Weight Loss in Obesity May Stall
Neuropathy Progress

Nancy A. Melville

October 09, 2020

Among obese people with polyneuropathy, significant weight loss appears to halt progression of the painful condition while improving some key measures, a new study suggests.

However, other measures showed no improvement, whereas other studies show greater effects with exercise interventions.

"Our study shows that dietary weight loss stabilizes or slightly improves neuropathy outcomes in obese patients with or without diabetes," first author Brian Callaghan, MD, of the University of Michigan in Ann Arbor, told Medscape Medical News.

"This was the first study to show a slowing of the progression of nerve fiber density with a primary weight loss intervention," he said.

The findings were presented this week as part of the American Neurological Association's 2020 annual meeting, held virtually this year because of the pandemic.

While neuropathy is most commonly associated with diabetes, studies show that obesity, a known key risk factor for diabetes, is also independently linked to polyneuropathy, with or without diabetes, with prevalence rates of neuropathy in the severely obese and elderly that are approximately two to three times that of the general population.

Glucose control is linked to improvement in neuropathy, but does not appear to be enough, Callaghan said. He noted that, in a previous Cochrane Review, Callaghan and his colleagues in fact found enhanced glucose control to have a much stronger effect in preventing diabetic neuropathy in type 1 vs type 2 diabetes.

Therefore, to further investigate the potential effects of weight loss on neuropathy, the researchers evaluated data on 131 patients with obesity at the University of Michigan who took part in a rigorous weight loss program.

The dietary program included a 12-week very-low-calorie period limited to 800 calories per day, followed by a transition to 1200-1500 calories per day for a total of 2 years.

Of the original 131 patients, 72 completed the 2-year follow-up. At that point, participants had lost a significant amount of weight compared with baseline (mean 12.4 kg; a 10.25% weight reduction; P < .01).

Their mean body mass index (BMI) declined from 40.8 to 36.5 and waist circumference was reduced from 123.1 cm to 114.7 cm (both P < .01).

However, for the coprimary endpoints of intraepidermal nerve fiber density in the thigh and distal leg, indicators of neuropathy, there were no significant changes (P = .73 and P = .32, respectively).

The proportion of patients meeting the clinical definition of polyneuropathy declined from 26% to 19%, which Callaghan said was likely not statistically significant, although that was not among the study's outcomes.

For secondary endpoints, improvements were observed on the Michigan Neuropathy Screening Instrument Questionnaire (-0.59; P < .01); on the Quality of Life in Neurological Disorders (NeuroQoL) components of pain and emotional symptoms (both P = .01), and quantitative sensory testing (QST) for response to cold (P < .01).

Improvements following the weight loss program were seen in components including waist circumference, diastolic blood pressure, triglycerides, and HDL (all P < .01). And fasting glucose and 2-hour glucose both also improved (P = .02 and P < .01, respectively), as did A1c (P = .01).

No significant changes were observed in other secondary outcomes, however, including the short-form McGill pain questionnaire and the NCS.

"Encouragingly, four secondary polyneuropathy outcomes revealed improvements after medical weight loss, but NCS, MNSI Examination, and the short-form McGill Pain Questionnaire remained unchanged," the authors report.

Slowing of Progression?

Importantly, despite there being no significant reductions in the intraepidermal nerve fiber density outcomes, the measures did remain stable over the 2 years, whereas research from 2016 suggests that typically those symptoms could have otherwise been expected to worsen.

"Given that natural history studies reveal decreases in intraepidermal nerve fiber density over time, medical weight loss may halt this progression, but randomized controlled trials are needed," Callaghan said.

Of note, previous studies looking into polyneuropathy and obesity have suggested that not all types of obesity are linked to the risk for polyneuropathy, with the risk appearing limited to those with central obesity (weight concentrated in the waist) compared with those with more of a "pear" shape, with weight in the hips and thighs.

In another previous study, Callaghan and colleagues in fact found that waist circumference was about 10 cm higher in obese patients with neuropathy compared with those without neuropathy; conversely, the hip and thigh measures were actually smaller in those with neuropathy.

Callaghan speculated that heightened pro-inflammatory effects of central obesity could play a role.

"We do not know why this is the case, but one strong possibility is that abdominal fat leads to increased inflammatory signals that harm peripheral nerves," he said.

As multiple studies that examined exercise interventions also showed similar results in terms of slowed progression of nerve fiber density, the researchers are taking a closer look at that issue in an ongoing randomized, controlled trial of 140 patients who either did or did not have bariatric weight loss surgery and who are randomly assigned to either routine exercise or a high-intensity interval training exercise regimen. That trial is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

In commenting on the current findings, Clifton Gooch, MD, professor and chair of neurology at the University of South Florida, Tampa, noted that one issue possibly affecting neuropathy improvement may have been the degree of weight loss.

"A 10% weight loss is the threshold for the start of clinically meaningful improvement in lipid profile, blood sugar levels and metabolic syndrome in general; however, it is just the threshold," he told Medscape Medical News.

"Many studies have shown that 'dropping 10 pounds' does have health benefits for all overweight patients, including reductions in long-term cardiovascular risk," he noted. "In this group, it would be important to know the degree of neuropathy at the start of the study; more severe injury would be less likely to respond to a mild intervention."

Other factors that could be informative include whether additional risk factors for neuropathy were present in a portion of the cohort, such as alcoholism, he said.

Furthermore, the very-low calorie 12-week weight loss regimen, involving meals substituted with shakes, could have been an important factor, Gooch noted.

"This was a 'crash diet,' and unless careful attention was paid to vitamin supplementation, then transient deficiencies, for instance [vitamin] B12, might also have been a counter-weight to improvement."

He added, however, that "other studies have shown that correction of prediabetes by normalizing blood sugar levels through weight loss, diet, and exercise can halt progression of neuropathy, and this [study] reinforces that concept."

The study received funding from a National Institute of Neurological Disorders and Stroke K23 award. Callaghan and Gooch have disclosed no relevant financial relationships.

ANA 2020: 145th Annual Meeting of the American Neurological Association. Presented October 4, 2020.


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