This study evaluated a new insulin delivery system designed to reduce insulin delivery when trends in continuous glucose monitoring (CGM) glucose concentrations predict future hypoglycemia.
...Individuals with type 1 diabetes (
= 103, age 6-72 years, mean HbA
7.3% 56 mmol/mol) participated in a 6-week randomized crossover trial to evaluate the efficacy and safety of a Tandem Diabetes Care t:slim X2 pump with Basal-IQ integrated with a Dexcom G5 sensor and a predictive low-glucose suspend algorithm (PLGS) compared with sensor-augmented pump (SAP) therapy. The primary outcome was CGM-measured time <70 mg/dL.
Both study periods were completed by 99% of participants; median CGM usage exceeded 90% in both arms. Median time <70 mg/dL was reduced from 3.6% at baseline to 2.6% during the 3-week period in the PLGS arm compared with 3.2% in the SAP arm (difference PLGS - SAP = -0.8%, 95% CI -1.1 to -0.5,
< 0.001). The corresponding mean values were 4.4%, 3.1%, and 4.5%, respectively, represent-ing a 31% reduction in the time <70 mg/dL with PLGS. There was no increase in mean glucose concentration (159 vs. 159 mg/dL,
= 0.40) or percentage of time spent >180 mg/dL (32% vs. 33%,
= 0.12). One severe hypoglycemic event occurred in the SAP arm and none in the PLGS arm. Mean pump suspension time was 104 min/day.
The Tandem Diabetes Care Basal-IQ PLGS system significantly reduced hypoglycemia without rebound hyperglycemia, indicating that the system can benefit adults and youth with type 1 diabetes in improving glycemic control.
Target trial emulation applies design principles from randomised controlled trials to the analysis of observational data for causal inference and is increasingly used within human epidemiology. ...Veterinary electronic clinical records represent a potentially valuable source of information to estimate real-world causal effects for companion animal species. This study employed the target trial framework to evaluate the usefulness on veterinary observational data. Acute diarrhoea in dogs was used as a clinical exemplar. Inclusion required dogs aged ≥ 3 months and < 10 years, presenting for veterinary primary care with acute diarrhoea during 2019. Treatment strategies were: 1. antimicrobial prescription compared to no antimicrobial prescription and 2. gastrointestinal nutraceutical prescription compared to no gastrointestinal nutraceutical prescription. The primary outcome was clinical resolution (defined as no revisit with ongoing diarrhoea within 30 days from the date of first presentation). Informed from a directed acyclic graph, data on the following covariates were collected: age, breed, bodyweight, insurance status, comorbidities, vomiting, reduced appetite, haematochezia, pyrexia, duration, additional treatment prescription and veterinary group. Inverse probability of treatment weighting was used to balance covariates between the treatment groups for each of the two target trials. The risk difference (RD) of 0.4% (95% CI -4.5% to 5.3%) was non-significant for clinical resolution in dogs treated with antimicrobials compared with dogs not treated with antimicrobials. The risk difference (RD) of 0.3% (95% CI -4.5% to 5.0%) was non-significant for clinical resolution in dogs treated with gastrointestinal nutraceuticals compared with dogs not treated with gastrointestinal nutraceuticals. This study successfully applied the target trial framework to veterinary observational data. The findings show that antimicrobial or gastrointestinal prescription at first presentation of acute diarrhoea in dogs causes no difference in clinical resolution. The findings support the recommendation for veterinary professionals to limit antimicrobial use for acute diarrhoea in dogs.
There are no commercially available hybrid closed-loop insulin delivery systems customized to achieve pregnancy-specific glucose targets in the U.S. This study aimed to evaluate the feasibility and ...performance of at-home use of a zone model predictive controller-based closed-loop insulin delivery system customized for pregnancies complicated by type 1 diabetes (CLC-P).
Pregnant women with type 1 diabetes using insulin pumps were enrolled in the second or early third trimester. After study sensor wear collecting run-in data on personal pump therapy and 2 days of supervised training, participants used CLC-P targeting 80-110 mg/dL during the day and 80-100 mg/dL overnight running on an unlocked smartphone at home. Meals and activities were unrestricted throughout the trial. The primary outcome was the continuous glucose monitoring percentage of time in the target range 63-140 mg/dL versus run-in.
Ten participants (HbA1c 5.8 ± 0.6%) used the system from mean gestational age of 23.7 ± 3.5 weeks. Mean percentage time in range increased 14.1 percentage points, equivalent to 3.4 h per day, compared with run-in (run-in 64.5 ± 16.3% versus CLC-P 78.6 ± 9.2%; P = 0.002). During CLC-P use, there was significant decrease in both time over 140 mg/dL (P = 0.033) and the hypoglycemic ranges of less than 63 mg/dL and 54 mg/dL (P = 0.037 for both). Nine participants exceeded consensus goals of above 70% time in range during CLC-P use.
The results show that the extended use of CLC-P at home until delivery is feasible. Larger, randomized studies are needed to further evaluate system efficacy and pregnancy outcomes.
Introduction: There is need to improve glucose control and QoL for type 1 diabetes (T1D) using automated insulin delivery (AID) . We evaluated non-glucose signals in subjects with T1D on AID using ...the multi-functional Empatica E4 device (E4) .
Method: During a 2-week prospective AID study for 12 participants with T1D, pharmacological stress was induced with three doses of hydrocortisone delivered at 9 am (40 mg) , 1 pm (20 mg) , and 5 pm (20 mg) . Frequent salivary cortisol measurements confirmed pharmacologic stress. The correlation of normalized power spectral density (PSD) of Electrodermal activity (EDA) data from E4 with the salivary cortisol (SC) gold standard was evaluated. EDA PSD was computed at min windows before and after the hydrocortisone administration. Subsequently, the impact of SC and EDA PSD on CGM and insulin delivery data was analyzed. Pearson's moment (R value) was utilized to evaluate correlation between two variables.
Results: Significant change in SC was observed after each dosage: 159.6 ±88.6 ng/dL before to 18247.6 ±18834 ng/dL after (Dose 1/D1) , 1911.9 ±7ng/dL to 7716.1±4485 ng/dL (D2) , and 798.4 ±629 ng/dL to 7458.1±9995 ng/dL (D3) . A positive change was also noted in the EDA PSD with all three doses: -96.5±13.9 dB/Hz to -95.5 ±21.2 dB/Hz (D1) , -96.1±14.02 dB/Hz to -94.6 ±9.1db/Hz (D2) , and -85.9 ±23.6dB/Hz to -81.6 ±23.6dB/Hz (D3) . R value between EDA PSD and SC was 0.82 (p = 0.015) . The post lunch time in hyperglycemia was 78.7 %±9.7 (p = 0.0paired t-test) with an average insulin delivery of 10.36 U±2.24
Conclusions: There is significant effect of pharmacological stress on cortisol and EDA PSD. AID has poor postprandial glycemic outcomes with pharmacological stress indicating need for detecting stress and updating control strategy. E4 EDA can be utilized to monitor pharmacological stress and can be incorporated for testing in Next Gen AID.
Disclosure
A.Banerjee: None. R.Kaur: None. I.Zaniletti: None. M.Church: None. S.K.Mccrady-spitzer: None. D.Desjardins: None. S.Gupta: None. Y.C.Kudva: Advisory Panel; Novo Nordisk, Research Support; Dexcom, Inc., Hemsley Charitable Trust, JDRF, National Institutes of Health, Roche Diabetes Care, Tandem Diabetes Care, Inc.
Funding
JDRF grant (2-SRA-2017-503-M-B)
Introduction: Psychological stress may adversely affect glucose control. However, the effect of stress on efficacy of automated insulin delivery (AID) in Type 1 Diabetes (T1D) is still unknown. We ...evaluated non-glucose signals in subjects with type 1 diabetes on AID using the Empatica E4 device (E4) during psychological stress.
Method: During a 2-week prospective AID study for 12 participants with T1D, psychological stress i.e Trier Social Stress Test (TSST) was induced. Heart rate (HR) measurements using the Nonin sensor 15 mins before and after TSST confirmed psychological stress. Physical activity (PA) was analyzed and HR fluctuations coinciding with PA was rejected. The correlation of HR from E4 with the Nonin HR monitor was evaluated to explore the feasibility of using E4 HR as a substitute for Nonin HR. Pearson's moment is used to evaluate correlation.
Results: The HR from both Nonin and E4 was observed to rise after application of stress from baseline levels. The mean difference of heart rate in Nonin HR was 13.1 bpm (6 bpm) in AID and in E4 was 10.8 bpm (5 bpm) in AID. The Pearson's correlation coefficient between the Nonin and E4 HR was 0.9 in AID (p = 0.0007) . There was a trend towards increase in E4 Electrodermal activity (EDA) of normalized power spectral density (PSD) -92.5 dB/Hz (28.8) before stress to -84.9 dB/Hz (21.9) after stress in AID (p = 0.06) .
Conclusions: The E4 HR can act as a substitute to the gold standard Nonin HR. E4 HR is a good indicator of psychological stress with simultaneous analyses of accelerometry data and could be used to inform the AID controller. E4 EDA PSD is also a good indicator for stress but has a delayed response. On the other hand, HR can be affected by physical activity. Psychological stress could be detected through a fusion of E4 HR, EDA, and accelerometer sensors and incorporated into Next Gen AID for testing.
Disclosure
A.Banerjee: None. R.Kaur: None. I.Zaniletti: None. M.Church: None. S.K.Mccrady-spitzer: None. D.Desjardins: None. S.Gupta: None. Y.C.Kudva: Advisory Panel; Novo Nordisk, Research Support; Dexcom, Inc., Hemsley Charitable Trust, JDRF, National Institutes of Health, Roche Diabetes Care, Tandem Diabetes Care, Inc.
Funding
JDRF grant (2-SRA-2017-503-M-B)
Decentralized sensing of analytes in remote locations is today a reality. However, the number of measurable analytes remains limited, mainly due to the requirement for time-consuming successive ...standard additions calibration used to address matrix effects and resulting in greatly delayed results, along with more complex and costly operation. This is particularly challenging in commonly used immunoassays of key biomarkers that typically require from 60 to 90 min for quantitation based on two standard additions, hence hindering their implementation for rapid and routine diagnostic applications, such as decentralized point-of-care (POC) insulin testing. In this work we have developed and demonstrated the theoretical framework for establishing a universal slope for direct calibration-free POC insulin immunoassays in serum samples using an electrochemical biosensor (developed originally for extended calibration by standard additions). The universal slope is presented as an averaged slope constant, relying on 68 standard additions-based insulin determinations in human sera. This new quantitative analysis approach offers reliable sample measurement without successive standard additions, leading to a dramatically simplified and faster assay (30 min vs 90 min when using 2 standard additions) and greatly reduced costs, without compromising the analytical performance while significantly reducing the analyses costs. The substantial improvements associated with the new universal slope concept have been demonstrated successfully for calibration-free measurements of serum insulin in 30 samples from individuals with type 1 diabetes using meticulous statistical analysis, supporting the prospects of applying this immunoassay protocol to routine decentralized POC insulin testing.
Automated Insulin Delivery (AID) hybrid closed-loop systems have not been well studied in the context of psychological and physiological stress. We evaluated our interoperable artificial pancreas ...system with in-clinic stress challenges in a randomized crossover trial. Fourteen adults with type 1 diabetes were randomized to 2 weeks of AID-based control and two weeks of sensor augmented pump (SAP)l therapy at home in random order. The AID system used the Zone-Model Predictive Control algorithm with a continuous function of glucose velocity and insulin-on-board to gradually increase insulin infusion under conditions of sustained hyperglycemia. During each two-week period, in-clinic stress assessments for psychological stress (TSST and SECPT) and pharmacological stress (hydrocortisone 40-20-20 mg) were performed. Ten subjects completed the study per protocol, with 48 stress sessions completed in 12 subjects. AID increased time 70-180mg/dL from 63.1 to 74.4% (p=0.001), decreased time <70mg/dL from 1.5 to 0.8% (p=0.04) and decreased time >180mg/dL from 35.4 to 24.8% (p=0.001) during the 2 weeks outpatient use. AID decreased glycemic variability as measured by CV (p=0.037) and time <70mg/dL (p=0.014) during psychological stress (Table 1) AID improved glucose control during outpatient use and improved CV and % time <70mg/dL during in-clinic psychologic stress compared to SAP.
There is growing evidence supporting clinically important associations between age at neutering in bitches and subsequent urinary incontinence (UI), although much of this evidence to date is ...considered weak. Target trial emulation is an innovative approach in causal inference that has gained substantial attention in recent years, aiming to simulate a hypothetical randomised controlled trial by leveraging observational data. Using anonymised veterinary clinical data from the VetCompass Programme, this study applied the target trial emulation framework to determine whether later-age neutering (≥ 7 to ≤ 18 months) causes decreased odds of early-onset UI (diagnosed < 8.5 years) compared to early-age neutering (3 to < 7 months). The study included bitches in the VetCompass database born from January 1, 2010, to December 31, 2012, and neutered between 3 and 18 months old. Bitches were retrospectively confirmed from the electronic health records as neutered early or later. The primary outcome was a diagnosis of early-onset UI. Informed from a directed acyclic graph, data on the following covariates were extracted: breed, insurance status, co-morbidities and veterinary group. Inverse probability of treatment weighting was used to adjust for confounding, with inverse probability of censoring weighting accounting for censored bitches. The emulated trial included 612 early-age neutered bitches and 888 later-age neutered bitches. A pooled logistic regression outcome model identified bitches neutered later at 0.80 times the odds (95% CI 0.54 to 0.97) of early-onset UI compared with bitches neutered early. The findings show that later-age neutering causes reduced odds of early-onset UI diagnosis compared with early-age neutering. Decision-making on the age of neutering should be carefully considered, with preference given to delaying neutering until after 7 months of age unless other major reasons justify earlier surgery. The study is one of the first to demonstrate successful application of the target trial framework to veterinary observational data.
Automated Insulin Delivery (AID) hybrid closed-loop systems have not been well studied in the context of prescribed meals. We evaluated our interoperable artificial pancreas system (iAPS) with ...scheduled meal challenges in a randomized crossover trial in an at-home setting.
Ten adults with type 1 diabetes completed two weeks of AID-based control and two weeks of conventional therapy (sensor-augmented pump/predictive low-glucose suspend) at home in random order. During each period, subjects consumed pasta or white rice as part of a complete dinner meal on six different occasions (each meal three times in random order).
The AID system increased time in range 70-180 mg/dL from 70.6 to 74.0% (3.4, 95% CI -2.3 to 9.1, p=0.22), while sensor time <70 mg/dL significantly decreased from 3.5 to 2.3% (-1.2, 95% CI -2.1 to -0.2, p=0.02). Postprandial glucose AUC difference between meals in conventional therapy was 10,919.0 mg/dL x min (95% CI 3,190.5 to 18,648.0, p=0.009) while for AID it was 6,522.1 mg/dL x min (p=0.24), highlighting the ability of AID to minimize glycemic excursions postprandially. The AID system decreased insulin delivery at 0-2h by 0.45 units (p=0.001) for pasta, while it increased at 2-4h by 0.47 units (p=0.18) for white rice (Table 1).
The AID system improved postprandial glucose control over conventional therapy in the handling of challenging meals in the at-home setting.
Disclosure
J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. S. Deshpande: None. M. Church: None. M. Piper: None. C.C. Andre: None. J.S. Massa: None. F.J. Doyle: Research Support; Self; DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Mode AGC. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. D.M. Eisenberg: Consultant; Self; Barilla Center For Food and Nutrition, Italy. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care.
Funding
Barilla Center for Food & Nutrition Foundation; National Institutes of Health (DP3DK104057, DP3DK113511); Harvard Accelerator; Dexcom, Inc. (IIS-2018-019)
PDF
