Changes of 1, 5-AG in Vitreous Humor of Rabbit Cadavers with Hyperglycemic Metabolism / 法医学杂志

OBJECTIVES@#To investigate the concentration and change characteristics of 1, 5-anhydroglucitol (1, 5-AG) in the vitreous humor of rabbit cadavers with hyperglycemic metabolism, and to explore the value of 1, 5-AG in forensic pathology identification of death caused by hyperglycemic metabolism disorders.@*METHODS@#A diabetic hyperglycemic rabbit model was established by using alloxan. Eighteen rabbits with fasting glucose concentration ≥13.80 mmol/L (experimental group) and 18 healthy rabbits with fasting glucose concentration ≤6.10 mmol/L (control group) were selected. After death from air embolism. The blood samples were collected immediately, and vitreous humor samples were collected at 0 h, 12 h, 24 h and 36 h after death. The concentration of 1, 5-AG in the blood and vitreous humor of rabbits was determined.@*RESULTS@#The blood glucose concentration in the experimental group was (25.10±3.14) mmol/L. At the time of death, there was no significant difference in the concentration of 1, 5-AG in the blood [(0.94±0.20) μg/mL] and in the vitreous humor (0.99±0.05 μg/mL, P>0.05). The concentration of 1, 5-AG in the vitreous humor of the experimental group was lower than that of the corresponding control group at all time points (P<0.05), and there was no significant difference betwwen 1, 5-AG concentration in vitreous humor between earch time point in the experimental group and the control group (P>0.05). Correlation analysis showed that the concentration of 1,5-AG in blood was negatively correlated with blood glucose in both control group and experimental group (control group: r=-0.79, P<0.05; experimental group: r=-0.97, P<0.05).@*CONCLUSIONS@#Vitreous humor can replace blood as an effective test sample for 1,5-AG detection. The concentration of 1, 5-AG in rabbit vitreous humor remains stable within 36 hours after death and is not affected by the change of postmortem interval. If the concentration of 1, 5-AG decreases significantly, it indicates the existence of hyperglycemia in rabbits before death.

Diagnostic accuracy of Serum 1,5-anhydroglucitol as a surrogate measure of Glycemic variability among adult Filipinos with Type 2 Diabetes Mellitus: A retrospective cross-sectional study

Background@#Among the various glycemic indices in current use, glycemic variability has the greatest contribution in the development of microvascular and macrovascular complications in Type 2 Diabetes mellitus (T2DM). Most metrics that are currently used to measure glycemic variability are derived from continuous glucose monitoring (CGM) data. However, CGM is burdensome to the patient due to its relatively high cost as well as the need for multiple visits with the health care provider. With the use of serum 1,5-anhydroglucitol (1,5-AG) as a biomarker of glucose fluctuations, physicians and patients alike could have an easier surrogate measure of glycemic variability thus aiding in achieving target glucose control. This study aims to determine the diagnostic accuracy of 1,5-AG as compared to the glycemic variability metrics derived from CGM as a surrogate measure of glycemic variability among adult Filipinos with T2DM.@*Methods@#Retrospective analysis of data of adult patients aged 20 years old and above diagnosed with T2DM referred for CGM at the Diabetes, Endocrine, Metabolic, and Nutrition Center of Cardinal Santos Medical Center from January 2017 to October 2021 who underwent serum 1,5-AG level determination within 2 weeks of CGM were collected. Diagnostic accuracy was obtained by computing the sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and Youden index. Pearson correlation coefficient was used to determine the correlation of 1,5-AG and the different metrics. Analysis of variance (ANOVA) was used to check for statistical significance with 99% confidence interval and a p < 0.05 considered as statistically significant.@*Results@#This study involving 37 subjects showed a good diagnostic accuracy of serum 1,5-AG levels with the different measures of glycemic variability derived from CGM namely mean amplitude of glycemic excursion (MAGE), continuous overlapping net glycemic action at 1-hour intervals (CONGA-1), and mean of daily differences (MODD) with significant correlation among patients with HbA1c ≤ 7%. Subjects were on CGM for approximately 6 ± 1 day with statistically significant difference between the good and poor glucose control group (p<0.05). Determination of diagnostic accuracy between 1,5- AG and MAGE showed good accuracy (Sensitivity = 95.3%, Specificity = 100%, PPV = 100%, NPV = 75.43%, Diagnostic accuracy 96%, and a Youden Index of 92.3) with a statistically significant correlation among subjects with HbA1c level ≤ 7% (p=0.021). There is likewise good diagnostic accuracy between CONGA-1 and 1,5-AG level (Sensitivity = 99%, Specificity = 75.29%, PPV = 89.1%, NPV = 97%, Accuracy = 89.50% and Youden index of 58.41) with a statistically significant correlation among subjects with HbA1c ≤ 7% (p=0.038). Comparison with interday glycemic variability showed fair diagnostic accuracy between MODD and 1,5-AG (Sensitivity = 79.17%, Specificity = 78%, PPV = 97%, NPV = 32%, Accuracy = 76.89%, and Youden index of 49.07) and a statistically significant correlation among subjects with HbA1c ≤ 7% (p=0.009).@*Conclusion@#There is good diagnostic accuracy of serum 1,5-AG levels with the different measures of glycemic variability derived from CGM namely MAGE, CONGA-1, and MODD with significant correlation among patients with HbA1c ≤ 7%. Among diabetics with HbA1c ≤7%, 1,5-AG could be used as a surrogate measure of glycemic variability and excursions.

Evaluation of 1, 5 -Anhydroglucitol as a Biomarker for Type 2 Diabetes Mellitus in Patients without Overt Nephropathy

1,5-Anhydroglucitol (1,5-AG) is a non-fasting glycemic marker that responds to hyperglycemia excursions. The reduction in serum levels of 1,5-AG is associated with an increase in postprandial glycemia and glycosuria, phenomena that increase the risk and severity of diabetic complications. The objective is to assess the ability of 1,5-AG to discriminate type 2 diabetes (T2D) patients without overt kidney disease, for screening or diagnostic purposes. The Human Research Ethics Committee of Universidade Federal do Paraná (UFPR) approved the project. Serum samples from 567 individuals classified as healthy subjects (n = 291) and T2D (n = 276) with moderate glycemic control (HbA1c of 7-8%), matched by gender, were analyzed. Serum 1,5-AG levels were measured using an automated enzymatic method (GlycoMark, Inc.). Receiver Operating Characteristic (ROC) curve analysis for 1,5-AG showed sensibility of 65.3% and specificity of 91.1% to detect T2D at cut-off point of 92 µmol/L. The results were similar to the groups' discrimination by glycemia (sensibility/specificity, 62.2%; 89.0%) at cut-off point of 6.3 mmol/L. HbA1c was the best discriminator (sensibility/specificity, 87.4%; 94.2%) at a cut-off point of 5.8% (40 mmol/mol). The serum 1,5-AG concentration was not able to discriminate T2D in the presence of moderate glycemic control with no overt nephropathy.

Correlation analysis of 1,5-anhydroglucitol and mild cognitive impairment / 第二军医大学学报

Objective To investigate the correlation between serum 1,5-anhydroglucitol (1,5-AG) and mild cognitive impairment (MCI). Methods According to the diagnostic criteria of MCI and the cognitive function test results by Montreal cognitive assessment (MoCA) scale Chinese version, 80 volunteers receiving health check in our hospital from Nov. to Dec., 2019 were divided into MCI group (33 cases) and normal control (NC) group (47 cases). The demographic and clinical data were collected, and the blood glucose-related indexes, including 1,5-AG, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and 2 h-postprandial glucose (2 h-PPG), were measured. Anxiety and depression were assessed by self-rating anxiety scale (SAS) and geriatric depression scale (GDS), respectively. Linear correlation analysis and multiple linear regression analysis were used to study the correlation between the blood glucose-related indexes and MCI. Results There were no significant differences in the demographic data, clinical data, SAS score or GDS score between the two groups (all P＞0.05). Compared with the NC group, the MoCA score and the level of 1,5-AG were significantly lower in the MCI group (P＜0.01, P＝0.023), and the levels of FPG and 2 h-PPG were significantly higher (P＝0.041, 0.027). Linear correlation analysis showed that the MoCA score was negatively correlated with the levels of FPG, 2 h-PPG and HbA1c (all P＜0.05), but not with 1,5-AG level (P＝0.134); the score of delayed recall, a cognitive domain of MoCA scale, was negatively correlated with the levels of FPG, 2 h-PPG and HbA1c (all P＜0.05), and positively correlated with the 1,5-AG level (P＝0.027). Multiple linear regression analysis showed that FPG was an independent factor of MoCA score (β＝－0.291, P＝0.009), and 1,5-AG and FPG were independent factors of delayed recall score (β＝0.199 and －0.390, P＝0.015 and 0.001). Conclusion 1,5-AG may be a potential biomarker for predicting cognitive impairment, especially for delayed recall; the blood glucose fluctuates greatly in MCI individuals at early stage, and maintaining the stability of blood glucose may be beneficial to the prevention of MCI.

Efficiency comparison of fasting plasma glucose combined with 1,5-anhydroglucitol and combined with glycated albumin in diabetes mellitus screening / 上海交通大学学报（医学版）

Objective: To analyze and compare the clinical value of serum 1,5-anhydroglucitol (1,5-AG) with glycated albumin (GA) combined with fasting plasma glucose (FPG),respectively,in screening diabetes mellitus in Chinese population at the risk of diabetes mellitus. Methods: A total of 701 subjects with high risk of diabetes were enrolled in this study,including 324 males and 377 females. All subjects underwent 75 g oral glucose tolerance test (OGTT). Diabetes was diagnosed according to the cut-off points of 2010 American Diabetes Association standards. The sensitivity,specificity and area under ROC curve (AUC) of GA combined with FPG and 1,5-AG combined with FPG in screening diabetes mellitus were analyzed. Results: Among 701 subjects,350 (49.93%) cases were diagnosed as having diabetes mellitus. The sensitivity,specificity,and AUC of 1,5-AG combined with FPG were 84.29%,91.45% and 0.939,respectively. The sensitivity of GA combined with FPG was 77.71%,and the specificity and AUC were 90.88% and 0.932,respectively. There was no significant difference in AUC between the two screening methods (P>0.05),but the sensitivity of 1,5-AG combined with FPG was higher than that of GA combined with FPG (P=0.001). The proportion of the subjects in need of further OGTT judged by 1,5-AG combined with FPG was 27.82%,which was 11.27% lower than that judged by FPG alone,and 2.57% lower than that judged by GA combined with FPG. Conclusion: In Chinese population with high risk of diabetes mellitus,serum 1,5-AG or GA combined with FPG can improve the efficiency of diabetes screening. Compared with GA combined with FPG,1,5-AG combined with FPG may have more clinical value.

1,5-Anhydro-D-Glucitol Could Reflect Hypoglycemia Risk in Patients with Type 2 Diabetes Receiving Insulin Therapy

BACKGROUND: The identification of a marker for hypoglycemia could help patients achieve strict glucose control with a lower risk of hypoglycemia. 1,5-Anhydro-D-glucitol (1,5-AG) reflects postprandial hyperglycemia in patients with well-controlled diabetes, which contributes to glycemic variability. Because glycemic variability is related to hypoglycemia, we aimed to evaluate the value of 1,5-AG as a marker of hypoglycemia. METHODS: We enrolled 18 adults with type 2 diabetes mellitus (T2DM) receiving insulin therapy and assessed the occurrence of hypoglycemia within a 3-month period. We measured 1,5-AG level, performed a survey to score the severity of hypoglycemia, and applied a continuous glucose monitoring system (CGMS). RESULTS: 1,5-AG was significantly lower in the high hypoglycemia-score group compared to the low-score group. Additionally, the duration of insulin treatment was significantly longer in the high-score group. Subsequent analyses were adjusted by the duration of insulin treatment and mean blood glucose, which was closely associated with both 1,5-AG level and hypoglycemia risk. In adjusted correlation analyses, 1,5-AG was negatively correlated with hypoglycemia score, area under the curve at 80 mg/dL, and low blood glucose index during CGMS (P=0.068, P=0.033, and P=0.060, respectively). CONCLUSION: 1,5-AG level was negatively associated with hypoglycemia score determined by recall and with documented hypoglycemia after adjusting for mean glucose and duration of insulin treatment. As a result, this level could be a marker of the risk of hypoglycemia in patients with well-controlled T2DM receiving insulin therapy.

1,5-Anhydroglucitol as a Useful Marker for Assessing Short-Term Glycemic Excursions in Type 1 Diabetes

BACKGROUND: Type 1 diabetes is associated with more severe glycemic variability and more frequent hypoglycemia than type 2 diabetes. Glycemic variability is associated with poor glycemic control and diabetic complications. In this study, we demonstrate the clinical usefulness of serum 1,5-anhydroglucitol (1,5-AG) for assessing changes in glycemic excursion in type 1 diabetes. METHODS: Seventeen patients with type 1 diabetes were enrolled in this study. A continuous glucose monitoring system (CGMS) was applied twice at a 2-week interval to evaluate changes in glycemic variability. The changes in serum glycemic assays, including 1,5-AG, glycated albumin and hemoglobin A1c (HbA1c), were also evaluated. RESULTS: Most subjects showed severe glycemic excursions, including hypoglycemia and hyperglycemia. The change in 1,5-AG level was significantly correlated with changes in the glycemic excursion indices of the standard deviation (SD), mean amplitude of glucose excursion (MAGE), lability index, mean postmeal maximum glucose, and area under the curve for glucose above 180 mg/dL (r=-0.576, -0.613, -0.600, -0.630, and -0.500, respectively; all P<0.05). Changes in glycated albumin were correlated with changes in SD and MAGE (r=0.495 and 0.517, respectively; all P<0.05). However, changes in HbA1c were not correlated with any changes in the CGMS variables. CONCLUSION: 1,5-AG may be a useful marker for the assessment of short-term changes in glycemic variability. Furthermore, 1,5-AG may have clinical implications for the evaluation and treatment of glycemic excursions in type 1 diabetes.

Alternative biomarkers for assessing glycemic control in diabetes: fructosamine, glycated albumin, and 1,5-anhydroglucitol

The growing attention to alternative glycemic biomarkers including fructosamine, glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), is attributable to the limitations of the glycated hemoglobin (HbA1c) assay. It is important to recognize the conditions in which HbA1c levels may be difficult to interpret. Serum fructosamine and GA have been proposed useful tools for monitoring of short-term glycemic control. These biomarkers not only reflect well glycemic control in hematologic disorder, but also represent postprandial glucose fluctuation. Serum 1,5-AG may be useful for estimating within-day glucose variation. Use of these nontraditional tests can be more helpful in the management of diabetes as complement traditional measures. Further larger cohort studies are warranted to determine whether nontraditional biomarkers have potential utility for early diagnosis, management of diabetes, and prevention of diabetic complications.

Value of serum 1,5-anhydroglucitol measurements in childhood obesity in the continuum of diabetes

PURPOSE: The prevalence of type 2 diabetes mellitus (T2DM) and obesity are currently increasing. Accordingly, the concept of "preventing diabetes" in high-risk groups has become more important in diabetic care, but the use of glycated hemoglobin (HbA1c) as a measure has limitations in this field. The aim of this study was to investigate the utility of 1,5-anhydroglucitol (1,5-AG) in assessing prediabetes status in obese children. METHODS: The medical records of 74 subjects aged 6-19 years (of which 27 were overweight/obese and 47 had diabetes) who had 1,5-AG data were reviewed retrospectively. We compared 1,5-AG with HbA1c using the Pearson correlation test to assess the clinical utility of 1,5-AG. RESULTS: 1,5-AG levels were higher (31.1+/-10.1 microg/mL vs. 7.4+/-7.3 microg/mL) and HbA1c levels were lower (5.5%+/-0.3% vs. 8.9%+/-2.7%) in the overweight/obese group than in the diabetics group. The range of 1,5-AG levels in obese children was wide (16.8-59.3 microg/mL), and did not have significance with HbA1c. A negative correlation between 1,5-AG and HbA1c was significant in the entire subject (r=-0.822, P<0.001), and also in the HbA1c range of 5.5% to 8% (r=-0.736, P<0.001). CONCLUSION: 1,5-AG is a valuable index in the HbA1c range of 5.5%-8% and it might be considered an early glycemic control index in insulin-resistant obese children with an HbA1c level above 5.5%. Moreover, the 1,5-AG level assessment should be presented as a supplementary tool for better compliance, as well as being an improvement in diabetes management for the short-term glucose control in relatively well-controlled diabetes patients with an HbA1c level below 8%.

Review of the Potential Glycemic Markers Glycated Albumin and 1,5-anhydroglucitol / 임상당뇨병

The measure of HbA1c is the gold standard index of glycemic control in clinical practice for diabetes treatment and is well known as a risk marker for diabetes complications. However, HbA1C does not accurately reflect glucose fluctuations or the actual status of glycemic control for several days or weeks. HbA1c measurement can be confounded in the anemia, hemoglobinopathy, or renal impairment. In comparison, glycated albumin (GA), a ketoamine formed by binding of albumin and glucose, more accurately reflects short-term changes in plasma glucose and postprandial plasma hyperglycemia (PPH). GA is not affected by hemoglobin or dialysis. 1,5-Anhydroglucitol (1,5-AG), another glycemic marker, structurally resembles glucose and decreases with spikes of hyperglycemia exceeding the average renal threshold for glucose. Especially, 1,5-AG level is reflective of PPH or glycemic variability and becomes an increasingly important contributor in a moderately controlled glycemic state, even when HbA1c level is within the target range. Herein, the usefulness of and recent studies on GA and 1,5-AG are summarized. Further investigations about the associations between these glycemic markers and diabetes complications are needed.

Serum 1,5-anhydroglucitol in pregnant women with different glucose tolerance status / 中国医师进修杂志

Objective To explore the diagnosing value of serum 1,5-anhydroglucitol(1,5-AG)for gestational diabetes mellitus(GDM)by determining 1,5-AG in pregnant women with different glucose tolerance status.Methods The levels of serum 1,5-AG,fasting plasma glucose(FPG),1 hour plasma glucose(1hPG)and glycosylated hemoglobin(HbA1c)were determined in 30 cases GDM(GDM group),32 cases gestational impair glucose tolerance(GIGT group)and 43 cases gestational normal glucose tolerance (GNGT group).Results The level of serum 1,5-AG in GDM group[(11.69 ± 3.92)mg/L]was obviously lower than that in GIGT group[(20.93 ± 3.43)mg/L]and GNGT group[(27.83 ± 4.03)mg/L](P ＜ 0.01),GIGT group was obviously lower than that in GNGT group(P ＜0.05).The level of serum 1,5-AG had significantly negative correlation with FPG,1hPG and HbA1c respectively(P＜ 0.01).Conclusion The level of serum 1,5-AG has significantly correlation with glucose tolerance,1,5-AG can be used as useful indicator in the diagnosis of GDM.

The diagnostic efficiency of 1,5-anhydroglucitol for diabetes mellitus / 中国糖尿病杂志

Objective To explore the value of serum 1,5-AG in the diagnosis of diabetes mellitus by applying the method of pyranose oxidase (PROD). Methods 1,5-AG,FPG、2hPG and HbA_1c were determined in 50 case of DM,100 case of IGT and 30 control subject. ROC curve was applied to evaluate the diagnostic efficiency of 1,5-AG,FPG and HbA_1c for DM. Results Serum 1,5-AG was obviously lower in the diabetes than in IGT and controls(P＜0.01). Compared with controls, IGT patients had lower serum 1,5-AG(P＜0.05).1,5-AG level had significantly negative correlation with FPG,2hPG and HbA_1c respectively. The area under the ROC curve of 1,5-AG,FPG and HbA_1c are 0.948、0.921、0.817,respectively. Conclusions 1,5-AG level shows significantly correlation with glucose tolerance. Serum 1,5-AG measurement could be used as useful indicator in the screening of diabetes mellitus as well as in the monitoring of glycemic control.

Analytical and Clinical Evaluation of Lana(TM), the Reagent Measuring 1,5-Anhydroglucitol / 대한임상병리학회지

BACKGROUND: There have been many reports that 1,5-Anhydroglucitol (1,5-AG) was a better marker than the hemoglobin A1c (HbA1c) or fructosamine for monitoring the control of glucose in patients with Diabetes Mellitus (DM). However, there was difficulty in performing the tests on the patient's samples in the hospital laboratory because the measurement was possible only with gas chromatog-raphy or high performance chromatography. Recently, a reagent that can measure 1,5-AG on the automatic chemistry analyzer was introduced. We evaluated the analytical and clinical characteris-tics of the reagent. METHODS: We measured the 1,5-AG with the Lana(TM) (Japan Chemistry Medicine, Tokyo, Japan) on the automatic chemistry analyzer, TBA-30FR (Toshiba, Otawara, Japan). We evaluated the pre-cision, the recovery rate, the lower detection limit, the reference value, and the correlation with other clinical markers for glucose control of the DM patient. RESULTS: The within-run precisions of abnormal and normal samples were 1.27% and 1.41%. The between-day precisions were 2.34% and 4.56%, respectively. The recovery rate was 100.1% and 100.7% in abnormal and normal samples, respectively. The lower detection limit was 0.05 mg/L. The reference value from the healthy people was from 12.7 to 50.9 mg/L. The correlation coefficients of the 1,5-AG with glucose and HbA1c were -0.45 and -0.63, respectively. CONCLUSIONS: The newly introduced reagent for 1,5-AG that could be applied with the automatic chemistry analyzer was enough to satisfy the analytical features and it showed better correlation with HbA1c than with the fasting blood glucose. We expect that the Lana(TM) can be used in hospital lab-oratories to monitor the blood glucose control of DM patients and more studies on the clinical value of the 1,5-AG can be done with the convenient reagent such as this.

1,5-Anhydroglucitol as a Marker of Glycemic Control / 대한임상병리학회지

BACKGROUND: 1,5-Anhydroglucitol(1,5-AG) has shown to be a better indicator for current status of glycemia than HbA1c or fructosamine. The concentration of 1,5-AG is stable because of large storage pool and metabolic inertness, little influenced by assay variation with broad range of values. Since its reabsorption is competitively inhibited by glucosuria, plasma 1,5-AG decreases with increasing hyperglycemia in diabetic patients. But impairment of renal function may also affect its concentration. We introduced 1,5-AG as a new marker of glycemic control and evaluated the clinical usefulness and the effect of renal function. METHODS: We assayed plasma concentration of 1,5-AG using gas chromatography mass spectrometry in 36 healthy controls, 39 diabetic patients with normal renal function, 19 nondiabetic patients with chronic renal failure. We examined the relationship bewteen 1,5-AG and HbA1c or glucose. Correlation between 1,5-AG and serum creatinine was also investigated. RESULTS: 1,5-AG concentrations were significantly reduced in diabetic patients and in patients with chronic renal failure, compared to healthy controls. 1,5-AG had negative correlation with plasma glucose and HbA1c in healthy controls and diabetic patients with normal renal function, but not in patients with chronic renal failure. The value of 1,5-AG varies wider than that of HbA1c. CONCLUSIONS: 1,5-AG showed close correlation with glucose and HbA1c and detected subtle changes in glycemia. Therefore, measurement of 1,5-AG would be useful in monitoring glycemic control in diabetic patients with normal renal fucntion. But it would be inappropriate to use 1,5-AG for the evaluation of glycemic control in patients with renal failure.