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1.
Tunis Med ; 102(4): 205-211, 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38746959

AIM: To assess the effect of diabetes self-management education (DSME) on health related quality of life (HRQoL) of Tunisian children/adolescents with type 1 diabetes mellitus and their parents. METHODS: This monocentral study used a randomized controlled trial design, during five-month intervention and five-month follow-up and including 110 patients (54 in the DSME intervention group and 56 in the Individual Education by Pediatrician (IEP) control group) and their parents. Pediatric Generic Core Quality-of-Life Inventory 4.0-Scale (PedsQL4.0) evaluated HRQoL. RESULTS: At baseline, both groups had similar clinical features and PedsQL4.0 scores (p>0.05). In DSME, clinical outcomes were significantly improved from baseline to follow-up (p<0.001), while in the IEP group, which received no intervention, these outcomes remained unchanged. During follow-up, DSME showed higher PedsQL4.0 scores in parents' proxy-report and children/adolescents self-report (p<0.001). According to parents' proxy-report, PedsQL4.0 scores were significantly higher during follow-up compared to baseline in DSME (p<0.001) while they remained the same in IEP (p>0.05). DSME had higher percentage of change in the PedsQL4.0 scores than IEP (p<0.01). The median change varied from -5.01% to 0% vs 5.41% to 36.36% in IEP and DSME, respectively. CONCLUSION: Encouraging healthcare professionals to incorporate these interventions could enhance the HRQoL of diabetic children and bolster their self-esteem.


Diabetes Mellitus, Type 1 , Parents , Patient Education as Topic , Quality of Life , Self-Management , Humans , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/psychology , Tunisia , Child , Male , Female , Parents/psychology , Self-Management/education , Self-Management/methods , Self-Management/psychology , Adolescent , Patient Education as Topic/methods , Follow-Up Studies
2.
Expert Rev Endocrinol Metab ; 19(3): 217-227, 2024 May.
Article En | MEDLINE | ID: mdl-38693782

INTRODUCTION: Type 1 diabetes (T1D) mellitus is an autoimmune disease in which immune cells, predominantly effector T cells, destroy insulin-secreting beta-cells. Beta-cell destruction led to various consequences ranging from retinopathy and nephropathy to neuropathy. Different strategies have been developed to achieve normoglycemia, including exogenous glucose compensation, whole pancreas transplantation, islet transplantation, and beta-cell replacement. AREAS COVERED: The last two decades of experience have shown that indigenous glucose compensation through beta-cell regeneration and protection is a peerless method for T1D therapy. Tremendous studies have tried to find an unlimited source for beta-cell regeneration, on the one hand, and beta-cell protection against immune attack, on the other hand. Recent advances in stem cell technology, gene editing methods, and immune modulation approaches provide a unique opportunity for both beta-cell regeneration and protection. EXPERT OPINION: Pluripotent stem cell differentiation into the beta-cell is considered an unlimited source for beta-cell regeneration. Devising engineered pancreas-specific regulatory T cells using Chimeric Antigen Receptor (CAR) technology potentiates an effective immune tolerance induction for beta-cell protection. Beta-cell regeneration using pluripotent stem cells and beta-cell protection using pancreas-specific engineered regulatory T cells promises to develop a curative protocol in T1D.


Diabetes Mellitus, Type 1 , Insulin-Secreting Cells , Islets of Langerhans Transplantation , Regeneration , Humans , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/immunology , Insulin-Secreting Cells/physiology , Islets of Langerhans Transplantation/methods , Animals , Pluripotent Stem Cells , Pancreas Transplantation/methods
3.
BMJ Open ; 14(5): e075559, 2024 May 06.
Article En | MEDLINE | ID: mdl-38719287

OBJECTIVES: The purpose of this qualitative study is to describe the acceptability and appropriateness of continuous glucose monitoring (CGM) in people living with type 1 diabetes (PLWT1D) at first-level (district) hospitals in Malawi. DESIGN: We conducted semistructured qualitative interviews among PLWT1D and healthcare providers participating in the study. Standardised interview guides elicited perspectives on the appropriateness and acceptability of CGM use for PLWT1D and their providers, and provider perspectives on the effectiveness of CGM use in Malawi. Data were coded using Dedoose software and analysed using a thematic approach. SETTING: First-level hospitals in Neno district, Malawi. PARTICIPANTS: Participants were part of a randomised controlled trial focused on CGM at first-level hospitals in Neno district, Malawi. Pretrial and post-trial interviews were conducted for participants in the CGM and usual care arms, and one set of interviews was conducted with providers. RESULTS: Eleven PLWT1D recruited for the CGM randomised controlled trial and five healthcare providers who provided care to participants with T1D were included. Nine PLWT1D were interviewed twice, two were interviewed once. Of the 11 participants with T1D, six were from the CGM arm and five were in usual care arm. Key themes emerged regarding the appropriateness and effectiveness of CGM use in lower resource setting. The four main themes were (a) patient provider relationship, (b) stigma and psychosocial support, (c) device usage and (d) clinical management. CONCLUSIONS: Participants and healthcare providers reported that CGM use was appropriate and acceptable in the study setting, although the need to support it with health education sessions was highlighted. This research supports the use of CGM as a component of personalised diabetes treatment for PLWT1D in resource constraint settings. TRIAL REGISTRATION NUMBER: PACTR202102832069874; Post-results.


Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1 , Qualitative Research , Humans , Malawi , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/psychology , Male , Female , Adult , Patient Acceptance of Health Care , Middle Aged , Blood Glucose/analysis , Interviews as Topic , Hospitals, Rural , Hospitals, District , Continuous Glucose Monitoring
4.
Sci Transl Med ; 16(746): eadn2404, 2024 May 08.
Article En | MEDLINE | ID: mdl-38718135

CD4+CD25hiCD127lo/-FOXP3+ regulatory T cells (Tregs) play a key role in preventing autoimmunity. In autoimmune type 1 diabetes (T1D), adoptive transfer of autologous polyclonal Tregs has been shown to be safe in adults in phase 1 clinical trials. We explored factors contributing to efficacy of autologous polyclonal expanded Tregs (expTregs) in a randomized phase 2 multi-center, double-blind, clinical trial (Sanford/Lisata Therapeutics T-Rex phase 2 trial, ClinicalTrials.gov NCT02691247). One hundred ten treated children and adolescents with new-onset T1D were randomized 1:1:1 to high-dose (20 × 106 cells/kilogram) or low-dose (1 × 106 cells/kilogram) treatments or to matching placebo. Cytometry as well as bulk and single-cell RNA sequencing were performed on selected expTregs and peripheral blood samples from participants. The single doses of expTregs were safe but did not prevent decline in residual ß cell function over 1 year compared to placebo (P = 0.94 low dose, P = 0.21 high dose), regardless of age or baseline C-peptide. ExpTregs were highly activated and suppressive in vitro. A transient increase of activated memory Tregs was detectable 1 week after infusion in the high-dose cohort, suggesting effective transfer of expTregs. However, the in vitro fold expansion of expTregs varied across participants, even when accounting for age, and lower fold expansion and its associated gene signature were linked with better C-peptide preservation regardless of Treg dose. These results suggest that a single dose of polyclonal expTregs does not alter progression in T1D; instead, Treg quality may be an important factor.


Diabetes Mellitus, Type 1 , T-Lymphocytes, Regulatory , Humans , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/therapy , T-Lymphocytes, Regulatory/immunology , Child , Adolescent , Male , Female , Double-Blind Method , Child, Preschool , Transplantation, Autologous
6.
Afr J Prim Health Care Fam Med ; 16(1): e1-e16, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38572859

BACKGROUND:  Increasing chronic diseases challenges the health systems of low- and middle-income countries, including Cameroon. Type 1 diabetes (T1D), among the most common chronic diseases in children, poses particular care delivery challenges. AIM:  We examined social representations of patients' roles and implementation of T1D care among political decision-makers, healthcare providers and patients within families. SETTING:  The study was conducted in Yaoundé, Cameroon. METHODS:  Eighty-two individuals were included in the study. The authors conducted semi-structured interviews with policy makers (n = 5), healthcare professionals (n = 7) and patients 'parents (n = 20). Questionnaires were administered to paediatric patients with T1D (n = 50). The authors also observed care delivery at a referral hospital and at a T1D-focused non-governmental organisation over 15 days. Data were analysed using thematic content analysis and descriptive statistics. RESULTS:  Cameroonian health policy portrays patients with T1D as passive recipients of care. While many practitioners recognised the complex social and economic determinants of adherence to T1D care, in practice interactions focused on specific biomedical issues and offered brief guidance. Cultural barriers and policy implementation challenges prevent patients and their families from being fully active participants in care. Parents and children prefer an ongoing relationship with a single clinician and interactions with other patients and families. CONCLUSION:  Patients and families mobilise experience and lay knowledge to complement biomedical knowledge, but top-down policy and clinical practice limit their active engagement in T1D care.Contribution: Children with T1D and their families, policy makers, healthcare professionals, and civil society have new opportunities to contribute to person-centred care, as advocated by the Sustainable Development Goals.


Diabetes Mellitus, Type 1 , Female , Humans , Child , Diabetes Mellitus, Type 1/therapy , Cameroon , Delivery of Health Care , Health Policy , Chronic Disease
8.
Indian Pediatr ; 61(5): 486-488, 2024 May 15.
Article En | MEDLINE | ID: mdl-38655887

Children and adolescents with Type 1 diabetes (T1D) require bolus insulin before each meal, necessitating self-care activities including blood glucose checking to determine insulin dose (or check for hypoglycemia) and injecting insulin during school hours. Though these activities are essential for optimizing glycemic control, they are met with reluctance from parents, the child, school authorities, and sometimes peers. This requires ongoing education and support for the child, school staff, and other students, by the diabetes care team. Many problems of performing self-care activities can be greatly reduced by allowing them in the child's classroom itself, a strategy which offers several logistical, safety, psychological and social benefits. The glucometer and strips, continuous glucose monitoring device, insulin in a cool case, and hypoglycemia kit are kept in the teacher's custody, and used by the child as needed, under supervision. This normalizes diabetes and its care, obviates concealment of diabetes, enhances the child's and teacher's confidence, optimizes diabetes care by ensuring timely and consistent insulin dosing, encourages hypoglycemia prevention and management, and reduces the chances of the child being bullied. It also promotes acceptance of diabetes by peers and greater community awareness. Other places for self-care like the medical room or the toilet have disadvantages. Possible limitations of this strategy could be objections occasionally raised by some school staff, lack of privacy needed by adolescents, or bullying by classmates: issues which need proactive handling. The diabetes care team may do well to emphasize performing self-care activities in the classroom, working with school staff and parents to this end.


Diabetes Mellitus, Type 1 , Schools , Self Care , Humans , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Self Care/methods , Child , Adolescent , Insulin/administration & dosage , Insulin/therapeutic use , Blood Glucose Self-Monitoring/methods
10.
Diabetes Care ; 47(6): 1048-1055, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38621411

OBJECTIVE: Mixed-meal tolerance test-stimulated area under the curve (AUC) C-peptide at 12-24 months represents the primary end point for nearly all intervention trials seeking to preserve ß-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy. RESEARCH DESIGN AND METHODS: We examined data from six Type 1 Diabetes TrialNet immunotherapy randomized controlled trials in a post hoc analysis and included additional stimulated metabolic indices beyond C-peptide AUC. We partitioned the analysis into successful and unsuccessful trials and analyzed the data both in the aggregate as well as individually for each trial. RESULTS: Among trials meeting their primary end point, we identified a treatment effect at 3 and 6 months when using C-peptide AUC (P = 0.030 and P < 0.001, respectively) as a dynamic measure (i.e., change from baseline). Importantly, no such difference was seen in the unsuccessful trials. The use of C-peptide AUC as a 6-month dynamic measure not only detected treatment efficacy but also suggested long-term C-peptide preservation (R2 for 12-month C-peptide AUC adjusted for age and baseline value was 0.80, P < 0.001), and this finding supported the concept of smaller trial sizes down to 54 participants. CONCLUSIONS: Early dynamic measures can identify a treatment effect among successful immune therapies in type 1 diabetes trials with good long-term prediction and practical sample size over a 6-month period. While external validation of these findings is required, strong rationale and data exist in support of shortening early-phase clinical trials.


C-Peptide , Diabetes Mellitus, Type 1 , Immunotherapy , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/immunology , Humans , C-Peptide/blood , C-Peptide/metabolism , Immunotherapy/methods , Female , Male , Adolescent , Treatment Outcome , Randomized Controlled Trials as Topic , Child , Adult , Area Under Curve
11.
Endocrinol Metab (Seoul) ; 39(2): 191-205, 2024 Apr.
Article En | MEDLINE | ID: mdl-38572534

In the quest to combat insulin-dependent diabetes mellitus (IDDM), allogenic pancreatic islet cell therapy sourced from deceased donors represents a significant therapeutic advance. However, the applicability of this approach is hampered by donor scarcity and the demand for sustained immunosuppression. Human induced pluripotent stem cells are a game-changing resource for generating synthetic functional insulin-producing ß cells. In addition, novel methodologies allow the direct expansion of pancreatic progenitors and mature ß cells, thereby circumventing prolonged differentiation. Nevertheless, achieving practical reproducibility and scalability presents a substantial challenge for this technology. As these innovative approaches become more prominent, it is crucial to thoroughly evaluate existing expansion techniques with an emphasis on their optimization and scalability. This manuscript delineates these cutting-edge advancements, offers a critical analysis of the prevailing strategies, and underscores pivotal challenges, including cost-efficiency and logistical issues. Our insights provide a roadmap, elucidating both the promises and the imperatives in harnessing the potential of these cellular therapies for IDDM.


Diabetes Mellitus, Type 1 , Induced Pluripotent Stem Cells , Insulin-Secreting Cells , Humans , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/transplantation , Induced Pluripotent Stem Cells/cytology , Diabetes Mellitus, Type 1/therapy , Islets of Langerhans Transplantation/methods , Cell Differentiation , Insulin/metabolism , Animals , Cell Culture Techniques/methods
12.
Front Immunol ; 15: 1384406, 2024.
Article En | MEDLINE | ID: mdl-38596681

Introduction: The autoimmune response in type 1 diabetes (T1D), in which the beta cells expressing aberrant or modified proteins are killed, resembles an effective antitumor response. Defective ribosomal protein products in tumors are targets of the anti-tumor immune response that is unleashed by immune checkpoint inhibitor (ICI) treatment in cancer patients. We recently described a defective ribosomal product of the insulin gene (INS-DRiP) that is expressed in stressed beta cells and targeted by diabetogenic T cells. T1D patient-derived INS-DRiP specific T cells can kill beta cells and are present in the insulitic lesion. T cells reactive to INS-DRiP epitopes are part of the normal T cell repertoire and are believed to be kept in check by immune regulation without causing autoimmunity. Method: T cell autoreactivity was tested using a combinatorial HLA multimer technology measuring a range of epitopes of islet autoantigens and neoantigen INS-DRiP. INS-DRiP expression in human pancreas and insulinoma sections was tested by immunohistochemistry. Results: Here we report the induction of islet autoimmunity to INS-DRiP and diabetes after ICI treatment and successful tumor remission. Following ICI treatment, T cells of the cancer patient were primed against INS-DRiP among other diabetogenic antigens, while there was no sign of autoimmunity to this neoantigen before ICI treatment. Next, we demonstrated the expression of INS-DRiP as neoantigen in both pancreatic islets and insulinoma by staining with a monoclonal antibody to INS-DRiP. Discussion: These results bridge cancer and T1D as two sides of the same coin and point to neoantigen expression in normal islets and insulinoma that may serve as target of both islet autoimmunity and tumor-related autoimmunity.


Diabetes Mellitus, Type 1 , Insulinoma , Pancreatic Neoplasms , Humans , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/therapy , Autoimmunity/genetics , Insulinoma/genetics , Insulinoma/therapy , Insulinoma/complications , Autoantigens , Insulin , Epitopes , Immunotherapy/methods
13.
JAMA Netw Open ; 7(4): e245656, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38578636

Importance: Youths with type 2 diabetes are at higher risk for complications compared with peers with type 1 diabetes, though few studies have evaluated differences in access to specialty care. Objective: To compare claims with diabetes specialists for youths with type 1 vs type 2 diabetes and the association between specialist claims with multidisciplinary and acute care utilization. Design, Setting, and Participants: This cross-sectional study used Optum Clinformatics Data Mart commercial claims. Individuals included in the study were youths younger than 19 years with type 1 or 2 diabetes as determined by a validated algorithm and prescription claims. Data were collected for youths with at least 80% enrollment in a commercial health plan from December 1, 2018, to December 31, 2019. Statistical analysis was performed from September 2022 to January 2024. Main Outcomes and Measures: The primary outcome was the number of ambulatory claims from an endocrine and/or diabetes physician or advanced practice clinician associated with a diabetes diagnosis code; secondary outcomes included multidisciplinary and acute care claims. Results: Claims were analyzed for 4772 youths (mean [SD] age, 13.6 [3.7] years; 4300 [90.1%] type 1 diabetes; 472 [9.9%] type 2 diabetes; 2465 [51.7%] male; 128 [2.7%] Asian, 303 [6.4] Black or African American, 429 [9.0%] Hispanic or Latino, 3366 [70.5%] non-Hispanic White, and 546 [11.4%] unknown race and ethnicity). Specialist claims were lower in type 2 compared with type 1 diabetes (incidence rate ratio [IRR], 0.61 [95% CI, 0.52-0.72]; P < .001) in propensity score-weighted analyses. The presence of a comorbidity was associated with increased specialist claims for type 1 diabetes (IRR, 1.07 [95% CI, 1.03-1.10]) and decreased claims for type 2 diabetes (IRR, 0.77 [95% CI, 0.67-0.87]). Pooling diagnosis groups and adjusted for covariates, each additional specialist claim was associated with increased odds of a claim with a diabetes care and education specialist (odds ratio [OR], 1.31 [95% CI, 1.25-1.36]), dietitian (OR, 1.14 [95% CI, 1.09-1.19]), and behavioral health clinician (OR, 1.16 [95% CI, 1.12-1.20]). For acute care claims, each additional specialist claim was associated with increased odds of admission (OR, 1.17 [95% CI, 1.11-1.24]) but not for emergency claims (OR, 1.03 [95% CI, 0.98-1.82]). Conclusions and Relevance: This cross-sectional study found that youths with type 2 diabetes were significantly less likely to have specialist claims despite insurance coverage, indicating other barriers to care, which may include medical complexity. Access to diabetes specialists influences engagement with multidisciplinary services. The association between increasing ambulatory clinician services and admissions suggests high utilization by a subgroup of patients at greater risk for poor outcomes.


Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Humans , Male , Adolescent , Female , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/complications , Cross-Sectional Studies , Retrospective Studies , Ethnicity
14.
Front Immunol ; 15: 1375177, 2024.
Article En | MEDLINE | ID: mdl-38650946

Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness and high risk of severe hypoglycemia. However, intensive immunosuppression is required to prevent immune rejection of the graft, that may in turn lead to undesirable side effects such as toxicity to the islet cells, kidney toxicity, occurrence of opportunistic infections, and malignancies. The shortage of cadaveric human islet donors further limits islet transplantation as a treatment option for widespread adoption. Alternatively, porcine islets have been considered as another source of insulin-secreting cells for transplantation in T1D patients, though xeno-transplants raise concerns over the risk of endogenous retrovirus transmission and immunological incompatibility. As a result, technological advancements have been made to protect transplanted islets from immune rejection and inflammation, ideally in the absence of chronic immunosuppression, to improve the outcomes and accessibility of allogeneic islet cell replacement therapies. These include the use of microencapsulation or macroencapsulation devices designed to provide an immunoprotective environment using a cell-impermeable layer, preventing immune cell attack of the transplanted cells. Other up and coming advancements are based on the use of stem cells as the starting source material for generating islet cells 'on-demand'. These starting stem cell sources include human induced pluripotent stem cells (hiPSCs) that have been genetically engineered to avoid the host immune response, curated HLA-selected donor hiPSCs that can be matched with recipients within a given population, and multipotent stem cells with natural immune privilege properties. These strategies are developed to provide an immune-evasive cell resource for allogeneic cell therapy. This review will summarize the immunological challenges facing islet transplantation and highlight recent bio-engineering and cell-based approaches aimed at avoiding immune rejection, to improve the accessibility of islet cell therapy and enhance treatment outcomes. Better understanding of the different approaches and their limitations can guide future research endeavors towards developing more comprehensive and targeted strategies for creating a more tolerogenic microenvironment, and improve the effectiveness and sustainability of islet transplantation to benefit more patients.


Diabetes Mellitus, Type 1 , Graft Rejection , Islets of Langerhans Transplantation , Islets of Langerhans Transplantation/methods , Humans , Animals , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/therapy , Graft Rejection/immunology , Graft Rejection/prevention & control , Biomedical Engineering/methods , Islets of Langerhans/immunology
15.
BMC Pediatr ; 24(1): 283, 2024 Apr 27.
Article En | MEDLINE | ID: mdl-38678194

BACKGROUND: Adequate sleep and exercise are important components of the human lifestyle. Paying attention to these two factors is very important to improve the condition of children with type 1 diabetes. Therefore, this study aimed to investigate the effect of exercise on sleep habits in children with type 1 diabetes. MATERIAL & METHODS: 62 children with type 1 diabetes participated in this clinical trial. They will be divided into the intervention group (31) and the control group (31). Sleep habits were measured using the Children's Sleep Habits Questionnaire (CSHQ). All children's parents completed the CSHQ. The intervention for the experimental group consisted of 8 weeks of regular exercise program. The exercise program was prepared as an educational video and provided to parents. Paired sample t-test and ANCOVA test were used with SPSS 23. RESULTS: 62 children with an average age of 9.32 ± 2.02 were studied. Fifty-four and eight% of the children were girls and the rest were boys. The analysis of the variance test showed a significant difference (F = 144.72, P ≤ 0.01) between the average score of the sleep habits of the control group (62.45 ± 5.12) and the experimental group (47.06 ± 4.39). CONCLUSION: Sleep habits in the experimental group improved after 8 weeks of exercise training using educational videos. Exercise as a non-pharmacological treatment is an effective way to manage diabetes and improve sleep quality in diabetic children.


Diabetes Mellitus, Type 1 , Exercise , Sleep , Humans , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/therapy , Male , Female , Child , Sleep/physiology , Exercise Therapy/methods , Habits , Surveys and Questionnaires
16.
Diabetes Obes Metab ; 26(6): 2439-2445, 2024 Jun.
Article En | MEDLINE | ID: mdl-38558524

AIM: To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. RESULTS: Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1ß, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1ß, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1ß (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. CONCLUSIONS: Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN13641847).


Biomarkers , Cross-Over Studies , Diabetes Mellitus, Type 1 , Plasminogen Activator Inhibitor 1 , Postprandial Period , Walking , Humans , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/physiopathology , Female , Postprandial Period/physiology , Male , Adult , Walking/physiology , Biomarkers/blood , Plasminogen Activator Inhibitor 1/blood , Tumor Necrosis Factor-alpha/blood , Interleukin-1beta/blood , Fibrinogen/metabolism , Fibrinogen/analysis , Young Adult , Insulin Resistance , Sedentary Behavior , Inflammation/blood , Blood Glucose/metabolism , Blood Glucose/analysis
18.
J Colloid Interface Sci ; 667: 54-63, 2024 Aug.
Article En | MEDLINE | ID: mdl-38615623

Type 1 diabetes mellitus (T1DM) is a chronic disease affecting millions worldwide. Insulin therapy is currently the golden standard for treating T1DM; however, it does not restore the normal glycaemic balance entirely, which increases the risk of secondary complications. Beta-cell therapy may be a possible way of curing T1DM and has already shown promising results in the clinic. However, low retention rates, poor cell survival, and limited therapeutic potential are ongoing challenges, thus increasing the need for better cell encapsulation devices. This study aimed to develop a mechanically reinforced vascular endothelial growth factor (VEGF)-delivering encapsulation device suitable for beta cell encapsulation and transplantation. Poly(l-lactide-co-ε-caprolactone) (PLCL)/gelatin methacryloyl (GelMA)/alginate coaxial nanofibres were produced using electrospinning and embedded in an alginate hydrogel. The encapsulation device was physically and biologically characterised and was found to be suitable for INS-1E beta cell encapsulation, vascularization, and transplantation in terms of its biocompatibility, porosity, swelling ratio and mechanical properties. Lastly, VEGF was incorporated into the hydrogel and the release kinetics and functional studies revealed a sustained release of bioactive VEGF for at least 14 days, making the modified alginate system a promising candidate for improving the beta cell survival after transplantation.


Alginates , Gelatin , Hydrogels , Insulin-Secreting Cells , Vascular Endothelial Growth Factor A , Hydrogels/chemistry , Alginates/chemistry , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/cytology , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/administration & dosage , Gelatin/chemistry , Animals , Polyesters/chemistry , Rats , Cell Survival/drug effects , Humans , Diabetes Mellitus, Type 1/therapy , Methacrylates/chemistry , Angiogenesis Inducing Agents/chemistry , Angiogenesis Inducing Agents/pharmacology , Angiogenesis Inducing Agents/administration & dosage , Surface Properties
19.
BMC Med Educ ; 24(1): 345, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38539183

BACKGROUND: Diabetic ketoacidosis (DKA) is a frequent manifestation at the onset of type 1 diabetes mellitus in children, possibly associated with a wide range of complications, often as a consequence of wrong or delayed treatment. Due to its complex and risky management, direct exposure to real situations alone is not sufficient to achieve adequate skills in pediatric DKA for residents. Simulation could be a valuable aid, allowing to practice a standardized scenario of a complex real-world situation. We aimed to test the effectiveness of a standardized scenario of pediatric DKA in teaching its recognition and treatment. METHODS: We develop a standardized scenario able to guide step-by-step the learners through the flowchart of DKA management and considering alternative evolutions in the case of possible deviations from guidelines. It was a real-life simulation with the use of a high-fidelity pediatric simulator. It was played by 78 pediatrics 20 and emergency medicine residents. At the end of the simulation, a validated questionnaire was administered to collect feedback from participants regarding the impact of the simulation on learning. All materials to reproduce the DKA scenario are provided. RESULTS: Overall, the scenario was rated as realistic (mean score 4.37 ± 0.68, from 1 to 5) and relevant to professional training (4.72 ± 0.47), useful in increasing confidence in interpreting laboratory tests (3.97 ± 0.65), group organization and communication strategies (3.49 ± 0.94), and managing the treatment of DKA (3.46 ± 0.92). CONCLUSIONS: The use of a standardized scenario of pediatric DKA may be a valid tool to reinforce theoretical knowledge in residents, both in pediatrics and in emergency medicine, and to directly and safely practice pediatric DKA management.


Diabetes Mellitus, Type 1 , Diabetic Ketoacidosis , Child , Humans , Diabetic Ketoacidosis/therapy , Diabetic Ketoacidosis/complications , Cross-Sectional Studies , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/therapy , Learning , Computer Simulation
20.
Rev Prat ; 74(3): S18-S22, 2024 Mar.
Article Fr | MEDLINE | ID: mdl-38551886

TOMORROW, WHAT EVOLUTIONS IN DIABETES ? Diabetes care has undergone a major digital nutation over the past decade. The devices used to treat and monitor patients with diabetes are increasingly "connected", generating large amounts of data. These data, hosted in clouds, facilitate the development of remote monitoring and teleconsultations in diabetology. The advent of continuous glucose monitoring (CGM) and insulin pumps has also enabled the development of control algorithms (known as "hybrid closed loops" (HCL) thhat automatically modulate insulin pump delivery rate according to real-time CGM data, in order to maintain glucose level in the normal range. HCL have proved high efficacy for patients with type 1 diabetes and are currently being assessed for other insulin-requiring diabetes type. Artificial intelligence (AI), which is currently being developed for all human actiiviities, also concerns diabetology, with a wide range of future applications in screening, diagnosis, therapy, support and research.


DEMAIN, QUELLES ÉVOLUTIONS EN DIATÉTOLOGIE? La diabétologie connaît une importante mutation mumériique depuis une décennie. Les dispositifs utilisés pour le traitement et la surveillance des patients atteints de diabète sont de plus en plus "connetés", générant de grandes quantités de données. Ces données sont hébergées sur des portails de surveillance qui facilitent le développement de la télésuurveillance et des téléconsultations en diabétologie. L'avènement des capteurs de glucose interstitiel et des pompes à insuline a également permis le développement d'algorithmes de contrôle (dits" boucles fermées"[BF]) qui modulent de façon automatisée le débit de la pompe à insuline en fonction des données du capteur en temps réel, afin de maintenir le glucose le plus proche possible de la zone normale. Ces systèmes de BF ont démontré leur grande efficacité pour les patients atteints de diabète de type 1 et sont en cours d'évaluation dans d'autres situations de diabète insulinorequérant. L'intelligence artificielle (IA), en cours de développement dans toutes les activités humaines, concerne également la diabétologie, avec des applications très diverses qui concerneront demain le dépistage, le diagnstic, la thérapeutique, l'accompagnement ou encore la recherche.


Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Humans , Blood Glucose Self-Monitoring , Artificial Intelligence , Blood Glucose , Diabetes Mellitus, Type 1/therapy , Insulin
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