Kaur, Ravinder Jeet

Background: Automated insulin delivery (AID) systems have proven effective in increasing time-in-range during both clinical trials and real-world use. Further improvements in outcomes for single-hormone (insulin only) AID may be limited by suboptimal insulin delivery settings. Methods: Adults (≥18 years of age) with type 1 diabetes were randomized to either sensor-augmented pump (SAP) (inclusive of predictive low-glucose suspend) or adaptive zone model predictive control AID for 13 weeks, then crossed over to the other arm. Each week, the AID insulin delivery settings were sequentially and automatically updated by an adaptation system running on the study phone. Primary outcome was sensor glucose time-in-range 70–180 mg/dL, with noninferiority in percent time below 54 mg/dL as a hierarchical outcome. Results: Thirty-five participants completed the trial (mean age 39 ± 16 years, HbA1c at enrollment 6.9% ± 1.0%). Mean time-in-range 70–180 mg/dL was 66% with SAP versus 69% with AID (mean adjusted difference +2% [95% confidence interval: −1% to +6%], P = 0.22). Median time <70 mg/dL improved from 3.0% with SAP to 1.6% with AID (−1.5% [−2.4% to −0.5%], P = 0.002). The adaptation system decreased initial basal rates by a median of 4% (−8%, 16%) and increased initial carbohydrate ratios by a median of 45% (32%, 59%) after 13 weeks. Conclusions: Automated adaptation of insulin delivery settings with AID use did not significantly improve time-in-range in this very well-controlled population. Additional study and further refinement of the adaptation system are needed, especially in populations with differing degrees of baseline glycemic control, who may show larger benefits from adaptation.

Background: Pregnancies in type 1 diabetes are high risk, and data in the United States are limited regarding continuous glucose monitoring (CGM)-based hypoglycemia throughout pregnancy while on sensor-augmented insulin pump therapy. Materials and Methods: Pregnant women with type 1 diabetes in the LOIS-P Study (Longitudinal Observation of Insulin use and glucose Sensor metrics in Pregnant women with type 1 diabetes using continuous glucose monitors and insulin pumps) were enrolled before 17 weeks gestation at three U.S. centers and we used their personal insulin pump and a study Dexcom G6 CGM. We analyzed data of 25 pregnant women for CGM hypoglycemia based on international consensus guidelines for percentage time <63 and 54 mg/dL, hypoglycemic events and prolonged hypoglycemia events for 24-h, daytime, and overnight periods, and severe hypoglycemia (SH) episodes. Results: For a 24-h period, biweekly median percentage of time <63 mg/dL ranged from 0.8% at biweek 4–5 to 3.7% at biweek 14–15 with high variability throughout pregnancy. Median percentage of time <63 and 54 mg/dL was higher overnight than daytime ( P < 0.01). Hypoglycemic events occurred throughout the pregnancy, ranged 1–4 events per 2 weeks, significantly decreased after the 20th week, and occurred predominantly during daytime ( P < 0.01). For overnight period, hypoglycemia and events were more concentrated from 12 to 3 am. Seven prolonged hypoglycemia events without any associated SH occurred in four participants (16%), primarily overnight. Three participants experienced a single episode of SH. Conclusions: Our results suggest a higher overall risk of hypoglycemia throughout pregnancy during the overnight period with continued daytime risk of hypoglycemic events in pregnancies complicated by type 1 diabetes.

Objective: Evaluating the feasibility of closed-loop insulin delivery with a zone model predictive control (zone-MPC) algorithm designed for pregnancy complicated by type 1 diabetes (T1D). Research Design and Methods: Pregnant women with T1D from 14 to 32 weeks gestation already using continuous glucose monitor (CGM) augmented pump therapy were enrolled in a 2-day multicenter supervised outpatient study evaluating pregnancy-specific zone-MPC based closed-loop control (CLC) with the interoperable artificial pancreas system (iAPS) running on an unlocked smartphone. Meals and activities were unrestricted. The primary outcome was the CGM percentage of time between 63 and 140 mg/dL compared with participants' 1-week run-in period. Early (2-h) postprandial glucose control was also evaluated. Results: Eleven participants completed the study (age: 30.6 ± 4.1 years; gestational age: 20.7 ± 3.5 weeks; weight: 76.5 ± 15.3 kg; hemoglobin A1c: 5.6% ± 0.5% at enrollment). No serious adverse events occurred. Compared with the 1-week run-in, there was an increased percentage of time in 63–140 mg/dL during supervised CLC (CLC: 81.5%, run-in: 64%, P = 0.007) with less time >140 mg/dL (CLC: 16.5%, run-in: 30.8%, P = 0.029) and time <63 mg/dL (CLC: 2.0%, run-in:5.2%, P = 0.039). There was also less time <54 mg/dL (CLC: 0.7%, run-in:1.6%, P = 0.030) and >180 mg/dL (CLC: 4.9%, run-in: 13.1%, P = 0.032). Overnight glucose control was comparable, except for less time >250 mg/dL (CLC: 0%, run-in:3.9%, P = 0.030) and lower glucose standard deviation (CLC: 23.8 mg/dL, run-in:42.8 mg/dL, P = 0.007) during CLC. Conclusion: In this pilot study, use of the pregnancy-specific zone-MPC was feasible in pregnant women with T1D. Although the duration of our study was short and the number of participants was small, our findings add to the limited data available on the use of CLC systems during pregnancy (NCT04492566).

Background: Automated insulin delivery (AID) systems have not been evaluated in the context of psychological and pharmacological stress in type 1 diabetes. Our objective was to determine glycemic control and insulin use with Zone Model Predictive Control (zone-MPC) AID system enhanced for states of persistent hyperglycemia versus sensor-augmented pump (SAP) during outpatient use, including in-clinic induced stress. Materials and Methods: Randomized, crossover, 2-week trial of zone-MPC AID versus SAP in 14 adults with type 1 diabetes. In each arm, each participant was studied in-clinic with psychological stress induction (Trier Social Stress Test [TSST] and Socially Evaluated Cold Pressor Test [SECPT]), followed by pharmacological stress induction with oral hydrocortisone (total four sessions per participant). The main outcomes were 2-week continuous glucose monitor percent time in range (TIR) 70–180 mg/dL, and glucose and insulin outcomes during and overnight following stress induction. Results: During psychological stress, AID decreased glycemic variability percentage by 13.4% ( P = 0.009). During pharmacological stress, including the following overnight, there were no differences in glucose outcomes and total insulin between AID and physician-assisted SAP. However, with AID total user-requested insulin was lower by 6.9 U ( P = 0.01) for pharmacological stress. Stress induction was validated by changes in heart rate and salivary cortisol levels. During the 2-week AID use, TIR was 74.4% (vs. SAP 63.1%, P = 0.001) and overnight TIR was 78.3% (vs. SAP 63.1%, P = 0.004). There were no adverse events. Conclusions: Zone-MPC AID can reduce glycemic variability and the need for user-requested insulin during pharmacological stress and can improve overall glycemic outcomes. Clinical Trial Identifier NCT04142229.

Abstract Context Hyperglycemia is a common complication of Cushing syndrome (CS). Objective We aimed to determine the impact of curative procedure on hyperglycemia and its management in patients with CS. Methods This retrospective longitudinal cohort study took place 2000 to 2019 in a referral center among adults with endogenous CS and hyperglycemia. Main outcome measures included glycated hemoglobin A1c (HbA1c), intensity of hyperglycemia therapy, and improvement of hyperglycemia. Results In 174 patients with CS (pituitary in 106, ectopic in 25, adrenal in 43), baseline median HbA1c was 6.9% (range, 4.9-13.1), with 41 (24%) patients not on any therapy for hyperglycemia, 93 (52%) on oral medications, and 64 (37%) on insulin (median daily units of 58; range, 10-360). Following CS remission, at the end of follow-up (median 10.5 months), 37 (21%) patients demonstrated resolution of hyperglycemia, 82 (47%) demonstrated improvement, and 55 (32%) had no change or worsening in hyperglycemia. At the end of follow-up, HbA1c decreased by 0.84% (P &lt; .001) and daily insulin dose decreased by a mean of 30 units (P &lt; .001). Biochemical hypercortisolism severity score (severe vs moderate/mild: odds ratio [OR] of 2.4 [95% CI, 1.1-4.9]), and CS subtype (nonadrenal vs adrenal: OR of 2.9 [95% CI, 1.3-6.4]), but not type of hyperglycemia (diabetes vs prediabetes: OR of 2.1 [0.9-4.9]) were associated with hyperglycemia improvement at the end of follow-up. Conclusion Two-thirds of patients with CS and hyperglycemia demonstrate resolution or improvement of hyperglycemia after a curative procedure. Close monitoring during CS recovery is needed to ensure appropriate therapy modification.