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

Background: Increasing chronic diseases challenges the health systems of low- and middleincome 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 semistructured 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 nongovernmental 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.

Risk factors for ketoacidosis in children/adolescents with type 1 diabetes mellitus and establishment of a predictive model / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for diabetic ketoacidosis (DKA) in children/adolescents with type 1 diabetes mellitus (T1DM) and to establish a model for predicting the risk of DKA.@*METHODS@#A retrospective analysis was performed on 217 children/adolescents with T1DM who were admitted to General Hospital of Ningxia Medical University from January 2018 to December 2021. Among the 217 children/adolescents,169 cases with DKA were included as the DKA group and 48 cases without DKA were included as the non-DKA group. The risk factors for DKA in the children/adolescents with T1DM were analyzed, and a nomogram model was established for predicting the risk of DKA in children/adolescents with T1DM.@*RESULTS@#For the 217 children/adolescents with T1DM, the incidence rate of DKA was 77.9% (169/217). The multivariate logistic regression analysis showed that high levels of random blood glucose, hemoglobin A1c (HbA1c), blood ketone body, and triglyceride on admission were closely associated with the development of DKA in the children/adolescents with T1DM (OR=1.156, 3.2031015, 20.131, and 9.519 respectively; P<0.05). The nomogram prediction model had a C-statistic of 0.95, with a mean absolute error of 0.004 between the risk of DKA predicted by the nomogram model and the actual risk of DKA, indicating that the model had a good overall prediction ability.@*CONCLUSIONS@#High levels of random blood glucose, HbA1c, blood ketone body, and triglyceride on admission are closely associated with the development of DKA in children/adolescents with T1DM, and targeted intervention measures should be developed to reduce the risk of DKA.

Isolation of bone marrow mesenchymal stem cells in transgenic pigs and co-culture with porcine islets / 器官移植

Objective To investigate the isolation and culture of porcine bone marrow mesenchymal stem cell (BMSC) with α-1, 3-galactosyltransferase (GGTA1) gene knockout (GTKO), GTKO/ human CD46 (hCD46) insertion and cytidine monopho-N-acetylneuraminic acid hydroxylase (CMAH)/GGTA1 gene knockout (Neu5GC/Gal), and the protective effect of co-culture with porcine islets on islet cells. Methods Bone marrow was extracted from different transgenic pigs modified with GTKO, GTKO/hCD46 and Neu5GC/Gal. Porcine BMSC were isolated by the whole bone marrow adherent method and then cultured. The morphology of BMSC was observed and the surface markers of BMSC were identified by flow cytometry. Meantime, the multi-directional differentiation induced by BMSC was observed, and the labeling and tracing of BMSC were realized by green fluorescent protein (GFP) transfection. The porcine BMSC transfected with GFP were co-cultured with porcine islet cells. Morphological changes of porcine islet cells were observed, and compared with those in the porcine islet cell alone culture group. Results BMSC derived from pigs were spindle-shaped in vitro, expressing biomarkers of CD29, CD44, CD73, CD90, CD105 and CD166 rather than CD34 and CD45. These cells were able to differentiate into adipocytes, osteoblasts and chondrocytes. Porcine BMSC with GFP transfection could be labeled and traced, which could be stably expressed in the daughter cells after cell division. Porcine BMSC exerted certain protective effect on islet cells. Conclusions GFP-labeled porcine BMSC modified with GTKO, GTKO/hCD46 and Neu5GC/Gal are successfully established, which exert certain protective effect upon islet cells.

Effects of metabolites of eicosapentaenoic acid on promoting transdifferentiation of pancreatic OL cells into pancreatic β cells / 中国药理学通报

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Application progress of mesenchymal stem cells in islet transplantation for type 1 diabetes mellitus / 器官移植

Islet transplantation is considered as one of the most effective approach for type 1 diabetes mellitus, although its efficacy is limited by several factors. Anoxia, stress and rejection occurring during the isolation, culturing and transplantation of islets may have impact on the outcome of the islet transplantation. Due to the biological properties such as anti-inflammation, angiogenetic promotion and immune regulation, mesenchymal stem cells (MSCs) are all the way focused by researchers. Additionally, exosome, a derivative of MSC, also plays an import role in regulating anoxia-induced oxidative stress modulation, angiogenetic promotion, and immune regulation. MSC-based islet transplantation may be a useful therapeutic tool in treating type 1 diabetes. Therefore, in this review, the potential effect of MSC prior and posterior to the operation of the islet transplantation, its clinical application as well as its limitations were reviewed, aiming to offer insights into the future application of islet transplantation in treating type 1 diabetes.

Carbohydrate counting as a strategy to optimize glycemic control in type 1 diabetes mellitus

ABSTRACT Objective: The objective of this study was to verify the impact of carbohydrate counting (CC) on glycemic control and body weight variation (primary and secondary outcomes, respectively) between consultations in patients with diabetes mellitus (T1D) followed at a tertiary hospital in southern Brazil in a public health system environment. We also sought to investigate CC adherence. Materials and methods: This retrospective cohort study included 232 patients with T1D who underwent nutritional monitoring at a referral hospital for diabetes care between 2014 and 2018. To assess primary and secondary outcomes, data from 229 patients, 49 of whom underwent CC during this period and 180 individuals who used fixed doses of insulin, were analyzed. The impact of CC on glycemic control was assessed with the mean glycated hemoglobin (HbA1c) level at all consultations during the follow-up period. Results: In the model adjusted for the most confounders (except pregnancy), the mean HbA1c was better in the CC group (8.66 ± 0.4% vs. 9.36 ± 0.39%; p = 0.016), and body weight variation was lower (0.13 ± 0.28 kg vs. 0.53 ± 0.24 kg; p = 0.024). Adherence to CC was reported in 69.2% of consultations. Conclusion: CC optimized the glycemic control of individuals with T1D, resulting in less weight variation than in the fixed insulin dose group, which indicates that CC is an important care strategy for these patients.

Body adiposity markers and insulin resistance in patients with type 1 diabetes

ABSTRACT Objectives: Body composition changes are associated with adverse effects such as increased insulin resistance (IR) in individuals with diabetes mellitus. This study aims to evaluate the association between different body adiposity markers and IR in adults with type 1 diabetes (T1D). Subjects and methods: The cross-sectional study included outpatient adults with T1D from a university public hospital in southern Brazil. The body adiposity markers studied were waist circumference (WC), waist-height ratio (WHtR), body mass index (BMI), conicity index (CI), lipid accumulation product (LAP) and body adiposity index (BAI). IR was calculated using an Estimated Glucose Disposal Rate (EGDR) equation (analyzed in tertiles), considering an inverse relation between EGDR and IR. Poisson regression models were used to estimate the odds ratio (OR) and 95% CIs of association of adiposity markers with IR. Results: A total of 128 patients were enrolled (51% women), with a median EGDR of 7.2 (4.4-8.7) mg.kg−1.min−1. EGDR was negatively correlated with WC (r = −0.36, p < 0.01), WHtR (r = −0.39, p < 0.01), CI (r = −0.44, p < 0.01), LAP (r = −0.41, p < 0.01) and BMI (r = −0.24, p < 0.01). After regression analyses, WC (OR = 2.07; CIs: 1.12-3.337; p = 0.003), WHtR (OR = 2.77; CIs: 1.59-4.79; p < 0.001), CI (OR = 2.59; CIs: 1.43-4.66; p = 0.002), LAP (OR = 2.27; CIs: 1.25-4.11; p = 0.007) and BMI (OR = 1.78; CIs: 1.09-2.91; p = 0.019) remained associated with IR. Conclusions: The authors suggest using the studied adiposity markers as a routine since they were shown to be suitable parameters in association with IR.

Evaluación de la calidad de vida en niños y adolescentes con diabetes de tipo 1 en dos instituciones de salud, Bogotá, D. C., Colombia / Evaluation of the quality of life in children and adolescents with type 1 diabetes in two health institutions, Bogotá, D. C., Colombia

Introducción. La diabetes mellitus es una de las enfermedades crónicas con mayor prevalencia en la población pediátrica y juvenil, con efectos en la calidad de vida de los pacientes. Objetivo. Evaluar la calidad de vida de una población pediátrica menor de 18 años con diagnóstico de diabetes de tipo 1, de dos instituciones pediátricas de la ciudad de Bogotá. Materiales y métodos. Se recolectaron los datos sociodemográficos, y se emplearon la versión validada en español del cuestionario PedsQL 4.0™ y el módulo 3.2 sobre diabetes. Los datos se procesaron en el software estadístico STATA 17™. Resultados. Con el puntaje global del módulo 3.2 sobre diabetes, de la versión validada del PedsQL™, se evaluó la correlación entre los valores de la hemoglobina A1c (HbA1c) y los del cuestionario. Los pacientes con valores por debajo del 9 % de HbA1c presentaron una mejor calidad de vida relacionada con la salud, mientras que, en el grupo con HbA1c mayor de 9 %, se observó una baja percepción de calidad de vida (p=0,025). En cuanto el tipo de terapia y la relación con los dominios del PedsQL™ 3.2, versión diabetes, los pacientes que utilizaban la bomba de insulina o microinfusor presentaban mejor puntaje en los dominios barreras, cumplimiento, preocupación y comunicación, y en el puntaje global, respecto a quienes usaban múltiples inyecciones de insulina como tratamiento (p=0,0363). Conclusiones. En nuestros pacientes, un mejor control metabólico (medido por el valor de HbA1c) y el uso de microinfusora contribuyen a una percepción de mejor calidad de vida.

Introduction: Diabetes mellitus is one of the most prevalent chronic diseases in the pediatric and juvenile population that affects the quality of life of patients. Objective: To evaluate the quality of life of a pediatric population under 18 years of age diagnosed with type 1 diabetes from two pediatric institutions in the city of Bogotá. Materials and methods: We collected of sociodemographic data and clinical variables and application of the PedsQL 4.0™ questionnaire, and the diabetes module 3.2 version validated in Spanish. The sociodemographic data, the clinical variables and the PedsQL™ were processed in the statistical software Stata 17™. Results: In the global score of the PedsQL™ 3.2, diabetes version, men presented better quality of life compared to women. The correlation between the hemoglobin A1c (HbA1c) values and the PedsQL scale in the global score was evaluated. Patients with HbA1c values below 9% presented a better health-related quality of life, while in the group with HbA1c greater than 9% a perception of low quality of life was observed (p=0.025). Regarding the type of therapy and the relationship with the domains of the PedsQL 3.2, diabetes version, patients who used insulin pumps had better scores in the domains barriers, adherence, concern, communication and in the global score compared to patients who used multiple daily injections of insulin as treatment (p=0.0363). Conclusions: In our patients, a better metabolic control (measured by the HbA1c value) and the use of an insulin pump contribute to a better perception of quality of life.

Evaluación del desempeño cognitivo en escolares y adolescentes con diabetes mellitus tipo 1 / Evaluation of cognitive performance in children and adolescents with type 1 diabetes mellitus

Resumen El objetivo del trabajo fue evaluar el funcionamiento cognitivo de niños y adolescentes con diabetes mellitus tipo 1 (DM1) de la consulta de Endocrinología del IAHULA, y compararlo al de niños no diabéticos, así como investigar la posible influencia de factores relacionados con la enfermedad sobre la cognición. Se realizó un estudio observacional analítico, transversal, que incluyó un grupo de 30 pacientes con DM1 de 8 a 16 años de edad (16 varones) y un grupo control de 30 individuos pareados por edad, género, escolaridad y condición socioeconómica. Se realizó interrogatorio y revisión de historias clínicas para obtener datos sobre las características clínicas y el tratamiento de la DM1. Se les aplicó el test WISC IV para evaluar cognición y cociente intelectual (CI). La edad promedio de los pacientes fue de 13,27 ± 2,31 años, la mitad de ellos masculinos. Se encontraron puntajes menores en los distintos dominios del WISC IV en el grupo con DM1 al compararlos con los del grupo control (p<0,01). El CI fue menor en los niños con DM1 que en los controles (75,47 ± 13,87 frente a 88,57±11,06; p=0,0001); así mismo, se observó con mayor frecuencia un puntaje del CI inferior al percentil 10 en los pacientes con DM1 en comparación con los controles (63,3% frente a 33,3%; p=0,02; Odds ratio: 3,45; IC95%: 1,19-9,99). Se concluyó que la DM1 impacta negativamente el desempeño cognitivo de niños y adolescentes. Se recomienda la evaluación cognitiva de estos pacientes, ya que podría repercutir en su vida diaria.

Abstract The study aimed to evaluate the cognitive functioning of children and adolescents with type 1 diabetes mellitus (T1DM) recruited from the IAHULA Endocrinology Outpatient Unit and to compare it to that of non-diabetics as to investigate the influence on cognition of factors related to the disease. An analytical, cross-sectional observational study was carried out on a group of 30 patients with T1DM between 8 and 16 years of age and on a control group of 30 individuals matched by age, gender, education, and socioeconomic status. Interrogation and review of medical records to obtain data on the clinical characteristics and treatment of T1DM were conducted. The WISC IV test was then applied to evaluate cognition and intellectual coefficient (IQ). The average age of the diabetic patients was 13.27±2.31 years, and half of them were male. Lower scores were found in the different domains of the WISC IV in the group with T1DM (p<0.01). The IQ was found to be lower in children with T1DM than in controls (75.47±13.87 vs. 88.57±11.06; p=0.0001). Likewise, a higher frequency of IQ scores below the 10th percentile was observed in the diabetic children (63.3% vs. 33.3%; p=0.02; Odds ratio: 3.45; 95%CI: 1.19-9.99). It was concluded that T1DM negatively impacts the cognitive performance of children and adolescents. Cognitive evaluation of these patients is recommended, as it could affect their daily life.

Debut de diabetes tipo 1 en niños durante la pandemia Covid-19 en el Hospital de Pediatría Juan P. Garrahan / Debut of type-1 diabetes in children during the COVID-19 pandemic at Hospital de Pediatría Juan P. Garrahan

Introducción: Según numerosos reportes, la pandemia por COVID­19 aumentó la incidencia de diabetes tipo 1 (DBT1) y cetoacidosis (CAD). Nuestro objetivo fue describir la frecuencia de nuevos casos de DBT1 y su severidad al ingreso en el Hospital J. P. Garrahan durante la pandemia, comparando con el periodo anterior. Material y métodos: Se realizó un estudio descriptivo, observacional, con análisis retrospectivo. Se incluyeron todos los nuevos casos entre 19/03/20- 31/12/21, comparados con el período 19/03/18-31/12/19. El diagnóstico de DBT1, CAD y su severidad se realizó según la International Society for Pediatric and Adolescent Diabetes. Se analizó el requerimiento de cuidados intensivos (UCI), presencia de COVID-19, hemoglobina glicosilada A1C (HbA1C) y autoanticuerpos (GADA, IAA, IA2, ZNT8). Se consideró significativa una p < 0,05. Resultados: En el período 2020-2021 se observó un incremento del 107% de nuevos casos, ingresando 56 pacientes con DBT1. La media y mediana de edad disminuyeron (8 vs 9,1 y 7,7 vs 10,4, respectivamente), con un incremento del 35% de menores de 5 años. Aumentó la frecuencia de CAD severa (41.1% vs 25.9%) y de requerimiento de UCI (17.9% vs 11.1%). La Hb A1C y la glucemia de ingreso mostraron incremento significativo (10.1% vs 12.32%, p<0.003 y 580 mg/dl ± 220 vs 490 mg/dl ± 188; p<0.05, respectivamente). Conclusión: En 2020-2021 se incrementó el número de nuevos casos de DBT1 en nuestra institución. Al ingreso hubo mayor proporción de niños pequeños y casos severos. Las dificultades de acceso a la consulta de atención primaria podrían relacionarse con nuestro hallazgo (AU)

Introduction: Numerous reports have shown that during the COVID-19 pandemic the incidence of type-1 diabetes (T1DB) and ketoacidosis (DKA) increased. The aim of this study was to describe the frequency of new cases and their severity on admission of T1DB at Hospital J. P. Garrahan during the pandemic, compared with the previous period. Material and methods: A descriptive, observational study with a retrospective analysis was conducted. All new cases seen between 19/03/20-31/12/21 were included and compared with the period 19/03/18-31/12/19. The diagnosis of T1DB, DKA, and its severity was made according to the International Society for Pediatric and Adolescent Diabetes. Intensive care (ICU) requirement, presence of COVID-19, glycosylated hemoglobin A1C (HbA1C), and autoantibodies (GADA, IAA, IA2, ZNT8) were analyzed. A p < 0.05 was considered significant. Results: In the period 2020-2021, a 107% increase in new cases was observed including 56 patients with T1DB. Mean and median age decreased (8 vs 9.1 and 7.7 vs 10.4, respectively), with a 35% increase in children under 5 years of age. The frequency of severe DKA (41.1% vs 25.9%) and ICU requirement (17.9% vs 11.1%) increased. Hb A1C and glycemia on admission also showed a significant increase (10.1% vs 12.32%, p<0.003 and 580 mg/dl ± 220 vs 490 mg/dl ± 188; p<0.05, respectively). Conclusion: In 2020-2021 an increase in the number of new cases of T1DB was observed at our institution. On admission, a higher rate of young children and severe cases was found. Difficulties to access primary care may have been related to our finding (AU)

Relação do ato de comer com o controle da doença e a qualidade de vida no diabetes mellitus tipo 1 / Relationship between eating behavior and disease control on the quality of life in type 1 diabetes mellitus

O objetivo deste estudo foi analisar a relação do ato de comer com o controle da doença e a qualidade de vida em adultos com diabetes tipo 1 (DM1). Trata-se de estudo transversal, realizado através de um questionário on-line com a versão brasileira do Diabetes Quality of Life Measure (DQOL-Brasil) e de perguntas sobre controle alimentar. Foram incluídos 103 voluntários (85,4% mulheres). Nas relações com a comida, 68,9% disseram sentir vontade de comer quando estão ansiosos, preocupados ou tensos. O escore global foi de 2,36 ± 0,75 no DQOL-Brasil, e os domínios "satisfação" e "preocupações relacionadas ao diabetes" apresentaram valores mais altos. A variável idade teve correlação negativa com o escore global do DQOL-Brasil e com os domínios "impacto", "preocupações sociais/vocacionais" e "preocupações com diabetes". Esta pesquisa demonstrou associação entre o ato de comer com o controle do DM1, o que pode prejudicar a qualidade de vida desses indivíduos.

This study aimed to analyze the relationship between eating behavior, disease control, and quality of life in adults with type 1 diabetes mellitus (DM1). This cross-sectional study was conducted using an online questionnaire based on the Brazilian version of the Diabetes Quality of Life Measure (DQOL-Brazil), comprising questions on dietary control. A total of 103 volunteers (85.4% women) were included in this study. In relation to food, 68.9% said that they felt like eating when they were anxious, worried, or tensed. The overall score was 2.36 ± 0.75 on the DQOL-Brazil, with higher scores for the domains "satisfaction" and "diabetes-related concerns." The age variable had a negative correlation with the global DQOL-Brazil score and with the domains "impact," "social/vocational concerns," and "diabetes-related concerns." This study demonstrated an association between the act of eating and DM1 control, affecting the quality of life in these individuals.

Peripheral edema in a child with a new diagnosis of insulin-dependent diabetes mellitus

Peripheral or generalized edema is an uncommon complication of insulin therapy in diabetes mellitus. The exact cause is yet not known. It is transient and self-limiting in nature. However, diuretics and aldosterone antagonists have been used in some cases. We report the case of a 14-year-old boy with newly diagnosed Type 1 diabetes who developed edema after the commencement of insulin therapy. Other causes of edema were excluded from the study. The child was managed conservatively and edema seemed to start decreasing after 72 h and completely disappear in 2 weeks.

Maternal-fetal outcomes of pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections during pregnancy - A Brazilian health care referral center cohort study

ABSTRACT Objective: Pregnant women with type 1 diabetes (T1D) have an increased risk of maternal-fetal complications. Regarding treatment, continuous subcutaneous insulin infusion (CSII) has advantages compared to multiple daily injections (MDI), but data about the best option during pregnancy are limited. This study's aim was to compare maternal-fetal outcomes among T1D patients treated with CSII or MDI during pregnancy. Subjects and methods: This study evaluated 174 pregnancies of T1D patients. Variables of interest were compared between the groups (CSII versus MDI), and logistic regression analysis was performed (p < 0.05). Results: Of the 174 included pregnancies, CSII was used in 21.3% (37) and MDI were used in 78.7% (137). HbA1c values improved throughout gestation in both groups, with no difference in the first and third trimesters. The frequency of cesarean section was significantly higher in the CSII group [94.1 vs. 75.4%, p = 0.017], but there was no significant difference in the frequency of other complications, such as miscarriage, premature delivery and preeclampsia. The mean birth weight and occurrence of neonatal complications were also similar, except for the proportion of congenital malformations, which was significantly lower in the CSII group [2.9 vs. 15.6%, p = 0.048]. In regression analysis, the association of CSII with cesarean section and malformations lost significance after adjusting for HbA1c and other covariates of interest. Conclusion: In this study, we observed a higher frequency of cesarean section and a lower occurrence of congenital malformations in the CSII group, but the adjusted results might indicate that these associations are influenced by glycemic control.

Knowledge about diabetes and its association with adherence to self-care and glycemic control in patients with type 1 diabetes in Southern Brazil

ABSTRACT Objective: To evaluate the association between knowledge about the disease, adherence to self-care, and glycemic control in people diagnosed with type 1 diabetes mellitus. Subjects and methods: A cross-sectional study of patients aged over 18 years diagnosed with type 1 diabetes mellitus, treated at an outpatient clinic of a Brazilian university hospital. Participants with other types of diabetes, cognitive impairment, pregnancy, and outpatient discharge were excluded. Data were collected from January to March 2021 (by telephone call), with questions about the participants' profile, diabetes knowledge questionnaire (DKN-A), and self-care inventory revised (SCI-R) translated into and adapted for Brazilian Portuguese. Data analysis involved chi-square associations, Mann-Whitney U tests, and Poisson regression. Results: Among 198 adult participants, the mean age was 42 ± 12 years, 53.5% were women, the mean glycated hemoglobin was 8.6 ± 1.6%, 140 (70.8%) had satisfactory knowledge about diabetes, 65 (32.8%) had adherence to self-care, and 46 (23.2%) had adequate glycemic control. We found an association between knowledge and adherence to self-care (p < 0.001). Knowledge was not associated with glycemic control (p = 0.705). Conclusion: Knowledge about diabetes was associated with greater adherence to self-care in people with type 1 diabetes mellitus, but it did not reflect in better glycemic control.

Cotransplantation of marginal mass allogeneic islets with 3D culture-derived adult human skin cells improves glycemia in diabetic mice

Islet transplantation represents a therapeutic option for type 1 diabetes (T1D). Long-term viability of transplanted islets requires improvement. Mesenchymal stromal cells (MSCs) have been proposed as adjuvants for islet transplantation facilitating grafting and functionality. Stem cell aggregation provides physiological interactions between cells and enhances the in situ concentration of modulators of inflammation and immunity. We established a hanging-drop culture of adult human skin fibroblast-like cells as spheroids, and skin spheroid-derived cells (SphCs) were characterized. We assessed the potential of SphCs in improving islet functionality by cotransplantation with a marginal mass of allogeneic islets in an experimental diabetic mouse model and characterized the secretome of SphCs by mass spectrometry-based proteomics. SphCs were characterized as multipotent progenitors and their coculture with anti-CD3 stimulated mouse splenocytes decreased CD4+ T cell proliferation with skewed cytokine secretion through an increase in the Th2/Th1 ratio profile. SphCs-conditioned media attenuated apoptosis of islets induced by cytokine challenge in vitro and importantly, intratesticular SphCs administration did not show tumorigenicity in immune-deficient mice. Moreover, SphCs improved glycemic control when cotransplanted with a marginal mass of allogeneic islets in a diabetic mouse model without pharmacological immunosuppression. SphCs' protein secretome differed from its paired skin fibroblast-like counterpart in containing 70% of up- and downregulated proteins and biological processes that overall positively influenced islets such as cytoprotection, cellular stress, metabolism, and survival. In summary, SphCs improved the performance of transplanted allogeneic islets in an experimental T1D model, without pharmacological immunosuppression. Future research is warranted to identify SphCs-secreted factors responsible for islets' endurance.

Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells / 中山大学学报(医学科学版)

BackgroundType 1 diabetes is caused by a chronic immune response that destroys islet beta cells， resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However， little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells （GMSCs） in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes. MethodsWe injected human GMSCs into NOD mice to observe the trend of blood glucose， observed the survival of pancreatic β-cells by immunohistochemistry， and detected the change of immune cells in the spleen of mice by flow analysis. Finally， the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice. ResultsGMSCs significantly reduced the incidence of diabetes in NOD mice， with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group， P=0.013. The percentage of Follicular B cells（FO B cell） in the spleen of GMSCs-treated mice decreased from （52.2±4.1）% to （43.2±5.3）%， P=0.008， while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells， which could continuously produce insulin to control blood glucose. Finally， we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice. ConclusionGMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.

Control status and influencing factors of glycated hemoglobin in children with type 1 diabetes in Tianjin 2020-2021 / 公共卫生与预防医学

Objective To analyze the control status and influencing factors of glycosylated hemoglobin (HbA1c) in children with type 1 diabetes mellitus (T1DM) in Tianjin from 2020 to 2021, and to provide a theoretical basis for controlling blood glucose in children with type 1 diabetes mellitus. Methods A total of 538 children with type 1 diabetes, including 275 males and 263 females, were selected from our hospital from January 2020 to June 2021. All the children were determined according to the level of HbA1c and divided into well-controlled group (HbA1c<7.0%, n=469) and poorly controlled group (HbA1c≥7.0%, n=69), 3ml fasting elbow venous blood was extracted from the two groups, and the levels of HbA1c, FPG, 2hPG, TC and LDL-C were compared between the two groups. Clinical data of the children were collected from the medical record system. The factors affecting the control of HbA1c in children with type 1 diabetes were analyzed by univariate analysis and logistic regression. Results The comparison of general data between the two groups showed no significant difference in age, sex and course of type 1 diabetes mellitus (P<0.05). The levels of HbA1c, FPG, 2hPG, TC and LDL-C in poorly controlled group were significantly higher than those in well controlled group (P<0.05). The blood glucose monitoring <60 times/month (OR=3.017), uncontrolled diet (OR=2.871), obesity (OR=2.623) were independent risk factors for poor control of HbA1c in children with type 1 diabetes (P<0.05). Conclusions Children with type 1 diabetes mellitus have a greater risk of poor control of HbA1c. It is necessary to strengthen publicity and education for parents of children with diabetes, regularly monitor blood glucose and control diet to effectively improve blood glucose control in children.

Expression of IL-35 and its regulatory effects on Th9 cells in patients with type 1 diabetes mellitus / 中华微生物学和免疫学杂志

Objective:To investigate the changes in IL-35 expression in patients with type 1 diabetes mellitus (T1DM) and to analyze the role of IL-35 in regulating Th9 cells.Methods:Thirty-one T1DM patients and 13 controls were enrolled. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. The levels of IL-35 and IL-9 in plasma were measured by ELISA. The expression of IL-35 subunits, EBI3 and IL-12p35, as well as Th9 transcription factor PU.1 at mRNA level was detected by real-time PCR. The percentages of Th9 cells were measured by flow cytometry. Changes in cell proliferation, the percentage of Th9 cells, PU.1 expression at mRNA level and IL-9 secretion were detected after stimulating PBMCs from T1DM patients and controls with recombinant human IL-35. CD4 + CCR4 -CCR6 -CXCR3 - cells and CD8 + T cells were isolated from PBMCs of 11 T1DM patients. CD4 + CCR4 -CCR6 -CXCR3 - cells were first stimulated with recombinant human IL-35 and then co-cultured with CD8 + T cells. IFN-γ and TNF-α in the culture supernatants were measured by ELISA. Perforin and granzyme B secretion was measured by enzyme-linked immunospot assay. Student′s t-test, paired t-test or LSD- t test was used for statistical analysis. Results:Plasma IL-35 level was lower in T1DM patients than in controls [(67.13±9.94) pg/ml vs (97.77±23.61) pg/ml, P<0.000 1]. Compared with controls, T1DM patients had decreased expression of EBI3 and IL-12p35 at mRNA level in PBMCs ( P<0.000 1). The percentage of Th9 cells, PU.1 expression at mRNA level and plasma IL-9 level were increased in T1DM patients as compared with those in controls [(3.47±0.99)% vs (2.76±0.75)%, P=0.029; P<0.000 1; (99.08±11.85) pg/ml vs (86.38±12.72) pg/ml, P=0.002 8]. IL-35 had no significant influence on the proliferation of PBMCs from both T1DM patients and controls ( P>0.05). The percentage of Th9 cells and PU.1 expression at mRNA level in PBMCs from T1DM patients were down-regulated in response to IL-35 stimulation ( P<0.01), while no significant difference was observed in the control group ( P>0.05). IL-9 secretion by PBMCs was down-regulated in response to IL-35 stimulation in both T1DM and control groups ( P<0.01). CD4 + CCR4 -CCR6 -CXCR3 - cells promoted the secretion of IFN-γ, TNF-α, perforin and granzyme B by CD8 + T cells from T1DM patients ( P<0.05), but the effects could be inhibited by IL-35 ( P<0.05). Conclusions:Decreased IL-35 in T1DM patients could not exert effective immunosuppressive activity, leading to the enhancement of Th9 cell activity and inflammatory injury.

PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats / 药物分析学报

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Influencing factors for overweight and obesity in children with type 1 diabetes mellitus / 中华实用儿科临床杂志

Type 1 diabetes mellitus (T1DM) in children used to be manifested as emaciation, and overweight and obese children with T1DM are less observed.Therefore, these special population has not been concerned.However, in recent years, with the increase in the prevalence of T1DM in children, the rates of overweight and obese children with T1DM have on the rise.Overweight and obesity not only affect the growth and development of children, but also increases the risk of complications of T1DM that negatively affect the prognosis.Therefore, overweight and obesity have become a new problem in the long-term management of T1DM.This review aims to summarize the influencing factors for overweight and obesity in children with T1DM during follow-up, thus highlighting the management of the special population.This review provides reference for the monitoring of risk population of children with T1DM, timely performing clinical management and optimizing the therapeutic strategy of T1DM.