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.

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.

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.

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.

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.

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.

PRE-084 ameliorated learning and memory impairment in T1DM via regulating neuronal MAM / 西安交通大学学报(医学版)

【Objective】 Diabetic mice could show learning and memory dysfunction, and we aimed to investigate the effect of Sigma-1 receptor agonist, PRE-084, on neurons and cognitive impairment in mice with type 1 diabetes (T1DM). 【Methods】 Twenty mice with T1DM induced by streptozocin, aged 8-10 weeks, and 20 control mice (CON) were randomly divided into four groups (CON+Vehicle, CON+PRE-084, T1DM+Vehicle and T1DM+PRE-084). Mouse primary neurons were cultured in high glucose medium with PRE-084 and control solvent, respectively. The body weight, food and water intake, and fasting blood glucose level of mice in each group were detected and recorded. The learning and memory abilities of mice were detected by new object recognition experiment. The mitochondria-associated endoplasmic reticulum membrane (MAM) structure of neurons in hippocampal CA1 area of mice was detected by transmission electron microscope. And the expression levels of ATP and reactive oxygen species (ROS) in hippocampus of mice were detected by biochemical kit. Cell viability and ROS level of primary neurons were detected by CCK8 and cellular ROS kit. 【Results】 PRE-084 reduced the increase of body weight, food and water intake, and blood glucose caused by diabetes. PRE-084 significantly ameliorated the learning and memory impairment of the mice with T1DM, improved the changes of MAM structure in neurons of hippocampal CA1 area of diabetic mice, increased the level of ATP in hippocampus of diabetic mice, and decreased the increase of ROS expression in diabetic hippocampus and neurons under high glucose conditions. 【Conclusion】 Sigma-1 receptor agonist, PRE-084, could improve learning and memory impairment in the mice with T1DM, which might be related to the structural changes of MAM, the increase of ATP production, and the decrease of ROS production in hippocampal neurons.

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.

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.

A study of continuous subcutaneous insulin infusion in children with type 1 diabetes mellitus / 国际儿科学杂志

Objective:To study the effect of continuous subcutaneous insulin infusion(CSII)on the emotional disorder of children and adolescents with type 1 diabetes mellitus(T1DM)and their parents.Methods:A total of 72 children and adolescents with T1DM were divided into CSII group( n=40)and multiple daily injection(MDI)group( n=32).There were 58 healthy children and adolescents with their parents selected as control group.The emotional condition of children and adolescents in T1DM group and control group was evaluated by Depression Self-rating Scale for Children(DSRS)and the Screen for Child Anxiety Related Emotional Disorders(SCARED)respectively, and Symptom Checklist-90(SCL-90)was used for evaluating the mental health of all parents. Results:The average glycated hemoglobin A1c(HbA1c)of T1DM group was at the optimal level(7.406±1.294)%.The average HbA1c of CSII group was significantly lower than that of MDI group[(7.040±1.082)% vs(7.863±1.404)%, t=2.728, P=0.008].The depression rate of children and adolescents in T1DM group increased significantly than that of control group(31.9% vs 15.5%, χ2 =4.671, P=0.031).There were statistically significant differences among CSII group, MDI group and control group(20.0% vs 46.9% vs 15.5%, χ2 =11.591, P=0.003).The depression rate of children and adolescents in MDI group increased significantly than that of CSII group and control group(all P<0.05).CSII group showed similar results as compared with control group( P>0.05).Concerning the anxiety in children and adolescents, there was no significant difference between T1DM group and control group(19.4% vs 13.8%, χ2=0.730, P=0.393), and there were no significant differences among CSII group, MDI group and control group(15.0% vs 25.0% vs 13.8%, χ2=1.994, P=0.369).The emotional disorder prevalence of parents in T1DM group was remarkably higher than that of the control group(31.9% vs 5.2%, χ2=52.927, P<0.01).The factor scores of obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, paranoia and psychotic symptoms in T1DM group were higher than that of control group( P<0.05).There were statistically significant differences among CSII group, MDI group and control group(17.5% vs 50.0% vs 5.2%, χ2=26.126, P<0.01).The emotional disorder prevalence of parents in MDI group increased significantly than that of CSII group and control group(all P<0.05).But CSII group was same as that of control group( P>0.05). Conclusion:The children and adolescents with T1DM and their parents were high-risk population of emotional disorder.CSII can reduce not only the depression in the children and adolescents with T1DM, but also emotional disorder of their parents, thus CSII can improve the mental health in families suffering from T1DM.

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.

Comprometimentos cognitivos na Diabetes Mellitus Tipo 1: revisão integrativa / Cognitive impairments in Type 1 Diabetes Mellitus: integrative review / Deficiencias cognitivas en la Diabetes Mellitus Tipo 1: revisión integradora

This review verified cognitive domains affected by type 1 diabetes mellitus (T1DM) and the instruments used for its assessment. We performed a search in three databases using the descriptors "type 1 diabetes" AND "cognitive dysfunction". Only six of the 120 articles found met the criteria for inclusion in the review. The anal-ysis of these articles indicates that the main cognitive functions compromised by T1DM are attention, visual attention, verbal memory, immediate and late recovery, and psychomotor speed. Among the selected articles, we found that the most used instruments were the Montreal Cognitive Assessment (MoCA), the Wechsler scales (WMS-III and WMS-RC), the Trail Making Test, The Grooved Pegboard, and substitution (letter-symbol, digit-symbol). Due to the different impairments found, we suggest the importance of standardizing a battery of cognitive assessments and greater efforts to understand the functional impairments resulting from dam-age to cognition in individuals with T1DM

Esta revisão verificou os domínios cognitivos afetados pela diabetes mellitus tipo 1 (type 1 diabetes mellitus [T1DM]). Realizamos busca em três bases de dados, utilizando os descritores "type 1 diabetes" AND "cognitive dysfunction". Apenas seis dos 120 artigos encontrados cumpriram critérios para inclusão na revisão. A análise desses artigos indica que as principais funções cognitivas comprometidas pela T1DM são atenção, atenção vi-sual, memória verbal, recuperação imediata e tardia e velocidade psicomotora. Nos artigos selecionados, veri-ficamos que os instrumentos mais utilizados foram o Montreal Cognitive Assessment (MoCA), as escalas Wechs-ler (WMS-III e WMS-RC), o Teste de Trilhas, The Grooved Pegboard e substituição (letra-símbolo, dígito-símbolo). Em virtude dos diferentes comprometimentos encontrados, sugerimos a importância da padronização de uma bateria de avaliações cognitivas e maiores esforços na compreensão dos prejuízos funcionais decorrentes dos danos à cognição em indivíduos com T1DM.

Esta revisión analizó los dominios cognitivos afectados por la diabetes mellitus tipo 1 (type 1 diabetes mellitus [T1DM]) y los instrumentos utilizados para su evaluación. Se realizó una búsqueda en tres bases de datos, utili-zando los descriptores "type 1 diabetes" AND "cognitive dysfunction". Solo seis de los 120 artículos encontra-dos cumplieron los criterios para su inclusión en la revisión. El análisis de estos artículos indica que las principa-les funciones cognitivas comprometidas por la TDM1 son la atención, la atención visual, la memoria verbal, la recuperación inmediata y tardía y la velocidad psicomotora. Entre los artículos seleccionados, encontramos que los instrumentos más utilizados fueron la Montreal Cognitive Assessment (MoCA), las escalas Wechsler (WMS-III y WMS-RC), la Prueba de Rastro, The Grooved Pegboard y la sustitución (letra-símbolo, dígito-símbo-lo). Debido a las diferentes deficiencias encontradas, sugerimos la importancia de estandarizar una batería de evaluaciones cognitivas y mayores esfuerzos para comprender las deficiencias funcionales que resultan del daño a la cognición en personas con TDM1.

Diabetes mellitus tipo 1 y enfermedad celíaca en niños y adolescentes / Type 1 diabetes mellitus and celiac disease in children and adolescents

Introducción: La asociación entre enfermedad celíaca y diabetes mellitus tipo 1 se ha publicado con mayor frecuencia que la enfermedad celíaca aislada, cuya historia natural puede variar considerablemente, con evidencia de síntomas gastrointestinales en la minoría de los pacientes. Objetivo: Caracterizar a pacientes con diabetes mellitus tipo 1 y enfermedad celíaca. Método: Estudio observacional, descriptivo y transversal en 63 niños atendidos en el Hospital Pediátrico Docente Centro Habana entre los años 2016-2017 con diagnóstico de diabetes mellitus tipo 1. Las variables estudiadas se expresaron en valores absolutos y relativa, medida de tendencia central y de dispersión. Resultados: El sexo masculino representó 58,73 por ciento de los pacientes, la mayoría entre 10 y 14 años de edad. El anticuerpo antitransglutaminasa fue positivo en menos de 10 por ciento de los niños, generalmente sin síntomas, signos o hallazgos relacionados con la enfermedad celíaca. La frecuencia de ambas enfermedades en los pacientes estudiados fue de 3,17 por ciento. Conclusiones: La diabetes mellitus tipo 1 predomina en el sexo masculino a diferencia de la enfermedad celíaca que se diagnostica en pacientes femeninas. Los resultados de anticuerpos antitransglutaminasa son negativos en la mayoría de los pacientes mientras que los positivos tienen más de un año de evolución de la diabetes, se encuentran eutróficos o sobrepeso, asintomáticos y con valores ligeramente superiores de hemoglobina glucosilada(AU)

Introduction: The association between celiac disease and type 1 diabetes mellitus has been published more frequently than isolated celiac disease, whose natural history can vary considerably, with evidence of gastrointestinal symptoms in the minority of patients. Objective: To characterize patients with type 1 diabetes mellitus and celiac disease. Method: Observational, descriptive and cross-sectional study in 63 children treated at Centro Habana Pediatric Teaching Hospital between the years 2016-2017 with a diagnosis of type 1 diabetes mellitus. The variables studied were expressed in absolute and relative values, a measure of central tendency and dispersion. Results: Males accounted for 58.73 percent of the patients, most of them between 10 and 14 years old. The anti-transglutaminase antibody was positive in less than 10 percent of the children, usually without symptoms, signs, or findings related to celiac disease. The frequency of both diseases in the patients studied was 3.17 percent. Conclusions: Type 1 diabetes mellitus predominates in males unlike celiac disease which is diagnosed in female patients. The results of anti-transglutaminase antibodies are negative in most patients while the positive ones have more than a year of evolution of diabetes, are eutrophic or overweight, asymptomatic and with slightly higher values of glycosylated hemoglobin(AU)

Cumplimiento de objetivos en pacientes adultos con diabetes mellitus tipo 1: tasa estimada de disposición de glucosa como marcador clínico / Achievement of objectives in adult patients with type 1 diabetes mellitus: estimated glucose disposition rate as a clinical marker

Resumen Introducción: las guías de práctica clínica en diabetes mellitus (DM) establecen objetivos clínicos precisos sobre el buen manejo de la enfermedad, pero poco se sabe sobre el adecuado cumplimiento en nuestro medio. El sobrepeso y el sedentarismo han generado estigmas de síndrome metabólico en la población con DM1. Objetivos: evaluar el cumplimiento en cinco de dichos criterios: HbA1c <7%, c-LDL ≤100 mg/dl, actividad física ≥3 veces/ semana, tensión arterial sistólica (TAS) <140 mm Hg y no tabaquismo, y su asociación con insulinorresistencia determinada por la tasa estimada de disposición de glucosa (TeDG). Materiales y métodos: en 415 DM1 ≥18 años, 52% mujer y una edad de 34,8±13,9 años, se evaluó HbA1c, c-LDL, frecuencia semanal de actividad física (AF) estructurada, TAS y tabaquismo actual. Se determinó el grado de asociación a género, edad, antigüedad de la DM, nivel de educación, cobertura médica, índice de masa corporal (IMC) y sensibilidad a la insulina medida a través de la TeDG. Las variables cualitativas se analizaron por test de chi. y las cuantitativas por test de ANOVA I con post hoc por test de Tukey. Un valor de p<0,05 se consideró estadísticamente significativo. En todos los casos se utilizó un intervalo de confianza del 95%. Resultados: el 94,8% presentó TAS <140 mm Hg, el 82,2% no tabaquismo actual, el 56,5% c-LDL ≤100 mg/dL, el 39% AF ≥3 veces/semana y el 20,3% HbA1c <7%. Solo 26 pacientes (6,2%) alcanzaron en forma combinada los cinco objetivos analizados. El cumplimiento de dichos objetivos se asoció a nivel de educación secundaria o mayor (p=0,002) y cobertura de salud con obra social o prepaga (p=0,002). Hubo asociación significativa entre la TeDG en quienes cumplieron los cinco objetivos (p=0,02) y en forma individual en cuatro de ellos (TAS, c-LDL, HbA1c y AF). Conclusiones: de los 415 pacientes evaluados, el 6,2% cumplió los cinco objetivos. Solo el control de la TAS, no fumar y un c-LDL <100 mg/dL lo cumplió la mayoría de los pacientes. Una HbA1c <7% fue el objetivo individual que presentó menor grado de cumplimiento.

Abstract Introduction: the clinical practice guidelines in diabetes mellitus (DM) establish precise clinical objectives for the good management of the disease, but little is known about adequate compliance in our environment. Being overweight and sedentary have generated stigmas of metabolic syndrome in the population with DM1. Objectives: to evaluate the compliance with 5 of these criteria: HbA1c <7%, c-LDL ≤100 mg/dL, physical activity (PA) ≥3 times/week, systolic blood preasure (SBP) <140 mm Hg, and no smoking and its association with insulin resistance determined by the estimated glucose disposition rate (eGDR). Materials and methods: in 415 DM1 ≥18 years, 52% women, age 34.8±13.9 years, HbA1c, c-LDL, weekly frequency of structured PA, SBP, and current smoking were evaluated. The degree of association with gender, age, age of DM, level of education, medical coverage, BMI, and insulin sensitivity measured through eGDR was determined. Qualitative variables were analyzed by chi-square test and quantitative variables by ANOVA I test and analysis post hoc by Tukey's test for multiple comparisons. A value of p<0.05 was considered statistically significant. A 95% confidence interval was used in all cases. Results: systolic BP <140 mm Hg presented 94.8%, current non-smoking 82.2%, c-LDL ≤ 100 mg/dL 56.5%, physical activity (PA) ≥3 times a week 39% and HbA1c <7% 20.3%. Only 26 patients (6.2%) achieved the 5 objectives analyzed in combination. The fulfillment of the 5 objectives was associated at the level of ≥ secondary education (p=0.002) and health coverage with social welfare or prepaid (p=0.002). There was a significant association between TeDG in those who fulfilled the 5 objectives (p=0.02) and individually in 4 of them (SPB, c-LDL, HbA1c, and PA). Conclusions: of the 415 patients evaluated in our study, only 6.2% met the 5 criteria under consideration. Only control of SBP, non-smoking and c-LDL <100 were complied with by the majority of the patients. HbA1c <7% was the individual objective with the lowest degree of compliance.

Crianças e adolescentes com diabetes: ações educativas no desenvolvimento de habilidades para o autocuidado / Niños y adolescentes con diabetes: acciones educativas eneldesarrollo de habilidades para el autocuidado / Children and adolescents with diabetes: educational actions in the development of skills for self-care

Objetivo: Analisar o processo de construção de uma proposta de orientação para o cuidado em Diabetes Mellitus tipo 1, a partir de conhecimentos e habilidades em práticas de cuidado de crianças, adolescentes e suas mães. Métodos: Estudo qualitativo, convergente-assistencial, com 16 crianças e adolescentes com diagnóstico de Diabetes Mellitus tipo 1, e suas mães, atendidos em um ambulatório de endocrinologia. Resultados: identificou-se dificuldades similares entre mães e filhos, acerca do conhecimento da doença, e das ações de cuidado. Tal diagnóstico subsidiou o desenvolvimento de intervenções educativas. Conclusão: os participantes não apresentavam conhecimentos suficientes sobre a doença e os cuidados para garantir o controle adequado do diabetes. A construção de proposta educativa proporcionou uma relação horizontal e dialógica entre as pesquisadoras e os participantes.(AU)

Objective: To analyze the process of building an orientation proposal for the care of type 1 Diabetes Mellitus,based on knowledge and skills in care practices for children, adolescents and their mothers. Methods: Qualitative, convergent-assistance study, with 16 children and adolescents diagnosed with type 1 Diabetes Mellituand their mothers, attended at anendocrinology outpatient clinic. Results: similar difficulties were identified between mothers and children regarding knowledge ofthe disease and care actions. This diagnosis supported the development of educational interventions. Conclusion: the participantsdid not have sufficient knowledge about the disease and care to ensure adequate control of diabetes. The construction of aneducational proposal provided a horizontal and dialogic relationship between the researchers and the participants.(AU)

Objetivo:Analizarelproceso de construcción de una propuesta de orientación para el cuidado de la Diabetes Mellitus tipo 1, a partir de conocimientos y habilidades enlasprácticas de cuidado a niños, adolescentes y sus madres. Métodos:Estudiocualitativo, asistencial convergente, con 16 niños y adolescentes con diagnóstico de Diabetes Mellitus tipo 1, y sus madres, atendidos enunambulatorio de endocrinología. Resultados: se identificarondificultades similares entre madres e hijosencuanto al conocimiento de laenfermedad y acciones de cuidado. Este diagnóstico apoyóeldesarrollo de intervenciones educativas. Conclusión:los participantes no poseíanconocimientos suficientes sobre laenfermedad y los cuidados para garantizarunadecuadocontrol de la diabetes. La construcción de una propuesta educativa proporcionó una relación horizontal y dialógica entre los investigadores y los participantes.(AU)

Recomendaciones para la práctica clínica sobre el manejo de la actividad física, ejercicio y deporte en niños, niñas y adolescentes con diabetes mellitus tipo 1 / Management of type 1 diabetes mellitus about physical activity, exercise and sports in children and adolescents

La presente recomendación busca brindar un marco de seguridad para la prescripción de actividad física en niños, niñas y adolescentes con diabetes mellitus tipo 1 (DM1), considerando la evaluación de las situaciones que puedan presentarse antes, durante y después de su práctica. Incluye las estrategias terapéuticas sobre el tipo de ejercicio, el control glucémico capilar (o mediante el uso de monitoreo continuo de glucosa, MCG) y la adecuación de la insulinoterapia y de la ingesta de hidratos de carbono. Se prioriza que, para optimizar los beneficios del ejercicio como parte del tratamiento de la DM1, es importante una completa y constante educación diabetológica para el paciente y sus cuidadores brindada por un equipo interdisciplinario entrenado en el manejo integral de niños, niñas y adolescentes con DM1.

These recommendations seek to provide a safety framework for the prescription of physical activity in children and adolescents with DM1, considering the evaluation of the situations that may arise before, during and after the practice of physical activity. It includes therapeutic strategies on the type of exercise, intensive capillary glycemic control or through the use of continuous glucose monitoring (CGM) and the adequacy of insulin therapy and carbohydrate intake. It is prioritized that to optimize the benefits of exercise as part of the treatment of DM1, a complete and constant diabetes education is important, provided by an interdisciplinary team trained in the comprehensive management of children and adolescents with DM1

O impacto do diabete melito tipo 1 nos pacientes pediátricos: análise através de desenhos / The impact of diabetes mellitus type 1 on pediatric patients: analysis through drawings

Introduction: Type 1 diabetes mellitus (DM1) is a chronic, multifactorial, autoimmune disease that is prevalent in children, adolescents and, in rarer cases, young people. Emotional and physical tensions accompany the patient and family from the moment the diagnosis was made. Initially, when DM1 is discovered, a series of restrictions, new habits are required from patients. In this scenario, it is important that the doctor-patient communication is effective, able to deal with all these adversities. Objective: To verify the quality of life of diabetic pediatric patients through a design analysis. Method: Qualitative analysis study which included: a) patients older than 6 and younger than 14 years old able to draw; b) have a minimum time of 6 months of diagnosis; c) having been applied and answered a pediatric quality of life questionnaire (PedsQL) by those responsible. Results: The drawings in general revolved around food deprivation and daily procedures, demonstrating the real understanding that the child has of the disease from the initial dilemmas to the daily confrontations. Conclusion: Through the interpretation of the drawings along with the questionnaires to the parents, it was possible to assess the emotional impact of DM1 on the lives of children, who were happier and freer when imagining the absence of the disease

Introdução: O diabete melito tipo 1 (DM1) é doença crônica, multifatorial, autoimune que tem por prevalência afetar crianças, adolescentes e em casos mais raro os jovens. As tensões emocionais e físicas acompanham o paciente e a família desde o momento em que foi feito o diagnóstico. Inicialmente ao se descobrir o DM1 uma série de restrições, novos hábitos passam a ser exigidos dos pacientes. Neste cenário é importante que a comunicação médico-paciente seja efetiva, que consiga lidar com todas estas adversidades. Objetivo: Verificar a qualidade de vida do paciente pediátrico diabético através de uma análise de desenho. Método: Estudo de análise qualitativa onde foram incluídos: a) pacientes maiores de 6 e menores que 14 anos capazes de desenhar; b) ter tempo mínimo de 6 meses de diagnóstico; c) ter sido aplicado e respondido questionário (PedsQL) de qualidade de vida pediátrica pelos responsáveis. Resultados: Os desenhos em geral giraram em torno da privação alimentar e dos procedimentos cotidianos, demostrando o real entendimento que a criança tem da doença desde os dilemas iniciais até os enfrentamentos diários cotidianos. Conclusão: Através da interpretação dos desenhos junto com os questionários aos pais, foi possível avaliar o impacto emocional da DM1 na vida das crianças, que se mostraram mais felizes e livres ao imaginarem a ausência da doença.

Precipitating factors of diabetic ketoacidosis in type 1 diabetes patients at a tertiary hospital: a cross-sectional study with a two-time-period comparison

ABSTRACT Objective: To evaluate the precipitating factors of diabetic ketoacidosis (DKA) in patients with type 1 diabetes hospitalized through the emergency department of a tertiary hospital. Materials and methods: Individuals with type 1 diabetes hospitalized for DKA from January 2005 to March 2010 (first period [P1], n = 75) and from April 2010 to January 2017 (second period [P2], n = 97) were identified through a query of electronic medical records. Data were collected by reviewing medical records. Only the first hospitalization of each participant in each period was included. Results: In P2, 44 patients (45.4%) were women, mean age was 26.2 ± 14.5 years, and 74 patients (76.3%) had a previous diagnosis of type 1 diabetes. Only 1 patient had glycated haemoglobin (HbA1c) below 64 mmol/mol (8.0%). Most patients (62.2%) had had a previous episode of DKA. In P1, non-adherence was the main cause of DKA (38.7%), followed by infection (24.0%). In P2, these rates were 34.0% and 24.7%, respectively; no statistical difference was observed between the two study periods (p = 0.790). Conclusion: Over time, non-adherence remained the main precipitating factor of DKA, followed by infection, and no significant difference was observed between the two study periods. Elevated HbA1c, outside the therapeutic range, indicates suboptimal diabetes care and may explain, at least in part, poor adherence as a precipitating factor of decompensation. Health strategies, such as improved self-management of type 1 diabetes, may contribute to a future reduction in DKA episodes.