AIMS:Postprandial administration of ultra-fast-acting insulin (PP-UFI) may offer greater flexibility for individuals with cystic fibrosis-related diabetes (CFRD). This study evaluated whether PP-UFI provides glycaemic control comparable to standard mealtime fast-acting insulin (MT-FI). METHODS:Adults with CFRD were enrolled in an open-label, multicentre, randomized phase IV crossover trial with a two-sequence, four-period design. Participants received MT-FI or PP-UFI using connected insulin pens for 3-month periods. The primary endpoint was time in range (TIR: 70-180 mg/dL). Mixed-effects models accounted for repeated measures and treatment sequence. RESULTS:Thirty-eight participants were enrolled (mean age: 33 ± 11 years; 56% receiving CFTR modulators), and 34 were included in the intention-to-treat analysis. Baseline TIR was 74% [68-83], time below range (<70 mg/dL) was 4.1% [1.9-6.7], and ppFEV1 was 71 ± 25%. The estimated difference between MT-FI and PP-UFI was + 1.1 percentage points (95% CI: -1.1 to + 3.3; p = 0.316), with no statistically significant difference observed. Formal equivalence was not demonstrated. Other CGM metrics, HbA1c, and insulin doses were comparable between treatments. CONCLUSION:These findings support the potential of postprandial ultra-fast-acting insulin as a flexible treatment option for adults with CFRD.

This protocol details an optimized method for the production of small stable spheroids, their culture, and 3D imaging, for the study of the endothelial and insulin-producing β cells interactions in a 3D model of pancreatic islets. The 150-200 µm spheroids, mirroring the lowest range of islet sizes, were prepared from a selected ratio combining 1 intra-islet endothelial cells (MS-1 cells) to 20 insulin-secreting cells (β-TC-6). Staining, clearing, and mounting challenges of small spheroids and their tackling by employing low-melting point agarose and the CUBIC clearing technique are detailed, as well as key points for an efficient analysis of the 3D structure with different probes. Data indicate that NTPDASE-ectonucleotidase 3 does not colocalize with insulin in the spheroid model, suggesting varying maturity and functional levels of β-TC6 and that the complete procedure can also be applied to isolated pancreatic islets, with clear probing of intra-islet vessels. These findings underscore the effectiveness of the 3D imaging protocol in revealing complex pancreatic cell organization and interactions within the islet model.

A limited subset of people living with type 1 diabetes (T1D) is affected by extreme glycemic lability and frequent unpredictable severe hypoglycemia, significantly impairing quality of life and associated with higher morbidity, mortality, and healthcare costs. Islet transplantation (IT) has demonstrated efficacy in stabilizing glucose control and preventing severe hypoglycemia in these people, but it carries risks related to the procedure and chronic immunosuppression. Automated insulin delivery (AID) has emerged as a new standard of care for T1D, offering significant improvements in glycemic control. However, the efficacy of AID in patients with high glucose variability, who are eligible for IT, remains poorly evaluated. This study aims to assess the suitability of AID as a therapeutic option for these people. This prospective, multicenter cohort study involves six clinical centers experienced in both IT and AID systems. All patients referred for unstable T1D management will be considered for enrollment. According to patient’s preference, registration for IT will be processed after inclusion, or AID will be initiated and IT could be later processed according to AID outcomes. Data will include clinical, glucose control, and quality of life assessments over a follow-up period of up to 4 years. For study analysis, participants will be categorized into three groups: (1) patients immediately registered for IT, (2) patients achieving improved glycemic stability under AID, and (3) patients in whom AID fails to achieve adequate glycemic control. The primary endpoint is the proportion of patients experiencing severe hypoglycemia under AID therapy. Secondary endpoints include changes in glucose metrics based upon continuous glucose monitoring (CGM), quality of life measurements, clinical evolution, and the medico-economic impact of IT versus AID. This first study of AID in patients eligible for islet transplantation includes clinical, psychosocial, and economic outcomes. Its strengths are the comprehensive evaluation and real-world design. Findings will support evidence-based guidance for treating severe glycemic instability in T1D. n°38RC24.0169, NCT07006272, name: Cohort Study to Refine the Positioning of Closed-loop Therapy Versus Islet Transplantation in the Management of Patients With Unstable Type 1 Diabetes, Version 1.0_10.12.24. Registered on June 5, 2025.

BACKGROUND:Several studies have shown improvements in glucose control after initiating elexacaftor/tezacaftor/ivacaftor (ETI) in cystic fibrosis-related diabetes (CFRD) patients. However, ETI's impact on insulin treatment remains unclear. This observational multicenter study aimed to analyze insulin treatment characteristics in adults with preexisting CFRD after ETI treatment initiation. METHODS:Data on diabetes treatment and continuous glucose monitoring (CGM) were retrospectively collected for 1 year before and up to 2 years after ETI treatment initiation in adults with CFRD from 13 French CF centers. We analyzed the type of insulin treatment, insulin doses, daily distribution, and CGM parameters after 1 year of ETI therapy. RESULTS:From April to December 2024, 107 individuals were included. The mean age was 33.2 ± 9.3 years, 49% were female, and diabetes treatment was diet for 14%, multiple daily injections for 65%, and pump for 21% of patients. After 1 year of ETI, total and bolus insulin doses decreased significantly from 0.37 IU/kg/day (0.19-0.60) to 0.30 IU/kg/day (0.17-0.49) (P = 0.02) and from 0.27 IU/kg/day (0.14-0.50) to 0.17 IU/kg/day (0.10-0.30), P = 0.0003) respectively. Among patients on a diet, 33.3% started insulin treatment, while 6.5% of patients on insulin treatment discontinued insulin. CGM parameters showed significant decreases in time below the range <70 mg/dL (from 3% [1-8.5] to 2% [0-4], P = 0.001) and coefficient of variation (from 35% [28.7-41.7] to 33.1% [26.8-39.2], P = 0.001). CONCLUSIONS:These findings indicate a reduction in insulin doses, particularly prandial insulin, as well as decreased glucose variability and hypoglycemia following ETI therapy in CFRD patients. Further long-term studies are needed to confirm these results.

BACKGROUND AND HYPOTHESIS:While physical activity (PA) is associated in observational studies with cardiovascular and renal protection few interventional studies have assessed its long-term effect on renal outcomes. This study is the first to specifically evaluate the impact of high-intensity PA on the slowing of renal function decline in type 2 diabetes (T2D) patients at high risk for kidney disease. METHODS:ActiDiaNe is an open, randomized controlled trial involving patients with T2D (pT2D) and rapid renal function decline (eGFR slope < -5 ml/min/year over 6-24 months). Participants were randomized to high-intensity PA (HIPA) or standard PA counseling (STPA) for two years. The primary endpoint was the slope of decline in cystatin C-derived eGFR (cys-eGFR). RESULTS:Across 21 centers, 178 patients were screened, 122 randomized, and 103 (29 women/74 men) analyzed for the primary endpoint (59 HIPA vs. 44 STPA). At baseline, mean age was 66 ± 8 years, median cys-eGFR was 54 ml/min/1.73m² (37; 65), and median eGFR decline was -9 ml/min/year (-12; -7). The primary endpoint showed a decline of -2.05 ml/min/year (95% CI: -3.46 to -0.64) in HIPA vs. -2.77 ml/min/year (95% CI: -4.40 to -1.14) in STPA (P = 0.512). Cardiovascular events and deaths occurred in 10 (17%) HIPA vs. 6 (14%) STPA patients (P = 0.646), with 3 deaths in HIPA (none of them protocol-related). Hypoglycemia was reported in 32 HIPA vs. 26 STPA patients (P = 0.623). CONCLUSION:In pT2D with rapid renal function decline, HIPA did not significantly alter renal function decline compared to STPA.

OBJECTIVE:To identify baseline determinants of achieving international continuous glucose monitoring (CGM) targets after 12 months of automated insulin delivery (AID) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS:This predefined sub-analysis of the nationwide French OB2F registry included adults with type 1 diabetes initiating MiniMed 780G or Tandem Control-IQ in 2022. Participants required ≥14 consecutive days of CGM data at baseline and 12 months. The primary outcome was achievement of combined CGM targets at 12 months, defined as TIR >70% and TBR <4%. Baseline predictors were assessed using multivariable logistic regression. RESULTS:Among 1,058 adults, 43% achieved combined CGM targets at 12 months (52% of MiniMed 780G users and 36% of Tandem Control-IQ users). Better baseline metabolic control, including higher TIR and lower HbA1c, TAR, GMI, and glucose variability, was independently associated with target achievement across both systems. Lower baseline TBR predicted target achievement only in MiniMed 780G users. GRI improved in both systems, from 44.1±19.4 to 30.2±13.6 with MiniMed 780G and from 49.4±20.0 to 36.7±14.9 with Tandem Control-IQ. CONCLUSIONS:Baseline glycaemic profile is the main determinant of achieving international CGM targets after AID initiation in adults with type 1 diabetes, despite substantial improvement in those with poorer baseline control.

There is a significant need for trials that evaluate the treatment of University of Texas (UT) grade 2 and 3 diabetic foot ulcers (bone, joint, or tendon exposed wounds). We undertook a trial looking at the effect of intact fish skin graft (IFSG) on these deep and difficult-to-heal ulcers. 262 patients Intent to Treat (ITT) patients with UT grade 2 and 3 DFUs were randomised to receive intact fish skin graft (IFSG) or a standardised treatment (SOC) that adhered to the International Working Group on the Diabetic Foot (IWGDF) guidelines. The secondary endpoints that were measured included wound area reduction (WAR), healing rates at 20 and 24 weeks; closure rates by UT grade, perfusion, quality of life, pain reduction and IFSG safety. We report ITT (all randomised) (mITT previosly reported) The (WAR) at 12 weeks was 65.53% for IFSG versus 30.82% for SOC (p = 0.007). UT 2 wounds (60% of total) exhibited a closure rate of 47% versus 23% at 16 weeks for IFSG versus SOC (p = 0.0033). Target wound infections were comparable (39 vs. 37) and major outcomes were comparable during the 24 week period (target-limb amputations 8% vs. 7%). Time-to-heal favoured IFSG (restricted mean to 24 weeks 17.31 vs. 19.37 weeks; KM/log-rank significant; Cox HR 1.59). The in the treatment of deep complex diabetic foot wounds the addition of IFSG significantly improved the number of patients with total wound closure as well as the time to wound closure without increased risk of complications. This improvement in total wound closure and time to wound closure was noted across prior amputation status, quality of perfusion, and UT grade.

BACKGROUND:Systematic screening for cystic fibrosis related diabetes (CFRD) is recommended for all people living with cystic fibrosis (pwCF) from the age of 10. However, adhering to these guidelines is challenging given the cumbersome nature and potential side effects of the current test of reference, the Oral Glucose Tolerance Test (OGTT). Continuous glucose monitoring (CGM) could become an alternative to OGTT, thanks to its ease of use and to the extensive information it provides. METHODS:We present the baseline data from a prospective observational multicentric French and Canadian cohort. Concomitant OGTT, CGM and collection of clinical data were performed in adult pwCF. RESULTS:Complete data were available in 107 participants (73 with normal glucose tolerance, 24 with impaired glucose tolerance and 10 with cystic fibrosis related diabetes), of whom 63 % were treated with Elexacaftor/Tezacaftor/Ivacaftor. Glycated hemoglobin (HbA1c), time above 7.8mmol/L and time above 10mmol/L were lower in participants with normal glucose tolerance than in those with CFRD. Several CGM parameters associated more strongly with diagnosis of CFRD at OGTT than HbA1c (Area under the ROC curves: 0.88 for time above 10mmol/L and 0.87 for time above 7.8mmol/L, vs 0.61 for HbA1c). Spending more than 10 % of the time above 7.8mmol/L detected CFRD with 100 % sensitivity and 46% specificity. CONCLUSIONS:Certain CGM parameters correlated more closely with diagnosis of CFRD at OGTT than HbA1c in adult pwCF, with or without treatment by Elexacaftor/Tezacaftor/Ivacaftor. If future studies confirm these results prospectively, CGM could be used as a first step to screen for CFRD.

AIMS:Patients living with highly unstable type 1 diabetes (T1D) are eligible for beta-cell replacement (βCR) therapy (islet or pancreas transplantation). This study aimed to evaluate glycemic control in patients treated with automated insulin delivery (AID) following failed βCR therapy, defined as secondary graft failure or marginal function. MATERIAL AND METHODS:A national, multicenter, retrospective study was conducted with 23 patients who had βCR failure treated with AID for at least three months. The primary outcome was the proportion of patients achieving recommended glucose targets (time in 70-180mg/dl range [TIR] > 70 %, time below range [TBR] < 4 % and HbA1c < 7 %). Secondary outcomes included TIR, glycemia risk index (GRI), HbA1c, coefficient of variation (CV), body weight, insulin doses, severe hypoglycemia and AID discontinuation. RESULTS:The proportion of patients achieving recommended glucose targets under AID increased from 5.0 % to 57.1 % after 12 months. TIR increased from 54.2 ± 18.0 % to 75.5 ± 9.6 % after 12-month AID, while GRI decreased from 45.8 ± 22.2 % to 25.6 ± 10.3 %. HbA1c levels decreased from 7.5 ± 0.9 % to 7.0 ± 1.1 % after 12-month AID. CV, body weight and insulin doses did not change. All patients were free from severe hypoglycemia under AID, including those who had experienced severe hypoglycemia after βCR failure. No patient discontinued the AID. CONCLUSIONS:This study highlights the effectiveness of AID in achieving glucose control targets and preventing severe hypoglycemia in patients with T1D following βCR failure. AID may serve as a valuable therapeutic option to improve glucose control when graft function declines.

AIMS:Health-related quality of life (HRQoL) assessment is increasingly integrated into type 1 diabetes (T1D) monitoring to promote a holistic approach. To investigate HRQoL in adults with T1D and to assess the impact of the severity of complications on HRQoL. MATERIALS AND METHODS:This is a cross-sectional analysis of baseline characteristics of adults living with T1D included in Société Francophone du Diabète - Cohorte Diabète de Type 1 (SFDT1), a French longitudinal cohort study. HRQoL was assessed using generic (EuroQol 5-Dimensions 5-Level questionnaire [EQ-5D-5L]) and diabetes-specific (Audit of Diabetes-Dependent Quality of Life) instruments. The severity of diabetes complications was measured using an adapted Diabetes Complication Score Index (DCSI) ranging from 0 to 14. We used multiple imputations to deal with missing data. RESULTS:We included 1892 adults, 48% women, with a median (interquartile range [IQR]) age of 38 (28; 51) years. The mean overall EQ-5D-5L HRQoL score was 71.1 ± 17.7 (maximum 100), with the following number of participants negatively impacted for each domain: 271 (14%) for mobility, 94 (5%) for self-care, 378 (19%) for usual activities, 853 (45%) for pain/discomfort and 983 (52%) for anxiety/depression. The median (IQR) DCSI was 1 (0; 2). In multivariable models, a one-step increase in DCSI was associated with a 1.5% decrease in overall EQ-5D-5L HRQoL. DCSI was also inversely associated with all domains of the generic scale except anxiety/depression and 17 domains of the diabetes-specific scale. CONCLUSIONS:We observed an inverse association between the severity of complications and overall HRQoL and most of its dimensions. Our results highlight the need to reinforce the prevention of complications to improve the overall well-being of people with T1D.

Les stylos à insuline connectés représentent une avancée prometteuse pour optimiser la gestion du diabète. Cette étude évalue leur impact sur le contrôle glycémique chez des patients atteints de diabète de type 1 ou de type 2 en France. Elle repose sur une observation rétrospective et longitudinale de 5535 patients traités par multi-injections d’insuline et utilisant un dispositif de mesure du glucose en continu (CGM). Les participants avaient débuté l’utilisation d’un stylo connecté pour administrer leur insuline prandiale dans les 3 mois avant l’inclusion, et ont été suivis pendant 9 mois. Les paramètres glycémiques analysés incluent le temps dans la cible (TIR : 70–180mg/dL), en dessous de la cible (TBR : <70mg/dL), au-dessus de la cible (TAR : >180mg/dL) et le coefficient de variation glycémique inter-journalière (CV). Le TIR moyen a augmenté de 1,4 % (p<0,001) et de 0,7 % (p<0,01) après 3 et 6 mois d’utilisation du stylo connecté, respectivement. Parallèlement, le TAR moyen a diminué de –1,4 % (p<0,001) après 3 mois et de –0,6 % (p=0,047) après 6 mois. Une réduction significative du TBR moyen de –0,4 % a également été observée à 9 mois (p<0,001). Le CV a diminué de façon continue entre le début de l’étude et le 9e mois d’utilisation du stylo connecté, avec des réductions significatives de –0,5 %, –0,4 % et –0,9 % aux 3e, 6e et 9e mois, respectivement (p<0,001 pour chacune). Les patients ayant un TIR initial<40 % ont eu la plus forte augmentation du TIR, soit 6,0 % après 9 mois d’utilisation du stylo connecté. Le nombre moyen d’injections d’insuline prandiale manquées est resté stable à 0,6 par jour tout au long de l’étude. En conclusion, ces données de vie réelle en France montrent une amélioration modeste mais significative du profil glycémique des patients atteints de diabète après l’introduction d’un stylo à insuline connecté.

INTRODUCTION:The main objective : To assess the efficacy of Intact fish skin graft (IFSG) for the closure of University of Texas (UT) Grade 2 and 3 Diabetic foot ulcers (DFUs) versus local standard of care (SOC). METHODS:In the French subgroup of a multinational randomized trial, 180 (179 in primary endpoint analysis) patients with UT grade 2 and 3 DFUs (8 centers) were randomized to receive IFSG or SOC, that adhered to the International Working Group on the Diabetic Foot (IWGDF) guidelines. Primary endpoint was complete epithelialization at 16 weeks. Secondary endpoints were healing curve, percentage of wounds healed to 80 % or more in an average of 16 weeks, percentage healed at 20 weeks. RESULTS:The primary endpoint was 41.6 % closure rate in IFSG group versus 22.2 % in SOC group (P = 0.0053). In the intent to treat analysis (ITT), there was a statistically significant difference (P < 0.05) in mean relative wound area between the IFSG and SOC arms at weeks 6.The proportion of patients with complete epithelialization at 20 weeks was 2.11 times higher in the IFSG group than in the SOC group. For those patients that healed a median of 7 graft applications was required. CONCLUSIONS:In France, the addition of IFSG to the care plan of patients with deep diabetic foot wounds improved the closure rate by 41.6 % in IFSG group versus 22.2 % in SOC.

AIMS:Fear of hypoglycemia limits sports in type 1 diabetes (T1D). This study aimed to evaluate the efficacy of Diabrasport glycemic management algorithms over a week with three real-life exercise sessions. METHODS:A multicenter non-inferiority study including 43 adults with T1D using insulin pumps, continuous glucose monitoring was conducted over three one-week periods: rest, exercise with personal insulin algorithms (PersonalAlgo), and exercise with Diabrasport insulin algorithms (DiabraAlgo). The exercise period consisted of three sessions of 45-60 min per week of physical activity. DiabraAlgo included: (i) 100% basal rate reduction for intense post-absorptive exercise, (ii) 80% basal rate reduction during moderate exercise in the post-absorptive period and for two hours afterwards, and (iii) 50% prandial bolus reduction for moderate postprandial exercise. RESULTS:Hypoglycemia (<70 mg/dL) was not more frequent with DiabraAlgo (0.88 ± 0.62) during exercise than during rest (1.03 ± 0.61) (95 % CI - 0.04 to 0.33, non-inferiority margin 0.35, p < 0.001). No difference was found between PersonalAlgo and DiabraAlgo in post-absorptive exercise, but during moderate postprandial exercise, DiabraAlgo resulted in less time in hypoglycemia (6.1 ± 9.8 % vs. 10.5 ± 12.8 %, p < 0.05) and fewer hypoglycemic episodes (1.0 ± 1.1 vs. 1.4 ± 1.3, p < 0.05). CONCLUSION:DiabraAlgo enables an effective adaptation of insulin levels during exercise, promoting their immediate applicability for individuals with T1D.

The MiniMed™ 780G system uses an advanced hybrid closed loop algorithm to improve outcomes in people with type 1 diabetes (T1D). The MiniMed™ 780G Glycemic Control and Quality of Life (EQOL) study aimed to provide routine clinical practice data on system effectiveness and associated patient-reported outcomes (PROs) in France. Individuals aged ≥ 7 years with T1D were enrolled. A 14-day run-in phase in Manual mode preceded a 12-month study phase using Auto mode. The primary endpoint was absolute change in time in range (TIR) from baseline to 6 months. Secondary endpoints included changes in glycemic targets, glycated hemoglobin (HbA1c), and hypoglycemia. PROs included treatment satisfaction, quality of life (QoL), and fear of hypoglycemia. Two-hundred seventy participants formed the intent-to-treat population at 6 months. TIR increased by 11.8 percentage points (standard deviation [SD] 8.96, 95

Objective. This study aimed to evaluate the impact of islet transplantation on diabetic complications, death and cancer incidence. Research Design and Methods. This was a retrospective, multicentre, cohort study including patients from three IT clinical trials (intervention group) and from the French Healthcare database (SNDS) (control group). Two cohorts of IT recipients were analysed: IT recipients after kidney transplantation (IAK) and IT recipients alone (ITA). They were matched with patients living with T1D from the SNDS using a propensity score. The primary outcome was a composite criterion including death, dialysis, amputation, non-fatal stroke, non-fatal myocardial infarction and transient ischemic attack. Secondary outcome was cancer. Hazard Ratio (HRs) and p-values were obtained with Cox proportional hazards analysis and log-rank test respectively. Results. The study included 61 ITA recipients matched to 610 T1D controls and 45 IAK recipients matched to 45 T1D controls, over a median follow-up period >10 years. Compared with T1D control subjects, ITA and IAK recipients had a lower composite outcome risk (HR, 0.39 [95%CI, 0.21-0.71]; p=0.002 and HR, 0.52 [0.30-0.88]; p=0.014 respectively), seem driven by reduced mortality (HR, 0.22 [0.09-0.54], p<0.001) for ITA and reduced dialysis (HR, 0.19 [0.07-0.50], p<0.001) for IAK. Both groups showed no significant changes in cancer risk. Conclusions. This study suggests the long-term benefits of IT on diabetes-related outcomes. Furthermore, despite the use of immunosuppressive drugs following IT, we observed no significant increase in the risk of cancer. Altogether, these findings highlight a favourable risk-benefit ratio of IT in managing patients with unstable T1D.