In a cohort of 234 patients with diabetes, obstructive sleep apnea was independently associated with diabetic peripheral neuropathy, researchers reported.
Obstructive sleep apnea (OSA) is independently associated with diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus, according to Abd Tahrani, MRCP, of the University of Birmingham in the UK, and colleagues. Their study, published online ahead of print June 21 by the American Journal of Respiratory and Critical Care Medicine, also noted correlations between the severity of DPN, the degree of OSA, and the severity of nocturnal hypoxemia in this population.
“OSA is known to be associated with inflammation and oxidative stress, so we hypothesized that it would be associated with peripheral neuropathy in patients with type 2 diabetes mellitus,” Tahrani said. “This is the first report to identify an independent association between OSA and DPN in these patients.”
The investigators performed a cross-sectional study of 234 adults with type 2 diabetes recruited from the diabetes clinic of two hospitals in the UK. DPN was diagnosed if a patient had a Michigan Neuropathy Screening Instrument (MNSI) examination score higher than 2 or an MNSI questionnaire score of 7 or higher. OSA, defined as apnea-hypopnea index (AHI) of five or more events per hour, was assessed through home-based, multi-channel respiratory monitoring. The researchers measured serum nitrotyrosine by enzyme-linked immunosorbent assay and lipid peroxide by spectrophotometry. They performed microvascular assessment by laser speckle contrast imaging in a representative patient subset.
An Independent Association
Of the 234 participants, 58% were men, 55% were white Caucasians, and 45% were South Asians. Their mean age was 57. Within the overall cohort, the prevalence of OSA was 65%. Of the OSA cases, 60% were classified as mild, 23% as moderate, and 17% as severe. The overall prevalence of DPN was 48%.
DPN was present in 60% of patients with OSA and in 27% of those without the condition, and the relationship between OSA and DPN was present irrespective of ethnicity. Patients with OSA were more likely than those without the condition to have foot insensitivity (50% vs 15%), skin hypersensitivity (33% vs 13%), and a previous history of an open foot sore (27% vs 7%). Following adjustment for such possible confounders as ethnicity, sex, age at diabetes diagnosis, diabetes duration, insulin use, BMI, mean arterial pressure, glycated hemoglobin, and alcohol intake, OSA remained independently associated with DPN (odds ratio, 2.82).
The researchers found significant correlations between DPN severity and both OSA and nocturnal hypoxia severity that were independent of age, obesity, diabetes duration, sex, and estimated glomerular filtration rate in the case of AHI. There was a significant trend of higher DPN prevalence with lower nocturnal nadir oxygen saturation. At 60%, 57%, and 62%, DPN prevalence did not differ significantly between patients with mild, moderate, and severe OSA, respectively.
Patients with OSA had higher nitrotyrosine and lipid peroxide levels than those who did not. Nitrotyrosine levels also correlated with both OSA severity and nocturnal hypoxemia measures. Among the 71 patients who received microvascular assessment, those with OSA had a higher prevalence of impaired cutaneous microvascular function.
Nitrosative/oxidative stress and impaired microvascular regulation are possible mechanisms for the association between OSA and diabetic peripheral neuropathy, according to the researchers. “In patients with type 2 diabetes mellitus, OSA may aggravate and amplify glucose toxicity, which has significant implications for tissues which are susceptible to the complications of diabetes,” said Tahrani. The finding that mild OSA is associated with DPN could have implications for the threshold of OSA treatment, as CPAP is not always offered to patients with mild OSA, the researchers noted.
As the study had some limitations, including its cross-sectional design and lack of an intervention arm, additional productive studies are needed to prove causation, they added. “Additional prospective and interventional studies are also needed to examine the role of OSA and intermittent hypoxemia in the development and progression of DPN in patients with both early and advanced diabetes, and to assess the potential impact of CPAP treatment on DPN,” said Tahrani.
Tahrani AA, Ali A, Raymond NT, et al. Obstructive sleep apnea and diabetic neuropathy: a novel association in patients with type 2 diabetes. Am J Respir Crit Care Med. 2012 Jun 21; [Epub ahead of print].