APOE Genotype Identified As Risk Factor for Diabetic Peripheral Neuropathy

MARCH 2003 - ST. PAUL, MN -- A cross-sectional study has convinced some researchers that the APOE genotype is a risk factor for diabetic neuropathy severity equal to having 15 extra years of age or diabetes duration. The study, led by Richard S. Bedlack, MD, Phd, of Duke University Medical Center in Durham, North Carolina, is reported in the March 25 issue of Neurology, the scientific journal of the American Academy of Neurology.

Patients with APOE 3/4 and 4/4 genotypes scored three points higher on the Neuropathy Impairment Score in the Lower Limbs (NISLL) than patients with other genotypes.

Patients were enrolled in the study from the diabetes clinic at Northeast Medical Center in Concord, North Carolina. The study took into account the patient's age, duration of diabetes, most recent and highest recorded hemoglobin, most recent and highest recorded triglycerides, and presence of the APOE gene.

"Interventions that prevent diabetic peripheral neuropathy (DPN) and its complications have been identified but are under-utilized," said Bedlack. "For example, tight control of blood sugar levels delays or prevents DPN. However, even 10 years after this finding was reported, only about 35 percent of patients achieve preferred blood sugar levels."

Bedlack believes the solution to the problem may lie in biomarkers that identify risk for DPN. "Biomarkers present at the time diabetes is diagnosed - such as the APOE 3/4 or 4/4 genotypes, which predict a higher risk for DPN - might be useful in that they would direct intensive interventions to the diabetic patients that need them most."

Limitations to the study were that the patients were seeking care at a comprehensive diabetes clinic and their glycemic and triglycerides may have been under better control and more uniform than the general population of patients with diabetes. Further, the study looked at only two APOE groups: those with E 3/4 and 4/4 genotypes and those with "everything else." The study was not able to ascertain whether the effect of DPN was the result of a harmful allele (such as E4) or a protective allele (such as E2) in the "other" groups. Only APOE genotypes were considered. There may be other genotypes for predicting neuropathy, Bedlack said.

Approximately 50 percent of patients with diabetes develop peripheral neuropathy in their lifetimes. Diabetic patients with peripheral neuropathy are at increased risk for foot ulcers, amputations, Charcot joints, intractable pain, impotence, and silent myocardial infarction.

Source: American Academy of Neurology