Differential effects of Diabetes Mellitus on nerve fibers by type of Diabetes

Abstract

Type 1 (T1D) and Type 2 diabetes mellitus (T2D) are often assumed to have similar effects on nerve fibers with a common etiology of hyperglycemia. Mounting evidence suggests that T2D preferentially affects non-myelinated C-fibers compared to myelinated fibers. To evaluate whether differential loss of myelinated and unmyelinated fibers occurs in T1D and T2D, we studied 9 patients with T1D, 11 patients with T2D and 10 age-matched control patients with nerve conduction studies, autonomic function tests, skin biopsy of distal and proximal leg (hairy skin) and glabrous skin biopsy of the index finger. T1D and T2D patients had similar HgA1c, neuropathy exam and symptom scores. T1D patients had longer length of diabetes and lower BMI compared to T2D patients. T1D patients had significant loss of myelinated and non-myelinated fibers with lower myelinated fiber densities, intra-epidermal nerve fiber density (IENFD) and composite autonomic system score (CASS). T2D patients had no significant loss of myelinated fibers (20.3 vs. 21.7 myelinated fibers /mm for healthy controls), but had significant decrease in non-myelinated fibers as evidenced by decreased IENFD and abnormal CASS. T1D and T2D patients had similar intraepidermal nerve fiber density at the distal leg, and similar sweat volumes using quantitative sudomotor axon reflex testing. T1D patients had a trend towards worse cardiac autonomic function with CASS score mean of 3 vs 2 for T2D patients. These results suggest that focus on distal, non-myelinated fiber function and pathology may be more sensitive for T2D patients than traditional myelinated fiber-based measures of diabetic neuropathy.