Turning the tides: achieving rapid and safe glucose control in adolescents with suboptimally controlled type 1 diabetes using advanced hybrid closed loop systems.

Aim: Many adolescents with T1D experience a decline in metabolic control due to erratic eating habits and subpar adherence to treatment regimens. The objective of our retrospective observational study was to assess the effect of the Tandem Control IQ (CIQ) advanced hybrid closed-loop (AHCL) system on a cohort of adolescents with suboptimal glucose control. Methods: We retrospectively evaluated 20 non-adherent patients with T1D, who were inconsistently using Multiple Daily Injections (MDIs) and flash glucose monitoring and were subsequently started and on CIQ. Glucometrics and the Glucose Risk Index were assessed at baseline and after 2 weeks, 1 month, and 6 months of CIQ use. Results: The study included 20 adolescents with T1D (HbA1c: 10.0% ± 1.7). Time in range (TIR) increased from 27.1% ± 13.7 at baseline to 68.6% ± 14.2 at 2 weeks, 66.6% ± 10.7 at 1 month, and 60.4% ± 13.3 at 6 months of CIQ use. Time above range (TAR) >250 mg/dL decreased from 46.1% ± 23.8 to 9.9% ± 9.5 at 2 weeks, 10.8% ± 6.1 at 1 month, and 15.5% ± 10.5 at 6 months of AHCL use. Mean glucose levels improved from 251 mg/dL ± 68.9 to 175mg/dL ± 25.5 after 6 months of CIQ use. The Glucose Risk Index (GRI) also significantly reduced from 102 to 48 at 6 months of CIQ. HbA1c also improved from 10.0% ± 1.7 at baseline to 7.0% ± 0.7 after 6 months. Two patients experienced a single episode of mild diabetic ketoacidosis (DKA). Conclusions: AHCL systems provide a significant, rapid, and safe improvement in glucose control. This marks a pivotal advancement in technology that primarily benefited those who were already compliant.

Type 1 diabetes care delivery in Yaoundé, Cameroon: Social and political representations.

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.

Differences in F pocket impact on HLA I genetic associations with autoimmune diabetes.

Introduction: Human leukocyte antigen (HLA) I molecules present antigenic peptides to activate CD8+ T cells. Type 1 Diabetes (T1D) is an auto-immune disease caused by aberrant activation of the CD8+ T cells that destroy insulin-producing pancreatic ß cells. Some HLA I alleles were shown to increase the risk of T1D (T1D-predisposing alleles), while some reduce this risk (T1D-protective alleles). Methods: Here, we compared the T1D-predisposing and T1D-protective allotypes concerning peptide binding, maturation, localization and surface expression and correlated it with their sequences and energetic profiles using experimental and computational methods. Results: T1D-predisposing allotypes had more peptide-bound forms and higher plasma membrane levels than T1D-protective allotypes. This was related to the fact that position 116 within the F pocket was more conserved and made more optimal contacts with the neighboring residues in T1D-predisposing allotypes than in protective allotypes. Conclusion: Our work uncovers that specific polymorphisms in HLA I molecules potentially influence their susceptibility to T1D.

Analysis and dynamical structure of glucose insulin glucagon system with Mittage-Leffler kernel for type I diabetes mellitus.

In this paper, we propose a fractional-order mathematical model to explain the role of glucagon in maintaining the glucose level in the human body by using a generalised form of a fractal fractional operator. The existence, boundedness, and positivity of the results are constructed by fixed point theory and the Lipschitz condition for the biological feasibility of the system. Also, global stability analysis with Lyapunov's first derivative functions is treated. Numerical simulations for fractional-order systems are derived with the help of Lagrange interpolation under the Mittage-Leffler kernel. Results are derived for normal and type 1 diabetes at different initial conditions, which support the theoretical observations. These results play an important role in the glucose-insulin-glucagon system in the sense of a closed-loop design, which is helpful for the development of artificial pancreas to control diabetes in society.

Association of autoimmune and allergic diseases with senile cataract: a bidirectional two-sample Mendelian randomization study.

Background: Many observational studies have been reported that patients with autoimmune or allergic diseases seem to have a higher risk of developing senile cataract, but the views are not consistent. In order to minimize the influence of reverse causality and potential confounding factors, we performed Mendelian Randomization (MR) analysis to investigate the genetic causal associations between autoimmune, allergic diseases and senile cataract. Methods: Single nucleotide polymorphisms associated with ten common autoimmune and allergic diseases were obtained from the IEU Open genome-wide association studies (GWAS) database. Summary-level GWAS statistics for clinically diagnosed senile cataract were obtained from the FinnGen research project GWAS, which consisted of 59,522 individuals with senile cataracts and 312,864 control individuals. MR analysis was conducted using mainly inverse variance weighted (IVW) method and further sensitivity analysis was performed to test robustness. Results: As for ten diseases, IVW results confirmed that type 1 diabetes (OR = 1.06; 95% CI = 1.05-1.08; p = 2.24×10-12), rheumatoid arthritis (OR = 1.05; 95% CI = 1.02-1.08; p = 1.83×10-4), hypothyroidism (OR = 2.4; 95% CI = 1.42-4.06; p = 1.12×10-3), systemic lupus erythematosus (OR = 1.02; 95% CI = 1.01-1.03; p = 2.27×10-3), asthma (OR = 1.02; 95% CI = 1.01-1.03; p = 1.2×10-3) and allergic rhinitis (OR = 1.07; 95% CI = 1.02-1.11; p = 2.15×10-3) were correlated with the risk of senile cataract. Celiac disease (OR = 1.04; 95% CI = 1.01-1.08; P = 0.0437) and atopic dermatitis (OR = 1.05; 95% CI = 1.01-1.10; P = 0.0426) exhibited a suggestive connection with senile cataract after Bonferroni correction. These associations are consistent across weighted median and MR Egger methods, with similar causal estimates in direction and magnitude. Sensitivity analysis further proved that these associations were reliable. Conclusions: The results of the MR analysis showed that there were causal relationships between type 1 diabetes, rheumatoid arthritis, hypothyroidism, systemic lupus erythematosus, asthma, allergic rhinitis and senile cataract. To clarify the possible role of autoimmune and allergy in the pathophysiology of senile cataract, further studies are needed.

Family-based association of HLA-DRB1 and DQB1 alleles and haplotypes in a group of Iranian Type 1 diabetes children.

This family-based study was conducted in a group of Iranians with Type 1 diabetes (T1D) to investigate the transmission from parents of risk and non-risk HLA alleles and haplotypes, and to estimate the genetic risk score for this disease within this population. A total of 240 T1D subjects including 111 parent-child trios (111 children with T1D, 133 siblings, and 222 parents) and 330 ethnically matched healthy individuals were recruited. High-resolution HLA typing for DRB1/DQB1 loci was performed for all study subjects (n = 925) using polymerase chain reaction-sequence-specific oligonucleotide probe method. The highest predisposing effect on developing T1D was conferred by the following haplotypes both in all subjects and in probands compared to controls: DRB1*04:05-DQB1*03:02 (Pc = 2.97e-06 and Pc = 6.04e-10, respectively), DRB1*04:02-DQB1*03:02 (Pc = 5.94e-17 and Pc = 3.86e-09, respectively), and DRB1*03:01-DQB1*02:01 (Pc = 8.26e-29 and Pc = 6.56e-16, respectively). Conversely, the major protective haplotypes included DRB1*13:01-DQB1*06:03 (Pc = 6.99e-08), DRB1*15:01-DQB1*06:02 (Pc = 2.97e-06) in the cases versus controls. Also, DRB1*03:01-DQB1*02:01/DRB1*04:02|05-DQB1*03:02 and DRB1*03:01-DQB1*02:01/DRB1*03:01-DQB1*02:01 diplotypes conferred the highest predisposing effect in the cases (Pc = 8.65e-17 and Pc = 6.26e-08, respectively) and in probands (Pc = 5.4e-15 and Pc = 0.001, respectively) compared to controls. Transmission disequilibrium test showed that the highest risk was conferred by DRB1*04:02-DQB1*03:02 (Pc = 3.26e-05) and DRB1*03:01-DQB1*02:01 (Pc = 1.78e-12) haplotypes and the highest protection by DRB1*14:01-DQB1*05:03 (Pc = 8.66e-05), DRB1*15:01-DQB1*06:02 (Pc = 0.002), and DRB1*11:01-DQB1*03:01 (Pc = 0.0003) haplotypes. Based on logistic regression analysis, carriage of risk haplotypes increased the risk of T1D development 24.5 times in the Iranian population (p = 5.61e-13). Also, receiver operating characteristic curve analysis revealed a high predictive power of those risk haplotypes in discrimination of susceptible from healthy individuals (area under curve: 0.88, p = 5.5e-32). Our study highlights the potential utility of genetic risk assessment based on HLA diplotypes for predicting T1D risk in individuals, particularly among family members of affected children in our population.

Access to Specialty Care for Commercially Insured Youths With Type 1 and Type 2 Diabetes.

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.

COCCOS study: Developing a transition program for adolescents with chronic conditions using Experience-Based Co-Design. A study protocol.

BACKGROUND: During adolescence, adolescents and young adults (AYAs) are expected to transfer their care from the pediatric environment towards an adult-focused setting. To prevent an abrupt transfer of care, it is recommended to provide AYAs with chronic conditions an adequate transition program. The aim of this paper is to describe the study protocol for the development of a transition program for AYAs with common chronic conditions (COCCOS study), using the Experience-Based Co-Design (EBCD) methodology. METHODS AND ANALYSIS: A qualitative, participatory study is conducted in Flanders (Belgium). Study participants are AYAs (n≥15, 14-25 years old, diagnosed with type 1 diabetes, asthma, or obesity), their families, and healthcare providers (n≥15). The study is composed of eight EBCD stages: clinical site observations, in-depth interviews, trigger film, healthcare providers' feedback event, AYAs' feedback event, joint event, co-design workshops, and a celebration event. Photovoice will take place as a starting point of EBCD. Data will be analyzed using thematic analysis. RESULTS: Data collection has started in January 2023 and is expected to be completed in May 2024. As of August 2023, over 15 clinical site observations have been conducted. A total of 18 AYAs, two parents, six healthcare providers have been enrolled and a total of 20 interviews have been conducted. CONCLUSION: Advancing transitional care is essential for tackling negative health outcomes. Applying the innovative participatory EBCD methodology will reveal key elements of transitional care for AYAs with common chronic conditions in the development of a person-centered transition program. PRACTICE IMPLICATIONS: Study findings will apply key elements of transitional care of AYAs with chronic conditions in the development of an adequate transition program.

Impact on diabetes control and patient-reported outcomes of a newer implantable continuous glucose monitoring system (Eversense® CGM System): a single-centre retro- and prospective observational study.

AIMS OF THE STUDY: The Eversense® CGM System is the first and only continuous glucose monitoring system (CGMS) that uses a fully subcutaneous implanted sensor. This study aimed to evaluate effectiveness, safety and patient-reported outcomes in patients using the Eversense® CGM System in a realistic clinical setting, assessed at a single Swiss diabetes centre (Luzerner Kantonsspital) with prolonged follow-up. METHODS: This was a prospective and retrospective observational study that included patients with type 1 diabetes mellitus in whom at least one Eversense® glucose sensor was implanted between 2017 and 2022. The primary endpoint was the change in HbA1c levels from the baseline (before implantation of the sensor) to 6 ± 2 and 12 ± 2 months and the last follow-up (newest available value) after implantation. The secondary outcome measures were the number of premature sensor breakdowns, adverse events related to the implantation procedure (infection, bleeding, difficulties with implantation or explantation) and patient-related outcomes (assessed with a questionnaire). RESULTS: A total of 33 patients participated in this study. The median follow-up time was 50 (IQR 22.3-58.5) months. In total, 178 sensor implantations were performed. Valid HbA1c results were available for 26 participants. Compared to the baseline values, HbA1c levels at 6 and 12 months and the last follow-up changed by -0.25%, -0.45 and -0.2 (p = 0.278, 0.308 and 0.296, respectively). We recorded 16 (9%) premature sensor breakdowns, all occurring between 2019 and 2020. Apart from one late-onset infection and four complicated sensor removals, no major complications were assessed. The results of the questionnaire showed a subjective improvement in hypoglycaemia rates, a better perception of hypoglycaemia and the impression of better diabetes management. Common issues with the device reported by the patients were technical errors (connection problems) and problems with the removal procedure. CONCLUSIONS: The use of the Eversense® CGM System resulted in changes in HbA1c of between -0.2% and -0.45%. The rate of premature sensor breakdown was low. Major complications following sensor implantation or removal were absent, apart from one case of infection and four cases of complicated removal. Patient-reported outcomes with the Eversense® CGM System showed a subjective positive impact on hypoglycaemia rates, greater confidence in managing hypoglycaemia and diabetes in general, and easy handling of the transmitter and mobile app. Technical issues must be considered but are nowadays, with the use of the newest sensor generation, very rare.

TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

Nephro-protective effects of alpha-lipoic acid in type I diabetes.

Type 1 diabetes (T1D) is an insulin-dependent autoimmune condition. Short chain fatty acids (SCFAs) are volatile fatty acids with 1-6 carbon atoms that influence glucose storage in the body and can reduce appetite, potentially decreasing T1D risk. Alpha-lipoic acid (α-LA), a type of SCFA, has previously been used to treat diabetic neuropathy and inflammation due to its antioxidant properties. This study aims to assess α-LA's protective effects against T1D and associated kidney damage in rats induced with streptozotocin. Diabetic rats were treated with α-LA orally for 15 days, resulting in improved blood glucose (56% decrease) and kidney function markers like blood urea nitrogen, creatinine and uric acid. α-LA also showed significant antioxidant effects by decreasing LPO as well as improving activities of antioxidant enzymes like superoxide dismutase, catalase and glutathione-S transferase and alleviated kidney damage caused by diabetes. Docking experiments suggest that α-LA may regulate diabetes-related changes at the epigenetic level through interactions with the SIRT1 protein, indicating its potential as a target for future antidiabetic drug development.

Efficacy of the hybrid closedloop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis.

The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucoselevel was > 180 mg/dL (WMD-10.46%, 95% CI-13.99 to-6.93%) and the mean levels of glucose (WMD-16.67 mg/dL, 95% CI-22.25 to-11.09 mg/dL) and HbA1c (WMD-0.50%, 95% CI-0.68 to-0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population.

Bioengineered MSCCxcr2 transdifferentiated keratinocyte-like cell-derived organoid potentiates skin regeneration through ERK1/2 and STAT3 signaling in diabetic wound.

Skin regeneration is severely compromised in diabetic foot ulcers. Allogeneic mesenchymal stem cell (MSC) transplantation is limited due to the poor engraftment, mitogenic, and differentiation potential in the harsh wound microenvironment. Thus, to improve the efficacy of cell therapy, the chemokine receptor Cxcr2 was overexpressed in MSCs (MSCCxcr2). CXCL2/CXCR2 axis induction led to the enhanced proliferation of MSCs through the activation of STAT3 and ERK1/2 signaling. Transcriptional upregulation of FGFR2IIIb (KGF Receptor) promoter by the activated STAT3 and ERK1/2 suggested trans-differentiation of MSCs into keratinocytes. These stable MSCCxcr2 in 2D and 3D (spheroid) cell cultures efficiently transdifferentiated into keratinocyte-like cells (KLCs). An in vivo therapeutic potential of MSCCxcr2 transplantation and its keratinocyte-specific cell fate was observed by accelerated skin tissue regeneration in an excisional splinting wound healing murine model of streptozotocin-induced type 1 diabetes. Finally, 3D skin organoids generated using MSCCxcr2-derived KLCs upon grafting in a relatively avascular and non-healing wounds of type 2 diabetic db/db transgenic old mice resulted in a significant enhancement in the rate of wound closure by increased epithelialization (epidermal layer) and endothelialization (dermal layer). Our findings emphasize the therapeutic role of the CXCL2/CXCR2 axis in inducing trans-differentiation of the MSCs toward KLCs through the activation of ERK1/2 and STAT3 signaling and enhanced skin regeneration potential of 3D organoids grafting in chronic diabetic wounds.

New and old criteria for diagnosing celiac disease: do they really differ? A retrospective observational study.

BACKGROUND: The aim of this study is to compare two groups of celiac patients: the first one, in which diagnosis was based on a "biopsy sparing" approach according to the 2012 ESPGHAN criteria, and the second one, based on the biopsy approach like the one of the 1991 Revised Criteria, in order to find relevant difference for sex, M/F ratio, age at diagnosis, clinical features at the onset, presence and prevalence of concomitant autoimmune disorders. METHODS: Our study involves 61 patients having the Celiac Disease (CD) onset from February 2013 to February 2020. The 32 patients who received diagnosis according "biopsy sparing" criteria were enrolled in group (1) The 29 patients who received diagnosis by duodenal biopsy were enrolled in group (2) Prevalence of comorbidities was analysed through chi-square test. RESULTS: In group 1 the prevalence of comorbidities such as Insulin-Dependent Diabetes Mellitus (IDDM) and thyroiditis was of 53%, while in group 2 it was only of 24%. Analysing the IDDM prevalence between the two groups we found a relevant difference. At the same time, the prevalence of thyroiditis was also significantly different. In group 1, male patients, in particular, would seem to have a higher incidence of CD related autoimmune disorders. CONCLUSIONS: An increased prevalence of IDDM, thyroiditis and juvenile idiopathic arthritis (JIA) in the first group would show that the "biopsy sparing" approach could expose patients to a greater length of disease activity that might be responsible for the onset of such comorbidities. Further studies should be carried out on more numerous samples of patients in order to confirm or not these data.