Associations of Cardiac, Kidney, and Diabetes Biomarkers With Peripheral Neuropathy among Older Adults in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background: The aim of this study was to assess the association of high-sensitivity cardiac troponin (hs-cTnT) and other cardiac, kidney, hyperglycemia, and inflammatory biomarkers with peripheral neuropathy (PN) in a community-based population.

Methods: We conducted a cross-sectional analysis of 3056 black and white participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent standardized monofilament PN testing and had measures of cardiac function (hs-cTnT, N-terminal pro-B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β-2 microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A1c [Hb A1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and inflammation (C-reactive protein) assessed at visit 6 (2016-2017; age 71-94 years). We used logistic regression to assess the associations of these biomarkers (modeled in diabetes-specific tertiles) with PN in older adults with and without diabetes after adjusting for traditional risk factors.

Results: In total, 33.5% of participants had PN (37.3% with diabetes and 31.9% without diabetes). There was an independent association of hs-cTnT with PN regardless of diabetes status (diabetes T3 vs. T1: odds ratio [OR], 2.15 [95% CI, 1.44-3.22]; no diabetes: OR, 2.31 [95%CI, 1.76-3.03]; P = 0.72 for interaction). Among participants without diabetes, there were also significant associations of NT-proBNP (OR, 1.40 [95% CI, 1.08-1.81]) and urine albumin-to-creatinine ratio (OR, 1.55 [95% CI, 1.22-1.97]) with PN. Associations of hyperglycemia biomarkers including Hb A1c (OR, 1.76 [95% CI, 1.22-2.54]), fructosamine (OR, 1.71 [95% CI, 1.19-2.46]), and glycated albumin (OR, 1.45 [95% CI, 1.03-2.03]) with PN were significant only among participants with diabetes.

Conclusions: Overall, hs-cTnT appears to be a global marker of end organ damage, including PN. Laboratory biomarkers may be able to help us identify those individuals with PN.

Keywords: ARIC; NT-proBNP; biomarker; diabetes; hs-cTnT; peripheral neuropathy.

Fig. 1.

Adjusted odds ratios and 95% CIs for the continuous associations of cardiac markers with prevalent PN. Odds ratios are from logistic regression adjusted for age, sex, race and center, education, body mass index, smoking status, alcohol status, hypertension, hyperlipidemia, prevalent cardiovascular disease, and prevalent peripheral artery disease. Biomarkers were modeled using a restricted cubic spline with knots at the 5th, 35th, 65th and 95th percentiles. The models were centered at the 50th percentile, and the display of graphs was truncated at the 95th percentile. The light gray bars denote the distribution of participants without diabetes, and dark gray bars denote the distribution of participants with diabetes.

Fig. 2.

Adjusted odds ratios and 95% CIs for the continuous associations of kidney markers with prevalent PN. Odds ratios are from logistic regression adjusted for age, sex, race and center, education, body mass index, smoking status, alcohol status, hypertension, hyperlipidemia, prevalent cardiovascular disease, and prevalent peripheral artery disease. Biomarkers were modeled using a restricted cubic spline with knots at the 5th, 35th, 65th and 95th percentiles. The models were centered at the 50th percentile, and the display of graphs was truncated at the 95th percentile. The light gray bars denote the distribution of participants without diabetes, and the dark gray bars denote the distribution of participants with diabetes.

Fig. 3.

Adjusted odds ratios and 95% CIs for the continuous associations of glycemic markers and inflammation marker with prevalent peripheral neuropathy. Odds ratios are from logistic regression adjusted for age, sex, race and center, education, body mass index, smoking status, alcohol status, hypertension, hyperlipidemia, prevalent cardiovascular disease and prevalent peripheral artery disease. Biomarkers were modeled using a restricted cubic spline with knots at the 5th, 35th, 65th, and 95th percentiles. The models were centered at the 50th percentile, and the displays of graph were truncated at the 95th percentile. The light gray bars denote the distribution of participants without diabetes, and the dark gray bars denote the distribution of participants with diabetes.