Evaluation of a novel artificial pancreas: closed loop glycemic control system with continuous blood glucose monitoring.

A closed-loop glycemic control system using an artificial pancreas has been applied with many clinical benefits in Japan since 1987. To update this system incorporating user-friendly features, we developed a novel artificial pancreas (STG-55). The purpose of this study was to evaluate STG-55 for device usability, performance of blood glucose measurement, glycemic control characteristics in vivo in animal experiments, and evaluate its clinical feasibility. There are several features for usability improvement based on the design concepts, such as compactness, display monitor, batteries, guidance function, and reduction of the preparation time. All animal study data were compared with a clinically available artificial pancreas system in Japan (control device: STG-22). We examined correlations of both blood glucose levels between two groups (STG-55 vs. control) using Clarke's error grid analysis, and also compared mean glucose infusion rate (GIR) during glucose clamp. The results showed strong correlation in blood glucose concentrations (Pearson's product-moment correlation coefficient: 0.97; n = 1636). Clarke's error grid analysis showed that 98.4% of the data fell in Zones A and B, which represent clinically accurate or benign errors, respectively. The difference in mean GIRs was less than 0.2 mg/kg/min, which was considered not significant. Clinical feasibility study demonstrated sufficient glycemic control maintaining target glucose range between 80 and 110 (mg/dL), and between 140 and 160 without any hypoglycemia. In conclusion, STG-55 was a clinically acceptable artificial pancreas with improved interface and usability. A closed-loop glycemic control system with STG-55 would be a useful tool for surgical and critical patients in intensive care units, as well as diabetic patients.

Characterization and comparison of insulin resistance induced by Cushing Syndrome or diestrus against healthy control dogs as determined by euglycemic- hyperinsulinemic glucose clamp profile glucose infusion rate using an artificial pancreas apparatus.

Euglycemic-hyperinsulinemic glucose clamp (EHGC) method is a gold standard for assessing insulin resistance in humans. However, this method has yet to be commonly used with dogs, due to the requirement of frequent blood sampling for glucose measurement and adjusting glucose infusion rate (GIR). The purpose of this study was to evaluate insulin resistance, induced either by Cushing Syndrome (CS) or diestrus in dogs, as determined by GIR by EHGC, using an artificial pancreas apparatus. Twenty animals were used in this study with ten (7 females and 3 males) serving as healthy controls, four (3 females, 1 male) diagnosed with CS, and six (all females) undergoing diestrus. A higher GIR value indicates increased insulin sensitivity and lower insulin resistance. GIR of healthy control animals was determined to be within a reference range of [10.6-21.3] with a median of 15.2 mg/kg/min. In comparison, the CS group had a median of 5.4 mg/kg/min; whereas the diestrus group exhibited a median of 8.9 mg/kg/min. Insulin resistant animals suffering from CS and undergoing diestrus demonstrated reductions of 65 and 40% in GIR, respectively; thus indicating differences in degree of insulin insensitivity can be discerned using the EHGC method.

Insulin responses to selective arterial calcium infusion under hyperinsulinemic euglycemic glucose clamps: case studies in adult nesidioblastosis and childhood insulinoma.

Selective arterial calcium stimulation and hepatic venous sampling (ASVS) for insulin secretion is used as a diagnostic procedure in patients with insulinomas or adult nesidioblastosis. In some of those patients, severe hypoglycemia requiring urgent glucose administration occurs during the procedure. Such glucose administration, however, may affect the results and damage the validity of the test. We report two cases of hyperinsulinemic hypoglycemia, in which ASVS tests were successfully performed under hyperinsulinemic euglycemic glucose clamps. A 40-year-old male with nesidioblastosis developed continual severe hypoglycemia several years after a Billroth II-Braun gastrectomy, and continuous glucose infusion could not be stopped even during ASVS tests. A 9-year-old girl with an insulinoma that showed atypical hypovascularity on imaging examinations had ASVS tests under a glucose clamp for safety. Hyperinsulinemic (approximately 100 microU/ml) euglycemic (approximately 90 mg/dl) clamps were achieved by an artificial endocrine pancreas. The insulin analogue lispro was utilized for clamps and endogenous insulin was measured with an assay that does not cross-react with the analogue. Diagnostically significant responses (more than twofold) of insulin secretion were observed under hyperinsulinemic clamps in both cases. The use of the hyperinsulinemic glucose clamp technique during the ASVS test should be considered for maintaining the safety of some hypoglycemic patients.