Apnea Linked to Neuropathy Risk in Diabetes

Future research hopes to find link between treating apnea and treating diabetes.

Obstructive sleep apnea (OSA) independently predicted coexistence of diabetic peripheral neuropathy, and the association remained significant after adjustment for multiple confounders, British investigators reported.

Two-thirds of a group of patients with type 2 diabetes had OSA, and 60 percent of the OSA subgroup had peripheral neuropathy. In contrast, the patients without OSA had a neuropathy prevalence of 27 percent.

The data also suggested potential mechanistic explanations involving nitrosative/oxidative stress and microvascular dysfunction, as reported online in the American Journal of Respiratory and Critical Care Medicine.

However, the authors stressed that because of the cross-sectional nature of the study and the lack of an interventional arm, causation could not be proven.

Still, “the data reported herein provide a rationale for further prospective and interventional studies to assess the impact of OSA and its treatment on diabetic peripheral neuropathy development and progression in patients with type 2 diabetes,” Abd Tahrani, MRCP, of the University of Birmingham, and co-authors wrote of the study’s potential clinical implications.

“To date, trials examining the impact of continuous positive airway pressure (CPAP in patients with type 2 diabetes) have mainly focused on metabolic indices. However, the impact of CPAP on diabetes complications is unknown,” they noted.

“The association between mild obstructive sleep apnea and diabetic peripheral neuropathy in this report, if confirmed, may also have implications for the threshold for OSA treatment, since some authorities only offer CPAP treatment in moderate to severe OSA,” the researchers added.

Despite accumulation of data about of the pathogenesis of diabetic neuropathy, understanding remains incomplete, as reflected in the lack of disease-modifying therapies. Sleep apnea has associations with multiple pathophysiologic deficits found in diabetes, making the condition a reasonable subject for investigation into the origin of diabetic neuropathy, the authors wrote.

Investigators recruited adults with type 2 diabetes for an observational cross-sectional study. Diabetic neuropathy was defined as a score >2 on the Michigan Neuropathy Screening Instrument (MNSI) examination or an MNSI questionnaire score =7.

Patients underwent a single overnight, at-home sleep study with a portable test device. Investigators defined OSA as an apnea hypopnea index (AHI) of five events or more per hour.

Serum nitrotyrosine and plasma lipid peroxide were measured in all patients who consented to providing a blood sample. Microvascular physiology was evaluated by means of laser speckle contrast imaging.

The final analysis included 234 patients. Men accounted for 58 percent of the study population, and the ethnic mix was 55 percent Caucasian and 45 percent South Asian.

Overall, 48 percent of the patients met diagnostic criteria for diabetic peripheral neuropathy, and 65 percent had positive apnea tests, which was mild or moderate in 83 percent of cases.

Patients with sleep apnea tended to be older, have a longer diabetes duration, have higher systolic blood pressure, were more likely obese, and exhibited higher levels of sleepiness on a validated scale.

Of the 151 patients with apnea, 91 (60 percent) had peripheral neuropathy compared with 22 of 83 patients (27 percent) who did not meet diagnostic criteria for OSA.

Patients with OSA had a significantly higher prevalence of foot insensitivity, skin hypersensitivity, and a prior open sore on foot.

Logistic regression analysis demonstrated that OSA had an independent association with neuropathy after adjustment for multiple confounding factors.

Other independent predictors of neuropathy were waist circumference, insulin use, and diabetes duration.

The association with neuropathy remained significant in analyses of mild versus moderate to severe OSA, AHI quartiles, and nadir nocturnal oxygen saturation.

Serum nitrotyrosine and plasma lipid peroxide levels were measured in 73 patients with and 29 without OSA. Nitrotyrosine levels were significantly higher in patients with neuropathy than in those without and in patients with OSA versus those without.

Levels increased in a stepwise fashion from no OSA to mild OSA to moderate/severe OSA.

Lipid peroxide levels were significantly higher in patients with peripheral neuropathy versus those without and in those with OSA versus without.

The associations remained significant after adjustment for age, body mass index, and diabetes duration.

By Charles Bankhead