Fully Integrated Artificial Pancreas in Type 1 Diabetes: Modular Closed-Loop Glucose Control Maintains Near Normoglycemia

Integrated closed-loop control (CLC), combining continuous glucose monitoring (CGM) with insulin pump (continuous subcutaneous insulin infusion [CSII]), known as artificial pancreas, can help optimize glycemic control in diabetes. We present a fundamental modular concept for CLC design, illustrated by clinical studies involving 11 adolescents and 27 adults at the Universities of Virginia, Padova, and Montpellier. We tested two modular CLC constructs: standard control to range (sCTR), designed to augment pump plus CGM by preventing extreme glucose excursions; and enhanced control to range (eCTR), designed to truly optimize control within near normoglycemia of 3.9-10 mmol/L. The CLC system was fully integrated using automated data transfer CGM→algorithm→CSII. All studies used randomized crossover design comparing CSII versus CLC during identical 22-h hospitalizations including meals, overnight rest, and 30-min exercise. sCTR increased significantly the time in near normoglycemia from 61 to 74%, simultaneously reducing hypoglycemia 2.7-fold. eCTR improved mean blood glucose from 7.73 to 6.68 mmol/L without increasing hypoglycemia, achieved 97% in near normoglycemia and 77% in tight glycemic control, and reduced variability overnight. In conclusion, sCTR and eCTR represent sequential steps toward automated CLC, preventing extremes (sCTR) and further optimizing control (eCTR). This approach inspires compelling new concepts: modular assembly, sequential deployment, testing, and clinical acceptance of custom-built CLC systems tailored to individual patient needs.     

Effects of Pulsatile Subcutaneous Injections of Insulin Lispro on Plasma Insulin Concentration Levels

Background

Most insulin pumps used for the treatment of diabetes perform subcutaneous insulin injections by pulses. The purpose of this work is to analyze the effects of pulsatile injections of modern insulins on plasma insulin levels compared with a continuous insulin infusion.

Method

We simulate pulsatile implementations of a basal rate profile over a day on a type 1 diabetes mellitus patient using insulin lispro. Pulse periods were varied between 1 and 60 min, and random pump errors were included, modeled as white noise, 1/f noise, or 1/f² noise with relative standard deviations up to 10% of the pump output.

Results

Oscillations in plasma insulin caused by the pulsatile injections were not significant with respect to the global variations for pulse periods below 15 min. This cutoff period was found to be robust to random pump errors with standard deviations up to 10% of the pump output and hence solely determined by the insulin kinetics. Additionally, we showed that the pulse period achieving the best implementation of a continuous profile is an increasing function of the error variance for a given type of noise.

Conclusions

Our findings support that continuous insulin infusion can be implemented by a pulsatile injection of insulin as infrequent as a pulse every 15 min without significant effects on plasma insulin levels. If clinically confirmed, this result would have important consequences on the design and in silico testing of automated insulin treatment strategies, as increased delivery intervals imply higher accuracy of insulin delivery and facilitated implementations of closed-loop control algorithms.     

Anorectal manometric examination in encopretic-constipated children

PURPOSE: We have investigated the use of anorectal manometry to distinguish encopretic-constipated children (n=88) from sibling controls (n=16) and nonsibling controls (n=11). METHODS: Study variables included manometrically determined resting and maximum voluntary anal sphincter pressure, depth and speed of rectoanal inhibitory reflex, minimum rectal volume sensation, critical distending volume for fecal urgency, rectal and anal pressure responses during attempted defecation, and ability to defecate a water-filled balloon. RESULTS: Change in anal sphincter pressure during attempted defecation (P=0.03), gradient between rectal and sphincter pressure during attempted defecation (P=0.02), critical distending volume for fecal urgency (P=0.02), and ability to defecate a water-filled balloon (P=0.05) distinguished encopretic-constipated from control children. The change in rectal pressure associated with the rectoanal inhibitory reflex just escaped significance at P=0.07. CONCLUSIONS: Anal sphincter spasm and megacolon are pathophysiologic abnormalities associated with pediatric constipation-encopresis.     

Pulp revascularization for immature replanted teeth: a case report

Immature avulsed teeth are not usually treated with pulp revascularization because of the possibility of complications. However, this therapy has shown success in the treatment of immature teeth with periapical lesions. This report describes the case of an immature replanted tooth that was successfully treated by pulp revascularization. An 8‐year‐old boy suffered avulsion on his maxillary left lateral incisor. The tooth showed incomplete root development and was replanted after 30 minutes. After diagnosis, revascularization therapy was performed by irrigating the root canal and applying a calcium hydroxide paste and 2% chlorhexidine gel for 21 days. In the second session, the intracanal dressing was removed and a blood clot was stimulated up to the cervical third of the root canal. Mineral trioxide aggregate was placed as a cervical barrier at the entrance of the root canal and the crown was restored. During the follow‐up period, periapical repair, apical closure and calcification in the apical 4 mm of the root canal was observed. An avulsed immature tooth replanted after a brief extra‐alveolar period and maintained in a viable storage medium may be treated with revascularization.