Association of 1,5-Anhydroglucitol with Diabetes and Microvascular Conditions

E. Selvin, A.M. Rawlings, M. Grams, R. Klein, M. Steffes, and J. Coresh

November 2014

www.clinchem.org/content/60/11/1409.full

© Copyright 2014 by the American Association for Clinical Chemistry

© Copyright 2009 by the American Association for Clinical Chemistry

IntroductionIntroductionBackground

1,5-Anhydroglucitol (1,5-AG) is a candidate biomarker for glycemic excursions

Previous studies have suggested associations of 1,5-AG concentrations with diabetic microvascular complications

However, studies have been prospective and all have been limited in sample size and the scope of endpoints

Aims Examine the association of 1,5-AG with:

- Prevalent retinopathy- Incident chronic kidney disease (CKD)- Incident diabetes

© Copyright 2009 by the American Association for Clinical Chemistry

MethodsMethodsStudy population

Participants from the Atherosclerosis Risk in Communities (ARIC) Study, attending visit 2 (1990-1992) for incident analyses, or visit 3 (1993-1995) for retinopathy analyses

1,5-AG measured in stored serum samples GlycoMarkTM assay using the Roche Modular P800 system Inter-assay CV = 5%, reliability coefficient for 610 masked

duplicate sample pairs = 0.99 1,5-AG categorized into a 5-level variable: Among persons without diabetes: ≥10, <10 μg/mL Among persons with diabetes: ≥10, 10-6, <6 μg/mL

Statistical analysis Adjusted Cox and logistic regression models

© Copyright 2009 by the American Association for Clinical Chemistry

QuestionsQuestions

Why are short-term biomarkers of

hyperglycemia of potential interest for

research and clinical practice?

What are some reasons to examine long-term

outcomes, along with cross-sectional

associations, when examining the utility of a

new biomarker?

© Copyright 2009 by the American Association for Clinical Chemistry© Copyright 2009 by the American Association for Clinical Chemistry

Table 1Table 1

a Continuous variables are mean (SD) or median [25th percentile, 75th percentile]. Categorical variables are reported as a percentage.

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Table 1 (continued)Table 1 (continued)

a Continuous variables are mean (SD) or median [25th percentile, 75th percentile]. Categorical variables are reported as a percentage.

© Copyright 2009 by the American Association for Clinical Chemistry© Copyright 2009 by the American Association for Clinical Chemistry

Table 2 – Prevalent RetinopathyTable 2 – Prevalent Retinopathy

a Model 1: age, race-center, sex b Model 2: variables in model 1 + LDL cholesterol, HDL -cholesterol, triglycerides, body mass index, waist-to-hip ratio, mean systolic blood pressure, blood pressure–lowering medication use, family history of diabetes, education, drinking status, smoking status, physical activity index.c Model 3: variables in model 2 + Hb A1c (per %-point)d Model 4: variables in model 2 + fasting glucose (per 1 mg/dL)

© Copyright 2009 by the American Association for Clinical Chemistry© Copyright 2009 by the American Association for Clinical Chemistry

Table 2 (cont) – Incident CKD and DiabetesTable 2 (cont) – Incident CKD and Diabetes

a Model 1: age, race-center, sex b Model 2: variables in model 1 + LDL cholesterol, HDL -cholesterol, triglycerides, body mass index, waist-to-hip ratio, mean systolic blood pressure, blood pressure–lowering medication use, family history of diabetes, education, drinking status, smoking status, physical activity index.c Model 3: variables in model 2 + Hb A1c (per %-point)d Model 4: variables in model 2 + fasting glucose (per 1 mg/dL)

© Copyright 2009 by the American Association for Clinical Chemistry

QuestionQuestion

1,5-AG was most strongly associated with prevalent retinopathy. What are some likely explanations for the differences in magnitude of associations of 1,5-AG with the clinical outcomes in this study?

© Copyright 2009 by the American Association for Clinical Chemistry© Copyright 2009 by the American Association for Clinical Chemistry

Figure 1. Adjusted associations for baseline 1,5-anhydroglucitol with prevalent retinopathy (ORs) and incident CKD and incident diabetes (HRs) in the overall population.Frequency histograms for 1,5-AG are shown separately for persons with diagnosed diabetes (dark grey bars) and without diagnosed diabetes (light grey bars).

Figure 1Figure 1

© Copyright 2009 by the American Association for Clinical Chemistry

QuestionQuestion

What do you notice about the distribution of 1,5-AG from Figure 1? How might this influence interpretation of results and utility of 1,5-AG as a biomarker?

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Figure 2. Prevalence of retinopathy (A) and 20-year cumulative incidence of CKD (B) by categories of 1,5-AG (<10 g/mL, >10 g/dL) within categories of glycemic control (HbA1c <7%, HbA1c >7%) among persons with diagnosed diabetes at baseline. Vertical bars are 95% CIs.

Figure 2Figure 2

© Copyright 2009 by the American Association for Clinical Chemistry

QuestionQuestion

Based on Figure 2, what information can be gained from 1,5-AG?

© Copyright 2009 by the American Association for Clinical Chemistry

ConclusionsConclusions

There were robust associations between low

concentrations of 1,5-AG and microvascular

complications, particularly in the setting of diabetes

Results support a possible role for 1,5-AG as a useful

biomarker of hyperglycemia in persons with diabetes

More studies needed to evaluate the clinical utility of

1,5-AG in the setting of diabetes management

© Copyright 2009 by the American Association for Clinical Chemistry

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