Diabetes technology & therapeutics最新文献

Background: ONWARDS 9 explored, for the first time, the effect of continuous glucose monitoring (CGM)-based titration of once-weekly insulin icodec (icodec) on glycemic control and safety outcomes in individuals with type 2 diabetes (T2D). Methods: In this 26-week, multicenter, single-arm, treat-to-target, phase 3b trial, insulin-naive adults with T2D (glycated hemoglobin [HbA1c] 7.0%-11.0%) initiated icodec at a starting dose of 70 U/week. Participants were provided with an intermittently scanned CGM device, and icodec doses were titrated weekly based on pre-breakfast CGM values (target: 80-130 mg/dL). The primary endpoint was change in HbA1c from week 0 to week 26. Exploratory endpoints included the percentage of time in range (TIR; 70-180 mg/dL), time above range (TAR; >180 mg/dL), and time below range (TBR; <54 mg/dL) from week 22 to week 26. Safety outcomes, including the number of hypoglycemia episodes, were assessed. Results: Of 58 participants screened, 51 received icodec treatment. HbA1c decreased from an observed mean of 8.18% at week 0 to an estimated mean of 7.00% at week 26. There was a statistically significant reduction in HbA1c of -1.17%-points (95% confidence interval: -1.36; -0.99, P < 0.0001). From week -2 to 0 to week 22-26, a concomitant clinically meaningful increase in TIR (54.4% to 76.4%) and decrease in TAR (45.2% to 22.9%) was observed; TBR remained low throughout the trial (week -2 to 0: 0.03%; week 22-26: 0.04%). No severe hypoglycemic episodes were reported during the trial, and no new safety concerns for icodec were identified. Conclusion: After 26 weeks of treatment with icodec titrated based on CGM data, there was a statistically significant reduction in HbA1c from baseline, and the internationally recommended CGM targets for TIR, TAR >180 mg/dL, and TBR <54 mg/dL were achieved. These findings suggest that CGM-based titration of icodec is a feasible method for initiating insulin therapy in T2D. Trial registration: ClinicalTrials.gov identifiers: NCT05823948.

Background: In a prior work, a virtual continuous glucose monitoring (CGM) trace was generated for each of the 1441 participants in the landmark Diabetes Control and Complications trial (DCCT). These new data allow us to compare whether time-in-tight-range (TITR) is a better predictor of diabetic microvascular complications (specifically retinopathy development or progression) than time-in-range (TIR). Methods: Discrete Cox proportional hazard models were used to calculate the hazard ratios (HRs) for the development/progression of retinopathy. Results: For a 1.0 standard deviation (SD) change, the adjusted HR (95% confidence interval) was 2.67 (2.33-3.06) for TIR, 2.74 (2.36-3.18) for TITR, and 2.37 (2.13-2.65) for HbA1c; a similar pattern of results was obtained for a 0.5 SD change. Computing Harrell's C-statistic showed that a survival model adjusted for TIR, TITR, or HbA1c had similar predictive performance. Conclusion: The associations of TIR and TITR with retinopathy development or progression were similar to HbA1c in the virtual DCCT CGM dataset.

Background: Diabetes mellitus is associated with significant health care resource utilization (HCRU), partly due to acute complications, including diabetic ketoacidosis (DKA) and hypoglycemia. Aim: To investigate glycated hemoglobin (HbA1c) levels and HCRU before and after adoption of FreeStyle Libre Systems (FSL) in people with diabetes on multiple daily injections of insulin (MDI). Methods: This retrospective longitudinal study used administrative health data in Ontario, Canada, housed at IC/ES. The cohort comprised people with diabetes on MDI with a first FSL claim between September 16, 2019, and August 31, 2020 (index date), who remained on FSL for 24 months. HCRU (emergency department [ED] visits and hospitalization) was measured for 12 months before the index date and the last 12 months of follow-up. HbA1c data were taken from the last tests in each period. Results: Mean HbA1c was statistically significantly reduced after FSL among people with type 1 diabetes mellitus (T1DM; n = 10,510; age <25 years, -0.8%; 25-65 years, -0.5%; >65 years, -0.1%; all P < 0.0001) or type 2 diabetes mellitus (T2DM; n = 12,668; age ≤65 years, -0.6%; >65 years, -0.3%; both P < 0.0001). Overall HCRU was statistically significantly reduced in the T1DM subgroups aged <25 and 25-65 years (ED visits only) and both T2DM age subgroups, with some subgroups having statistically significant reductions in DKA- or hypoglycemia-associated HCRU. Conclusions: Among people with T1DM or T2DM on MDI, HbA1c was statistically significantly reduced after FSL, with statistically significant reductions in HCRU in some subgroups.

Background: Hybrid closed-loop (HCL) systems combine continuous glucose monitoring (CGM) with insulin pumps to automate insulin delivery through specific algorithms and user input. This real-world study aimed to evaluate the effectiveness of the Omnipod5 HCL system on HbA1c, time-in-range (TIR), hypoglycemia frequency, and sensor glucose variability over 3 and 6 months in children and young people with type 1 diabetes at two National Health Service (NHS)-funded pediatric diabetes centers in North West England. Methods: Children younger than 18 years in two teaching hospital-based diabetes centers were started on Omnipod5 between August 2023 and January 2024. Sensor glucose metrics and HbA1c were collected within 3 months before Omnipod5 initiation and compared at 3 and 6 months postinitiation. Metrics included % TIR (sensor glucose 70-180 mg/dL), % time above range (TAR) (sensor glucose >180 mg/dL and >250 mg/dL), and % time below range (TBR) (sensor glucose <70 mg/dL mmol/L and <54 mg/dL), with variability assessed by coefficient of variation (CV) and standard deviation (SD). Results: A total of 144 children were included, with 46% males and a mean age of 7.1 years (SD 4.3). The cohort was predominantly White (80%), with diabetes duration averaging 4.4 years (SD 3.9). Before Omnipod5, 54% used multiple daily injections, 41% a nonintegrated pump, and 5% another HCL system. At 3 and 6 months postinitiation, there were significant improvements in HbA1c from 7.7% (60.2 mmol/mol) to 7.1% (54.4 mmol/mol) at 3 months and 7.2% (55.2 mmol/mol) at 6 months. TIR improved from 53.3% at baseline to 67.4% at 3 months and 68.8% at 6 months), and reductions in TAR, TBR, and CV were also observed. Conclusions: These findings highlight the Omnipod5 system's safety and effectiveness in improving glycemic control for children and young people (CYP) with type 1 diabetes in a real-world NHS setting. Further research is needed to explore the long-term benefits and cost-effectiveness of this tubeless HCL system in routine clinical care.

Hemoglobin A1c (A1c) is the standard for glycemic control in type 1 diabetes. With recent increase in continuous glucose monitoring (CGM), other metrics (time in range 70-180 mg/dL [TIR]) are increasingly available. Data are limited for youth. We evaluated the association between A1c and time in range in a large pediatric cohort. We included patients from 2018 through 2020, aged <22 years with ≥70% CGM usage (n = 2393). A linear correlation between A1c and TIR was observed (correlation coefficient -0.73), similar to studies in adults. Each 1% increase in A1c was associated with a 9.1% lower TIR. The R² for A1c versus mean sensor glucose was 0.66 (P < 0.001) and A1c versus TIR was 0.55 (P < 0.001). TIR correlates with A1c in children with type 1 diabetes. TIR should be considered alongside A1c. Further research is warranted to establish long-term outcomes associated with TIR in children.

Background: Previous studies have evaluated the associations between HbA1c discordance and diabetes complications using indices of glycation. The ideal index would allow for identification of those at increased risk for microvascular complications. This analysis evaluates the association of a newly published index, the glycation ratio (GR), with diabetic retinopathy (DR) and diabetic kidney disease (DKD). Methods: This is a retrospective review of 661 patients with diabetes seen at the University of Washington. All patients used continuous glucose monitoring (CGM) before the study. Diabetes duration was greater than 20 years in 59%. Median age was 45 years. GR was defined as the ratio of the glucose management indicator (GMI) to the HbA1c. The associations of GR with microvascular complications were each assessed using logistic regression. Results: Modeling GR as a continuous linear variable, each increase in GR of 0.20 units was associated with a 38% relative reduction in the odds of DR (adjusted odds ratio [OR] = 0.62; 95% confidence interval [CI]: 0.45-0.86, P = 0.004] and a similar reduction in the odds of DKD (OR = 0.61; 95% CI: 0.41-0.93, P = 0.02). Conclusions: GR may be a useful marker for risk of diabetic microvascular complications. Longitudinal assessment will be required to see how well GR compares with GMI or HbA1c alone.

Objective: Rapid improvements in glucose control may lead to early worsening of diabetic retinopathy (EWDR). There is a need to demonstrate safety in people commencing automated insulin delivery (AID) due to the known efficacy in rapid glycemic improvement. We aimed to investigate short-term DR outcomes in people (aged ≥13 years) with type 1 diabetes after initiation of AID (use ≥6 months). Research Design and Methods: Retrospective four center observational study with participants drawn from hospital databases (Dunedin and Christchurch, New Zealand) and also from two research studies based out of Auckland, New Zealand, and Perth, Australia. Demographic and clinical characteristics and DR grading data before and after AID initiation were collected, and statistical analysis was performed. Results: DR grading data from 165 people using AID (three different AID systems) were available, and mean improvement in HbA1c for the total sample was 1.0 ± 1.3 percentage points. Improvements in grading were seen in 32/165 (19%), 99/165 (60%) were stable, and 34/165 (21%) worsened in their R- and/or M-grade. Age at AID initiation ≥18 years was the only significant risk factor for any worsening of DR (P = 0.028). Proliferative change and need for photocoagulation were uncommon but did occur in 3% (5/165); all noted to have prior DR, diabetes duration >10 years, and with at least another diabetes complication or prior DR treatment. Conclusions: In this study, stable or improved DR grades were evident in most who had recently commenced AID. Age at AID initiation <18 years appears protective.

Background: Early feasibility studies have demonstrated safe and effective automated insulin delivery use in individuals with suboptimally controlled type 2 diabetes (T2D). The present study investigated MiniMed™ 780G advanced hybrid closed-loop (AHCL) therapy safety and effectiveness in adults with insulin-requiring T2D. Materials and Methods: This 13-site, single-arm, open-label study included 95 adults (mean ± standard deviation [SD] age of 60.3 ± 10.8 years and T2D duration of 18.6 ± 8.6 years) using basal-bolus insulin therapy. Participants underwent a run-in period (∼21 days) of open-loop or HCL followed by a study period (∼90 days) of AHCL. The primary safety end point was mean change in glycosylated hemoglobin (HbA1c) from baseline to the end of the 3-month study period. The primary and secondary effectiveness end points were noninferiority and superiority in the percentage of time in range (%TIR 70-180 mg/dL) during the last 6 weeks of the study period (computed by the Hodges-Lehmann method). Safety metrics, including the rates of severe hypoglycemia, diabetic ketoacidosis (DKA), and hyperosmolar hyperglycemic state (HHS), were summarized. Results: HbA1c was reduced from 7.9% ± 1.0% (62.4 ± 10.4 mmol/mol) at baseline to 7.2 ± 0.7% (54.7 ± 8.0 mmol/mol) (P < 0.001). The %TIR estimate was 80.9% (95% confidence interval: 78.4%, 83.1%), and the significance criteria for both the primary and secondary effectiveness end points were met (P < 0.001). While total daily insulin dose was increased from run-in to the end of the study (77.4 ± 38.5 U vs. 91.8 ± 49.3 U, P < 0.0001), announced carbohydrates were unchanged, and the number of daily user-initiated boluses was reduced (3.9 ± 1.9 vs. 3.2 ± 1.8, P < 0.0001). There was no significant change in participant weight or body mass index, no severe hypoglycemia, DKA, or HHS, and no serious or unanticipated adverse device effects. Conclusions: These findings show that MiniMed 780G AHCL use provides safe insulin intensification in type 2 diabetes and significantly improves mean HbA1c and %TIR.