Diabetes technology & therapeutics最新文献

Objective: In hospitalized inpatients, timely administration of prandial insulin with meals is challenging. Furthermore, the glycemic impact of snacking after dinner ("bedtime snacking") without prandial insulin administration has not been previously explored. We present an analysis of the impact of delayed mealtime insulin administration and bedtime snacking on inpatient glycemic control. Research Design and Methods: We conducted a post hoc analysis from the In-Fi study: a randomized controlled trial comparing Fiasp versus insulin aspart (Novolog) in inpatients with type 2 diabetes. Glycemic outcomes were assessed using the Dexcom G6 PRO continuous glucose monitoring (CGM). We analyzed CGM and insulin administration data from 122 randomized subjects who completed the primary study protocol, which included wearing a CGM for ≥4 meals. This analysis evaluates the impact of delayed mealtime insulin administration and bedtime snacking on glucose control. Results: Four-hour postprandial time in range (TIR_70-180) was 48% for insulin boluses administered before meals (n = 149) versus 24% when a meal bolus was delayed for >5 min after a meal (mean delay 58.7 min; n = 112; P < 0.001). Bedtime snacking (9 pm-12 am) was associated with significantly higher fasting glucose the next morning (35.2 mg/dL, standard error [SE] = 15.4, P = 0.026) and with a reduced overnight (9 pm-6 am) TIR_70-180 (31.9%, SE = 8.06, P < 0.001), adjusting for bedtime sensor glucose. Bedtime snacking was associated with higher overnight glucose standard deviation (12.3 mg/dL, SE = 3.46, P < 0.001) and with higher overnight glucose percentage coefficient of variation (3.6%; SE = 1.7, P = 0.044), adjusting for initial bedtime sensor glucose. Conclusions: Delayed mealtime insulin administration and bedtime snacking without insulin administration are significant causes of postprandial and overnight hyperglycemia in hospitalized inpatients. Adjustments in mealtime insulin protocols, attention to food intake, and the potential inpatient adoption of technology, such as CGM and automated insulin delivery systems, are needed to address this shortcoming in inpatient diabetes care.

The Automated Insulin Delivery in Elderly with Type 1 Diabetes (AIDE T1D) trial randomized 82 adults ≥65 years with type 1 diabetes (T1D) to hybrid closed loop (HCL), predictive low glucose suspend (PLGS), and sensor-augmented pump (SAP) therapy in a randomized crossover trial. Seventy-five of the 78 completers joined an extension phase in which they were offered the pump mode of their choice for an additional 3 months. Mean age was 71 ± 4 years (range 65-86 years) and mean duration of T1D was 42 ± 17 years (range 1-68 years). Use of HCL was selected by 91%, PLGS by 8%, and continuous glucose monitoring with injections by 1%. For participants selecting HCL, time-in-range 70-180 mg/dL was similar in the randomized controlled trial and extension phase (mean 75% ± 10%). One severe hypoglycemic event was reported. HCL was preferred over PLGS or SAP and remained effective in older adults with T1D. Clinical Trial Registration: NCT04016662.

Background: Skin reactions and discomfort associated with insulin infusion pumps limit user adherence. A recent histopathological study by Kalus et al. (DERMIS study) reported increased eosinophilic infiltration and imputed an inflammatory response to an allergen delivered at the catheter tip. This finding might explain the pruritus reported by pump users. As eosinophils migrate to inflammatory foci, primarily due to IL-5 and CCL11, we aimed to evaluate insulin phenolic preservative (IPP) as a potential allergen in vitro and assess tissue eosinophilic infiltration in vivo. Methods: Histopathological evaluations for eosinophil recruitment were performed over 1 week following IPP infusions in swine tissue. Additional histopathological investigations of eosinophilic infiltration were conducted using three commercial glucose sensors implanted in swine for up to 3 weeks. Results: Eosinophilic infiltration in the dermis and subcutaneous tissue was observed following saline and IPP infusion and at glucose sensor implantation at all time points examined. In vitro studies revealed IPP eosinophil cytotoxicity. However, neither CCL11 nor IL-5 was detected in any of the tested tissue cells after IPP treatment. Conclusion: These findings suggest that IPP is not the only triggering allergen, as IPP did not induce eosinophils in vitro, while glucose sensors also indicated increased eosinophilic infiltration. Therefore, factors other than IPP trigger eosinophil recruitment to insulin infusion pump sets.

Background: Continuous glucose monitoring (real-time CGM [RT-CGM] and retrospective [professional] CGM [non-RT-CGM]) is an emerging tool to assess glucose levels and variability. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of RT/non-RT-CGM on type 1 (T1D), type 2 (T2D), and diabetes in pregnancy (DiP) compared with self-monitoring of blood glucose (BGM). Methods: We searched PubMed/EMBASE/Cochrane Central Register of Controlled Trials until October 2024. The coprimary outcomes were the weighted mean change differences (WMCDs and absolute differences) from baseline in glycated hemoglobin (HbA1c) and in time in range (TIR%), time below range (TBR%), and time above range (TAR%). Results: A total of 64 RCTs were analyzed: (1) RT-CGM/T1D: CGM was superior to BGM for HbA1c reduction (WMCD -0.24, 95% confidence interval [CI]: -0.35; -0.14, I²= 71%), decrease in TBR <70 mg/dL (WMCD -2.41, 95% CI: -3.46; -1.35, I²= 96%), decrease in TBR < 54 mg/dL (WMCD -1.18 95% CI: -1.9; -0.47, I²= 97%), decrease in TAR >180 mg/dL (WMCD -2.99, 95% CI: -5.28; -0.71, I² = 92%), decrease in TAR >250 mg/dL (WMCD -3.99, 95% CI: -5.76; -2.21, I²= 92%), and increase in TIR 70-180 mg/dL (WMCD 5.57, 95% CI: 4.13; 7.01, I²= 84%); (2) RT-CGM/T2D: CGM was superior to BGM for HbA1c reduction (WMCD -0.40, 95% CI: -0.55; -0.24, I²= 52%), decrease in TAR > 180 mg/dL (WMCD -6.32, 95% CI: -9.87; -2.78, I²= 84%), decrease in TAR > 250 mg/dL (WMCD -5.73, 95% CI: -8.96; -2.49, I²= 89%), and increase in TIR 70-180 mg/dL (WMCD 5.46, 95% CI: 2.76; 8.16, I²= 69%); (3) RT-CGM/DiP: CGM was superior to BGM for TIR 63-140 mg/dL (WMCD: 17.77, 95% CI: 4.17; 31.36, I²= 92%). No benefit was shown for HbA1c, TBR < 63 mg/dL, TAR > 140 mg/dL, and most of the maternal and neonatal outcomes of interest; (4) Non-RT CGM: HbA1c significantly decreased with non-RT CGM compared with BGM in T2D (WMCD -0.35, 95% CI: -0.5; -0.2, I²= 19%). Discussion: In T1D and T2D, RT-CGM decreased HbA1c and increased time in target range for glycemia (70-180 mg/dL) while decreasing time spent in hypoglycemia (T1D) and time in hyperglycemia (T1D, T2D).

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.