Use of Sitagliptin With Closed-Loop Technology to Decrease Postprandial Blood Glucose in Type 1 Diabetes.

BACKGROUND: Postprandial hyperglycemia poses a challenge to closed-loop systems. Dipeptidyl peptidase-4 (DPP-4) inhibitors, like sitagliptin, reduce postprandial glucose concentrations in patients with type 2 diabetes. The objective of this study was to assess sitagliptin's role in type 1 diabetes (T1DM) as an adjunct therapy in reducing postprandial blood glucose with an insulin-only closed-loop system. METHODS: This was a randomized, double-blinded, placebo controlled, crossover design trial. The participants were18-35 years old, had T1DM, and an HbA1c of ≤ 8.5%. A dose determination study included eight subjects with T1DM. There were three study visits. Four hours after receiving study drug (placebo, sitagliptin 50 mg, sitagliptin 100 mg), subjects underwent a mixed meal tolerance test with assessment of hormone concentrations. In a second study, 15 subjects underwent two visits receiving either placebo or 100 mg of sitagliptin plus an insulin only closed-loop system for 25 hours with timed meals. Blood glucose and other hormone concentrations were analyzed using repeated measures ANOVA. RESULTS: For the dose determination study, sitagliptin 100 mg resulted in reduced postprandial blood glucose ( P = .006). For the closed-loop study, glucose concentrations were lower in the treatment group, most prominently during the first two study meals ( P = .03). There was no difference in glucagon concentrations, but insulin concentrations and insulin delivery were lower in the treatment group. CONCLUSIONS: Sitagliptin may be considered as an adjunct therapy in a closed-loop setting. Larger studies are needed to determine the role of oral agents like sitagliptin to lower postprandial hyperglycemia with closed loop.

Adjuvant Liraglutide and Insulin Versus Insulin Monotherapy in the Closed-Loop System in Type 1 Diabetes: A Randomized Open-Labeled Crossover Design Trial.

BACKGROUND: The closed-loop (CL) system delivers insulin in a glucose-responsive manner and optimal postprandial glycemic control is difficult to achieve with the algorithm and insulin available. We hypothesized that adjunctive therapy with liraglutide, a once-daily glucagon-like peptide-1 agonist, would be more effective in normalizing postprandial hyperglycemia versus insulin monotherapy in the CL system, in patients with type 1 diabetes. METHODS: This was a randomized, controlled, open-label, crossover design trial comparing insulin monotherapy versus adjuvant subcutaneous liraglutide 1.2 mg and insulin, using the CL system in 15 patients. Blood glucose (BG), insulin, and glucagon concentrations were analyzed. RESULTS: The liraglutide arm was associated with overall decreased mean BG levels (P = .0002). The average BG levels from 8:00 pm (day 1) to 9:00 pm (day 2) were lower in the liraglutide arm (144.6 ± 36.31 vs 159.7 ± 50.88 mg/dl respectively; P = .0002). Two-hour postbreakfast and lunch BG profiles were better in the liraglutide arm (P < .05) and the insulin and glucagon assay values were lower (P < .0001). Postprandially, the area under the curve (AUC) for 2-hour postbreakfast and lunch BG levels were significant (P = .01, P = .03) and the AUC for glucagon, postbreakfast (P < .0001) and lunch (P < .05), was also significant. The incidence of hypoglycemia did not differ between arms (P = .83, Fisher's exact test). Overall, adjunct liraglutide therapy plus CL was well tolerated even with expected side effects. CONCLUSION: This is a proof-of-concept study showing liraglutide can be a potential adjunctive therapy in addition to CL with insulin to reduce postprandial hyperglycemia in type 1 diabetes.

Evaluating emergency preparedness and impact of a hurricane sandy in pediatric patients with diabetes.

BACKGROUND: Natural disasters have always been associated with significant adverse events including medical and mental health problems. Children with chronic disease such has diabetes have also been believed to be affected to a greater extent by any natural disaster. The purpose of this study was to assess and compare emergency preparedness post-disaster and post-traumatic stress effects of Hurricane Sandy in affected and relatively unaffected populations. METHODS: The study was conducted between February and July 2013. A total of 142 families caring for children with Type 1 Diabetes Mellitus (T1DM) who attended clinics were recruited from hospitals in Bronx, NY (control) and in NJ (affected) by Hurricane Sandy. Subjects were recruited to participate in a survey 3-6 months after the hurricane. Data on demographics, glycemic control and insulin regimens were collected. Families were surveyed for socio-economic status (SES), using Hollingshead questionnaire, general and diabetes preparedness and the Hurricane Related Traumatic Experiences (HURTE) questionnaire was used to evaluate for symptoms of post-traumatic stress. RESULTS: Ninety-five percent of families reported to be generally well to moderately prepared for the hurricane and 83 % reported to be very well prepared with regards to their child's diabetes during the disaster. There was no difference between the sites for preparedness for the disaster, age or gender. There was a trend toward significance (p < 0.06) in New Jersey subjects as to a greater psychological impact from the hurricane. Poor glycemic control was significantly associated with lower SES (p < 0.008). Most importantly, SES was unrelated to preparedness for diabetes management during the hurricane. CONCLUSIONS: Despite low SES, families were generally well to moderately prepared for hurricane. In children with diabetes, interventional studies should be designed and implemented so that glycemic control remains unaffected, following any major disaster.

Pediatric Type 1 Diabetes: Reducing Admission Rates for Diabetes Ketoacidosis.

BACKGROUND: Diabetes ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM). Reducing DKA admissions in children with T1DM requires a coordinated, comprehensive management plan. We aimed to decrease DKA admissions, 30-day readmissions, and length of stay (LOS) for DKA admissions. METHODS: A multipronged intervention was designed in 2011 to reach all patients: (1) increase insulin pump use and basal-bolus regimen versus sliding scales, (2) transform educational program, (3) increased access to medical providers, and (4) support for patients and families. A before-after study was conducted comparing performance outcomes in years 2007-2010 (preintervention) to 2012-2014 (postintervention) using administrative data and Wilcoxon rank sum and Fischer exact tests. RESULTS: DKA admissions decreased by 44% postintervention (16.7 vs 9.3 per 100 followed patient-years; P = .006), unique patient 30-day readmissions decreased from 20% to 5% postintervention (P = .001), and median LOS significantly decreased postintervention (P < .0001). Although not an original goal of the study, median hemoglobin A1C of a subset of the population transitioned from sliding scale decreased, 10.3% to 8.9% (P < .02). CONCLUSIONS: When clinical and widespread program interventions were used, significant reductions in DKA hospitalizations, 30-day readmissions, and LOS occurred for pediatric T1DM. Continuous performance improvement efforts are needed for improving DKA outcomes.