Diabetes technology & therapeutics最新文献

Aims: Diabetic ketoacidosis (DKA) is a serious life-threatening condition caused by a lack of insulin, which leads to elevated plasma glucose and metabolic acidosis. Early identification of developing DKA is important to start treatment and minimize complications and risk of death. The aim of the present study is to develop and test prediction model(s) that gives an alarm about their risk of developing elevated ketone bodies during hyperglycemia. Methods: We analyzed data from 138 type 1 diabetes patients with measurements of ketone bodies and continuous glucose monitoring (CGM) data from over 30,000 days of wear time. We utilized a supervised binary classification machine learning approach to identify elevated levels of ketone bodies (≥0.6 mmol/L). Data material was randomly divided at patient level in 70%/30% (training/test) dataset. Logistic regression (LR) and random forest (RF) classifier were compared. Results: Among included patients, 913 ketone samples were eligible for modeling, including 273 event samples with ketone levels ≥0.6 mmol/L. An area under the receiver operating characteristic curve from the RF classifier was 0.836 (confidence interval [CI] 90%, 0.783-0.886) and 0.710 (CI 90%, 0.646-0.77) for the LR classifier. Conclusions: The novel approach for identifying elevated ketone levels in patients with type 1 diabetes utilized in this study indicates that CGM could be a valuable resource for the early prediction of patients at risk of developing DKA. Future studies are needed to validate the results.

Background: To evaluate the long-term safety and effectiveness of the Omnipod^® 5 Automated Insulin Delivery (AID) System in very young children with type 1 diabetes with up to 2 years of use. Methods: Following a 13-week single-arm, multicenter, pivotal trial that took place after 14 days of standard therapy data collection, participating children (2-5.9 years of age at study enrollment) were provided the option to continue use of the AID system in an extension phase. HbA1c was measured every 3 months, up to 15 months of total use, and continuous glucose monitor metrics were collected through the completion of the extension study (for up to 2 years). Results: Participants (N = 80) completed 18.2 [17.4, 23.4] (median [interquartile range]) total months of AID, inclusive of the 3-month pivotal trial. During the pivotal trial, HbA1c decreased from 7.4% ± 1.0% (57 ± 10.9 mmol/mol) to 6.9% ± 0.7% (52 ± 7.7 mmol/mol, P < 0.0001) and was maintained at 7.0% ± 0.7% (53 ± 7.7 mmol/mol) after 15 months total use (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 57.2% ± 15.3% during standard therapy to 68.1% ± 9.0% during the pivotal trial (P < 0.0001) and was maintained at 67.2% ± 9.3% during the extension phase (P < 0.0001 from standard therapy). Participants spent a median 97.1% of time in Automated Mode during the extension phase, with one episode of severe hypoglycemia and one episode of diabetic ketoacidosis. Conclusion: This evaluation of the Omnipod 5 AID System indicates that long-term use can safely maintain improvements in glycemic outcomes with up to 2 years of use in very young children with type 1 diabetes. Clinical Trials Registration Number: NCT04476472.

Background: Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. Methods: We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Results: Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). Conclusions: These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.

Background: Few studies have evaluated the implications of the alarm thresholds of continuous glucose monitoring (CGM) systems for individuals with diabetes. The present study aimed to investigate the influence of hypoglycemia and hyperglycemia alarm thresholds on glycemic control in adults with type 1 diabetes (T1DM) and the characteristics of patients who use these alarms more frequently. Methods: This observational cross-sectional study included 873 users of the FreeStyle Libre 2 system (501 men, median age 48 years, range 18-90 years) with T1DM from a single center. We investigated the role of demographic and metabolic factors on the use of alarms and the impact of hypoglycemia and hyperglycemia alarms and their thresholds on glycemic control. Results: Alarm users were older than nonusers (median age 49 vs. 43 years, respectively; P < 0.001). The hypoglycemia alarms were set by 76.1% of women and by 69.1% of men (P = 0.022). The hypoglycemia alarms reduced hypoglycemia features and glucose variability, although at the expense of shorter time in range. The higher the hypoglycemia alarm threshold, the greater these effects. The hyperglycemia alarms were effective in reducing hyperglycemia and lowering the glucose management indicator, although at the expense of a greater tendency to hypoglycemia. The lower the hyperglycemia alarm threshold, the greater these effects. Conclusions: CGM alarms contribute to better glycemic control. However, hypoglycemia and hyperglycemia alarms have advantages and disadvantages. Adults with T1DM should explore, under medical supervision, which alarm thresholds will best help them achieve their individual glycemic goals.

Background: Despite advances in technology, glycemic outcomes in people with type 1 diabetes (T1D) remain suboptimal. The MiniMed 780G (MM780G) advanced hybrid closed-loop (AHCL) system is the latest technology for T1D management with established safety and efficacy. This study explores the cost-effectiveness of MM780G AHCL compared against multiple daily injections (MDI) plus intermittently scanned continuous glucose monitor (isCGM). Methods: A cost-utility analysis was conducted, simulating lifetime outcomes for 1000 T1D individuals, with baseline hemoglobin A1c of 8.4%, using the IQVIA Core Diabetes Model (CDM) v9.5. A Singapore health care payer perspective was taken with 2023 costs applied. Treatment effects were taken from the ADAPT study and treatment-related events from a combination of sources. T1D complication costs were derived from local literature, and health state utilities and disutilities from published literature. Scenario analyses and probabilistic sensitivity analyses (PSAs) explored uncertainty. Cost-effectiveness was assessed based on willingness-to-pay (WTP) thresholds set to Singapore Dollars (SGD) 45,000 (United States Dollars [USD] 33,087) per quality-adjusted life year (QALY) and Singapore's gross domestic product (GDP) per capita of SGD 114,165 (USD 83,941) per QALY. Results: A switch from MDI plus isCGM to MM780G resulted in expected gains in life-years (+0.78) and QALYs (+1.45). Cost savings through reduction in T1D complications (SGD 25,465; USD 18,723) partially offset the higher treatment costs in the AHCL arm (+SGD 74,538; +USD 54,805), resulting in an estimated incremental cost-effectiveness ratio of SGD 33,797 (USD 24,850) per QALY gained. Findings were robust, with PSA outputs indicating 81% and 99% probabilities of cost-effectiveness at the stated WTP thresholds. Conclusion: MM780G is a cost-effective option for people with T1D managed in a Singapore setting.

Advanced hybrid closed-loop (AHCL) therapy with the Medtronic MiniMed™ 780G system improves glycemia; however, the clinical outcomes in younger children remain less established. This pilot study aimed to explore the continuous glucose monitoring (CGM) metrics in very young children on AHCL. Children between 2 and 7 years of age and on insulin pump therapy were recruited. A 2-week phase in manual mode was followed by a 6-week AHCL phase. CGM metrics were analyzed to review glycemic outcomes. Out of 11 participants enrolled [mean (standard deviation [SD]) age 5.3 (0.8) years], 10 completed the study. Time in closed loop was 96.7 (3.9)%. In AHCL, participants had a mean (SD) time in range of 72.6 (7.4)% and spent 3.0 (1.74)% and 0.63 (0.46)% in time <70 and <54 mg/dL, respectively. AHCL is a feasible option for management of young children with type 1 diabetes.

Background: Treatment of type 1 diabetes mellitus (T1DM) has become increasingly technical with rapid developments in integration of pumps and sensors to regulate insulin dosage, and patient-initiated solutions as open-source automated insulin delivery (OS-AID) systems, have gained popularity in people with diabetes. Studies have shown increased glycemic control and mental wellbeing in users of OS-AID systems. The aim of this study was to estimate the prevalence, the effect on metabolic control, the risk, and the effect on everyday life for users and their parents of OS-AID systems in Danish children and adolescents with T1DM. Methods: This retrospective cohort study recruited participants through pediatric diabetes outpatient clinics and social media. Surveys were distributed and current and retrospective data on glycemic control (HbA1c, time in range [TIR] etc.) were collected. Results: Fifty-six users of OS-AID systems out of 2950 Danish children and adolescents with T1DM were identified from all outpatient clinics in Denmark. Thirty-one responded on contact and were included (55% of the identified), median age 12 [interquartile range: 11-14] years, 51% females, and mean duration of use of OS-AID systems 2.37 ± 0.86 years. Glycemic control increased significantly with TIR increasing from mean 62.29% ± 13.68% to 70.12% ± 10.08%, *P < 0.01, and HbA1c decreasing from mean 50.13 ± 5.76 mmol/mol (6.7% ± 2.7%) to 47.86 ± 6.24 mmol/mol (6.5% ± 2.7%), **P < 0.05. No changes were found in safety parameters. Parents reported better quality of sleep evaluated by Pittsburgh Sleep Quality Index. Conclusion: This study is the first to provide knowledge on pediatric users of OS-AID systems in Denmark and found a prevalence of 1.89% for OS-AID systems, improved TIR, and no increased risk associated with use of OS-AID systems.

Older adults with type 1 diabetes may face challenges driving safely. Glucose "above-5-to-drive" is often recommended for insulin-treated diabetes to minimize hypoglycemia while driving. However, the effectiveness of this recommendation among older adults has not been evaluated. Older drivers with type 1 diabetes were assessed while using sensor-augmented insulin pumps during a 2-week clinical trial run-in. Twenty-three drivers (median age 69 years [interquartile range; IQR 65-72]; diabetes duration 37 years [20-45]) undertook 618 trips (duration 10 min [5-21]). Most trips (n = 535; 87%) were <30 min duration; 9 trips (1.5%) exceeded 90 min and 3 trips (0.5%) exceeded 120 min. Pre-trip continuous glucose monitoring (CGM) was >5.0 mmol/L for 577 trips (93%) and none of these had CGM <3.9 mmol/L during driving (including 8 trips >90 min and 3 trips >120 min). During 41 trips with pre-trip CGM ≤5.0 mmol/L, 11 trips had CGM <3.9 mmol/L. Seventy-one CGM alerts occurred during 60 trips (10%), of which 54 of 71 alerts (76%) were unrelated to hypoglycemia. Our findings support a glucose "above-5-to-drive" recommendation to avoid CGM-detected hypoglycemia among older drivers, including for prolonged drives, and highlight the importance of active CGM low-glucose alerts to prevent hypoglycemia during driving. Driving-related CGM usability and alert functionality warrant investigation. Clinical trial ACTRN1261900515190.

Background: We evaluated accuracy and safety of a seventh-generation real-time continuous glucose monitoring (CGM) system during pregnancy. Materials and Methods: Evaluable data for accuracy analysis were obtained from 96 G7 sensors (Dexcom, Inc.) worn by 96 of 105 enrolled pregnant women with type 1 (n = 59), type 2 (n = 21), or gestational diabetes (n = 25). CGM values were compared with arterialized venous glucose values from the YSI comparator instrument during 6-h clinic sessions at different time points throughout the sensors' 10-day wear period. The primary endpoint was the proportion of CGM values in the 70-180 mg/dL range within 15% of comparator glucose values. Secondary endpoints included the proportion of CGM values within 20% or 20 mg/dL of comparator values ≥ or <100 mg/dL, respectively (the %20/20 agreement rate). Results: Of the 1739 pairs with CGM in the 70-180 mg/dL range, 83.2% were within 15% of comparator values. The lower bound of the 95% confidence interval was 79.8%. Of the 2102 pairs with CGM values in the 40-400 mg/dL range, the %20/20 agreement rate was 92.5%. Of the 1659 pairs with comparator values in the 63-140 mg/dL range, the %20/20 agreement rate was 92.3%. The %20/20 agreement rates on days 1, 4 and 7, and 10 were 78.6%, 96.3%, and 97.3%, respectively. Consensus error grid analysis showed 99.8% of pairs in the clinically acceptable A and B zones. There were no serious adverse events. The sensors' 10-day survival rate was 90.3%. Conclusion: The G7 system is accurate and safe during pregnancies complicated by diabetes and does not require confirmatory fingerstick testing. Clinical Trial Registration: clinicaltrials.gov NCT04905628.