Peripheral neuropathy, with or without diabetes, is associated with increased mortality

 

Following the progressive increase in cases of obesity and diabetes, the incidence of peripheral neuropathy has also grown over the years, so much that it has become the most common cause of this neurological pathology in developed countries.

Although peripheral neuropathy is usually considered to be a complication of diabetes, there are a variety of pathogenetically heterogeneous disorders that can lead to impairment of the peripheral nervous system. These include amyloidosis, some vitamin deficiencies, dyslipidemias, alcohol abuse, autoimmune and infectious diseases, as well as exposure to some toxins and chemotherapy.

Different studies have shown that the combination of these diseases can worsen the manifestations of diabetic peripheral neuropathy. An effect that is more pronounced when metabolic and non-metabolic pathologies are associated and lead to cumulative damage.

In diabetic subjects, the diagnosis of peripheral neuropathy is considered an unfavorable prognostic index, but a recent study, published in the Annals of Internal Medicine, showed that its occurrence was common in the general population and independently associated with mortality, even in the absence of diabetes.

In this new prospective, cohort study, the researchers evaluated the associations of peripheral neuropathy with all-cause and cardiovascular mortality in the adult population of United States.

More than 7,000 adults aged 40 years and over were included. All of them were previously enrolled in the National Health and Nutrition Examination Survey and underwent a monofilament test.

This test has consisted in placing the tip of a special standardized nylon filament, mounted on a plastic handle, by applying light pressure to the base of each foot on 3 sites. If the participant’s first response at one site was correct, the test was not repeated at that site. If the participant was unable to correctly identify where pressure was applied, the test was repeated a maximum of three times per site, until two similar responses were obtained. A site was defined with impaired sensitivity if the participant had provided two incorrect or indeterminable answers for that site. Peripheral neuropathy was defined by the presence of at least one affected site on both feet.

The results of the study evidenced that the overall prevalence of peripheral neuropathy in the population studied was 13.5%. As expected, the higher number of cases was found among diabetic patients compared to non-diabetic patients.

During a median follow-up of 13 years, all-cause mortality rates in patients with peripheral neuropathy were 57.6 in adults with diabetes and 34.3 in non-diabetic adults. In diabetic and nondiabetic patients without peripheral neuropathy, the rates were 27.1 and 13, respectively.

In the adjusted analysis models, in participants with diabetes, peripheral neuropathy was associated with all-cause mortality with a hazard ratio of 1.49 and with cardiovascular mortality with a hazard ratio of 1.66.

The authors admit that the cause of peripheral neuropathy in the absence of diabetes is unclear, albeit in some cases could be linked to the presence of impaired glucose tolerance or a state of prediabetes. However, they found a persistent association between peripheral neuropathy and all-cause mortality among adults with normal blood glucose values.

Although it may seem rather limiting to base the diagnosis of peripheral neuropathy on the monofilament test alone, the results of this study are noteworthy. An increase in overall mortality of about 50% in diabetic patients is certainly impressive. However, perhaps even more impressive is the almost 30% increase in risk in non-diabetic subjects.

The researchers point out that adults with peripheral neuropathy had elevated levels of high-sensitive cardiac troponin T, brain natriuretic peptide, and renal biomarkers, suggesting that the presence of an alteration in nerve pathways may reflect the presence of a systemic subclinical microvascular disease.

The authors conclude that the prevalence of peripheral neuropathy is substantial in the population of United States, even among adults without diabetes, and that this disease is independently associated with mortality.

A significant association even in people without diabetes and which is confirmed regardless of the classic cardiovascular risk factors. Based on these results, they propose to consider decreased foot sensitivity as a risk factor for death in the general population.

This post is also available in: Chinese (Simplified)

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