Bariatric Surgery May Reverse Peripheral Neuropathy

Bariatric surgery may reverse peripheral nerve injury and slow the progression of cardiovascular autonomic neuropathy and retinopathy in patients with severe obesity, according to a cohort study recently published in Diabetologia.

Two years after bariatric surgery, patients reported improved peripheral neuropathy at the proximal thigh but not at the distal leg, as well as stable cardiovascular autonomic neuropathy and retinopathy, Evan L. Reynolds, PhD, and colleagues write.

"Our findings suggest that bariatric surgery likely enables the regeneration of the peripheral nerves and, therefore, may be an effective treatment for millions of individuals with obesity who are at risk of developing diabetes and peripheral neuropathy," said senior author Brian C. Callaghan, MD, a neurologist at University of Michigan Health and professor of neurology at the University of Michigan Medical School, in a press release from the university.

"Given the natural history of peripheral neuropathy [worsening] in patients with obesity, even stability in nerve fiber density may be considered a successful result," added Reynolds, who is lead statistician for the NeuroNetwork for Emerging Therapies at the University of Michigan Medical School.

"Our findings probably indicate an improvement compared with the natural history of worsening [peripheral neuropathy, cardiovascular autonomic neuropathy] and retinopathy over time," the researchers summarize before concluding that "controlled trials are needed."

Obesity Is the Second-Leading Cause of Peripheral Neuropathy

Obesity, particularly central obesity, is the second-leading risk factor for peripheral neuropathy after diabetes, the researchers write.

Recent meta-analyses and systematic reviews have shown that bariatric surgery typically improves diabetes complications; however, the studies were either small or didn't consider multiple diabetes complications in the same population.

Reynolds and colleagues performed a prospective cohort study of individuals with class II/III obesity (body mass index [BMI] > 35 kg/m² up to 70 kg/m²) seen at the University of Michigan bariatric surgery clinic in 2015-2018.

Of 127 participants who completed baseline visits and had bariatric surgery, 26 patients withdrew from the study (mostly lost to follow-up), 79 patients completed in-person 2-year follow-up, and 22 patients completed virtual 2-year follow-up. The patients in the three groups had similar baseline characteristics.

The 79 patients were a mean age of 46 and 73% were women, and most were White (80%) and non-Hispanic (99%).

Researchers determined the patients' metabolic risk factors, which included lipid profile, blood pressure, height, weight, BMI, A1c, fasting glucose, and waist circumference.

Patients had a mean weight of 130 kg and a mean BMI of 46 kg/m².

They had a mean A1c of 6%, and 30% had normal glycemic values, 40.5% had prediabetes, and 29% had diabetes.

At the 2-year follow-up, diabetes had worsened in one patient, was stable in 60 patients (46%), and improved in 43 patients (54%).

Patients lost a mean of 31 kg and had improvements in all metabolic risk factors except for blood pressure and total cholesterol.

The number of patients receiving antihypertensive medications decreased.

Researchers assessed peripheral neuropathy by taking skin biopsies to measure nerve fiber density in the thigh and lower leg.

At follow-up, one of two primary peripheral neuropathy outcomes — change in intra-epidermal nerve fiber density (IENFD) in the proximal thigh — signficantly improved (P < .01). The other primary outcome, IENFD in the distal leg, was stable.

The primary cardiovascular autonomic neuropathy outcome (change in expiration/inspiration ratio) and the retinopathy outcome (mean deviation using frequency doubling technology) remained stable.

Patients with greater reductions in fasting glucose had improved retinopathy.

Patients also had significant improvements in measures of quality of life, pain, and depression.

The researchers were surprised that the primary cardiovascular autonomic neuropathy and retinopathy outcomes were stable (rather than improved) after bariatric surgery, in contrast to previous studies.

They speculated that improvement late in the disease course may not be enough to significantly reverse even mild autonomic and retinal nerve damage, or alternatively, improvement may only show up after more than 2 years.

In a previous study of 72 participants, those who lost weight by medical means versus bariatric surgery had greater weight loss (23.8% vs 10.3%) and more robust improvement in peripheral neuropathy symptoms at 2 years.

The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Callaghan has reported being a consultant for DynaMed, receiving research support from the American Academy of Neurology, and performing medical-legal consultations, including consultations for the Vaccine Injury Compensation Program. A study co-author has reported receiving research support from Novo Nordisk. Reynolds and the other authors have reported no relevant financial relationships.

Diabetologia. Published online March 14, 2023. Full text

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