Standardized modulation of the injection site allows for insulin dose reduction without deterioration of metabolic control.

OBJECTIVES: Use of an injection site modulation device (InsuPad) in intensive insulin treatment reduces frequency of hypoglycemia and prandial insulin requirements by enhancing subcutaneous microcirculation. This meal tolerance test (MTT) investigation was performed as a sub-study during the real-world BARMER study to demonstrate non-inferiority of the reduced insulin doses observed in this study with respect to metabolic control. METHODS: The MTT was performed at baseline and after 3 months in insulin treated diabetes patients using the modulation device vs. a control group without device. The dose used for the MTT was individually calculated based on the prandial insulin records from the patient diaries before the test. Blood was drawn for determination of glucose, insulin, C-peptide, proinsulin, triglycerides, free fatty acids, nitrotyrosine, and asymmetric dimethyl-arginine (ADMA) at multiple time-points from 0 to 300 min. A total of 32 patients from one site were included into this MTT study (8 female, 7 type 1 diabetes, age: 49.9 ± 12.5 yrs, HbA1c: 7.2 ± 0.5%). RESULTS: During the BARMER study, mean HbA1c was treated to target (<6.5%) in both groups. The prandial insulin dose decreased in the MTT modulation device group by -17.1%, but remained unchanged in the control group (-0.1%, p < 0.001). No change was seen for the basal insulin dose in both treatment arms. There were no differences between the groups with respect to the postprandial curves for glucose, C-peptide, intact proinsulin, free fatty acids, and triglycerides. Insulin absorption was faster with the modulation device (Tmax: 60 ± 28 min vs. 99 ± 46 min, p < 0.05). Key limitations are the small patient sample size and impossibility to determine the short-term effects of device use. CONCLUSIONS: The results of this meal tolerance sub-study confirm that the observed prandial insulin dose reduction when using the injection site modulation device has no negative impact on postprandial metabolism.

Three dimensional numerical modeling of multiphase flow and transport.

The coupled multiphase flow and transport problem is solved by the finite element method, using linear three-dimensional tetraeder elements. The three-phase flow problem is solved simultaneously for the fluid pressures. The strong nonlinearities are treated with a Newton-Raphson iteration scheme with relaxation. Due to the kinetic of interphase mass transfer and reactions, the equations for water, gas, and solid phase concentrations are strongly coupled. Therefore, both transport equations for water and gas are solved simultaneously, while the equation for the solid phase is solved directly. The numerical model was tested with analytical, quasi-analytical and other numerical models. After the verification first applications were performed.