Importance of Early Intervention

At present, researchers believe that pathogenesis of peripheral neuropathy in patients with prediabetes may involve microvascular abnormalities, dyslipidemia, and metabolic syndrome. As a way of monitoring patients with these conditions for peripheral neuropathy, Singleton urges endocrinologists to measure intraepidermal nerve fiber density (IENFD).

“The number of nerve fibers matters,” said Singleton. “Thin nerve fibers seem more vulnerable to injury in prediabetes.”

Early intervention with lifestyle changes involving diet and exercise may be vital to preventing the severity of nerve damage, he said.


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In another study published in 2006 in Diabetes Care, Singleton and his colleagues found that diet and exercise counseling can result in cutaneous reinnervation and improved pain in patients with prediabetes.3 

The study involved 32 patients with prediabetes. The researchers performed 3-mm skin biopsies with measurement of IENFD at the distal leg and proximal thigh at baseline and after 1 year.

Results showed improvements in distal IENFD and proximal IENFD over the 12-month study period. The researchers also found that the change in proximal IENFD correlated with decreased neuropathic pain and a change in sural sensory amplitude.

Available Therapies

“Unfortunately, to date, there are no available treatments to reverse the damage of nerve fibers associated with diabetic neuropathy once established. Intensive treatment of glucose in patients with type 1 diabetes and other risk factors in patients with type 2 diabetes may prevent the development of these complications,” Rodica Busui, MD, PhD, professor of internal medicine, endocrinology, metabolism and diabetes, and co-director of the Neuropathy Center at the University of Michigan in Ann Arbor, said.

Currently, in most cases, clinicians may only treat the symptoms of neuropathy, such as pain, and prescribe alone or in combination gabapentin, pregabalin, fluoxetine and amitriptyline as first-line therapy. 

“Even though in U.S. there are only three agents approved by the FDA to treat neuropathic pain in diabetes, which include pregabalin, duloxetine and tapentadol, which is a narcotic, there are other agents that we know work as well and have a high effectiveness in treating neuropathic pain,” Busui said.