Double blind placebo controlled trial of vitamins in diabetic patients with peripheral neuropathy of the lower limbs at Muhimbili medical centre, Dar es salaam, Tanzania

Objectives :To determine the blood levels of thiamine in diabetic patients with symptoms of peripheral neuropathy and the response of the symptoms and signs to therapeutic doses of thiamine and vitamin B6. Setting Diabetic outpatient clinic at Muhimbili Medical Centre, Dar es salaam, Tanzania. Patients and study design: Two hundred among 786 consecutive patients attending an outpatient diabetic clinic had symptoms of peripheral neuropathy. One hundred of these were randomly allocated to treatment with therapeutic oral doses of both thiamine and vitamin B6 and the rest were allocated to treatment with an identical placebo. Neither the patients nor the doctor who evaluated the patients knew the treatment the patients were receiving. A standardized questionnaire was filled and a physical examination done in exactly the same way at the first visit and on follow up one month later. The symptoms (pain, numbness or paraesthesia) and the signs (impairment of sensation and ankle reflex) of neuropathy in the legs were graded into none, mild, moderate or severe. Subjects were considered to have improved if on the follow up visit the grade was less than on the first visit. The frequency of intake of some foods reported to have appreciable quantities of the B vitamins was recorded. Blood thiamine levels were measured using HPLC flowmetry, in all patients on the first visit and on the second visit, in 12 treatment and 12 placebo randomly selected patients. Results: The prevalence of peripheral neuropathy among the patients at th e clinic was 23.4% in men and 28.1% in w omen. For all the patients together, the mean (s.d.) blood thiamine levels were only 55 .6 AO (+-20.6) compared with the quoted mean (s.d.) blood level of 63.5 pg/1 (+ -6.5) for normal subjects. The mean (s.d.) blood thiamine levels decreased with increasing severity of symptoms: 64.2 (13.5), 57.7 (22.8) and 52.2 (20.2) pg/l for those with mild, moderate and severe symptoms respectively (analysis of variance, p=0.03). The distribution of patients by symptom severity was more favourable in patients who ate groundnuts at least daily than in those whose frequency of intake was less (21.3, 46.8, and 31.9% versus 11.7, 24.2 and 64.2% with mild, moderate and severe symptoms respectively, p=0.001). However, those who took bread at least daily had more severe symptoms than those who ate bread less frequently(4.8,33.3 and61.9% versus 20.2,28.8 and 51.0% with mild, moderate and severe symptoms respectively, p =0.02). Similarly those who threw away the water in which they boiled their rice had more severe symptoms than those who did not (2.4, 31.7 and 65.9% versus 17.5, 29.1 and 53.4% with mild, moderate and severe symptoms respectively, p=0.05). Four weeks after treatment the blood thiamine levels increased by 86.6 µg/1 in the treatment group (paired t-test t =6.37, p <0.001) but by only 28.3 p.g/1 in the placebo group (paired t-test t=2.97, p=0.013). There was improvement in 88.9% of those whose worst symptom was pain, in 82.5% of those whose worst symptom was numbness and in 89.7% of those whose worst symptom was paraesthesia for those in the vitamin group. Only 36.7% of those in the placebo group improved. Conclusion Diabetic peripheral neuropathy is common among diabetic outpatients in Dar es Salaam and is associated with a high prevalence of nutritional thiamine deficiency. Dietary guidelines for diabetic patients should emphasize a balanced diet and for those with peripheral neuropathy vitamins should be considered.