Disease-modifying drugs in the treatment of intermittent claudication in patients with diabetes mellitus: the pilot study
Irina Kuzina, Irina Gurieva, Sergey Smirnov, Inna Begma & Svetlana Kalinchenko
Neuropathy and ischemia play paramount roles in the pathogenesis of diabetic vascular complications. Reduced tissue blood flow in experimental diabetic complications can be corrected by several disease-modifying drugs. Actovegin (deproteinised hemoderivative product) is considered to be a potential agent to stimulate cellular energy metabolism and improve cell function. Testosterone vascular effects can be mediated via increasing cardiac and muscle activity and endothelium dependent vasodilatation.
Pilot open-labeled 8 weeks studies were conducted to evaluate the efficacy of treating diabetic patients with peripheral neuropathy and ischemia with Actovegin (1st trial) and testosterone undecanoate (2nd trial). Twenty-six type 2 patients aged 64.5±2.1 years (HbA1C=7.6±1.2%) with intermittent claudication and sensory-motor neuropathy (Neuropathy Score 14.5±1.2) were enrolled in the 1st study. 8 men aged 46±5.5 years (HbA1C=9.6±2.2%) with androgen deficiency, intermittent claudication and sensory-motor neuropathy (Neuropathy Score 17.5±5.2) are enrolled into 2nd study (ongoing). Two injections of testosterone undecanoate (1000 mg) were performed on the 1st visit and in the 6th week of treatment. Evaluation of peripheral blood flow was determined with toe plethysmography and ultrasound ankle Doppler; sensory and autonomic neuropathy was assessed with battery of tests. Treadmill (Gardner protocol) performed for evaluation of peak walking time (PWT) before study, after 2 weeks, and at the end of study. Both kinds of treatment brought about a progressive increase in the maximum walking time during treadmill test. Relative difference in PWT with Actovegin increased after 8 weeks: relative increase was 95.1%, (absolute increase 435.9±53, 2 s, P<0.01); treatment with testosterone undecanoate increased PWT by 75% (absolute increase 537.9±83, 1 s, P<0.05). Neuropathy Score decreased at termination of both studies.
Conclusion: Treatment over 8 weeks with Actovegin and testosterone undecanoate increased peak walking time and neuropathy score. Efficacy can possibly be improved by increasing the duration of treatment.