Glycated albumin and HbA1c as markers of lower extremity disease in US adults with and without diabetes

We evaluated the associations of two biomarkers of hyperglycemia-hemoglobin A1c(HbA1c) and glycated albumin-with lower extremity disease in US adultsoverall and by diabetes status.We conducted a cross-sectional study of adult participants aged ≥ 40 years who attended the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (unweighted N = 5,785). We used logistic regression to evaluate the associations of HbA1c and glycated albumin with lower extremity disease: peripheral neuropathy (assessed by monofilament test), peripheral artery disease (assessed by ankle-brachial index), history of foot ulcer, or amputation. All analyses were weighted and accounted for the complex NHANES sample survey design.The prevalence of lower extremity disease was 17.4% (15.9% in adults without diabetes and 33.2% in adults with diabetes). HbA1c and glycated albumin were not significantly associated with lower extremity disease in adults without diabetes. However, we observed significant associations of both HbA1c (OR 1.19 per 1-% point increase, 95 %CI 1.06-1.34) and glycated albumin (OR 1.06 per 1-% point increase, 95 %CI 1.02-1.10) with lower extremity disease in adults with diabetes after adjustment. The patterns of association were similar for HbA1c and glycated albumin (P-for-seemingly-unrelated-regression = 0.60), with strong linear associations observed at high (diabetic) levels of both biomarkers.Our study suggests the importance of diabetes prevention and glycemic control in adults with diabetes to reduce the burden of lower extremity disease.