Abstract P034: Comparison of the Prognostic Value of 1,5-anhydroglucitol (1,5-AG) and the Oral Glucose Tolerance Test (OGTT) in the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: 1,5-AG is a biomarker that reflects hyperglycemic excursions. Unlike the OGTT, 1,5-AG requires only a single blood draw and is a non-fasting test. It is unknown if 1,5-AG could serve as a substitute for OGTT and whether it provides complementary information to fasting glucose (FG) for prediction of diabetes and long-term clinical outcomes. Methods: We included 6,711 ARIC participants without diagnosed diabetes, chronic kidney disease (CKD), and CVD that attended visit 4 (1996-98). Participants were followed for up to 18 years for incident diagnosed diabetes, CKD, CVD, and all-cause mortality. We used Harrell’s C-statistic from Cox models to compare the prognostic value of 1,5-AG to OGTT beyond a base model of demographic factors and body mass index. Restricted cubic splines (4 knots) were used to flexibly model the biomarkers with each of the outcomes. Results: Both OGTT and 1,5-AG provided information beyond the base model for risk discrimination of incident diagnosed diabetes ( p <0.05; Table). However, OGTT provided statistically significantly more information than 1,5-AG (difference in C-statistic: 0.087 (95%CI, 0.075, 0.099)). While 1,5-AG otherwise did not provide more information for future outcomes than the base model, OGTT statistically significantly improved the base model for prediction of CKD, CVD, and all-cause mortality. For incident diagnosed diabetes, inclusion of FG in the models maintained that OGTT provided more information than 1,5-AG for risk discrimination. Inclusion of all three biomarkers (FG, 1,5-AG, and OGTT) was not statistically significantly better than a model with FG and OGTT for future diagnosed diabetes ( p =0.687). Conclusion: 1,5-AG could not sufficiently substitute for the OGTT as a test to identify those at risk of future diabetes. Additionally, glycemic excursions captured by 1,5-AG did not provide additional prognostic value beyond glucose-based tests among those without diagnosed diabetes, suggesting the utility of 1,5-AG is limited to persons with overt diabetes.

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Glycemic Measures and Risk of Mortality in Older Chinese: The Guangzhou Biobank Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz173 ◽

2019 ◽

Vol 105 (3) ◽

pp. e181-e190 ◽

Cited By ~ 1

Author(s):

Chao Qiang Jiang ◽

Lin Xu ◽

Tai Hing Lam ◽

Ya Li Jin ◽

Wei Sen Zhang ◽

...

Keyword(s):

Cohort Study ◽

Confidence Interval ◽

Mortality Risk ◽

Fasting Glucose ◽

Tolerance Test ◽

Hazard Ratio ◽

Oral Glucose ◽

Risk Of Mortality ◽

All Cause Mortality ◽

Diagnosed Diabetes

Abstract Context China has the largest number of people with type 2 diabetes mellitus (T2DM) in the world. Data from previous studies have suggested that up to one-fifth of individuals with diabetes would be missed without an oral glucose tolerance test (OGTT). To date, there is little information on the mortality risk of these individuals. Objective We estimated the association of different indicators of hyperglycemia with mortality in the general Chinese population. Design Prospective cohort study. Setting China. Participants A total of 17 939 participants aged 50+ years. Exposures Previously diagnosed diabetes and newly detected diabetes defined by fasting glucose (≥7.0 mmol/L), 2-hour postload glucose (≥11.1 mmol/L), or hemoglobin A1c (HbA1c, ≥6.5%). Main Outcomes Measures Deaths from all-cause, cardiovascular disease, and cancer were identified by record linkage with death registration. Results During 7.8 (SD, 1.5) years’ follow-up, 1439 deaths were recorded. Of 3706 participants with T2DM, 2126 (57%) had known T2DM, 118 (3%) were identified by isolated elevated fasting glucose, 1022 (28%) had isolated elevated postload glucose, and 440 (12%) had both elevated fasting and postload glucose. Compared with normoglycemia, the hazard ratio (95% confidence interval) of all-cause mortality was 1.71 (1.46-2.00), 0.96 (0.47-1.93), 1.43 (1.15-1.78), and 1.82 (1.35-2.45) for the 4 groups, respectively. T2DM defined by elevated HbA1c was not significantly associated with all-cause mortality (hazard ratio, 1.17; 95% confidence interval, 0.81-1.69). Conclusion Individuals with isolated higher 2-h postload glucose had a higher risk of mortality by 43% than those with normoglycemia. Underuse of OGTT leads to substantial underdetection of individuals with a higher mortality risk and lost opportunities for early intervention.

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Associations of 1,5-Anhydroglucitol and 2-Hour Glucose with Major Clinical Outcomes in the Atherosclerosis Risk in Communities (ARIC) Study

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa066 ◽

2020 ◽

Vol 5 (6) ◽

pp. 1296-1306

Author(s):

Bethany Warren ◽

Alexandra K Lee ◽

Christie M Ballantyne ◽

Ron C Hoogeveen ◽

James S Pankow ◽

...

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Clinical Outcomes ◽

Atherosclerosis Risk In Communities ◽

C Statistic ◽

Atherosclerosis Risk ◽

All Cause Mortality ◽

Diagnosed Diabetes ◽

Aric Study

Abstract Background 1,5-Anhydroglucitol (1,5-AG) is a novel biomarker of glycemic control proposed to monitor recent hyperglycemic excursions in persons with diabetes. The clinical utility of 1,5-AG outside of diagnosed diabetes is unclear, but it may identify people at high risk for diabetes and its complications. We compared associations of 1,5-AG with 2-h glucose for risk of major clinical complications. Research Design and Methods We prospectively followed 6644 Atherosclerosis Risk in Communities (ARIC) Study participants without diagnosed diabetes for incident diagnosed diabetes, chronic kidney disease, cardiovascular disease, and all-cause mortality for ∼20 years. We assessed associations of 1,5-AG and 2-h glucose (modeled categorically and continuously with restricted cubic splines) with adverse outcomes using Cox models and evaluated improvement in risk discrimination using Harrell’s c-statistic. Results 1,5-AG <10 µg/mL was statistically significantly associated with incident diabetes (HR: 2.70, 95% CI 2.31, 3.15), and showed suggestion of association with the other outcomes compared to 1,5-AG ≥10 µg/mL. Continuous associations of 1,5-AG with outcomes displayed a clear threshold effect, with risk associations generally observed only <10 µg/mL. Comparing associations of 1,5-AG and 2-h glucose with outcomes resulted in larger c-statistics for 2-h glucose than 1,5-AG for all outcomes (difference in c-statistic [2-h glucose -1,5-AG] for diagnosed diabetes: 0.17 [95%CI, 0.15, 0.19]; chronic kidney disease 0.02 [95%CI 0.00, 0.05]; cardiovascular disease 0.03 [95%CI, 0.00, 0.06]; and all-cause mortality 0.04 [95%CI, 0.02, 0.06]). Conclusions In this community-based population without diagnosed diabetes, low 1,5-AG was modestly associated with major clinical outcomes and did not outperform 2-h glucose.

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Frequency of Diabetes and Prediabetes in Heart Failure Patients and Their Association with In-Hospital Outcome

Chattagram Maa-O-Shishu Hospital Medical College Journal ◽

10.3329/cmoshmcj.v13i1.19409 ◽

2014 ◽

Vol 13 (1) ◽

pp. 1-6

Author(s):

Noortaj Begum ◽

Abu Sadique Abdullah ◽

Md. Aminul Haque Khan ◽

AN Wahida Sultana ◽

DMMF Osmany ◽

...

Keyword(s):

Heart Failure ◽

Hospital Admissions ◽

Length Of Hospital Stay ◽

Tolerance Test ◽

Oral Glucose ◽

College Hospital ◽

Cross Sectional ◽

Impaired Fasting Glycaemia ◽

Heart Failure Patients ◽

Diagnosed Diabetes

Background: There are an increasing number of hospital admissions due to heart failure with diabetes or prediabetes in different hospitals in Bangladesh. But very little is known about the frequency of diabetes and prediabetes and the effect of its presence on the characteristics and outcome in patients hospitalized for heart failure. The objective of this study was to find out the frequency of diabetes and prediabetes in heart failure patients and to assess their association with in-hospital outcome.Methods: This cross sectional analytical study was done in the department of Biochemistry and Cardiology of Bangabandhu Sheikh Mujib Medical University in collaboration with department of Cardiology of National Institute of Cardiovascular Diseases, and Dhaka Medical College Hospital from July 2010 to June 2011. After proper ethical consideration a total two hundred and fifty heart failure patients were enrolled in the study by nonrandom sampling. Fasting blood sugar was done in all patients and oral glucose tolerance test was done in patients with impaired fasting glycaemia. Results: The frequency of prediabetes among the total population was 12.8% (95% CI, 8.7-16.8) and that of diabetes was 37.2% (95% CI, 31.2-43.2%). Improvement was achieved in 27 (84.4%) cases in prediabetic group, 75 (80.6%) cases in diabetic group and 105 (84.0%) cases in nondiabetic group. Mortality rates in prediabetes, diabetes and nondiabetes were 5 (15.6%); 18 (19.4%) and 20 (16.0%) respectively. The differences found among the three groups were not statistically significant (p>0.05). Length of hospital stay was also similar in all groups of study subjects. Conclusion: Frequency of diabetes among heart failure patients is high and pre-diabetes is not negligible in our country. Future studies in this field should focus on all types of glucose abnormalities rather than previously diagnosed diabetes only.DOI: http://dx.doi.org/10.3329/cmoshmcj.v13i1.19409

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Glycated hemoglobin (HbA1c) as diagnostic criteria for diabetes: the optimal cut-off points values for the Pakistani population; a study from second National Diabetes Survey of Pakistan (NDSP) 2016–2017

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-001058 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001058

Author(s):

Abdul Basit ◽

Asher Fawwad ◽

Khalid Abdul Basit ◽

Nazish Waris ◽

Bilal Tahir ◽

...

Keyword(s):

Glucose Tolerance ◽

Diagnostic Tool ◽

Glycated Hemoglobin ◽

Tolerance Test ◽

Normal Glucose Tolerance ◽

Oral Glucose ◽

Pakistani Population ◽

Epidemiological Surveys ◽

Diabetes Survey ◽

Diagnosed Diabetes

AimGlycated hemoglobin (HbA1c) cut-off values as diagnostic tool in diabetes and prediabetes with its concordance to oral glucose tolerance test (OGTT) in Pakistani population.MethodologyData for this substudy was obtained from second National Diabetes Survey of Pakistan (NDSP) 2016–2017. With this survey, 10 834 individuals were recruited and after excluding known subjects with diabetes, 6836 participants fulfilled inclusion criteria for this study. Demographic, anthropometric and biochemical parameters were obtained. OGTT was used as standard diagnostic tool to screen population and HbA1c for optimal cut-off values. Participants were categorized into normal glucose tolerance (NGT), newly diagnosed diabetes (NDD) and prediabetes.ResultsOut of 6836 participants, 4690 (68.6%) had NGT, 1333 (19.5%) had prediabetes and 813 (11.9%) had NDD by OGTT criteria with median (IQR) age of 40 (31–50) years. Optimal HbA1c cut-off point for identification of diabetes and prediabetes was observed as 5.7% ((AUC (95% CI)=0.776 (0.757 to 0.795), p<0.0001)) and 5.1% ((AUC (95% CI)=0.607 (0.590 to 0.624), p<0.0001)), respectively. However, out of 68.6% NGT subjects identified through OGTT, 24.1% and 9.3% participants were found to have prediabetes and NDD, respectively by using HbA1c criteria. By using both OGTT and HbA1c criteria, only 7.9% and 7.3% were observed as prediabetes and diabetes, respectively.ConclusionFindings from second NDSP demonstrated disagreement between findings of OGTT and HbA1c as diagnostic tool for Pakistani population. As compared with international guidelines, HbA1c threshold for prediabetes and NDD were lower in this part of world. HbA1c as diagnostic tool might require ethnic or regional-based modification in cut-off points, validated by relevant community-based epidemiological surveys.

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The Reproducibility of an Abbreviated Fat Tolerance Test in Young Healthy Participants: A Pilot Study (P12-029-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz035.p12-029-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Madison Dixon ◽

Christina Sciarrillo ◽

Nicholas Koemel ◽

Sam Emerson

Keyword(s):

Tolerance Test ◽

Mean Difference ◽

Oral Glucose ◽

High Fat ◽

Cvd Risk ◽

Blood Draw ◽

Fat Tolerance Test ◽

The Mean ◽

Internal Sources ◽

Healthy Participants

Abstract Objectives Triglyceride (TG) responses following a high-fat meal are more strongly associated with cardiovascular disease (CVD) risk compared with fasting TG levels. The current protocol for assessing post-meal TG is a burdensome process, involving serial blood draws for up to 8 hours. We have developed an abbreviated fat tolerance test (AFTT) that yields highly similar TG results relative to the standard protocol. The objective of this study is to determine whether the AFTT is reproducible and how it compares to the reproducibility of the oral glucose tolerance test (OGTT), a metabolic challenge already in clinical use. Methods In a randomized crossover design, 6 healthy participants (2 M/4F, age: 25.8 ± 9.4 years, BMI: 22.6 ± 2.6 kg/m², fasting TG: 69.8 ± 9.8 mg/dL, fasting glucose: 93.5 ± 5.1 mg/dL, A1C: 5.3% ± 0.34%) completed 2 AFTT's separated by 1 week followed by 2 OGTT's separated by 1 week, or vice versa. There was a 2-week washout period between the AFTT's and OGTT's. For each AFTT and OGTT, a baseline blood draw was taken followed by either consumption of a high-fat shake (73% fat, 26% CHO; 9 kcal/kg) (AFTT) or a standard 75 g glucose drink (OGTT). Following consumption of the AFTT, participants left the lab and returned 4 hours later for a post-meal blood draw. Following consumption of the OGTT, participants remained in the lab for 2 hours and a post-meal blood draw was taken. Results The mean difference in 4-hour postprandial TG change from baseline between the 2 AFTTs was 5.2 mg/dL, while the mean difference in 2-hour glucose change between the 2 OGTTs was 17.5 mg/dL. The 4-hour TG change results from the 2 AFTT's were highly correlated (r = 0.96, P = 0.003), while the 2-hour change results from the 2 OGTTs were not (r = 0.17, P = 0.75). The within-subjects coefficient of variation (WCV) for 4-hour TG concentrations between the 2 AFTT's was 16%, suggesting moderate reproducibility, while the WCV for 2-hour glucose concentrations between the 2 OGTT's was 24%, indicating low reproducibility. Conclusions These preliminary data suggest that the AFTT response is reproducible, potentially more than the OGTT. While further assessment in a larger sample is necessary, the AFTT could advance postprandial TG testing toward greater clinical feasibility. Funding Sources Funding provided by internal sources at Oklahoma State University.

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Prognostic Value of Serial Changes in High-Sensitivity Cardiac Troponin I and T over 3 Months Using Reference Change Values in Hemodialysis Patients

Clinical Chemistry ◽

10.1373/clinchem.2015.251835 ◽

2016 ◽

Vol 62 (4) ◽

pp. 631-638 ◽

Cited By ~ 26

Author(s):

Yader Sandoval ◽

Charles A Herzog ◽

Sara A Love ◽

Jing Cao ◽

Yan Hu ◽

...

Keyword(s):

Cardiac Troponin ◽

Prognostic Value ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Adverse Outcomes ◽

Cox Models ◽

Reference Change Value ◽

Hazard Ratios ◽

All Cause Mortality

Abstract INTRODUCTION Serial changes in cardiac troponin in hemodialysis (HD) patients have uncertain clinical implications. We evaluated associations of adverse outcomes in HD patients with reference change value (RCV) data and tertile concentrations for cardiac troponin I (cTnI) and cTnT measured by high-sensitivity (hs) assays. METHODS RCV data and tertiles for hs-cTnI and hs-cTnT were determined from plasma samples collected 3 months apart in 677 stable outpatient HD patients and assessed for their associations with adverse outcomes using adjusted Cox models. Primary outcomes were all-cause mortality and sudden cardiac death (SCD). RESULTS During a median follow-up of 23 months, 18.6% of patients died. RCVs were: hs-cTnI +37% and −30%; hs-cTnT +25% and −20%. Patients with serial hs-cTnI and hs-cTnT changes >RCV (increase or decrease) had all-cause mortality of 25.2% and 23.8% respectively, compared to 15.0% and 16.5% with changes ≤RCV [adjusted hazard ratios (aHRs): 1.9, P = 0.0003 and 1.7, P = 0.0066), respectively]. Only hs-cTnI changes >RCV were predictive of SCD (aHR 2.6, P = 0.005). hs–Cardiac troponin changes >RCV improved all-cause mortality prognostication compared to changes ≤RCV in tertile 2: hs-cTnI aHR, 2.70 (P = 0.003); hs-cTnT aHR, 1.98 (P = 0.043). The aHR of changes in hs-cTnI in tertile 2 >RCV for SCD was 5.62 (P = 0.039). CONCLUSIONS Changes over 3 months in hs-cTnI and hs-cTnT of >RCV identified patients at greater risk of all-cause mortality, and for hs-cTnI were also predictive of SCD. Among patients with middle tertile cardiac troponin concentrations, hs-cTnI changes >RCV provided additive prognostic value for both SCD and all-cause mortality, whereas those for hs-cTnT provided additive prognostic value only for all-cause mortality.

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Glucose patterns during an oral glucose tolerance test and associations with future diabetes, cardiovascular disease and all-cause mortality rate

Diabetologia ◽

10.1007/s00125-017-4468-z ◽

2017 ◽

Vol 61 (1) ◽

pp. 101-107 ◽

Cited By ~ 20

Author(s):

Adam Hulman ◽

Dorte Vistisen ◽

Charlotte Glümer ◽

Michael Bergman ◽

Daniel R. Witte ◽

...

Keyword(s):

Cardiovascular Disease ◽

Mortality Rate ◽

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

All Cause Mortality ◽

Future Diabetes

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Abstract P129: Biomarkers of Hyperglycemia With All-cause Mortality in Older Adults With and Without Diagnosed Diabetes

Circulation ◽

10.1161/circ.141.suppl_1.p129 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Mary R Rooney ◽

Olive Tang ◽

James S Pankow ◽

Elizabeth Selvin

Keyword(s):

Older Adults ◽

Cox Regression ◽

Glycated Albumin ◽

Cohort Analysis ◽

Undiagnosed Diabetes ◽

Atherosclerosis Risk In Communities ◽

All Cause Mortality ◽

Before And After ◽

Diagnosed Diabetes ◽

Glycemic Markers

Introduction: HbA1c is central to diagnosis and management of diabetes. However, our understanding of the associations of HbA1c with clinical outcomes is based primarily on studies of middle-aged adults. Objective: To characterize the associations between HbA1c and mortality among older adults with and without diabetes. We compared the HbA1c-mortality associations with those for alternative glycemic markers (fructosamine and glycated albumin). Methods: We conducted a prospective cohort analysis of 6370 participants (32% with diagnosed diabetes, mean age 76, 59% female, 23% black) in the Atherosclerosis Risk in Communities (ARIC) Study, baseline visit 5 (2011-13). We used Cox regression models to examine the association of each glycemic biomarker (modeled as a linear spline) with all-cause mortality through 2017, stratified by diagnosed diabetes. Model discrimination was tested using c-statistics. Results: There were 1022 deaths over 6 years of follow-up. In persons with diabetes, there was a J-shaped association between HbA1c and mortality ( Figure ). Associations were largely similar for fructosamine and glycated albumin. Among persons without diabetes, HbA1c was not strongly associated with mortality, but confidence intervals were wide for HbA1c <5.0% and ≥6.5% (undiagnosed diabetes); whereas, higher levels of fructosamine and glycated albumin were associated with an elevated mortality risk. Associations were similar before and after adjustment for cardiovascular risk factors. The addition of individual glycemic markers to the models modestly improved discrimination in both persons with and without diabetes. C-statistics were similar when the glycemic markers were added individually to the diabetes-stratified models (Figure). Conclusions: Among older adults, HbA1c and other glycemic markers tend to have similar associations with mortality. HbA1c, fructosamine, and glycated albumin, including low levels, may reflect common markers of risk in older adults, particularly in those with diabetes.

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