1. 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
© Copyright 2014 by the American Association for Clinical Chemistry

2. Introduction Background Aims
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

3. Methods Study population 1,5-AG measured in stored serum samples
Participants from the Atherosclerosis Risk in Communities (ARIC) Study, attending visit 2 ( ) for incident analyses, or visit 3 ( ) 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

4. Questions
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?

5. Table 1
a Continuous variables are mean (SD) or median [25th percentile, 75th percentile]. Categorical variables are reported as a percentage.

6. Table 1 (continued)
a Continuous variables are mean (SD) or median [25th percentile, 75th percentile]. Categorical variables are reported as a percentage.

7. Table 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)

8. Table 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)

9. Question
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?

10. Figure 1
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).

11. Question
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?

12. Figure 2
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.

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

14. Conclusions
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

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