Search

Aims: This study aimed to evaluate the ability of HbA 1c combined with glycated albumin (GA) or 1,5-anhydroglucitol (1,5-AG) to detect diabetes in residents of Jiangsu, China., Methods: The oral glucose tolerance test (OGTT) was performed on 2184 people in Jiangsu. HbA 1c , GA, 1,5-AG and other serum biochemical parameters were measured. Receiver operating characteristic curves were plotted to determine the optimal thresholds of HbA 1c , GA and 1,5-AG according to the Youden index., Results: (1) The optimal thresholds of HbA 1c , GA and 1,5-AG for the screening of diabetes were ≥45 mmol/mol (6.3%), ≥13.0% and ≤23.0 μg/ml, respectively. (2) The sensitivities of HbA 1c combined with GA and 1,5-AG were both 85%, higher than that of HbA 1c (70%, p < 0.001)., Conclusions: This study is suitable for cases where plasma glucose is unavailable. Among the residents of Jiangsu, HbA 1c combined with GA or 1,5-AG can improve the sensitivity of diabetes screening, reduce the miss rate and save the use of OGTT. GA and 1,5-AG are superior in individuals with mild glucose metabolism disorder. GA enhances the detection of diabetes in the nonobese, and 1,5-AG enhances the detection in those with hyperuricaemia., (© 2021 Diabetes UK.)

Aims: This study aimed to explore the level of and changes in the 1,5-anhydroglucitol × glycated hemoglobin A 1c /100 (AH index, AHI) associated with different glucose metabolism statuses and to evaluate the islet function and insulin sensitivity of patients with type 2 diabetes (T2DM) with different AHI levels., Methods: Of the 3562 subjects enrolled in this study, 1697 had T2DM. The disposition index (DI) was the product of islet secretion function and insulin sensitivity-related indexes., Results: The mean AHI level was 1.0 (0.7-1.3) in the general population, while the mean AHI level in the T2DM group was 0.8 (0.5-1.2), which was significantly lower than that in the impaired glucose regulation and normal glucose tolerance group (both 1.2 (0.9-1.5), both P < 0.01). We further divided patients with T2DM into four subgroups according to the quartile of AHI. The results showed that with the increase in AHI level, the homeostasis model assessment of insulin resistance (HOMA-IR) decreased, while HOMA-β, insulin generation index, insulin sensitivity index, and DI increased (all P for trend  < 0.01). Multivariate logistic regression showed that the odds ratios for a low DI for increasing levels of AHI were 1.00, 0.22 (0.16-0.29), 0.16 (0.11-0.22), and 0.09 (0.06-0.13), showing a decreasing trend (P for trend  < 0.05)., Conclusion: The AHI could reflect the variation in glycemic disorder and the function of islet β cells. The lower the AHI, the worse the glycemic disorder, as well as the islet β-cell function.

Objective: Dysglycemia is prevalent in cystic fibrosis (CF) but screening with annual oral glucose tolerance tests (OGTT) can be burdensome. We investigated alternate glycemic markers-hemoglobin A1c (HbA1c), 1,5-anhydroglucitol (1,5AG), fructosamine (FA), and glycated albumin (GA)-as screening tests for CF-related diabetes (CFRD) and pre-diabetes (CFPD) in youth with CF as defined by the gold-standard OGTT 2-hour glucose (2hG)., Methods: Youth 10 to 18 years with CF had a 1,5AG, FA, GA, HbA1c, and 2-hour OGTT collected. Correlations between all glycemic markers and 2hG were evaluated. Area under the receiver operative characteristic (ROC-AUC) curves were generated. Optimal cut points for predicting CFPD (2hG ≥ 140 mg/dL) and CFRD (2hG ≥ 200 mg/dL) were determined., Results: Fifty-eight youth with CF were included (2hG < 140, n = 16; CFPD, n = 33; CFRD, n = 9; 41% male, mean ± SD age 14.2 ± 3.6 years, BMI z-score 0.0 ± 0.8, % predicted forced expiratory volume in 1 second [FEV1] 89.9 ± 15.1, % predicted forced vital capacity [FVC] 103.2 ± 14.6). ROC-AUC's for all alternate markers were low for CFPD (0.52-0.67) and CFRD (0.56-0.61). At a cut point of 5.5%, HbA1c had 78% sensitivity (95% CI: 0.45-0.94) and 41% specificity (95% CI: 0.28-0.55) for identifying CFRD, correlating to a ROC-AUC of 0.61 (95% CI: 0.42-0.8)., Conclusions: All alternate markers tested demonstrate poor diagnostic accuracy for identifying CFRD by 2hG., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Strict glycaemic management is the cornerstone of metabolic control in gestational diabetes mellitus (GDM). Current monitoring standards involve self-monitoring plasma glucose (SMBG) and haemoglobin A1c (HbA1c). However, both have important limitations. SMBG only reflects instantaneous blood glucose and the inconvenience of self-collecting blood frequently results in poor compliance. HbA1c provides information on blood glucose levels from the previous 2 to 3 months and it is influenced by iron-deficient states, common during pregnancy. There is an urgent need for new shorter-term glycaemic markers, as glycated albumin, fructosamine or 1,5-anhydroglucitol. Glycated albumin seems especially interesting as it provides information on blood glucose levels over the foregoing 2-3 weeks and it is not influenced by iron deficiency or the dilutional anaemia of pregnancy. Fructosamine has a precise and inexpensive measurement and it is not affected by haemoglobin characteristics. This review further discusses the potential value of these non-traditional indicators of glycaemic control in patients with GDM, outlining their possible future applications.

Background and Aims: Traditional glycemic markers, fasting glucose and hemoglobin A1c (HbA1c), predict incident peripheral artery disease (PAD). However, it is unknown whether nontraditional glycemic markers, fructosamine, glycated albumin, and 1,5-anhydroglucitol, are associated with PAD and whether these glycemic markers demonstrate particularly strong associations with severe PAD, critical limb ischemia (CLI)., Methods: We quantified the associations of these five glycemic markers with incident PAD (hospitalizations with PAD diagnosis or leg revascularization) in 11,634 ARIC participants using Cox regression models. Participants were categorized according to diabetes diagnosis and clinical cut-points of glycemic markers (nontraditional glycemic markers were categorized according to percentiles corresponding to the HbA1c cut-points)., Results: Over a median follow-up of 20.7 years, there were 392 cases of PAD (133 were CLI with tissue loss). HbA1c was more strongly associated with incident PAD than fasting glucose, with adjusted hazard ratios (HR) 6.00 (95% CI, 3.73-9.66) for diagnosed diabetes with HbA1c ≥ 7% and 3.53 (2.39-5.22) for no diagnosed diabetes with HbA1c ≥ 6.5% compared to no diagnosed diabetes with HbA1c <5.7%. Three nontraditional glycemic markers demonstrated risk gradients intermediate between HbA1c and fasting glucose and their risk gradients were substantially attenuated after adjusting for HbA1c. All glycemic markers consistently demonstrated stronger associations with CLI than PAD without CLI (p for difference <0.02 for all glycemic markers)., Conclusions: Nontraditional glycemic markers were associated with incident PAD independent of fasting glucose but not necessarily HbA1c. Our results also support the importance of glucose metabolism in the progression to CLI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: This study aimed to investigate alterations in HbA 1c , glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) in Chinese first-degree relatives of individuals with diabetes (FDR) in pursuit of an index for early screening of glucose metabolism disturbance., Methods: A total of 467 participants (age range: 20-78 years) with normal weight and normal glucose tolerance, as determined by a 75-g oral glucose tolerance test, were enrolled. HbA 1c was measured using high-performance liquid chromatography. Serum GA and 1,5-AG levels were determined by enzymatic methods. Serum insulin levels were measured using an electrochemiluminescence immunoassay., Results: The study population included 208 FDR and 259 non-FDR. Serum 1,5-AG levels were lower in FDR than that in non-FDR (20.4 ± 7.5 vs 23.8 ± 8.3 μg/ml, P < 0.001), but HbA 1c and GA levels did not differ between them (P = 0.835 and 0.469, respectively). Logistic regression analysis revealed an independent relationship between a first-degree family history of diabetes and reduced serum 1,5-AG levels (odds ratio = 0.944, P < 0.001). Multiple regression analysis showed that a first-degree family history of diabetes (β = -3.041, P < 0.001) and insulinogenic index (β = 0.081, P = 0.001) were independently associated with serum 1,5-AG levels., Conclusion: In a Chinese population with normal glucose tolerance, serum 1,5-AG levels were lower among FDR, and serum 1,5-AG levels were independently associated with FDR status. For FDR, serum 1,5-AG levels were more sensitive than HbA 1c or GA levels to early-phase abnormality in glucose metabolism., (© 2017 Diabetes UK.)

Background: Diabetes mellitus is considered an important risk factor for cardiovascular diseases. High hemoglobin A1c (HbA1c) levels, which indicate poor glycemic control, have been associated with occurrence of cardiovascular diseases. There are few parameters which can predict cardiovascular risk in patients with well-controlled diabetes. Low 1,5-anhydroglucitol (1,5-AG) levels are considered a clinical marker of postprandial hyperglycemia. We hypothesized that low 1,5-AG levels could predict long-term mortality in acute coronary syndrome (ACS) patients with relatively low HbA1c levels., Methods: The present study followed a retrospective observational study design. We enrolled 388 consecutive patients with ACS admitted to the cardiac intensive care unit at the Juntendo University Hospital from January 2011 to December 2013. Levels of 1,5-AG were measured immediately before emergency coronary angiography. Patients with early stent thrombosis, no significant coronary artery stenosis, malignancy, liver cirrhosis, a history of gastrectomy, current steroid treatment, moderately to severely reduced kidney function (estimated glomerular filtration rate < 45 ml/min/1.73 m 2 ; chronic kidney disease stage 3B, 4, and 5), HbA1c levels ≥ 7.0%, and those who received sodium glucose co-transporter 2 inhibitor therapy were excluded., Results: During the 46.9-month mean follow-up period, nine patients (4.5%) died of cardiovascular disease. The 1,5-AG level was significantly lower in the cardiac death group compared with that in the survivor group (12.3 ± 5.3 vs. 19.2 ± 7.7 µg/ml, p < 0.01). Kaplan-Meier survival analysis showed that low 1,5-AG levels were associated with cardiac mortality (p = 0.02). Multivariable Cox regression analysis showed that 1,5-AG levels were an independent predictor of cardiac mortality (hazard ratio 0.76; 95% confidence interval 0.41-0.98; p = 0.03)., Conclusion: Low 1,5-AG levels, which indicate postprandial hyperglycemia, predict long-term cardiac mortality even in ACS patients with HbA1c levels < 7.0%.

1,5-anhydroglucitol (1,5-AG), uric acid and urinary proteins are excreted into the urine with increasing glucosuria. In the present retrospective study we analyzed whether these factors could be used as indicators for type 2 diabetes mellitus (T2DM) glucose control in 6,766 (T2DM) patients. There were 3,988 cases (58.9%) with HbA1c ≤ 6.5%, 853 cases (12.61%) with HbA1c levels ranging from 6.5% to 7% and 1,925 cases (28.5%) with HbA1c > 7%. HbA1c percentages were correlated with age, MA and 1,5-AG serum concentrations (P < 0.001). The serum uric acid concentration (P < 0.001) was significantly lower in elevated MA (P < 0.001) and 24-hour urinary protein (P = 0.024) patients. Hb1Ac percentages (P < 0.001) were significantly enhanced in patients with 1,5-AG serum concentrations ≤10 mg/L compared to >10 mg/L. With a derived receiver operating characteristic (ROC) curve, a 1,5-AG cut-off value of 11.55 mg/L for hyperglycemia could be diagnosed with a specificity of 71.2 (69.7-72.6) and a sensitivity of 75.3 (73.6-76.9). The serum 1,5-AG concentration is a marker for hyperglycemia and may be particularly useful as an indicator for short-term glycemic excursions in order to improve treatments in T2DM patients.

Background: 1,5-Anhydroglucitol (1,5-AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5-AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5-AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA)., Methods: The following parameters were measured in 377 patients with type 2 diabetes: HbA1c, serum concentrations of 1,5-AG, GA and creatinine, hemoglobin, urinary albumin/creatinine ratio, and urinary excretion of α1 -microglobulin (A1M). Estimated glomerular filtration rate (eGFR) was calculated according to the Cockgroft-Gault formula., Results: There was a negative correlation between 1,5-AG and renal function (r = -0.18; P < 0.001). Concentrations of 1,5-AG were, on average, 27.2% lower in patients with glomerular hyperfiltration (eGFR >120 mL/min) compared with patients with moderate renal impairment (eGFR 30-59 mL/min; P = 0.016). In contrast, HbA1c, GA levels and urinary A1M excretion did not differ between the two patient groups. The mean age of patients with eGFR 30-59 mL/min was substantially higher than that of patients with glomerular hyperfiltration (P < 0.001). Thus, an age-related change in the renal glucose threshold could be the reason for the observed correlation between 1,5-AG and renal function., Conclusions: In clinical practice, age and renal function must be taken into consideration when interpreting 1,5-AG levels, even in the absence of advanced renal impairment., (© 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Despite the centrality of nutrition in the management of type 1 diabetes, the association of diet quality and macronutrient distribution with glycemic control is ambiguous., Objective: This study examined longitudinally the association of dietary intake with multiple indicators of glycemic control in youth with type 1 diabetes participating in a behavioral nutrition intervention study., Design: Participants in a randomized clinical trial of a behavioral nutrition intervention [n = 136; mean ± SD age: 12.8 ± 2.6 y; glycated hemoglobin (HbA1c): 8.1% ± 1.0%; 69.1% using an insulin pump] completed 3-d diet records at baseline and months 3, 6, 9, 12, and 18; masked continuous glucose monitoring (CGM) data were obtained concurrently with the use of the Medtronic iPro CGM system. HbA1c was obtained every 3 mo; 1,5-anhydroglucitol was obtained every 6 mo. Linear mixed-effects regression models estimated associations of time-varying dietary intake variables with time-varying glycemic control indicators, controlling for age, height, weight, sex, Tanner stage, diabetes duration, regimen, frequency of blood glucose monitoring, physical activity, and treatment assignment., Results: HbA1c was associated inversely with carbohydrate and natural sugar, and positively with protein and unsaturated fat. 1,5-Anhydroglucitol was associated positively with fiber intake and natural sugar. Greater glycemic control as indicated by ≥1 CGM variable was associated with higher Healthy Eating Index-2005, whole plant food density, fiber, carbohydrate, and natural sugar and lower glycemic index and unsaturated fat., Conclusions: Both overall diet quality and macronutrient distribution were associated with more optimal glycemic control. Associations were more consistent for CGM variables obtained concurrently with dietary intake than for biomarkers of longer-term glycemic control. These findings suggest that glycemic control may be improved by increasing intake of high-fiber, low glycemic-index, carbohydrate-containing foods. This trial was registered at clinicaltrials.gov as NCT00999375., (© 2016 American Society for Nutrition.)

Postprandial hyperglycemia is a risk factor for cardiovascular disease and mortality. Serum 1,5-anhydroglucitol (1,5-AG) level is an useful clinical marker of glucose metabolism which reflects postprandial hyperglycemia more robustly compared to hemoglobin A1c (HbA1c). Relationship between serum 1,5-AG level and cardiovascular disease has been reported; however, comparison between HbA1c and 1,5-AG as markers of cardiovascular disease was not performed. We included 227 consecutive patients who underwent coronary angiography meeting the following inclusion criteria: (1) patients who had no history of coronary artery disease (CAD); (2) patients without acute coronary syndrome; (3) patients without poorly controlled diabetes mellitus; (4) patients without anemia, liver dysfunction, acute, and chronic renal failure and malnutrition; and (5) patients without adhibition of acarbose or Chinese herbal medicine. We measured HbA1c, glycoalbumin, and 1,5-AG. Serum 1,5-AG was significantly lower in patients with CAD (16.6 ± 8.50 vs. 21.1 ± 7.97 μg/ml, P < 0.001). Multivariable logistic regression analysis showed decrease in serum 1,5-AG was independently associated with the presence of denovo CAD (0.93, 95% CI 0.88-0.98, P = 0.006). Serum 1,5-AG was also independently associated with the presence of denovo CAD in patients without diabetes mellitus (0.94, 95% CI 0.88-0.99, P = 0.046). In conclusion, lower serum 1,5-AG was associated with the presence of denovo CAD. Serum 1,5-AG may identify high cardiovascular risk patients for denovo CAD in both diabetic and non-diabetic patients.

Background: The aim of this study was to investigate the associations of two nontraditional glycemic markers, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG), as well as glycated hemoglobin A1c (HbA1c) with coronary artery disease (CAD)., Methods: In total, 272 subjects (178 men and 94 postmenopausal women) were enrolled in this study. All of them underwent coronary angiography which was used to diagnose CAD. The severity of coronary artery stenosis was assessed by the coronary stenosis index (CSI). GA and 1,5-AG were assayed using the enzymatic method, and HbA1c was detected by high-pressure liquid chromatography., Results: The HbA1c and GA levels were significantly higher in CAD group than those in non-CAD group (both P < 0.01). While the 1,5-AG level was significantly lower in CAD group than that in non-CAD group (P < 0.05). After adjustment for traditional risk factors of CAD, HbA1c, 1,5-AG, and GA, multivariate logistic regression analysis showed that GA was an independent risk factor for CAD (odds ratio = 1.143, 95% confidence interval: 1.048-1.247, P = 0.002). With CSI as a dependent variable, multiple stepwise regression analysis demonstrated an independent positive correlation between GA and CSI (standardized β = 0.184, P = 0.003), beyond gender, age, and lipid-lowering therapy, after adjustment for traditional risk factors of CAD, HbA1c, 1,5-AG, and GA., Conclusions: GA was more closely correlated with CAD than HbA1c and 1,5-AG in a Chinese population with high risk of CAD.

Background: Several studies have reported that insulin resistance was a major risk factor for the onset of type 2 diabetes mellitus in individuals without diabetes or obesity. We aimed to clarify the association between insulin resistance and glycemic control in Japanese subjects without diabetes or obesity., Methods: We conducted a community-based cross-sectional study including 1083 healthy subjects (323 men and 760 women) in an urban area. We performed multivariate regression analyses to estimate the association between the homeostasis model assessment of insulin resistance (HOMA-IR) values and markers of glycemic control, including glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5-AG), and fasting plasma glucose (FPG) levels, after adjustment for potential confounders., Results: Compared with the lowest tertile of HOMA-IR values, the highest tertile was significantly associated with HbA1c and FPG levels after adjustment for potential confounders, both in men (HbA1c: β = 1.83, P = 0.001; FPG: β = 0.49, P < 0.001) and women (HbA1c: β = 0.82, P = 0.008; FPG: β = 0.39, P < 0.001). The highest tertile of HOMA-IR values was inversely associated with 1,5-AG levels compared with the lowest tertile (β = -18.42, P = 0.009) only in men., Conclusions: HOMA-IR values were associated with markers of glycemic control in Japanese subjects without diabetes or obesity. Insulin resistance may influence glycemic control even in a lean, non-diabetic Asian population.

Increasing evidence has indicated that postprandial hyperglycemia affects coronary artery disease (CAD). The serum 1,5-anhydro-d-glucitol (1,5-AG) value is a useful clinical marker to evaluate short-term glycemic status and reflects glycemic excursions with greater sensitivity when compared with hemoglobinA1c (HbA1c), especially for patients in the postprandial state. The aim of this study was to evaluate the predictive value of 1,5-AG for CAD in patients without diabetes mellitus.This study included 729 consecutive patients who had undergone their first coronary angiography. A total of 284 patients (246 diabetic patients and 38 patients with stage 4 or 5 chronic kidney disease) were excluded. The predictive values of 1,5-AG and HbA1c for CAD were evaluated by multivariable logistic regression analysis.Patients with CAD demonstrated significantly lower 1,5-AG values and higher HbA1c values than did patients without CAD (18.6 μg/mL [12.0, 23.3] versus 19.2 μg/mL [14.4, 25.2], P = 0.036, and 5.7% [5.5, 5.9] versus 5.6% [5.4, 5.8], P = 0.016, respectively). In multivariable logistic regression analysis, the HbA1c values did not indicate a predictive value for the prevalence of CAD. In contrast, the 1,5-AG levels were still an independent predictor of CAD (adjusted odds ratio 0.96, 95% confidence interval 0.93-0.99, P = 0.0097).Serum 1,5-AG is superior to HbA1c for predicting CAD prevalence in patients without diabetes mellitus.

The clinical goal of diabetes management is a good quality of life that is not different from that of a healthy subjects. To fulfill the goal, prevention of complications is needed under good glycemic control. Although blood glucose measurement is essential for glycemic control, there are diurnal variations in blood glucose levels. An indicator of long-term glycemic control is necessary. HbA1c is the gold standard measurement for the assessment of glycemic control, and worldwide large scale clinical studies of diabetes complications have greatly valued HbA1c as an indicator of glycemic control. In addition, recently, HbA1c was recommended for use in the diagnosis of diabetes in Japan and in the United States. Although HbA1c is used widely and internationally, international standardization of the HbA1c value has not been achieved. In Japan, from April 2014, it has been decided to adopt the National Glycohemoglobin Standardization Program (NGSP) value, which is used by many countries globally, as the first step toward internationalization. Recently, cardiovascular disease in diabetic patients has been increasing in Japan. Relationships between postprandial hyperglycemia and cardiovascular disease have been noted. Therefore, the correction of postprandial hyperglycemia is one of the important goals of glycemic control to prevent cardiovascular disease. HbA1c or glycated albumin (GA) results from the glycation of hemoglobin or serum albumin and represents 2-month or 2-week glycemia, respectively. In addition, the glycation speed of GA is ten times faster than HbA1c, so GA is likely to reflect the variation in blood glucose and postprandial hyperglycemia in combination with HbA1c and its value. 1,5-anhydroglucitol (AG) is a marker of glycemia-induced glycosuria, since reabsorption of filtered 1,5-AG in the proximal tubule is competitively inhibited by glucose. It is an indicator to identify rapid changes in hyperglycemia. Understanding the characteristics of the indicators above, it is important to use them suitably for each diabetes subject and to recognize glycemic control conditions more accurately.

We evaluated whether 1,5-anhydroglucitol (1,5-AG) (GlycoMark(®)), a test for measuring postprandial glucose and glucose variability, could be a tool for assessing short-term glycemic control in islet cell transplant (ICT) subjects. Data of 21 subjects, with type 1 DM and allogenic islet transplantation, who had concomitant fructosamine, HbA1c, 1,5-AG (n = 85 samples), and capillary glucose self-monitoring measurements (n = 2,979) were analyzed retrospectively at different time points after ICT. A significant negative association was observed between 1,5-AG and HbA1c (p = 0.02), but not with fructosamine. When HbA1c was divided in quartiles as <5.6, 5.6-5.9, 5.9-6.2, and >6.2, a decrease of an estimated 0.70 ± 0.30 µg/ml in 1,5-AG was associated with each quartile of increase in HbA1c (p < 0.0001). There was a significant decline of 1.64 ± 0.3mg/dl in postprandial glucose values for each 1 unit increase in 1,5-AG (p < 0.0001). For those with HbA1c ≥ 6.0% when 1,5-AG was ≥8.15 µg/ml, the mean estimated glucose level was 103.71 ± 3.66 mg/dl, whereas it was 132.12 ± 3.71 mg/dl when 1,5-AG was <8.15 µg/ml. The glucose variability (Glumax - Glumin) in subjects with 1,5-AG <8.15 µg/ml was 46.23 mg/dl greater than the subjects with 1,5-AG ≥8.15 µg/ml (HbA1c ≥ 6.0%). There was no significant association between GlycoMark and glucose variability where HbA1c < 6%. 1,5-AG significantly associated with postprandial glucose levels and glucose variability in ICT recipients with near-normal HbA1c (6.0-6.5%) levels. These findings suggest that 1,5-AG can be used to differentiate those ICT subjects with higher glucose variability despite having near-normal HbA1c. However, prospective studies are needed to evaluate the association between GlycoMark levels and the parameters of graft dysfunction/failure.

Background: 1,5-Anhydroglucitol (1,5-AG), fructosamine, and glycated albumin are of increasing interest as alternative measures of hyperglycemia. We characterize the associations of these nontraditional glycemic markers with hemoglobin A(1c) (Hb A(1c)) and fasting glucose and assess their ability to identify people with diabetes., Methods: We conducted a cross-sectional comparison of 1,5-AG, fructosamine, and glycated albumin with Hb A(1c) and fasting glucose measurements in 1719 participants from the Atherosclerosis Risk in Communities Study. We evaluated nonlinear relationships using R(2) and F-statistics. Performance for identification of cases of diabetes was determined using the area under the curve (AUC). Diabetes was defined by Hb A(1c) ≥6.5%, fasting glucose ≥126 mg/dL (≥6.99 mmol/L), and/or a self-reported history of diagnosed diabetes., Results: Median values of Hb A(1c) and fasting glucose were 5.8% and 109 mg/dL (6.05 mmol/L), respectively; 17.3% of the study population had diagnosed diabetes. Glycated albumin, fructosamine, and 1,5-AG were more strongly correlated with Hb A(1c) compared with fasting glucose (all P values <0.05). Nonlinear models provided the best fit for describing the relationships of the alternative markers to Hb A(1c). When diabetes was defined by an Hb A(1c) ≥6.5%, fructosamine (AUC 0.83; 95% CI, 0.79-0.87) and glycated albumin (AUC 0.87; 95% CI, 0.83-0.90) performed comparably to fasting glucose (AUC 0.83; 95% CI, 0.79-0.87), while 1,5-AG performed worse (AUC 0.74; 95% CI, 0.69-0.78) for identifying cases of undiagnosed diabetes., Conclusions: Fructosamine and glycated albumin may be useful adjuncts to Hb A(1c) and fasting glucose. Future studies should examine these markers in situations in which fasting glucose or Hb A(1c) measurements are invalid or not available., (© 2012 American Association for Clinical Chemistry)

Background: Blood glucose excursion is an important component of the glycaemic burden, but there are no indexes that can directly reflect them. The aim was to evaluate the values and significance of serum 1,5-anhydroglucitol (1,5-AG) in people with type 2 diabetes mellitus in China and to elucidate the relationship between 1,5-AG and traditional indexes of glycaemic excursions by continuous glucose monitoring., Methods: A total of 576 healthy adults and 292 patients were included, and their 1,5-AG, fasting blood glucose and postprandial blood glucose and glycated haemoglobin were measured. For the 34 patients, their mean blood glucose, standard deviation of blood glucose, mean amplitude of glucose excursion, mean of daily differences, low blood glucose M-value index and the area under the curve for blood glucose above 180 mg/dL were calculated by use of a continuous glucose monitoring system., Results: Serum levels of 1,5-AG among healthy adults were 28.44 ± 8.76 µg/mL with a significant gender bias rather than age bias. The 1,5-AG levels in people with type 2 diabetes mellitus were 4.57 ± 3.71 µg/mL, which were lower than those seen in the healthy adults. There was a correlation between 1,5-AG and glycated haemoglobin, fasting blood glucose, and postprandial blood glucose (r = -0.251, -0.195 and -0.349, respectively; all had p < 0.05). The continuous glucose monitoring system demonstrated that 1,5-AG presents a negative correlation with mean blood glucose, standard deviation of blood glucose, mean amplitude of glucose excursion and mean of daily differences for 7 days and with the area under the curve for blood glucose above 180 mg/dL on the third, fourth and seventh days., Conclusions: 1,5-AG may serve as a marker of hyperglycaemia and 7-day hyperglycaemic excursions as well as being a useful adjunct to glycated haemoglobin for blood glucose monitoring in patients with diabetes., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background and Objective: Serum 1,5-anhydroglucitol (1,5-AG) is a marker of hyperglycemic excursions in adults with diabetes and hemoglobin A1c (HbA1c) < 8%. We compared 1,5-AG levels among youth and young adults with and without type 1 diabetes (T1D) and investigated the utility of 1,5-AG in the assessment of glycemic status in pediatric T1D., Methods: We compared 1,5-AG, HbA1c, and plasma glucose levels in 138 patients with T1D (duration ≥1 yr) and 136 healthy controls, aged 10-30 yr. Within each group, we investigated associations between 1,5-AG and clinical characteristics, HbA1c and random plasma glucose. For patients with T1D, 1,5-AG was further analyzed according to HbA1c strata: <8, 8-9, and >9%., Results: Compared to controls, patients with T1D had higher HbA1c (8.5 ± 1.6 vs. 5.1 ± 0.4%, p < 0.0001), lower 1,5-AG (4.0 ± 2.0 vs. 24.7 ± 6.4 µg/mL, p < 0.0001), and higher glucose (11.1 ± 5.2 vs. 5.1 ± 0.9 mmol/L, p < 0.0001). Males had higher 1,5-AG than females within patients (4.5 ± 2.3 vs. 3.4 ± 1.6 µg/mL, p = 0.003) and controls (26.0 ± 6.6 vs. 23.5 ± 6.0 µg/mL, p = 0.02). 1,5-AG was not correlated with glucose in either group. 1,5-AG was significantly correlated to HbA1c in patients, but not controls. For patients with HbA1c < 8%, 1,5-AG demonstrated the widest range and was not predicted by HbA1c; 1,5-AG levels were narrowly distributed among patients with HbA1c ≥ 8%., Conclusions: Youth and young adults with T1D demonstrate similar 1,5-AG levels which are distinct from controls. 1,5-AG assessment may provide unique information beyond that provided by HbA1c in the mid-term assessment of glycemic control in young patients with T1D and HbA1c < 8%., (© 2011 John Wiley & Sons A/S.)

An assay of plasma 1,5-anhydroglucitol was evaluated. Assay CVs, effects of four plasma freeze-thaw cycles, glucose up to 80 mmol/L and triglycerides up to 20 mmol/L were acceptable. 1,5-anhydroglucitol levels were significantly lower in diabetic vs. non-diabetic subjects and correlated inversely with renal function, but not with HbA1c., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To describe the interrelationships of glycemic control measures: hemoglobin A1c (HbA1c), glycated albumin, fructosamine, 1,5-anhydroglucitrol (1,5-AG), and continuous glucose monitoring (CGM) in children and adolescents with type 1 diabetes., Methods: In total, 26 subjects of age 4-17 had HbA1c measurement followed within 14 d by three laboratory measures of glycemia and the collection of CGM glucose data (N = 21)., Results: Glycated albumin and fructosamine levels had a higher correlation with each other than with HbA1c. The correlation of 1,5-AG with HbA1c was lower (absolute r value = 0.25). All four measures had a similar degree of correlation with CGM-measured mean glucose (absolute r value = 0.50-0.56) and with hyperglycemic area under the curve (AUC) at 180 mg/dL (0.50-0.60)., Conclusion: Each of the four measures (i.e., HbA1c, glycated albumin, fructosamine, and 1,5-AG) had a similar correlation with mean glucose and hyperglycemic AUC-180. 1,5-AG did not correlate with hyperglycemic AUC-180 better than did HbA1c., (© 2011 John Wiley & Sons A/S.)

Background: Although differences between black and white persons in hemoglobin A(1c) (HbA(1c)) values are well established, recent studies suggest that this might not reflect differences in glycemia., Objective: To investigate racial disparities in glycemic markers, including those that reflect biological processes independent of hemoglobin glycation and erythrocyte turnover., Design: Cross-sectional., Setting: Community-based., Participants: 1376 nondiabetic and 343 diabetic adults in a substudy of the Atherosclerosis Risk in Communities Study., Measurements: Hemoglobin A(1c), fasting glucose, glycated albumin, fructosamine, and 1,5-anhydroglucitol levels., Results: Among persons with and without diabetes, black persons had significantly higher HbA(1c), glycated albumin, and fructosamine levels than white persons before and after adjustment for covariates and fasting glucose concentration. Serum 1,5-anhydroglucitol levels, which are reduced in the setting of hyperglycemia-induced glycosuria, were lower in black persons than in white persons, although this difference was statistically significant only in nondiabetic adults., Limitation: The design was cross-sectional, a limited number of participants with a history of diabetes was included, and the study did not include integrated measures of circulating nonfasting glycemia., Conclusion: Differences between black and white persons in glycated albumin, fructosamine, and 1,5-anhydroglucitol levels parallel differences between these groups in HbA(1c) values. Racial differences in hemoglobin glycation and erythrocyte turnover cannot explain racial disparities in these serum markers. The possibility that black persons have systematically higher levels of nonfasting glycemia warrants further study., Primary Funding Source: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

Content: Recent studies have reported hemoglobin A(1c) (A1c) differences across racial/ethnic groups. Our diverse population allows for further investigation of potential differences in measurements of glycemia., Objectives: Our objectives were to describe and explore baseline racial/ethnic differences in self-monitored plasma glucose profiles, A1c, and 1,5-anhydroglucitol (1,5-AG) in patients with type 2 diabetes enrolled in the Assessing DURAbility of Basal vs. Lispro Mix 75/25 Insulin Efficacy trial., Design, Setting, Patients: The trial enrolled 2094 patients with type 2 diabetes, ages 30-80 yr, from 11 countries., Main Outcome Measures: Estimated mean plasma glucose (MPG), A1c, and 1,5-AG were compared among racial/ethnic groups before and after adjusting for factors affecting glycemia: age, sex, duration of diabetes, body mass index, and MPG., Results: Baseline estimated MPG +/- sd was 220.0 +/- 82.0 mg/dl, mean A1c was 9.0 +/- 1.3%, and 1,5-AG was 5.0 +/- 4.1microg/ml. Estimated MPG did not differ between Caucasian and non-Caucasian groups. A1c was higher in Hispanics (9.4 +/- 1.4%; P < 0.001), Asians (9.2 +/- 1.4%; P < 0.01), and patients of other racial/ethnic groups (9.7 +/- 1.5%; P < 0.001) compared with Caucasians (8.9 +/- 1.2%). Paradoxically, 1,5-AG was higher for Asian (5.7 +/- 4.6 microg/ml) and African patients (6.2 +/- 5.4 microg/ml) vs. Caucasians (4.9 +/- 3.9 microg/ml) (P < 0.01). After adjusting for factors affecting glycemia, A1c was higher (all P

Aim: Recent data have suggested that effective control of postprandial blood glucose can reduce the risk of macroangiopathic complications of diabetes, especially cardiovascular risk. 1,5-Anhydro-D-glucitol (1,5-AG) has been proposed as a marker of short-term hyperglycaemic excursions. We aimed to evaluate its usefulness in patients with type 2 diabetes and have attempted to indicate when 1,5-AG monitoring should be used in ordinary diabetes care settings., Methods: The study group consisted of 130 type 2 diabetic patients aged 36-69 years. 1,5-AG plasma level, HbA&#95;1c concentrations and daily glucose profile were measured. Mean blood glucose (MBG), M-value were calculated and maximal daily glycaemia (MxG) was established as indicators of short-term hyperglycaemic episodes., Results: 1,5-AG plasma level was negatively and HbA&#95;1c was positively correlated with fasting glycaemia (FG), MBG, M-value and MxG. Multivariate regression analysis revealed that 1,5-AG plasma level is determined by MxG only, while FG determined HbA&#95;1c concentration in blood. The analysis of 1,5-AG level and HbA&#95;1c distributions in well and poorly controlled patients revealed that persons with low HbA&#95;1c values may have decreased 1,5-AG plasma level., Conclusion: 1,5-AG plasma level monitoring is the useful method to identify well controlled, exclusively based on HbA&#95;1c levels type 2 diabetic patients with transient hyperglycaemia, accordingly patients at high risk of macroangiopathic complications.

Objective: 3-Deoxyglucosone (3-DG), a highly reactive intermediate of the glycation reaction, has been suggested to contribute to the development of diabetes complications. To verify this hypothesis, we assessed the relation between serum 3-DG concentrations and the severity of diabetic microangiopathy in diabetic patients., Research Design and Methods: We conducted a high-performance liquid chromatography assay to determine the serum 3-DG concentrations of 110 diabetic patients with different degrees of severity of diabetic microangiopathy and 57 age-matched control subjects., Results: The fasting serum 3-DG level in diabetic patients was significantly (P < 0.001) higher than that in control subjects (353 +/- 110 vs. 199 +/- 53 nmol/l). The 3-DG levels were significantly (P < 0.001) elevated even in the diabetic patients showing normoalbuminuria (n = 62, 322 +/- 79 nmol/l) compared with control subjects. The 3-DG levels were further elevated in the patients with microalbuminuria (n = 30, 383 +/- 146 nmol/l) and overt proteinuria (n = 18, 410 +/- 100 nmol/l) (P = 0.027 and P < 0.001 vs. normoalbuminuria group, respectively). This phenomenon was basically reproduced in a category of retinopathy. Furthermore, the diabetic patients with low nerve conduction velocity showed a tendency to display higher 3-DG levels., Conclusions: The present results show that the fasting serum 3-DG level is elevated in diabetic patients and that the patients with relatively higher 3-DG levels were prone to suffer from more severe complications, indicating a possible association of 3-DG with diabetic microangiopathy.

Background: the optimal indicator for screening for diabetes mellitus without relying on fasting conditions was clarified., Methods: the subjects were 891 men ages 26 through 80 years (48.5 +/- 8.5). The objectives of this study were (1) to elucidate the efficacy of 1,5-anhydroglucitol (1,5-AG), glycosylated hemoglobin, and fructosamine (FRA) as screening tests for non-insulin-dependent diabetes mellitus (NIDDM) or for impaired glucose tolerance (IGT) and (2) to perform an economic evaluation for each indicator. The efficacy of each indicator was evaluated by drawing the receiver operating characteristic curves and calculating the areas under these curves (AUCs). An original model was developed for the pur pose of cost-effectiveness analysis., Results: each indicator was evaluated as a screening test for NIDDM alone and for both IGT and NIDDM. The AUCs of 1,5-AG and fasting plasma glucose were the largest in the case of the detection of NIDDM alone and the detection of both IGT and NIDDM, respectively. FRA was, however, the most cost-effective in Japan., Conclusion: using equations, we indicated the equi librium points at which the cost-effectiveness ratios of each indicator intersected in order to generalize the results. By calculating the appropriate-actual ratios of costs for each indicator, we could ascertain the optimal indicator for each country., (Copyright 1999 American Health Foundation and Academic Press.)

Objective: To clarify the effects of glycemic control on the level of 3-deoxyglucosone (3-DG), a reactive dicarbonyl compound, in plasma from diabetic patients., Research Design and Methods: Fasting plasma samples were collected from 15 healthy volunteers and 27 patients with NIDDM. Samples were collected from six poorly controlled patients before and after improved glycemic control for at least 2 months. Plasma 3-DG was determined by high-performance liquid chromatography (HPLC) as a 2,3-diaminonaphthalene derivative. We observed the relationship of 3-DG levels with plasma glucose or HbA1c levels and examined changes in 3-DG levels after glycemic control in the six patients., Results: Plasma 3-DG was significantly more increased in diabetic patients than in nondiabetic control subjects (31.8 +/- 11.3 vs. 12.8 +/- 5.2 ng/ml, means +/- SD, P < 0.001), but there was an approximately threefold difference in 3-DG levels among diabetic patients. 3-DG levels were well correlated with plasma glucose (r = 0.56, P < 0.005) and HbA1c levels (r = 0.74, P < 0.001) in diabetic patients. The improvement of hyperglycemia in six patients resulted in a significant decrease in 3-DG (35.2 +/- 13.2 vs. 21.3 +/- 3.4 ng/ml, P < 0.05)., Conclusions: The results indicate that the plasma glucose level is a predominant determinant of the plasma 3-DG level in diabetic patients and good glycemic control would be important to reduce this reactive metabolite.

Objective: To investigate the effect of a family history of NIDDM on HbAlc and serum 1,5-anhydroglucitol (AG) in nondiabetic subjects., Research Design and Methods: A 75-g oral glucose tolerance test was performed; 258 subjects with normal glucose tolerance and 106 subjects with impaired glucose tolerance (IGT) were selected HbAlc and serum AG were compared between subjects with and without a family history of NIDDM. The relationships between age, BMI, HbAlc, serum AG, fasting and 2-h plasma glucose, and urinary glucose were also examined using principal component analysis with a varimax rotation., Results: In the normal group, only serum AG was lower in subjects with a positive family history than in those with no family history. On the other hand, in the IGT group, subjects with a positive family history were younger and had a higher 2-h plasma glucose, a higher urinary glucose, and a lower serum AG than those with no family history, whereas there was no difference in HbAlc. Principal component analysis identified three factors. The first factor, a linear combination of HbAlc and fasting plasma glucose, was labeled an average glycemic factor. The second factor, which included serum AG, 2-h plasma glucose, and urinary glucose, was labeled an oscillatory glycemic factor. The third factor, which contrasted age against BMI, was labeled an environmental factor., Conclusions: Serum AG is related to glycosuria even among nondiabetic subjects, and its concentrations are decreased in those with a family history of NIDDM. Our results suggest that serum AG rather than HbAlc reflects early metabolic abnormalities in these subjects.

The diagnostic accuracy of glycated haemoglobin (HbA1c) and 1,5-anhydroglucitol (AG) and their association with age and obesity in the community screening for Type 2 diabetes were investigated. HbA1c and AG were measured in 368 subjects at the time of an oral glucose tolerance test (OGTT) based on WHO criteria. The impact of age and obesity on the probability of diabetes was evaluated by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to assess diagnostic accuracy of each method. The areas under ROC curves were compared for subjects aged 30-59 and 60-82 years. In the logistic analysis, age was associated with the probability of diabetes, while body mass index did not contribute to the model. The paired ROC analyses indicated that HbA1c was superior to AG only in the younger subjects. When the areas for two age groups were compared, both HbA1c and AG performed better in the younger than older subjects. We conclude that for the younger subjects, HbA1c value is highly sensitive (100.0%) and specific (90.4%) and is helpful for the diagnosis of Type 2 diabetes. On the other hand for the older subjects, both HbA1c and AG are poor screening tests in reference to the OGTT standard.

To evaluate the efficacy of hemoglobin-Alc, fructosamine, and 1,5-anhydroglucitol tests in screening for diabetes mellitus in communities, the sensitivity and the specificity of these tests were observed on the island of Ojika, Goto islands, Nagasaki prefecture Japan. A 75 gram glucose tolerance test was performed simultaneously on every participant, and WHO diabetes mellitus criteria were used to classify individuals. A total of 554 males and 820 females, older than 34 years, participated in the examination, representing a response rate of 42% and 52% respectively, and 86 were classified as diabetic. The sensitivity and the specificity of several screening levels were determined for each test. Each of the tests attained greater than 70% sensitivity and specificity simultaneously, but could not achieve greater than an 80% level simultaneously. If screening levels are selected for a sensitivity of as low as 50%, it is possible to produce a high specificity of 97-98%. These results provide valuable information for the planning of efficient diabetes mellitus detection programs in communities.

To evaluate the use of serum 1,5-anhydroglucitol (AG) levels in screening for diabetes mellitus, we compared the sensitivity and specificity of HbA1c, fructosamine (FA), and AG in 1620 randomly selected subjects in 11 institutions throughout Japan. Most individuals were receiving diet and/or drug therapy for diabetes. Subjects were separated into four groups based on World Health Organization criteria: nondiabetic control subjects, subjects with impaired glucose tolerance (IGT), patients with diabetes, and patients with other disorders without IGT. The overlap of AG values between each group was less than that of HbA1c or FA values. AG levels were significantly correlated with fasting plasma glucose (r = -0.627), HbA1c (r = -0.629), and FA (r = -0.590) levels. If we took 14 micrograms/ml as the normal lower limit, AG level was highly specific (93.1%), and a decreased AG level indicated diabetes mellitus (84.2% sensitivity). According to the selectivity index (sensitivity value times specificity value), AG determinations were superior to both HbA1c and FA measurements for diabetes screening. When combinations of these tests were used, only AG and HbA1c together were slightly better than AG alone. Thus, together with other advantages of AG, e.g., its wide variance with relatively fair glycemic control and the negligible influence of the sampling conditions, AG level has more potential than HbA1c or FA level as a screening criterion for diabetes.