Diabetes technology & therapeutics最新文献

Objective: Inhaled insulin offers an alternative to subcutaneous administration, although concerns remain regarding pulmonary risks. We assessed the real-world safety of inhaled insulin versus rapid-acting analogue (RAA) insulin on lung malignancy and chronic obstructive pulmonary disease (COPD) in adults with diabetes.

Materials and methods: This retrospective cohort study used the TriNetX Network to evaluate risk of lung malignancy and COPD in adults with type 1 or type 2 diabetes prescribed either inhaled insulin or RAA insulin.

Results: After propensity score matching, between the inhaled insulin versus RAA insulin cohorts there was no difference in risk of any lung cancer (n ≤ 10/2530 vs. n ≤ 10/2531, risk ratio [RR] = 1; 95% confidence interval [CI]: 0.42, 2.40, P = 0.999). The risk of developing the composite COPD outcome was greater in the inhaled insulin cohort versus the RAA insulin cohort (n = 41/2493, risk 1.6% vs. n = 12/2514, risk 0.5%; RR = 3.45; 95% CI: 1.82, 6.54, P < 0.001).

Conclusions: No association was found between inhaled insulin and any lung malignancy. Inhaled insulin was associated with a threefold increase in COPD versus RAA although the absolute risk was low. The biological plausibility of this association is not definitive. Given the retrospective design and potential for ascertainment bias, causal inference is limited although findings underscore the need for continued evaluation of inhaled insulin's pulmonary safety.

Background and aim: Very young children with type 1 diabetes (T1D) and low total daily dose (TDD) struggle to achieve optimal glucose control despite hybrid closed-loop (HCL) system. The aim of the study was to evaluate the impact of diluted insulin on glucose control in a real-world setting.

Methods: This retrospective multicentric French study included 35 children with T1D (below 6 years of age) using CamAPS FX HCL system. Participants were transitioned from U100 insulin to a diluted formulation (U10, U20, or U50). Clinical and continuous glucose monitoring (CGM) data were collected before (predilution) and at 1, 3, and 6 months postdilution. Comparisons between predilution and each postdilution period were performed using linear mixed models.

Results: Participants had a median TDD of 9.7 (7.7-11.4) UI/day before dilution and a suboptimal glucose control. Insulin dilution was associated with a reduction of time below range (TBR₇₀), glucose variability (coefficient of variation) and pump alarms during the night, with TBR₇₀ decreasing by 3-fold between 4 to 7AM. Transition to diluted insulin led to a significant increase of time in range (TIR_70-180) and a decrease of time above range (TAR₁₈₀) by, respectively, 1.5 h and 1 h per day. These results were observed independently of the time of dilution. No episodes of severe hypoglycemia or ketoacidosis occurred during the follow-up.

Conclusions: In very young children with T1D and low TDD who are exhibiting suboptimal glucose control despite HCL, insulin dilution may be a safe and efficient option.

Background: Automated insulin delivery (AID) systems integrate continuous glucose monitoring (CGM) and insulin pumps with algorithms that adjust insulin delivery. While randomized controlled trials (RCTs) demonstrate improvements in glycemic outcomes with AID, large-scale real-world data (RWD) analyses are needed to evaluate performance in routine care.

Methods: This retrospective, registry-based cohort study included adults (≥18 years) with type 1 diabetes (T1D) in the Swedish National Diabetes Register (NDR) from 2014 to 2024. Hemoglobin (Hb)A1c values were averaged per person-year and aggregated by clinic. Insulin delivery/glucose monitoring combinations included multiple daily injections (MDIs) with blood glucose meter (MDI-BG), MDI with CGM (MDI-CGM, reference), conventional continuous subcutaneous insulin infusion with blood glucose meter (CSII-BG), CSII with CGM (CSII-CGM), and AID systems (Tandem Control-IQ technology, Medtronic 670G, and Medtronic 780G). Mixed-model regression assessed HbA1c outcomes, with treatment, year, age, diabetes duration, gender, body mass index, physical activity level, smoking habits, and clinic size as fixed effects; with random effects for clinics; and weighting by clinic sample size.

Results: After adjusting for the covariates, AID systems were associated with significantly lower HbA1c compared with MDI-CGM: β = -4.0 mmol/mol (95% confidence interval [CI] -4.3 to -3.7, P < 0.001), with individual system effects, Tandem Control-IQ technology β = -4.8 mmol/mol (95% CI -5.2 to -4.5, P < 0.001), Medtronic 780G β = -3.1 (-3.5 to -2.7, P < 0.001), and Medtronic 670G β = -2.9 (95% CI -3.5 to -2.4, P < 0.001). CSII-CGM also outperformed MDI-CGM: β = -1.7 mmol/mol (95% CI -1.9 to -1.4, P < 0.001). Differences between the Tandem and Medtronic AID systems were significant (P < 0.001).

Conclusions: In a nationwide RWD analysis, AID use was consistently associated with clinically and statistically significant HbA1c reductions in adults with T1D, with the greatest effect for Tandem Control-IQ technology. These findings align with RCTs and international RWD, supporting AID as a preferred technology in routine diabetes care for T1D.

Introduction: Optimizing hybrid closed-loop (HCL) performance around exercise in children with type 1 diabetes (T1D) is challenging.

Methods: In this prospective, randomized, controlled pilot study conducted during a 7-day holiday camp, participants using Medtronic MiniMed 780 G and continuous glucose monitoring (CGM) were randomized to two strategies of HCL use for physical activity (1-2 sessions/day): pump kept connected in auto-mode versus suspended and disconnected. Meal boluses before exercise were not reduced, and all participants used 90-min pre-exercise temporary glucose target 150 mg/dL.

Results: Of 20, 8 and 7 participants from connected and disconnected arms were eligible for analysis. Median age was 11 (10-11) years, diabetes duration was 1.6 (0.7-6.0) years, HbA1c was 6.4 (6.05-7.3)% (46, 43-56 mmol/mol), and BMI z-score was -0.25 (-0.53-1.36). HCL exercise disconnection resulted in lower time below range <70 mg/dL [3.9 mmol/L] during camp (-2.91 ± 1.3%point difference, P = 0.0250), with no difference in time in range 70-180 mg/dL [3.9-10.0 mmol/L] (+0.3 ± 4.8%point, P = 0.1677).

Conclusion: Temporary HCL disconnection for exercise significantly reduces hypoglycemia risk without compromising glucose control.

Purpose: To identify retinal microvascular features that distinguish normoglycemia from diabetes mellitus (DM)[Study-1] and prediabetes (PreDM)[Study-2] among Asian Indians using artificial intelligence (AI); evaluate their diagnostic accuracy; and examine independent associations of oculomics scores [Oculomic Diabetes Score (ODiS) and Prediabetes Score (OPreS)] with glycemic status.

Methods: We analyzed 273 retinal images from 139 participants (19 = normoglycemia, 100 = DM, 20 = PreDM; mean age: 49.4 ± 12.9 yrs; male: 71.2%) with dataset randomly split (50:50) into training and test sets. We extracted 226 quantitative vessel tortuosity features separately for arteries and veins using machine vision-based approaches. Top six discriminating features were separately selected (using Wilcoxon Rank-Sum test and Linear Discriminant Analysis) on training sets and validated on independent blinded test sets. Model performances were evaluated using area under precision-recall curve (AUPRC) for DM and area under the receiver operating characteristic curve (AUC) for PreDM. Independent association of ODiS and OPreS (adjusting for age, sex, height, weight, blood pressure, serum cholesterol, serum creatinine) was assessed by multivariable logistic regression.

Results: Specific oculomics-based retinal vascular features distinguished DM/PreDM from normoglycemia. Vein-only model achieved AUPRC = 0.96 (95% confidence interval [95% CI]: 0.9-1.00) (sensitivity = 95%, specificity = 72.2%, precision = 95%) on S_v1 for DM and an AUC = 0.80 (95% CI: 0.63-0.94) (sensitivity = 70%, specificity = 80%, precision = 82.35%) on S_v2 for PreDM. Oculomics scores were independently associated with DM(ODiS) [Adjusted Odds ratio (AdjOR): 2.00 (95% CI: 1.56-2.57, P < 0.001)] but not with PreDM(OPreS) [AdjOR: 1.32 (95% CI: 0.65-2.71, P = 0.48)].

Conclusions: In this proof-of-concept study, AI-informed retinal venous features on routine fundus images, with further prospective and multisite validation, could potentially serve as noninvasive DM detection using AI models among Asian Indians.

Background: Inhalation of technosphere insulin (TI) has been shown to significantly reduce postmeal glucose excursions compared with injections of rapid-acting analogue (RAA) insulin in people with diabetes. However, TI has not gained widespread use in part due to concern about pulmonary toxicity, although clinical trials have not suggested a safety signal. To evaluate the pulmonary toxicity of TI, an analysis was performed using real-world data (RWD) in the Epic Cosmos database of approximately 300 million patients.

Methods: From the Cosmos database, individuals with diabetes were identified who had at least two prescriptions for TI (cases) or RAA insulin with no TI prescriptions ("controls") between January 1, 2015, and October 8, 2024, with >365 days between the first and last prescription. The first TI or RAA prescription was considered as the index date. Exclusion criteria for selection of cases and controls included diagnoses or testing suggesting increased risk of pulmonary disease prior to or within 1 year postindex date. Controls were matched 3:1 to cases on a variety of factors. Outcomes were assessed for diagnosis codes for lung cancer, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis at least 1 year after the index date.

Results: Inclusion criteria were met for 647 cases, which were matched to 1830 controls. Beginning 1 year postindex date, a lung cancer diagnosis was recorded in no cases and in two controls (0.11%), while a diagnosis of COPD, emphysema, or chronic bronchitis was recorded in 1 (0.16%) case and in 27 (1.48%) controls (odds ratio = 0.107, 95% CI: 0.014-0.787, P = 0.007).

Conclusions: While there are limitations to the interpretation of results from a study using RWD, it is reassuring that there was no increase in pulmonary toxicity attributable to inhaled TI for treatment of diabetes with respect to lung cancer, COPD, emphysema, and chronic bronchitis.

Objective: To evaluate the long-term effectiveness and safety of the AndroidAPS (AAPS) system in adults with type 1 diabetes (T1D) under real-world clinical conditions.

Methods: This retrospective, single-center study included 27 adults with T1D (mean age 39 ± 9.6 years; 55.6% women; diabetes duration 21.5 ± 11.3 years) who initiated AAPS and were followed for 12 months. Glycemic metrics were obtained from real-time continuous glucose monitoring (rtCGM) data. Primary outcomes were changes in time in range (TIR; 70-180 mg/dL) and HbA1c. Secondary outcomes included time in tight range (TITR; 70-140 mg/dL), time below range (TBR), coefficient of variation (CV), and the glycemic risk index (GRI). Safety outcomes included severe hypoglycemia and diabetic ketoacidosis (DKA).

Results: TIR increased from 67.8% at baseline to 84.1% at 6 months and 79.9% at 12 months (P < 0.001). HbA1c decreased from 6.6% to 6.1% and 6.0%, respectively. TITR improved by 14.8% at 6 months and 10.6% at 12 months, while GRI decreased from 40.2 to 21.3. Over 88% of participants achieved TIR > 70% and CV < 36% at both follow-ups, and up to 74% achieved TITR > 50% at 6 months, remaining at 63% at 12 months. No episodes of severe hypoglycemia or DKA were reported.

Conclusions: AAPS demonstrated sustained long-term effectiveness and safety in adults with T1D under real-world clinical practice conditions. Glycemic outcomes were comparable to those reported with commercially available closed-loop automated insulin delivery systems, supporting AAPS as a viable and effective advanced management option for T1D.

Introduction and Objective: Fasting presents unique metabolic challenges for individuals with T1D. The 25-h Yom Kippur complete fast provides an opportunity to evaluate whether automated insulin delivery (AID) systems can maintain metabolic stability, prevent hypoglycemia and ketosis, and determine basal insulin requirements during prolonged fasting. Methods: This real-world, noninterventional study included 54 adolescents and young adults with T1D (mean age 17.3 ± 3.3 years, HbA1c 6.8 ± 1.0%). Participants used MiniMed 780 G (n = 34), Control-IQ (n = 10), or open-source AID systems (n = 10). Common system-specific adjustments included setting a 150 mg/dL exercise target, activating sleep mode, and modifying basal or glucose targets, while 11 participants made no changes. Ketone levels were measured after the 25-h fast and a routine overnight fast. Analyses compared glucose and insulin across fasting periods and different 780 G settings and assessed predictors of hypoglycemia and ketone levels. Results: All participants successfully completed the fast. Mean TIR increased from 71.6 ± 13.9% during routine days to 82 ± 13.2% during fasting (P < 0.01), while time <70 mg/dL decreased from 2.6% to 2.2% (P = 0.017). Ten mild hypoglycemic events occurred after the pre-fast meal and one during fasting. A higher baseline percentage of time <70 mg/dL was the only predictor of hypoglycemia. No significant difference was found between 780 G users with exercise mode and those with no or minor changes. Participants received 43.4 ± 16.8% (range 9.3%-90%) of their usual insulin dose. Median (IQR) end-of-fast ketone levels were 0.4 (0.3, 0.7) mmol/L vs 0.1 (0, 0.1) mmol/L on a regular morning (n = 31); insulin doses <30% of usual dose were associated with higher ketone levels. No severe hypoglycemia or serious adverse events occurred. Conclusion: AID systems enable safe 25-h fasting by maintaining glucose control and reducing the risk of hypoglycemia and ketonuria. Fasting adjustments should be individualized and can often be minor.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) with or without glucose-dependent insulinotropic polypeptide (GIP) are Food and Drug Administration approved for patients with type 2 diabetes (T2D) and weight loss and are increasingly being used off-label in patients with type 1 diabetes (T1D). We evaluated all-cause mortality and health care resource utilization (HCRU) among patients with T1D receiving GLP-1 RA or GLP-1 RA/GIP dual agonist over a 2-year period. Methods: Using the TriNetX database, we identified patients with T1D using ICD-10 codes, excluding those with T2D or sodium-glucose cotransporter-2 inhibitor use. Patients with T1D were divided into two cohorts of 4212 patients each based on whether or not they received a GLP-1 single/dual receptor agonist (comparison cohort vs. control cohort). We performed 1:1 propensity matching for demographics (age, sex, race), body mass index, hemoglobin A1c, and several comorbidities. Primary outcomes included all-cause mortality, HCRU, endoscopic procedures, and use of gastrointestinal prescriptions. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for all outcomes except all-cause mortality, for which Cox regression analysis was performed to obtain the hazard ratio (HR) over 2 years. Results: The cohorts were predominantly white and female. Compared to the control cohort, patients taking GLP-1 single/dual receptor agonists had lower rates of all-cause mortality (HR = 0.18, 95% CI: 0.11-0.30, P < 0.0001), all-cause hospitalizations (OR = 0.30, 95% CI: 0.20-0.45, P < 0.0001), emergency department (ED) visits (OR = 0.56, 95% CI: 0.43-0.71, P < 0.0001), endoscopy use (OR = 0.52, 95% CI: 0.38-0.70, P < 0.0001), laxative prescription (OR = 0.52, 95% CI: 0.43-0.63, P < 0.0001), and prokinetic prescription (OR = 0.74, 95% CI: 0.57-0.96, P = 0.0238). No significant differences were observed for diabetic ketoacidosis (P = 0.1030), antiemetic prescription (P = 0.2950), and hypoglycemia (P = 0.7474). Discussion: These findings suggest that use of GLP-1 RA/GIP analogs in patients with T1D was associated with significantly lower HCRU, including hospitalizations and ED visits, and reduced all-cause mortality. Further studies are warranted to confirm these observational findings.