A pilot study to test the effect of pulsatile insulin infusion on cardiovascular mechanisms that might contribute to attenuation of renal compromise in type 1 diabetes mellitus patients with proteinuria

We hypothesized that correction of insulin deficiency by pulsatile intravenous insulin infusion in type 1 diabetes mellitus patients with nephropathy preserves renal function by mechanisms involving cardiac autonomic function, cardiac mass, or efficiency, or by hemostatic mechanisms. The control group (8 patients) received subcutaneous insulin (3-4 injections per day). The intravenous infusion group (10 patients) received three 1-hour courses of pulsed intravenous insulin infusion on a single day per week in addition to subcutaneous insulin. Laboratory measurements included 2-dimensional Doppler echocardiography, 24-hour ambulatory monitoring with heart rate variation analysis, platelet aggregation and adhesion, plasma fibrinogen, factor VII, von Willebrand factor, fibrinolytic activity, plasminogen activator inhibitor, and viscosity measured at baseline and 12 months. Blood pressure control was maintained preferentially with angiotensin-converting enzyme inhibitors. Ratio of carbon dioxide production to oxygen utilization was measured with each infusion and showed rapid increase from 0.8 to 0.9 (P = .005) at weekly treatments through 12 months. We observed an annualized decrease in creatinine clearance of 9.6 mL/min for controls vs 3.0 mL/min for infusion patients. Annualized fall in blood hemoglobin was 1.9 vs 0.8 g/dL, respectively (P = .013). There were no differences between the control and infusion group with respect to glycohemoglobin, advanced glycated end products, cholesterol, or triglycerides. No differences between the study groups for hemodynamic or hemostatic factors were evident. Blood pressures were not significantly different at baseline or 12 months. We conclude that although preservation of renal function with attenuation of loss of blood hemoglobin during 12 months of intravenous insulin infusion was associated with improvement in the efficiency of fuel oxidation as measured by respiratory quotient, this occurred without differences in metabolic/hemostatic factors, cardiac autonomic function, cardiac wall, or chamber size. Our hypothesis that preservation of renal function in type 1 diabetes mellitus patients with proteinuria by weekly pulsed insulin infusion involves mechanisms from the autonomic nervous system, cardiac size, and function, or elements of hemostasis was not confirmed.