnosed diabetes: adjusted OR 11.26 (95%CI 6.17-20.53) for <6 ug/mL compared to 1,5-AG ≥10 ug/mL. This result remained significant after further adjustment for HbA1c (OR 4.85, 95%CI 2.42-9.74). In persons with diagnosed diabetes: low 1,5-AG (<6 ug/mL vs ≥10 ug/mL) was also associated with a greater than 2-fold increased risk of incident chronic kidney disease (adjusted HR 2.83, 95% CI 2.15-3.74) and remained significant after adjustment for HbA1c (HR 1.43, 95%CI 1.02-2.00). Nondiabetic participants with high 1,5-AG (≥ 10 ug/mL) had the lowest prevalence of retinopathy and lowest risk of kidney disease. In persons without diagnosed diabetes at baseline, 1,5-AG <10 ug/mL was also associated with incident diabetes (adjusted HR 2.29, 95%CI 2.03-2.58). Conclusions 1,5-AG was associated with long-term risk of important microvascular outcomes, particularly in persons with diagnosed diabetes and even after adjustment for HbA1c. Our results suggest 1,5-AG may capture risk information associated with hyperglycemic excursions.

Glycemic Variability and Diabetes Complications: Does It Matter? Of Course It Does!

“…In those with diagnosed diabetes, those with the lowest levels of 1,5-AG (,6 mg/mL, representing the most GV) were 11 times more likely to have retinopathy compared with those with the highest levels of 1,5-AG (.10 mg/mL, representing the least GV). In those with diagnosed diabetes, low 1,5-AG was also associated with a greater than twofold increased risk of incident chronic kidney disease (21). These relationships for the entire study population are shown in Fig.…”

“…Another important supporting study was a recent publication reviewing the association of 1,5-anhydroglucitol (1,5-AG), a biomarker associated with GV, and outcomes in the Atherosclerosis Risk in Communities (ARIC) Study (21). 1,5-AG is a metabolically inert monosaccharide present in the diet.…”

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.…”

Race, APOL1 Risk, and eGFR Decline in the General Population

“…Additional outcomes were determined through ARIC study surveillance using both annual telephone interviews and abstraction of hospitalization records, with follow-up until December 31, 2011. [35][36][37] Incident hypertension was assessed at each annual telephone interview as self-reported hypertension diagnosis or antihypertension medication use, or systolic BP $140 mmHg, diastolic BP $90 mmHg, or the use of antihypertension medications at a subsequent study visit. Incident diabetes was defined as self-reported diabetes diagnosis or use of diabetes medications during study visits or annual telephone interviews.…”