Primary Preventive and Secondary Interventionary Effects of Acetyl-

The abnormalities underlying diabetic neuropathy appear to be multiple and involve metabolic neuronal and vasomediated defects. The accumulation of long-chain fatty acids and impaired b -oxidation due to deficiencies in carnitine and/or its esterified derivatives, such as acetylL -carnitine, may have deleterious effects. In the present study, we examined, in the diabetic bio-breeding Worcester rat, the shortand long-term effects of acetylL -carnitine administration on peripheral nerve polyols, myoinositol, Na 1 /K 1 -ATPase, vasoactive prostaglandins, nerve conduction velocity, and pathologic changes. Short-term prevention (4 mo) with acetylL -carnitine had no effects on nerve polyols, but corrected the Na 1 /K 1 -ATPase defect and was associated with 63% prevention of the nerve conduction defect and complete prevention of structural changes. Long-term prevention (8 mo) and intervention (from 4 to 8 mo) with acetylL carnitine treatment normalized nerve PGE 1 whereas 6-keto PGF 1 a and PGE 2 were unaffected. In the prevention study, the conduction defect was 73% prevented and structural abnormalities attenuated. Intervention with acetylL -carnitine resulted in 76% recovery of the conduction defect and corrected neuropathologic changes characteristic of 4-mo diabetic rats. AcetylL -carnitine treatment promoted nerve fiber regeneration, which was increased two-fold compared to nontreated diabetic rats. These results demonstrate that acetylL -carnitine has a preventive effect on the acute Na 1 / K 1 -ATPase defect and a preventive and corrective effect on PGE 1 in chronically diabetic nerve associated with improvements of nerve conduction velocity and pathologic changes. ( J. Clin. Invest. 1996. 97:1900-1907.)