Changes Over 10 Years in Peripheral Nerve Function in People With Well-Controlled Type 2 Diabetes and Those With Normal Glucose Tolerance

Abstract

Background and objectives: There is a lack of knowledge on the changes in peripheral nerve function in people with well-controlled, recently diagnosed type 2 diabetes compared with those with normal glucose tolerance (NGT). In this study, we aimed to investigate the natural course of the function of lower extremity small and large nerve fibers in people with NGT and its decline in those with well-controlled type 2 diabetes.

Methods: This prospective observational study assessed changes in nerve function in participants of the German Diabetes Study with recently diagnosed (≤1 year) type 2 diabetes and age-matched and sex-matched individuals with NGT after 5 years and in a larger group of participants with type 2 diabetes after 5 and 10 years. Reference tests of lower extremity peripheral nerve function included peroneal motor nerve conduction velocity (MNCV) and sural sensory nerve conduction velocity (SNCV), sural sensory nerve action potential (SNAP), malleolar vibration perception threshold (VPT), and thermal detection thresholds (TDTs). Data were analyzed using multiple linear or logistic regression analyses.

Results: At baseline, all 5 nerve function measures showed impairment in the 52 individuals in the diabetes group (33% female, median age 51.7 years) compared with the 52 individuals in the matched NGT group (33% female, median age 51.4 years). After 5 years, 2 nerve indices declined in the diabetes group (peroneal MNCV and VPT) and 3 in the NGT group (peroneal MNCV, VPT, and TDT for cold), with similar 5-year declines observed in both groups after adjustment for baseline values and pairwise matching. In addition, the Neuropathy Disability Score increased in the NGT group but not in the diabetes group. Comparable patterns of decline after 5 and 10 years were found in the larger diabetes cohort of 141 individuals (39% female, median baseline age 53.6 years). The observed 10-year prevalence of abnormal NCVs closely matched estimates based on natural aging-related decline (14.2% vs 12.8% for peroneal MNCV and 30.2% vs 31.0% for sural SNCV).

Discussion: These findings suggest that nerve function deterioration in well-controlled type 2 diabetes is primarily influenced by nerve function status at diagnosis and physiologic aging, rather than diabetes-related progression.

Figure 1. Individual Changes in Nerve Function Indices After 5 Years in People With Normal Glucose Tolerance and Type 2 Diabetes

Bars are mean ± SD. Differences between the groups were assessed using the Wilcoxon signed rank test.

Figure 2. Individual Changes in Nerve Function After 5 Years in People With Normal Glucose Tolerance and Type 2 Diabetes in Relation to Baseline Age

Linear regression analyses with nerve function measures as the dependent variable and baseline age as the independent variable were used to determine the deviation from zero.

Figure 3. Individual Changes in Nerve Function in People With Type 2 Diabetes From Baseline to 5 Years and From 5 to 10 Years

Bars are mean ± SD. Differences between the groups were assessed using the Wilcoxon signed rank test. BL = baseline, 5 years = 5-year follow-up, 10 years = 10-year follow-up.

Figure 4. Individual Changes in Nerve Function After 10 Years in People With Type 2 Diabetes in Relation to Baseline Age

Linear regression analyses with nerve function measures as the dependent variable and baseline age as the independent variable were used to determine the deviation from zero.