Taking the weight off the feet

Aims. To assess progression or regression of neuropathy in patients with type 2 diabetes mellitus (T2DM) undergoing bariatric surgery.

Methods. In this prospective observational longitudinal study, n=29 patients with known T2DM for at least 5 years listed for bariatric surgery were recruited after exclusion of potential confounders. Patients underwent assessment of neuropathy by the total neuropathy score-clinical version (mTNS), biothesiometry, non-contact corneal aethesiometry (NCCA), corneal confocal microscopy (CCM), and retinopathy at 4 timepoints namely pre-surgery (baseline), 12, 26, and 52 weeks. Nerve conduction studies of the sural and peroneal nerves were performed at baseline and 52 weeks.

Results. N=19 and n=10 patients underwent gastric sleeve and bypass respectively. At baseline, patients had increased mean HbA1c (56.6 ± 15.0 mmol/mol), body mass index (BMI) (44.7 ± 6.4 kg/m2), mTNS (3.29 ± 3.55), peroneal nerve compound muscle action potential (261.58 ± 38.24), along with reduced peroneal nerve latency (4.34 ± 0.94), corneal nerve fiber length (CNFL) (12.2 ± 5.3 mm/mm2) and NCCA (1.11 ± 0.8 mbar). Following bariatric surgery, there was a progressive significant reduction in HbA1c (by week 52: 47.56 ± 13.64, P<0.0001 by timepoint), BMI (by week 52: 33.49 ± 4.71, P<0.0001 by timepoint), and triglycerides (P<0.0001). Metabolic and weight improvement was paralleled by an early significant improvement in CNFL (by week 12: 17.4 ± 5.64, P<0.0001), which remained stable throughout the study, along with a gradual significant improvement in NCCA (by week 52: 0.62 ± 0.55, P<0.0001 by timepoint), mTNS (by week 52: 0.76 ± 1.48, P<0.0001), and NCS measures of peroneal nerve compound muscle action potential (by week 52: 235.53 ± 35.52, P=0.038) and increase in latency (by week 52: 4.68 ± 0.97). There was a significant negative relationship between CNFL and mTNS (P<0.001) and a positive relationship between NCCA and mTNS (P<0.001). By contrast, there was no difference in retinopathy or maculopathy for the entire study duration. Notably, 8 (27.5%) patients refused to undergo nerve conduction studies.

Conclusions. Bariatric surgery leads to a significant improvement in measures of small and large fiber neuropathy through weight loss and improved metabolic control. CNFL improved as early as 12 weeks after surgery, which was predictive of regressing symptoms and signs.

Comments. Diabetic neuropathy lacks effective disease modifying treatments, partly due to lack of sensitive endpoints to assess treatment response. Using a panel of small and large fiber endpoints, the authors elegantly demonstrate reversal of neuropathy over 52 weeks in morbidly obese T2DM patients undergoing bariatric surgery. Confirming previous observations in several clinical trials across different centers, CNFL showed the earliest signs of improvement followed by symptoms, signs and nerve conduction studies, suggesting high sensitivity. CNFL is an easy-to-measure parameter on CCM images, which integrates nerves branches and fibers, and thus may be advantageous in capturing early degeneration and regeneration. Another important finding is the lack of improvement in retinopathy for the duration of the study, suggesting a differential effect of bariatric surgery on microvascular complications. Despite the relatively small sample size, the present study highlights the potential benefits of bariatric surgery for suitable patients. Availability of novel, less invasive, and widely accessible treatments for weight loss warrants further and larger studies to determine the comparative benefits on microvascular complications, particularly neuropathy.

Ioannis N. Petropoulos

Reference. Misra SL, Slater JA, Makam R, Braatvedt GD, Beban G, Pradhan M, Mankowski JL, Oakley JD, McGhee CNJ. Remission of corneal and peripheral neuropathy after bariatric surgery in people with diabetes. Ocul Surf. 2024 Jul 23;34:140-145. doi: 10.1016/j.jtos.2024.07.006. Epub ahead of print. PMID: 39053583.

https://www.sciencedirect.com/science/article/pii/S1542012424000752#appsec1