[Diabetic nephropathy: oral anti-diabetic agents or insulin?]

Diabetic nephropathy is a microvascular complication, as well as retinopathy and neuropathy of type 1 and type 2 diabetes mellitus. The pathogenesis directly correlates with hyperglycemia. The direct glucose toxicity, hypercoagulability, oxidative stress and endothelial dysfunctions play a role. Strict glycemic control with HbA1c levels <7% for 10 yrs is associated with a 25% microvascular end point reduction. Patients underwent pancreas transplantation, and after 10 yrs the present nephropathy and functional and structural abnormalities have regressed. Diabetic nephropathy alters the pharmacokinetic profile of almost all oral anti-diabetic agents, as well as insulin metabolism; therefore, it is imperative to determine creatinine clearance. Renal failure requires insulin therapy. Incipient diabetic nephropathy allows very limited indications to oral anti-diabetic agents because of the altered pharmacokinetic profile and side effects (hypoglycemia with secretagogues agents, lactic-acidosis with metformin and other biguanides, and hydric retention and weight gain with thiazolidinediones). Moreover, oral anti-diabetic agents reduce the percentage of HbA1c by no more than 1.5%. Insulin therapy is preferred, with a dose reduction when creatinine clearance is <60 mL/m. To control better the post-prandial glycemic peak, it is useful to use bolus insulin analogues at each meal and basal intermediate-acting insulin at bedtime to mimic the natural insulin patterns as far as possible.