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

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

Methods Study population 1,5-AG measured in stored serum samples 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

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?

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

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

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)

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)

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?

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).

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?

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.

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

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

Thank you for participating in this month’s Clinical Chemistry Journal Club. Additional Journal Clubs are available at www.clinchem.org Download the free Clinical Chemistry app on iTunes for additional content! Follow us