Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body

Yamanouchi, Toshikazu; Tachibana, Yumi; Akanuma, Hiroshi; Minoda, Susumu; Shinohara, Takaomi; Moromizato, Hitoshi; Miyashita, Hideo; Akaoka, Ieo

doi:10.1152/ajpendo.1992.263.2.e268

Cited by 117 publications

(158 citation statements)

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“…The body pool may originate from an accumulation of small amounts of retained dietary 1,5AG or from biosynthesis. There is some evidence to support de novo biosynthesis of 1,5AG in the amount of ϳ0.5 mg/day (10), but this has neither been extensively investigated nor confirmed.…”

mentioning

confidence: 97%

“…The structure was identified in 1943, and the presence of the compound in human blood (8) and cerebrospinal fluid (9) was established in 1972 and 1973, respectively. Research studies have shown that 1,5AG originates mostly from foods with a mean intake of ϳ4.4 mg/day, that the closed pyran ring structure confers metabolic stability, that the rate of intake is matched by the daily excretion rate, and that a bodily pool of ϳ500 -1,000 mg of 1,5AG is constantly maintained (10). The body pool may originate from an accumulation of small amounts of retained dietary 1,5AG or from biosynthesis.…”

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confidence: 99%

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

et al. 2004

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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.

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confidence: 97%

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confidence: 99%

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

et al. 2004

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“…An automated assay (Glycomark) has recently been approved in the U.S. as a short-term marker for glycemic control (8), and a similar assay has been in use in Japan for over a decade (9). During normoglycemia, 1,5-AG is maintained at constant steadystate levels due to a large body pool compared with the amount of intake (10) and due to a lack of metabolism (10,11). Normally, in the kidneys, 1,5-AG is filtered and completely reabsorbed (12).…”

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confidence: 99%

1,5-Anhydroglucitol and Postprandial Hyperglycemia as Measured by Continuous Glucose Monitoring System in Moderately Controlled Patients With Diabetes

Dungan¹,

Buse

Largay³

et al. 2006

Diabetes Care

214

176

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OBJECTIVE -Postprandial hyperglycemia is often inadequately assessed in diabetes management. Serum 1,5-anhydroglucitol (1,5-AG) drops as serum glucose rises above the renal threshold for glucose and has been proposed as a marker for postprandial hyperglycemia. The objective of this study is to demonstrate the relationship between 1,5-AG and postprandial hyperglycemia, as assessed by the continuous glucose monitoring system (CGMS) in suboptimally controlled patients with diabetes.RESEARCH DESIGN AND METHODS -Patients with type 1 or type 2 diabetes and an HbA 1c (A1C) between 6.5 and 8% with stable glycemic control were recruited from two sites. A CGMS monitor was worn for two consecutive 72-h periods. Mean glucose, mean postmeal maximum glucose (MPMG), and area under the curve for glucose above 180 mg/dl (AUC-180), were compared with 1,5-AG, fructosamine (FA), and A1C at baseline, day 4, and day 7.RESULTS -1,5-AG varied considerably between patients (6.5 Ϯ 3.2 g/ml [means Ϯ SD]) despite similar A1C (7.3 Ϯ 0.5%). Mean 1,5-AG (r ϭ Ϫ0.45, P ϭ 0.006) correlated with AUC-180 more robustly than A1C (r ϭ 0.33, P ϭ 0.057) or FA (r ϭ 0.38, P ϭ 0.88). MPMG correlated more strongly with 1,5-AG (r ϭ Ϫ0.54, P ϭ 0.004) than with A1C (r ϭ 0.40, P ϭ 0.03) or FA (r ϭ 0.32, P ϭ 0.07).CONCLUSIONS -1,5-AG reflects glycemic excursions, often in the postprandial state, more robustly than A1C or FA. 1,5-AG may be useful as a complementary marker to A1C to assess glycemic control in moderately controlled patients with diabetes. Diabetes Care 29:1214 -1219, 2006T he importance of tight glycemic control in preventing the complications of diabetes has been well documented (1-3). More recently, studies indicate that postprandial glucose may be an independent risk factor for the development of macrovascular complications (4 -6). Many patients who are otherwise well controlled by HbA 1c (A1C), the current standard indicator of overall glycemia, also have significant postprandial hyperglycemia (7). Currently, available markers for measuring glycemic control, including A1C and fructosamine (FA), only reflect average glucose, potentially missing important hyperglycemic excursions that may be balanced out by hypoglycemia. Therefore, an alternative marker that robustly reflects postprandial glucose excursions could be useful in the management of patients with diabetes.Plasma 1,5-anhydroglucitol (1,5-AG) is a naturally occurring dietary polyol that has been proposed as a marker for postprandial hyperglycemia. An automated assay (Glycomark) has recently been approved in the U.S. as a short-term marker for glycemic control (8), and a similar assay has been in use in Japan for over a decade (9). During normoglycemia, 1,5-AG is maintained at constant steadystate levels due to a large body pool compared with the amount of intake (10) and due to a lack of metabolism (10,11). Normally, in the kidneys, 1,5-AG is filtered and completely reabsorbed (12). However, with elevated serum glucose concentrations (generally Ͼ180 mol/l, the average renal threshold fo...

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“…Its main source in humans is dietary ingestion, particularly meats and cereals (1). In addition, ϳ10% of 1,5-AG is derived from endogenous synthesis.…”

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confidence: 99%

Clinical Application of 1,5-Anhydroglucitol Measurements in Patients with Hepatocyte Nuclear Factor-1α Maturity-Onset Diabetes of the Young

et al. 2008

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OBJECTIVE -1,5-anhydroglucitol (1,5-AG) is a short-term marker of metabolic control in diabetes. Its renal loss is stimulated in hyperglycemic conditions by glycosuria, which results in a lowered plasma concentration. As a low renal threshold for glucose has been described in hepatocyte nuclear factor-1␣ (HNF-1␣) maturity-onset diabetes of the young (MODY), the 1,5-AG level may be altered in these patients. The purpose of this study was to assess the 1,5-AG levels in patients with HNF-1␣ MODY and in type 2 diabetic subjects with a similar degree of metabolic control. In addition, we aimed to evaluate this particle as a biomarker for HNF-1␣ MODY.RESEARCH DESIGN AND METHODS -We included 33 diabetic patients from the Polish Nationwide Registry of MODY. In addition, we examined 43 type 2 diabetic patients and 47 nondiabetic control subjects. The 1,5-AG concentration was measured with an enzymatic assay (GlycoMark). Receiver operating characteristic (ROC) curve analysis was used to evaluate 1,5-AG as a screening marker for HNF-1␣ MODY.RESULTS -The mean 1,5-AG plasma concentration in diabetic HNF-1␣ mutation carriers was 5.9 g/ml, and it was lower than that in type 2 diabetic patients (11.0 g/ml, P ϭ 0.003) and in nondiabetic control subjects (23.9 g/ml, P Ͻ 0.00005). The ROC curve analysis revealed 85.7% sensitivity and 80.0% specificity of 1,5-AG in screening for HNF-1␣ MODY at the criterion of Ͻ6.5 g/ml in patients with an A1C level between 6.5 and 9.0%.CONCLUSIONS -1,5-AG may be a useful biomarker for differential diagnosis of patients with HNF-1␣ MODY with a specific range of A1C, although this requires further investigation. However, the clinical use of this particle in diabetic HNF-1␣ mutation carriers for metabolic control has substantial limitations.

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Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body

Cited by 117 publications

References 2 publications

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

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

1,5-Anhydroglucitol and Postprandial Hyperglycemia as Measured by Continuous Glucose Monitoring System in Moderately Controlled Patients With Diabetes

Clinical Application of 1,5-Anhydroglucitol Measurements in Patients with Hepatocyte Nuclear Factor-1α Maturity-Onset Diabetes of the Young

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