Circulating 1,5-Anhydroglucitol Levels in Adult Patients With Diabetes Reflect Longitudinal Changes of Glycemia

Abstract

OBJECTIVE -1,5-Anhydroglucitol (1,5AG) is a major circulating polyol arising primarily from ingestion and excreted competitively with glucose. Japanese studies have demonstrated reduced concentrations of 1,5AG in serum in hyperglycemic patients in comparison with euglycemic subjects and a gradual normalization of 1,5AG values for patients responding to antihyperglycemic therapies. In this first U.S. study, we assessed the ability of 1,5AG measurements to monitor glycemic control in a cohort of 77 patients with diabetes (22 with type 1 diabetes, 55 with type 2 diabetes) who presented with suboptimal glycemic control at baseline (defined as HbA 1c Ն7%).RESEARCH DESIGN AND METHODS -Each patient received therapies consisting of combinations of diabetes education, nutritional counseling, and addition or dose adjustment of various insulins or oral antihyperglycemic medications. Therapy was targeted to reduce mean HbA 1c by Ն1.0% over the monitoring period. 1,5AG, HbA 1c , fructosamine, and random glucose measurements were performed at baseline and at 2, 4, and 8 weeks after the initiation of therapy.RESULTS -1,5AG, fructosamine, and glucose values progressed significantly toward euglycemia by week 2 of monitoring (Wilcoxon's signed-rank test, P Ͻ 0.05), with median changes of 93, Ϫ7, and Ϫ13% for 1,5AG, fructosamine, and glucose, respectively. In contrast, HbA 1c values did not respond significantly to therapy until week 4. On an individual patient basis, 89.6% of patients displayed longitudinal changes of 1,5AG from baseline to week 8 in concordance with HbA 1c . 1,5AG was also highly correlated with HbA 1c and fructosamine (Spearman ϭ Ϫ0.6459 and Ϫ0.6751, respectively; both P Ͻ 0.0001).CONCLUSIONS -We conclude that 1,5AG responds sensitively and rapidly to changes in glycemia and monitors glycemic control in accordance with established markers.

Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus

“…It is possible that lesser degrees of post-prandial hyperglycaemia (defined using a cut-off point <8.89 mmol/l) contribute to diabetes complications, although no data are available [10]. It is also possible that with the use of novel markers of post-meal glucose levels, such as depressed 1,5-anhydroglucitol levels [20], the prevalence of clinically significant postprandial hyperglycaemia might be different. In addition, we based our definition of a deleterious post-prandial excursion (≥2.22 mmol/l) on risk associated with post-OGTT glucose levels [9].…”

The effect of basal–bolus therapy varies with baseline 1,5‐anhydroglucitol level in people with Type 2 diabetes: a post hoc analysis

“…Plasma 1,5‐anhydroglucitol (1,5‐AG) has been proposed as a marker to assess short‐term glycaemic control in people with Type 1 and Type 2 diabetes 3, 4, 5. 1,5‐AG is an endogenous dietary polyol, structurally similar to glucose, that is maintained at a constant steady state in the blood 6.…”

“…1,5‐AG is an endogenous dietary polyol, structurally similar to glucose, that is maintained at a constant steady state in the blood 6. When blood glucose is in the normal range, 1,5‐AG is reabsorbed in the proximal tubules of the kidney and is stable in the range of 6.8–29.3 μg/ml in women and 10.7–32.0 μg/ml in men 4. When blood glucose exceeds the renal threshold (~180 mg/dl), glucose blocks reabsorption of 1,5‐AG and circulating levels decrease.…”

A computational model of 1,5-AG dynamics during pregnancy

“…1,5‐AG intake is mainly through ingestion (average of 5 mg daily) (McGill et al. 2004) and the major route of elimination is through urinary excretion, with intake and elimination at approximate equilibrium. Normally, 1,5‐AG is filtered in the kidneys and completely reabsorbed in the renal tubules back into the bloodstream (Buse et al.…”

“…Although an automated enzymatic assay (Glycomark) has been approved in the U.S. to measure plasma 1,5‐AG levels (McGill et al. 2004), and a similar assay has been used in Japan for over two decades (Fukumura et al. 1994), some studies do not recommend monitoring 1,5‐AG for glycemic control during pregnancy, since physiological changes in glomerular filtration rate, plasma volume, and other hemodynamic parameters during gestation may bias 1,5‐AG concentrations in the blood (Kilpatrick et al.…”