Progressive loss of corneal nerve fibers is associated with physical inactivity and glucose lowering medication associated with weight gain in type 2 diabetes

Abstract

Aims/Introduction: Limited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk factors with change in neuropathy measures over 2 years. Materials and Methods: Participants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow-up. Results: Participants with type 2 diabetes had a lower corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P ≤ 0.0001) and a higher VPT (P ≤ 0.01) compared with controls. Over 2 years, despite a modest reduction in HbA1c (P ≤ 0.001), body weight (P ≤ 0.05), and LDL (P ≤ 0.05) the prevalence of DPN (P = 0.28) and painful DPN (P = 0.21) did not change, but there was a significant further reduction in CNBD (P ≤ 0.0001) and CNFL (P ≤ 0.05). CNFD, CNBD, and CNFL decreased significantly in physically inactive subjects (P < 0.05-0.0001), whilst there was no change in CNFD (P = 0.07) or CNFL (P = 0.85) in physically active subjects. Furthermore, there was no change in CNFD (P = 0.82), CNBD (P = 0.08), or CNFL (P = 0.66) in patients treated with glucose lowering medication associated with weight loss, whilst CNBD (P = 0.001) decreased in patients on glucose lowering medication associated with weight gain. Conclusions: In participants with type 2 diabetes, despite a modest improvement in HbA1c, body weight, and LDL there was a progressive loss of corneal nerve fibers; except in those who were physically active or on glucose lowering medication associated with weight loss.

Diet and exercise are a fundamental part of comprehensive care for type 2 diabetes

“…Regular exercise not only improves blood glucose levels but also reduces cardiovascular risk factors and contributes to weight loss. Moreover, physical activity also demonstrated the benefits for diabetic neuropathy in a previous study 22 . In that study, type 2 diabetes mellitus was associated with neuropathy and a progressive loss of corneal nerve fibers.…”

Corneal confocal microscopy detects early nerve regeneration after pharmacological and surgical interventions: Systematic review and meta‐analysis

“…55 Furthermore, in diabetic patients treated with CSII, there was evidence of corneal nerve regeneration, without an improvement in NCS over 24 months. 29 We have also shown corneal nerve regeneration in physically active patients with type 2 diabetes over 24 months, 56 whereas a recent meta-analysis showed no change in peroneal and sural NCV in patients who exercise. 57 In an early study, we showed corneal nerve regeneration after 24 months of improvement in HbA1c, lipids and blood pressure, 48 whilst in a recent study from Japan, a decrease in HbA1c and weight was associated with improved nerve conduction and corneal nerve regeneration over 4 years.…”

How does the clinical practice of Aotearoa New Zealand podiatrists align with international guidelines for the prevention of diabetes‐related foot disease? A cross‐sectional survey

“…Despite NZ podiatrists advocating for the importance of physical exercise and mobility, the results indicate that the education provided to patients around exercise is still largely based on the clinician’s individual experience. Exercise has been identified as potentially playing an important role as an intervention in the non-pharmacological treatment of DFD, including on the progression of diabetes-related peripheral neuropathy [ 31 ]. However, despite an increased number of studies investigating the provision of foot and mobility-related exercise as an intervention to prevent foot ulcers there continues to be a small research evidence base in this area [ 24 , 32 ].…”