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A one-time algorithmic adjustment of open-loop settings did not alter glucose control in a relatively short duration outpatient closed-loop study. The CLC system proved very robust and adaptable, with minimal (<2%) time spent in the hypoglycemic range in either arm.

OBJECTIVEArtificial pancreas (AP) systems are best positioned for optimal treatment of type 1 diabetes (T1D) and are currently being tested in outpatient clinical trials. Our consortium developed and tested a novel adaptive AP in an outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks.RESEARCH DESIGN AND METHODSThirty adults with T1D completed a continuous glucose monitor (CGM)-augmented 1-week sensor-augmented pump (SAP) period. After the AP was started, basal insulin delivery settings used by the AP for initialization were adapted weekly, and carbohydrate ratios were adapted every 4 weeks by an algorithm running on a cloud-based server, with automatic data upload from devices. Adaptations were reviewed by expert study clinicians and patients. The primary end point was change in hemoglobin A1c (HbA1c). Outcomes are reported adhering to consensus recommendations on reporting of AP trials.RESULTSTwenty-nine patients completed the trial. HbA1c, 7.0 ± 0.8% at the start of AP use, improved to 6.7 ± 0.6% after 12 weeks (−0.3, 95% CI −0.5 to −0.2, P < 0.001). Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved during the day from 5.0 to 1.9% (−3.1, 95% CI −4.1 to −2.1, P < 0.001) and overnight from 4.1 to 1.1% (−3.1, 95% CI −4.2 to −1.9, P < 0.001). Whereas carbohydrate ratios were adapted to a larger extent initially with minimal changes thereafter, basal insulin was adapted throughout. Approximately 10% of adaptation recommendations were manually overridden. There were no protocol-related serious adverse events.CONCLUSIONSUse of our novel adaptive AP yielded significant reductions in HbA1c and hypoglycemia.

-To determine the effects of exercise on postprandial glucose metabolism and insulin action in type 1 diabetes (T1D), we applied the triple tracer technique to study 16 T1D subjects on insulin pump therapy before, during, and after 75 min of moderate-intensity exercise (50% V O2max) that started 120 min after a mixed meal containing 75 g of labeled glucose. Prandial insulin bolus was administered as per each subject's customary insulin/carbohydrate ratio adjusted for meal time meter glucose and the level of physical activity. Basal insulin infusion rates were not altered. There were no episodes of hypoglycemia during the study. Plasma dopamine and norepinephrine concentrations rose during exercise. During exercise, rates of endogenous glucose production rose rapidly to baseline levels despite high circulating insulin and glucose concentrations. Interestingly, plasma insulin concentrations increased during exercise despite no changes in insulin pump infusion rates, implying increased mobilization of insulin from subcutaneous depots. Glucagon concentrations rose before and during exercise. Therapeutic approaches for T1D management during exercise will need to account for its effects on glucose turnover, insulin mobilization, glucagon, and sympathetic response and possibly other blood-borne feedback and afferent reflex mechanisms to improve both hypoglycemia and hyperglycemia. exercise; postprandial glucose kinetics; insulin mobilization EXERCISE INCREASES PERIPHERAL GLUCOSE UPTAKE [rate of glucose disappearance (R d )] via insulin-dependent and -independent mechanisms. Simultaneously, rates of endogenous glucose production (EGP) increase to minimize risks of hypoglycemia (5, 9, 31, 33). These changes in glucose fluxes are facilitated by falling insulin and rising glucagon and catecholamine (34) concentrations in plasma together with emerging roles for potential blood-borne feedback and afferent reflex mechanisms in stimulating glucose rate of appearance (R a ) (6,18,19) and pancreatic islet hormone secretion (24).However, the increment in EGP may not sufficiently compensate for the increase in glucose disposal, thus predisposing to exercise-induced hypoglycemia in type 1 diabetes (T1D) (27). This could, at least in part, be due to impaired glucagon and/or catecholamine secretion and responsiveness because of concomitant dysfunction of ␣-cell or autonomic systems, respectively, that often afflicts patients with T1D (8, 17). Furthermore, the increase in insulin sensitivity can persist for several hours after cessation of exercise, according to a study in rats (14), hence, further predisposing individuals with T1D to delayed hypoglycemia (20,22). Although there have been numerous reports (11,12,25) evaluating glucose kinetics during and after exercise in individuals without diabetes, a comprehensive assessment of glucose turnover during and immediately after exercise applying state-of-the-art isotope dilution techniques has, to the best of our knowledge, not been conducted in individuals with T1D. In this context, in...

Assess the efficacy of inControl AP, a mobile closed-loop control (CLC) system. RESEARCH DESIGN AND METHODSThis protocol, NCT02985866, is a 3-month parallel-group, multicenter, randomized unblinded trial designed to compare mobile CLC with sensor-augmented pump (SAP) therapy. Eligibility criteria were type 1 diabetes for at least 1 year, use of insulin pumps for at least 6 months, age ‡14 years, and baseline HbA 1c <10.5% (91 mmol/mol). The study was designed to assess two coprimary outcomes: superiority of CLC over SAP in continuous glucose monitor (CGM)-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L. RESULTSBetween November 2017 and May 2018, 127 participants were randomly assigned 1:1 to CLC (n 5 65) versus SAP (n 5 62); 125 participants completed the study. CGM time below 3.9 mmol/L was 5.0% at baseline and 2.4% during follow-up in the CLC group vs. 4.7% and 4.0%, respectively, in the SAP group (mean difference 21.7% [95% CI 22.4, 21.0]; P < 0.0001 for superiority). CGM time above 10 mmol/L was 40% at baseline and 34% during follow-up in the CLC group vs. 43% and 39%, respectively, in the SAP group (mean difference 23.0% [95% CI 26.1, 0.1]; P < 0.0001 for noninferiority). One severe hypoglycemic event occurred in the CLC group, which was unrelated to the study device. CONCLUSIONSIn meeting its coprimary end points, superiority of CLC over SAP in CGM-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L, the study has demonstrated that mobile CLC is feasible and could offer certain usability advantages over embedded systems, provided the connectivity between system components is stable.People with type 1 diabetes face a life-long optimization problem: limiting their exposure to hyperglycemia while simultaneously avoiding hypoglycemia (1). Classic studies have shown that many complications from diabetes are predicted by average glycemia, typically assessed by hemoglobin A 1c (HbA 1c ), and can be reduced with intensive insulin therapy (2,3); however, the risk for hypoglycemia remains the primary barrier to optimal glycemic control (1). At present, closed-loop control (CLC), known as the artificial pancreas, offers the best solution to this optimization problem: day-and-night real-time fine-tuning of insulin delivery by an automated system.In the past few years, the volume of CLC clinical trials increased dramatically. In 2018, the National Library of Medicine included 132 publications in the CLC field, and in the first 6 weeks of 2019 alone, 25 new articles were published. Research results are

Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.

Overnight-only CLC increased the time in the target range over 24 hours and decreased the time in hypoglycemic range over 24 hours in a supervised outpatient setting. A pilot extension study at home showed a similar nonsignificant trend.

Background: Current therapy for Type 1 diabetes (T1D) is characterized by significant glucose variability (GV). Pancreas transplantation (PT) is performed in certain T1D patients with and without end-stage renal disease. To date, GV has been examined to a limited extent after PT. Methods:We investigated GV using continuous glucose monitoring (CGM) 3-6 weeks after PT. Results: Eleven patients had simultaneous kidney pancreas transplantation (SPK),nine pancreas after kidney (PAK), and six pancreas transplantation alone (PTA). Mean CGM showed no difference between SPK, 126.5 ± 13.9, PAK 119.9 ± 12.8, and PTA 131.1 ± 29 mg/dL (P value .6). Percentage of time in range (TIR, 70-180 mg/dL) was 92% for SPK, 93.4% in PAK, and 88.5% in PTA with only 0.3%, 1.5%, and 0.3% of time <70 mg/dL. Percentage >180 mg/dL was 7.9% for SPK, 4.9% PAK, and 11% in PTA. Other measures of GV were similar in the three cohorts. In six patients, CGM was performed before and after PT and improved significantly. GV was also better compared with a matched cohort of T1D patients. Conclusions: All 3 types of PT resulted in excellent glucose control 3-6 weeks postprocedure. CGM outcomes represent an important objective outcome after PT. K E Y W O R D S continuous glucose monitor, glycemic variability, hyperglycemia and hypoglycemia, pancreas transplantation, Type 1 diabetes S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Dadlani V, Kaur RJ, Stegall M, et al. Continuous glucose monitoring to assess glycemic control in the first 6 weeks after pancreas transplantation. Clin