Predictive Biomarkers for Peripheral Neuropathy in Adults

The Neuropathy Spectrum
The Neuropathy Spectrum
Several cardiac and kidney biomarkers may be used to identify older adults with peripheral neuropathy.

Several cardiac and kidney biomarkers may be used to identify older adults with peripheral neuropathy (PN), according to study results published in Clinical Chemistry.

Previous studies have shown that PN is common in the general population and the prevalence is higher among adults aged ≥70 years, and in those with diabetes. However, as limited data are available on risk factors for PN, the goal of the current study was to explore the association of a panel of cardiac, kidney, inflammatory and diabetes biomarkers with PN in a community-based population of older adults.

The researchers used data from the Atherosclerosis Risk in Communities (ARIC) study on adults with and without diabetes between the ages 71 and 94 years, who underwent monofilament PN testing between 2016 and 2017.

The cross-sectional analysis included 3056 participants with available monofilament PN testing and measures of cardiac function (high-sensitivity cardiac troponin [hs-cTnT], N-terminal pro-B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β2-microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A1c [HbA1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and C-reactive protein.

Of the 3056 participants, 1024 (33.5%) had PN, including 332 of 890 (37.3%) of those with diabetes and 692 of 2166 (31.9%) of subjects without diabetes. Participants with PN were older, were predominantly male, and had higher body mass index than participants without PN.

In patients with and without diabetes, there were higher median levels of hs-cTnT, NT-proBNP, GDF15, creatinine, cystatin C, β2 microglobulin, urine albumin-to-creatinine ratio, fasting glucose, HbA1c, fructosamine, and glycated albumin in those with PN, compared to those without PN (all, P <.05).

Following adjustment for age, sex, race and cardiovascular risk factors, only the association of hs-cTnT with PN remained significant in participants with without diabetes. The association of hs-cTnT with PN was similar regardless of diabetes status (P =.72 for interaction).

In patients without diabetes, compared to reference hs-cTnT levels (≤9 ng/L), levels between 10.0-14.0 ng/L (2nd tertile) were associated with a 33% increased risk for PN (odds ratio [OR] 1.33, 95% CI, 1.02-1.73), and levels ≥15.0 ng/L (3rd tertile) were associated with more than a 2-fold increased risk for PN (OR 2.33, 95% CI, 1.76-3.03). In those with diabetes, compared to reference levels (≤10 ng/L), levels between 11.0 to 18.0 ng/L (2nd tertile) were associated with a 44% increased risk for PN (OR 1.44, 95% CI, 1.00-2.09) and levels ≥19.0 ng/L (3rd tertile) were associated with a 2-fold increased risk (OR 2.15, 95% CI, 1.44-3.22).

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In participants with diabetes there were persistent 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. In those with there were significant association between HbA1c (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 (all, P <.05).

The researchers acknowledged several study limitations, including the cross-sectional design, lack of clinical neuropathy-related outcomes, and potentially unmeasured confounders.

“Our findings support the hypothesis that cardiac and kidney biomarkers may be useful global measures of end organ damage and that laboratory biomarkers—specifically hs-cTnT—may help us identify individuals who have PN,” concluded the researchers.


Hicks CW, Wang D, Daya NR, et al. Associations of cardiac, kidney, and diabetes biomarkers with peripheral neuropathy among older adults in the Atherosclerosis Risk in Communities (ARIC) study [published online ahead of print, 2020 Apr 8]. Clin Chem. 2020;hvaa051. doi:10.1093/clinchem/hvaa051

This article originally appeared on Neurology Advisor