Clinical Briefs

By Louis Kuritzky, MD

Acetyl-L-Carnitine Improves Pain, Nerve Regeneration, and Vibratory Perception in Diabetes Patients

Diabetic peripheral neuropathy (DPN), with or without diabetic peripheral neuropathic pain (DPNP), is a commonplace and consequential complication of diabetes (DM). Treatment of DPNP has been enhanced by the recent FDA approval of duloxetine and pregabalin, but clinicians desire a broad range of therapies. Good control of DM has been shown to reduce progression of neuropathy, but other convincing preventative tools are lacking.

DM patients have been shown to be deficient in acetyl-L-carnitine (ALC), which may be etiologic in development of DPN. Animal data confirm preventative and therapeutic effects of ALC, including favorable impact upon generation of nitric oxide, lipid peroxidation, and prostaglandins.

To evaluate the potential clinical role of ALC, 2 identical one-year, double-blind, placebo-controlled studies were undertaken (total n = 1348). Study subjects underwent sural nerve biopsy, nerve conduction study, scoring of vibration sense, and symptom scores. Ranked symptoms included pain, numbness, paresthesias, weakness, postural dizziness, dyshidrosis, GI problems, and sexual dysfunction.

Sural nerve biopsy showed positive effects, although nerve conduction velocity and amplitude did not improve. Vibration sense was improved, and pain was reduced in subjects receiving 1000 mg t.i.d. No patient discontinued ALC due to adverse effects. ALC shows promise as a therapeutic tool for diabetic peripheral neuropathy.

Sima AF, et al. Diabetes Care. 2005; 28:96-101.

Levodopa and the Progression of Parkinson’s Disease

Levodopa (LDPA) has proven a very valuable treatment for Parkinson’s disease (PAR). Since PAR is characterized by a progressive decline in production of dopamine due to degeneration of the substantia nigra, it is pathophysiologically attractive to consider replacing insufficient dopamine by means of LDPA. Some concern has existed about whether LDPA treatment might actually accelerate decline in neurons of the substantia nigra. To address this question, the Parkinson Study Group enlisted patients with early PAR (n = 361) for randomization in a placebo controlled trial.

Subjects underwent daily treatment with carbidopa-levodopa at doses from 37.5/150 mg to 150/600 mg for 40 weeks, after which there was a 2-week withdrawal. No other anti-Parkinsonian medications were permitted during the trial. Symptoms and signs of PAR were assessed, as well as SPECT imaging to monitor the status of substantia nigra functionality.

As would be expected, PAR symptom severity was greater in patients treated with placebo than LDPA. SPECT data indicated a decrease in activity of the nigrostriatal dopamine nerve terminals, suggesting acceleration of the decline in CNS dopamine productivity (although a medication-induced alteration of the dopamine transporter could not be ruled out).

These contrasting end points leave the issue of whether LDPA treatment alters disease progress unsettled. Despite convincing evidence for favorable effects upon signs and symptoms, the underlying pathology may be unaffected, or possibly even worsened.

The Parkinson Study Group. N Engl J Med. 2004;351:2498-2508.

Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 years after Bariatric Surgery

The long-term consequences of obesity include increased cardiovascular disease (CVD), diabetes (DM), and dyslipidemia. Although surgical interventions have provided meaningful short-term reductions in BMI and surrogate markers of cardiovascular risk, little is known about long-term impact.

This prospective study compared outcomes in subjects (n = 851) surgically treated for obesity (gastric banding, banded gastroplasty, or gastric bypass) with matched obese controls (n = 852) treated with conservative management such as lifestyle changes. Study groups did not differ meaningfully at baseline for cardiovascular risk profile. In addition to BMI, end points included mortality, incidence of diabetes, hypertriglyceridemia, and hyperuricemia.

Gastric bypass produced the greatest degree of weight loss amongst the surgical procedures; overall at 2 years, the conservative management group had experienced no statistically significant weight loss, compared to a 23.4% decrease in the surgery group. Perisurgical mortality was 0.25%. Incident hypetriglyceridemia, DM, and hyperuricemia were lower in the surgery group. Similarly, improvement in pre-existing hypertension and DM were greater amongst patients treated surgically. Differences in mortality at 10 years were not specified, but were not sufficient to merit early study closure (either due to perceived benefit or harm). The balance of long-term effects of bariatric surgery appears favorable.

Sjostrom L, et al N Engl J Med. 2004;351:2683-2693.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.