Intensive insulin therapy attenuates renal thiamine mishandling in streptozotocin-induced diabetic rats

Fang Zhang, James Larkin, Lisa Godfrey, Naila Rabbani and Paul J Thornalley

Poster at Diabetes UK Annual Professional Meeting, London, UK (2011)

Diabetic Medicine 28 Supp s1 63. DOI: 10.1111/j.1464-5491.2011.03233.x


Aims: Experimental and clinical diabetes is associated with increased clearance and fractional excretion of thiamine linked to subsequent development of diabetic nephropathy. In this study we investigated if improvement in metabolic control by intensive insulin therapy in experimental diabetes can improve thiamine mishandling by the kidney.

Methods: Diabetes was induced in male Sprague-Dawley rats (300 g) by streptozotocin (55 mg/kg). Diabetic rats with body weight and moderate hyperglycaemia maintained by daily insulin injections (4 U, glargine) were randomised to two groups, diabetic control (DC) and diabetic with intensive therapy (DIT). After 6 weeks the DIT group received intensive therapy by insulin implants (6 U insulin per day). Treatment was continued for a further 6 weeks. A healthy control (NC) group was also studied. Diabetic status was assessed by plasma glucose concentration and glycated haemoglobin HbA1. Renal thiamine mishandling was assessed by renal clearance of thiamine and fractional excretion of thiamine.

Results: Plasma glucose concentration was increased ļ¬vefold in DC and twofold in DIT (P < 0.001); DIT had improved glycaemic control (P < 0.001). Clearance of thiamine increased 71 per cent and fractional excretion of thiamine increased twofold in DC (P < 0.01). DIT reversed this increase in fractional excretion of thiamine by 50 per cent (P < 0.01). For the diabetic groups combined, HbA1 correlated positively with clearance (r = 0.64, P < 0.05; Spearman) and fractional excretion (r = 0.68, P < 0.01) of thiamine.

Conclusion: This indicates that intensive insulin therapy attenuates but does not correct renal thiamine mishandling in streptozotocin-induced diabetic rats.