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

Diabetes Res Clin Pract. 2022 Feb;184:109212. doi: 10.1016/j.diabres.2022.109212. Epub 2022 Jan 20.


Aim: 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.

Methods: 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.

Results: 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.

Conclusions: Our study suggests the importance of diabetes prevention and glycemic control in adults with diabetes to reduce the burden of lower extremity disease.

Keywords: Amputation; Glycated albumin; Lower extremity disease; Peripheral artery disease; Peripheral neuropathy; hemoglobin A1c.

MeSH terms

  • Adult
  • Biomarkers
  • Blood Glucose
  • Cross-Sectional Studies
  • Diabetes Mellitus* / diagnosis
  • Glycated Hemoglobin A / analysis
  • Glycation End Products, Advanced*
  • Humans
  • Lower Extremity / blood supply
  • Nutrition Surveys
  • Risk Factors
  • Serum Albumin


  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Serum Albumin
  • glycated serum albumin