Plasma 1,5‐anhydroglucitol concentrations are influenced by variations in the renal threshold for glucose

Kilpatrick, E; Keevil, BG; Richmond, K. L.; Newland, PL; Addison, G. M.

doi:10.1046/j.1464-5491.1999.00093.x

Cited by 42 publications

(39 citation statements)

References 19 publications

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“…The 1,5-AG excretion rate depends on the renal threshold for glucose (7). Thus, its clinical usefulness in evaluation of some groups of patients, for example, pregnant women and subjects with endstage renal disease, is obvious (7,8).…”

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confidence: 99%

“…Thus, its clinical usefulness in evaluation of some groups of patients, for example, pregnant women and subjects with endstage renal disease, is obvious (7,8). Interestingly, the decreased renal threshold for glucose was observed in patients with hepatocyte nuclear factor-1␣ (HNF-1␣) maturity-onset diabetes of the young (MODY), formerly classified as MODY3, and in nondiabetic mutation carriers of this gene (9,10).…”

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confidence: 99%

“…1,5-AG is accepted by the U.S. Food and Drug Administration as a tool of monitoring glycemic control of diabetic patients. There were already some groups of patients described for whom 1,5-AG should not be recommended as a diabetes control measure owing to a low renal threshold for glucose, such as pregnant women and patients with end-stage renal disease (7,8), although some promising attempts of its use in gestational diabetes were described (15). In addition, there were some efforts to use 1,5-AG as a screening tool in diabetes (16,17).…”

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confidence: 99%

“…There are, however, important indirect arguments on the key effect of renal tubulopathy. First, it was shown in two other clinical groups, pregnant women and patients with end-stage renal disease, that the renal threshold for glucose, which is substantially different from normal, seriously influenced the circulating 1,5-AG level (7,8). Because renal tubulopathy in HNF-1␣ MODY has been well documented previously (9,10), its influence on 1,5-AG seems inevitable.…”

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confidence: 99%

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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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confidence: 99%

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confidence: 99%

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confidence: 99%

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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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“…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. 1999; Tam et al. 2001).…”

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confidence: 99%

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

et al. 2017

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The importance of 1,5‐anhydroglucitol (1,5‐AG) as an intermediate biomarker for diabetic pregnancy is multi‐fold: (1) it serves as a reliable indicator of moderate‐level glycemic control, especially during early gestation; (2) it has been associated with increased risk of diabetes, independent of HbA1c and fasting glucose; and (3) it is an independent risk factor for the development of eclampsia during pregnancy. However, the clinical use of this biomarker during pregnancy has been underutilized due to physiological changes in glomerular filtration rate, plasma volume, and other hemodynamic parameters which have been hypothesized to bias gestational serum 1,5‐AG concentrations. Here, we develop an in‐silico model of gestational 1,5‐AG by combining pre‐existing physiological data in the literature with a two‐compartment mathematical model, building off of a previous kinetic model described by Stickle and Turk (1997) Am. J. Physiol., 273, E821. Our model quantitatively characterizes how renal and hemodynamic factors impact measured 1,5‐AG during normal pregnancy and during pregnancy with gestational diabetes and diabetes mellitus. During both normal and diabetic pregnancy, we find that a simple two‐compartment model of 1,5‐AG kinetics, with all parameters but reabsorption fraction adjusted for time in pregnancy, efficiently models 1,5‐AG kinetics throughout the first two trimesters. Allowing reabsorption fraction to decrease after 25 weeks permits parameters closer to expected physiological values during the last trimester. Our quantitative model of 1,5‐AG confirms the involvement of hypothesized renal and hemodynamic mechanisms during pregnancy, clarifying the expected trends in 1,5‐AG to aid clinical interpretation. Further research and data may elucidate biological changes during the third trimester that account for the drop in 1,5‐AG concentrations, and clarify physiological differences between diabetes subtypes during pregnancy.

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1,5-Anhydroglucitol as a marker of maternal glycaemic control and predictor of neonatal birthweight in pregnancies complicated by type 1 diabetes mellitus

Nowak

Skupień

Cyganek³

et al. 2013

Diabetologia

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Aims/hypothesisMost pregnant women with type 1 diabetes mellitus achieve HbA1c targets; however, macrosomia remains prevalent and better pregnancy glycaemic markers are therefore needed. 1,5-Anhydroglucitol (1,5-AG) is a short-term marker of glycaemia, reflecting a period of 1 to 2 weeks. Its excretion rate depends on the renal glucose threshold and thus it is unclear whether it may be used in pregnant type 1 diabetes women. We evaluated 1,5-AG as a glycaemic marker and birthweight predictor in pregnant women with type 1 diabetes, and compared its performance with HbA1c.Methods1,5-AG and HbA1c were measured in 82 pregnant women with type 1 diabetes. In addition, 58 continuous glucose monitoring system (CGMS) records were available. Macrosomia was defined as birthweight >90th centile. The data were analysed with Pearson’s correlations, and linear and logistic regression models. Receiver operating characteristic (ROC) analysis was used to evaluate third trimester 1,5-AG as a predictor of macrosomia.ResultsUnlike HbA1c, 1,5-AG strongly correlated with CGMS indices: the AUC above 7.8 mmol/l (r = −0.66; p < 0.001), average maximum glucose (r = −0.58; p < 0.001) and mean glucose (r = −0.54; p < 0.001). In the third trimester, 1,5-AG was the strongest predictor of macrosomia, with ROC AUC 0.81 (95% CI 0.70, 0.89). In contrast, HbA1c in the third trimester had a ROC AUC of 0.69 (95% CI 0.58, 0.81). The best discrimination was achieved when both markers were used jointly, yielding a ROC AUC of 0.84 (95% CI 0.76, 0.93).Conclusions/interpretationIn pregnant women with type 1 diabetes, 1,5-AG is a better glycaemic marker than HbA1c, as assessed by CGMS. A decreased third trimester 1,5-AG level, either singly or with HbA1c, is a strong predictor of macrosomia.

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Plasma 1,5‐anhydroglucitol concentrations are influenced by variations in the renal threshold for glucose

Abstract: People with the same glucose tolerance may demonstrate variable plasma 1,5AG concentrations depending on their renal threshold for glucose. This inherent characteristic is likely to limit the usefulness of the test when monitoring or screening for diabetes.

Cited by 42 publications

References 19 publications

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

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

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

1,5-Anhydroglucitol as a marker of maternal glycaemic control and predictor of neonatal birthweight in pregnancies complicated by type 1 diabetes mellitus

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