Real time continuous glucose monitoring in high-risk people with insulin-requiring type 2 diabetes: A randomised controlled trial.

AIMS: To investigate the impact of real-time continuous glucose monitoring (rtCGM) on glycaemia in a predominantly indigenous (Maori) population of adults with insulin-requiring type 2 diabetes (T2D) in New Zealand. METHODS: Twelve-week, multicentre randomised controlled trial (RCT) of adults with T2D using ≥0.2 units/kg/day of insulin and elevated glycated haemoglobin (HbA1c) ≥64 mmol/mol (8.0%). Following a 2-week blinded CGM run-in phase, participants were randomised to rtCGM or control (self-monitoring blood glucose [SMBG]). The primary outcome was time in the target glucose range (3.9-10 mmol/L; TIR) during weeks 10-12, with data collected by blinded rtCGM in the control group. RESULTS: Sixty-seven participants entered the RCT phase (54% Maori, 57% female), median age 53 (range 16-70 years), HbA1c 85 (IQR 74, 94) mmol/mol (9.9 [IQR 8.9, 10.8]%), body mass index (36.7 ± 7.7 kg/m2). Mean (±SD) TIR increased from 37 (24)% to 53 (24)% [Δ 13%; 95% CI 4.2 to 22; P = 0.007] in the rtCGM group but did not change in the SMBG group [45 (21)% to 45 (25)%, Δ 2.5%, 95% CI -6.1 to 11, P = 0.84]. Baseline-adjusted between-group difference in TIR was 10.4% [95% CI -0.9 to 21.7; P = 0.070]. Mean HbA1c (±SD) decreased in both groups from 85 (18) mmol/mol (10.0 [1.7]%) to 64 (16) mmol/mol (8.0 [1.4]%) in the rtCGM arm and from 81 (12) mmol/mol (9.6 [1.1]%) to 65 (13) mmol/mol (8.1 [1.2]%) in the SMBG arm (P < 0.001 for both). There were no severe hypoglycaemic or ketoacidosis events in either group. CONCLUSIONS: Real-time CGM use in a supportive treat-to-target model of care likely improves glycaemia in a population with insulin-treated T2D and elevated HbA1c.

Use of a decision support tool and quick start onboarding tool in individuals with type 1 diabetes using advanced automated insulin delivery: a single-arm multi-phase intervention study.

BACKGROUND: Multiple clinician adjustable parameters impact upon glycemia in people with type 1 diabetes (T1D) using Medtronic Mini Med 780G (MM780G) AHCL. These include glucose targets, carbohydrate ratios (CR), and active insulin time (AIT). Algorithm-based decision support advising upon potential settings adjustments may enhance clinical decision-making. METHODS: Single-arm, two-phase exploratory study developing decision support to commence and sustain AHCL. Participants commenced investigational MM780G, then 8 weeks Phase 1-initial optimization tool evaluation, involving algorithm-based decision support with weekly AIT and CR recommendations. Clinicians approved or rejected CR and AIT recommendations based on perceived safety per protocol. Co-design resulted in a refined algorithm evaluated in a further identically configured Phase 2. Phase 2 participants also transitioned to commercial MM780G following "Quick Start" (algorithm-derived tool determining initial AHCL settings using daily insulin dose and weight). We assessed efficacy, safety, and acceptability of decision support using glycemic metrics, and the proportion of accepted CR and AIT settings per phase. RESULTS: Fifty three participants commenced Phase 1 (mean age 24.4; Hba1c 61.5mmol/7.7%). The proportion of CR and AIT accepted by clinicians increased between Phases 1 and 2 respectively: CR 89.2% vs. 98.6%, p < 0.01; AIT 95.2% vs. 99.3%, p < 0.01. Between Phases, mean glucose percentage time < 3.9mmol (< 70mg/dl) reduced (2.1% vs. 1.4%, p = 0.04); change in mean TIR 3.9-10mmol/L (70-180mg/dl) was not statistically significant: 72.9% ± 7.8 and 73.5% ± 8.6. Quick start resulted in stable TIR, and glycemic metrics compared to international guidelines. CONCLUSION: The co-designed decision support tools were able to deliver safe and effective therapy. They can potentially reduce the burden of diabetes management related decision making for both health care practitioners and patients. TRIAL REGISTRATION: Prospectively registered with Australia/New Zealand Clinical Trials Registry(ANZCTR) on 30th March 2021 as study ACTRN12621000360819.

Glucose and Psychosocial Outcomes 12 Months Following Transition from Multiple Daily Injections to Advanced Hybrid Closed Loop in Youth with Type 1 Diabetes and Suboptimal Glycemia.

Objective: To investigate 12-month glycemic and psychosocial changes following transition from multiple daily injections (MDI) to advanced hybrid closed-loop (AHCL) therapy in youth (aged 13-25 years) with type 1 diabetes and suboptimal glycemia (glycated hemoglobin [HbA1c] ≥8.5% [69 mmol/mol]). Research Design and Methods: Prospective, single arm, dual-center study in 20 participants. Extension phase outcomes reported after 12 months, including HbA1c, time in glycemic ranges, AHCL system performance, and psychosocial questionnaires assessing quality of life, diabetes treatment, and sleep. Results: After 12 months, 19 out of 20 participants continued to use AHCL. Average time-in-range 70-180 mg/dL (3.9-10.0 mmol/L) improved from 27.6% ± 13.2% to 62.5% ± 11.4%. This translated to an average 2.5 percentage-point (27.1 mmol/mol) improvement in HbA1c from 10.5% ± 2.1% (91.2 mmol/mol) at baseline to 8.0% ± 0.9% (64.1 mmol/mol) at 12 months. Psychosocial questionnaires and very high HbA1c at study entry indicated significant diabetes-associated burden for both individuals and parents. After 12 months, improvements were observed in general and diabetes-specific health-related quality of life, as well as in diabetes treatment satisfaction. Safety data were reassuring with a diabetic ketoacidosis rate of 0.15 per participant-year after 12 months of AHCL (compared to 0.25 per participant-year in the 12 months before the study). Conclusions: After 12 months of AHCL usage, this study highlights the potential for substantial and sustained glycemic and psychosocial improvements among individuals experiencing considerable diabetes burden and suboptimal glycemia, following their switch from MDI to AHCL.

Acceptability and experiences of real-time continuous glucose monitoring in adults with type 2 diabetes using insulin: a qualitative study.

Aims: To explore the lived experiences of initiating real-time continuous glucose monitoring (rt-CGM) use in individuals with type 2 diabetes using insulin. Methods: Twelve semi-structured interviews were conducted amongst individuals with type 2 diabetes taking insulin who were enrolled in the 2GO-CGM randomised controlled trial and had completed 3 months of rtCGM. Interviews were transcribed verbatim and analysed to identify common themes regarding their experiences. Results: The interviews revealed three key themes: i) rtCGM as a facilitator of improved health behaviours; ii) the acceptability of rtCGM systems compared to capillary blood glucose testing; and iii) barriers to the continual usage of rtCGM technology - including: connection difficulties, longevity of the sensors, and local cutaneous reactions to the sensor adhesive. Conclusion: Adults on insulin with type 2 diabetes find rtCGM systems widely acceptable, and easier to engage with than traditional self-monitoring of capillary blood glucose. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01403-9.

Derivation and Validation of Thresholds Using Synthetic Data Methods for Single-Test Screening of Emergency Department Patients with Possible Acute Myocardial Infarction Using a Point-of-Care Troponin Assay.

BACKGROUND: Single-sample (screening) rule-out of acute myocardial infarction (AMI) with troponin requires derivation of a single-test screening threshold. In data sets with small event numbers, the lowest one or two concentrations of myocardial infarction (MI) patients dictate the threshold. This is not optimal. We aimed to demonstrate a process incorporating both real and synthetic data for deriving such thresholds using a novel pre-production high-precision point-of-care assay. METHODS: cTnI concentrations were measured from thawed plasma using the Troponin I Next (TnI-Nx) assay (i-STAT; Abbott) in adults on arrival to the emergency department with symptoms suggestive of AMI. The primary outcome was an AMI or cardiac death within 30 days. We used internal-external validation with synthetic data production based on clinical and demographic data, plus the measured TnI-Nx concentration, to derive and validate decision thresholds for TnI-Nx. The target low-risk threshold was a sensitivity of 99% and a high-risk threshold specificity of >95%. RESULTS: In total, 1356 patients were included, of whom 191 (14.1%) had the primary outcome. A total of 500 synthetic data sets were constructed. The mean low-risk threshold was determined to be 5 ng/L. This categorized 38% (95% CI, 6%-68%) to low-risk with a sensitivity of 99.0% (95% CI, 98.6%-99.5%) and a negative predictive value of 99.4% (95% CI, 97.6%-99.8%). A similarly derived high-risk threshold of 25 ng/L had a specificity of 95.0% (95% CI, 94.8%-95.1%) and a positive predictive value of 74.8% (95% CI, 71.5%-78.0%). CONCLUSIONS: With the TnI-Nx assay, we successfully demonstrated an approach using synthetic data generation to derive low-risk thresholds for safe and effective screening.

Study protocol: glycaemic outcomes in people with type 2 diabetes initiating continuous glucose monitoring: the 2GO-CGM study.

Purpose: Improving glycaemic control in type 2 diabetes (T2D) is essential to reducing social and health-economic burden of diabetes-related complications. Continuous glucose monitoring (CGM) has been established as beneficial in improving glycaemic control and reducing hypoglycaemia in people with type 1 diabetes, however data in T2D is limited. This study has been designed to assess the effect of initiating real-time CGM (rtCGM) on glycaemic control in a high-risk population of adults with T2D. Secondary objectives are to assess the cost-effectiveness and safety of rtCGM, and the effects of rtCGM on diet/lifestyle and the burden of diabetic complications, including cardiovascular risk. Methods: This multicentre randomised controlled trial (RCT) will be conducted at three sites in New Zealand (Waikato, Christchurch and Dunedin). Eighty adults with T2D on insulin with suboptimal glycaemic control (HbA1c > 8.0% or 64 mmol/mol) will be randomised 1:1 to rtCGM or routine care with self-monitoring of blood glucose levels (SMBG) for three months. This intervention phase will be followed by a three-month continuation phase where SMBG group crossover to use rtCGM. Participants will then be invited to join the extension phase with continued use of rtCGM for a further 12 months. During the extension phase, both groups will independently titrate their insulin under the remote supervision of prescribing diabetes nurse specialists following an insulin titration algorithm. The primary outcome of the study is time in target glucose range (3.9-10 mmol/L or 70-180 mg/dL; TIR). Secondary outcomes include CGM metrics as per consensus statement recommendations, and HbA1c. Additional planned analyses include cardiovascular risk profile, incremental cost-effectiveness analyses, dietary patterns, and qualitative analyses. Trial registration number: The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000889853) on 8 July 2021 and the World Health Organisation International Clinical Trial Registry Platform (Universal Trial Number U1111-1264-5822).

Impact of Advanced Hybrid Closed Loop on Youth With High-Risk Type 1 Diabetes Using Multiple Daily Injections.

OBJECTIVE: To evaluate glycemic outcomes in youth (aged 13-25 years) with type 1 diabetes and high-risk glycemic control (HbA1c ≥8.5% [69 mmol/mol]) on multiple daily injection (MDI) therapy after transitioning to advanced hybrid closed loop (AHCL) therapy. RESEARCH DESIGN AND METHODS: This prospective, 3-month, single-arm, dual-center study enrolled 20 participants, and all completed the study. RESULTS: HbA1c decreased from 10.5 ± 2.1% (91.2 ± 22.8 mmol/mol) at baseline to 7.6 ± 1.1% (59.7 ± 11.9 mmol/mol), and time spent in target range 70-180 mg/dL (3.9-10.0 mmol/L) increased from 27.6 ± 13.2% at baseline to 66.5 ± 9.8% after 3 months of AHCL. Two episodes of diabetic ketoacidosis attributed to infusion set failure occurred. CONCLUSIONS: AHCL has the potential to improve suboptimal glycemia in youth with type 1 diabetes previously on MDI therapy.

A prospective multi-centre study assessing the safety and effectiveness following the implementation of an accelerated chest pain pathway using point-of-care troponin for use in New Zealand rural hospital and primary care settings.

AIMS: Most rural hospitals and general practices in New Zealand (NZ) are reliant on point-of-care troponin. A rural accelerated chest pain pathway (RACPP), combining an electrocardiogram (ECG), a structured risk score (Emergency Department Assessment of Chest Pain Score), and serial point-of-care troponin, was designed for use in rural hospital and primary care settings across NZ. The aim of this study was to evaluate the safety and effectiveness of the RACPP. METHODS AND RESULTS: A prospective multi-centre evaluation following implementation of the RACPP was undertaken from 1 July 2018 to 31 December 2020 in rural hospitals, rural and urban general practices, and urgent care clinics. The primary outcome measure was the presence of 30-day major adverse cardiac events (MACEs) in low-risk patients. The secondary outcome was the percentage of patients classified as low-risk that avoided transfer or were eligible for early discharge. There were 1205 patients enrolled in the study. 132 patients were excluded. Of the 1073 patients included in the primary analysis, 474 (44.0%) patients were identified as low-risk. There were no [95% confidence interval (CI): 0-0.3%] MACE within 30 days of the presentation among low-risk patients. Most of these patients (91.8%) were discharged without admission to hospital. Almost all patients who presented to general practice (99%) and urgent care clinics (97.6%) were discharged to home directly. CONCLUSION: The RACPP is safe and effective at excluding MACEs in NZ rural hospital and primary care settings, where it can identify a group of low-risk patients who can be safely discharged home without transfer to hospital.

Study protocol for an observational study to evaluate an accelerated chest pain pathway using point-of-care troponin in New Zealand rural and primary care populations.

INTRODUCTION Accelerated diagnostic chest pain pathways are used widely in urban New Zealand hospitals. These pathways use laboratory-based troponin assays with good analytical precision. Widespread implementation has not occurred in many of New Zealand's rural hospitals and general practices as they are reliant on point-of-care troponin assays, which are less sensitive and precise. An accelerated chest pain pathway using point-of-care troponin has been adapted for use in rural settings. A pilot study in a low-risk rural population showed no major adverse cardiac events at 30 days. A larger study is required to be confident that the pathway is safe. AIMS To assess the safety and effectiveness of an accelerated chest pain pathway adapted for rural settings and general practice using point-of-care troponin to identify low-risk patients and allow early discharge. METHODS This is a prospective observational study of an accelerated chest pain pathway using point-of-care troponin in rural hospitals and general practices in New Zealand. A total of 1000 patients, of whom we estimate 400 will be low risk, will be enrolled in the study. OUTCOME MEASURES The primary outcome is the proportion of patients identified by the pathway as low risk for a 30-day major adverse cardiac event. Secondary outcomes include the proportion of low-risk patients who were discharged directly from general practice or rural hospitals, the proportion of patients reclassified as having acute myocardial infarction by the pathway and the proportion of patients with low and intermediate risk safely managed in the rural hospital.

Early kinetic profiles of troponin I and T measured by high-sensitivity assays in patients with myocardial infarction.

The early concentration kinetic profiles of cardiac troponin in patients with non-ST-elevated myocardial infarction (NSTEMI) measured by high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays have not been described. In intermediate-to-high-risk of NSTEMI patients we measured serial cTn concentrations on ED arrival, at 1, 2, 3, 6-12, 24 and 48-hours with hs-cTnI and hs-cTnT assays. Log-normal curves were fitted to concentrations from time from symptom onset, and the time to rule-out decision thresholds estimated (hs-cTnI: 2 ng/L and 5 ng/L; hs-cTnT: 5 ng/L). Among 164 patients there were 58 NSTEMI. The hs-cTnI to hs-cTnT ratio increased linearly over the first 6-12 h following symptom onset. The estimated times from symptom onset to the 2 ng/L and 5 ng/L thresholds for hs-cTnI were 1.8 (0.1-3.1) and 1.9 (1.1-3.5) hours, and to the 5 ng/L threshold for hs-cTnT 1.9 (1.1-3.8) hours. The estimated time to exceed 5 ng/L was ≥3 hours in 32.6% (95%CI: 20.0% to 48.1%) cases for hs-cTnI and 33.3% (19.6% to 50.0%) for hs-cTnT. cTnI concentrations increased at a much more rapid rate than cTnT concentrations in patients with NSTEMI. Concentrations of a high proportion of patients took longer than 3 hours from symptom onset to exceed the 5 ng/L rule-out decision threshold.

Validity of a Novel Point-of-Care Troponin Assay for Single-Test Rule-Out of Acute Myocardial Infarction.

Importance: Emergency department (ED) investigations of patients with suspected acute myocardial infarction (AMI) are time consuming, partly because of the turnaround time of laboratory tests. Current point-of-care troponin assays shorten test turnaround times but lack precision at lower concentrations. Development of point-of-care troponin assays with greater analytical precision could reduce the decision-making time in EDs for ruling out AMI. Objective: To determine the clinical accuracy for AMI of a single troponin concentration measured on arrival to ED with a new-generation, higher precision point-of-care assay with a 15-minute turnaround time. Design, Setting, and Participants: This observational study occurred at a single urban regional ED. Adults presenting acutely from the community to the ED with symptoms suggestive of AMI were included. Troponin concentrations were measured on ED arrival with both a novel point-of-care assay (i-STAT TnI-Nx; Abbott Point of Care) and a high-sensitivity troponin I assay (Architect hs-cTnI; Abbott Diagnostics). Main Outcomes and Measures: The primary outcome was type 1 AMI during index presentation. We compared the discrimination ability of the TnI-Nx assay with the hs-cTnI assay using the area under receiver operator characteristic curve (AUC) and sensitivity, negative predictive value, and the proportion of negative test results at thresholds with 100% sensitivity. Results: Of 354 patients (255 [72.0%] men; mean [SD] age, 62 [12] years), 57 (16.1%) experienced an AMI. Eighty-five patients (24.0%) presented to the ED less than 3 hours after symptom onset. No difference was found between the AUC of the TnI-Nx assay (0.975 [95% CI, 0.958-0.993]) and the hs-cTnI assay (0.970 [95% CI, 0.949 to 0.990]; P = .46). A TnI-Nx assay result of less than 11 ng/L identified 201 patients (56.7%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 98.2%-100%). In comparison, an hs-cTnI assay result of less than 3 ng/L identified 154 patients (43.5%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 97.6%-100%). Conclusions and Relevance: A novel point-of-care troponin assay that can produce a result 15 minutes after blood sampling had comparable discrimination ability to an hs-cTnI assay for ruling out AMI after a single blood test. Use in the ED may facilitate earlier decision making and could expedite the safe discharge of a large proportion of low-risk patients.