Impact of the metabolic syndrome on peripheral nerve structure and function in type 2 diabetes

Background and purpose There is a strong association between the metabolic syndrome in diabetes and the development of peripheral neuropathy; however, the pathophysiological mechanisms remain unknown. Methods Participants with type 2 diabetes and metabolic syndrome (T2DM/MetS, n = 89) and type 2 diabetes alone (T2DM; n = 59) underwent median nerve ultrasound and excitability studies to assess peripheral nerve structure and function. A subset of T2DM/MetS (n = 24) and T2DM (n = 22) participants underwent confocal microscopy to assess central and inferior whorl corneal nerve structure. Neuropathy severity was assessed using the modified Toronto Clinical Neuropathy Score (mTCNS). Diabetes groups were similar for age, sex distribution, diabetes duration, hemoglobin A(1c), insulin treatment, and renal function. Sixty healthy controls similar for age and sex distribution were recruited for comparison. Results Participants with T2DM/MetS manifested with a greater mTCNS compared to T2DM (p < 0.05). Median nerve cross-sectional area was larger in the T2DM/MetS group compared to the T2DM cohort (p < 0.05). Participants with T2DM/MetS had reductions in central (all p < 0.01) and inferior whorl (all p < 0.05) nerve measures. Compared to T2DM, the T2DM/MetS group demonstrated more severe changes in nerve excitability measures, which was due to reduced sodium channel permeability and sodium-potassium pump function. In comparison, only sodium channel permeability was reduced in the T2DM group. Conclusions Compared to participants with type 2 diabetes alone, those with diabetes and metabolic syndrome manifested greater alterations in peripheral nerve structure and function, which may be due to reduced function of the sodium-potassium pump.

Automated summary

Participants with diabetes and metabolic syndrome showed more severe alterations in peripheral nerve structure and function compared to those with diabetes alone, likely due to reduced function of the sodium-potassium pump.