Functional and structural abnormalities in the nerves of Type I diabetic baboons: aminoguanidine treatment does not improve nerve function

Aims/hypothesis, To improve understanding of the pathophysiology of diabeti c neuropathy and to establish a primate model for experimental studies, we examined nerve changes in baboons with Type I (insulin-dependent) diabetes mellitus. We also examined the effect of aminoguanidine (an inhibitor of th e formation of advanced glycation end products) on nerve function. Methods. Male baboons (Papio hamadryas) were assigned to four groups; contr ol, diabetic, control and diabetic treated with aminoguanidine. Diabetes wa s induced with streptozotocin (60 mg/kg, intravenous). Insulin and aminogua nidine (10 mg/kg) were injected subcutaneously daily, Motor and sensory ner ve conduction velocity was measured using standard techniques. Autonomic fu nction was examined by measuring heart rate response to positional change. Sural nerve morphometry was analysed in the diabetic group (mean duration 5 .5 years) along with their age-matched controls. Results. The diabetic groups were smaller in size with a mean HbA(1c) of 8. 9 +/- 1.2%. The nerve conduction velocity and heart rate response was reduc ed in the diabetic groups. Morphometric analysis of the diabetic sural nerv e showed smaller axon diameter (2.99 +/- 0.06 mu m vs 3.29 +/- 0.06 mu m; p < 0.01) accompanied by thinner myelin (1.02 +/- 0.02 mu m vs 1.15 +/- 0.02 mu m, p < 0.01) with no change in the axon density. Treatment with aminogu anidine for 3 years had no effect on glycaemic control and did not restore conduction velocity or autonomic dysfunction in the diabetic animals, contr ary to the studies in rats. Conclusions/interpretation. These results show that the primate is a good m odel to study diabetic neuropathy and suggest that the accumulation of adva nced glycation end products are not an early mechanism of nerve damage in t his disorder.