Effect of insulin analogs on the decline of hemoglobin in diabetic patients with nephropathy

Decrease of hemoglobin occurs in diabetic patients with nephropathy earlier than in nondiabetic patients, probably due to impaired synthesis of erythropoietin (EPO). Apart from EPO, insulin also stimulates erythropoiesis. We investigate whether there are differences between human insulin and insulin analogs in respect of their erythropoiesis stimulating effect.

Hemoglobin concentration and other factors which may influence hemoglobin levels were analyzed retrospectively in 203 type 1 diabetic patients with various degrees of kidney function. Eighty-six patients were treated with human insulin and 117 patients received an insulin analog.

Hemoglobin concentration did not differ in patients with normal renal function (creatinine clearance (CCL) >90 ml/min) treated with human insulin or insulin analogs. In patients with impaired renal function (CCL<90 ml/min) there was a significant decrease of hemoglobin with declining kidney function in patients treated with human insulin (r=0.463; p<0.003) but not in patients treated with insulin analog (r=-0.12; p=0.4). This result remained significant after adjustment of multiple potential confounders such as age, gender, diabetes duration, BMI, metabolic control, kidney function, chronic inflammation or use of ACE-inhibitors or AT1-blockers.

Insulin analogs mitigate the decline of hemoglobin in diabetic patients with impaired renal function. This might be due to a stimulating effect of insulin analogs on erythropoiesis via IGF receptor or a sustained activation of the insulin receptor.