Presencia de autoanticuerpos anti islotes pancreáticos en diabetes tipo 1 durante la edad pediátrica / Presence of anti-pancreatic islet autoantibodies in type 1 diabetes in children

En la Diabetes tipo 1 (DM1) la pérdida de células ß pancreáticas es consecuencia de un proceso de autoinmunidad que cursa con la presencia de autoanticuerpos anti-islotes pancreáticos (AAPs). Estos AAPs son marcadores útiles para la clasificación de la enfermedad. En un centro pediátrico de tercer nivel se analizó la frecuencia de presentación de GADA, IA-2A, ZnT8A e IAA en un grupo con reciente debut entre enero 2018 y agosto 2021 (n= 90). Además, se investigó la frecuencia de presentación y relación de los AAPs con la edad, sexo y tiempo de evolución en pacientes en seguimiento (n= 240). En el grupo de debut se obtuvo positividad de GADA, IA-2A, ZnT8A y IAA en 77,8; 60; 62 y 47,8% de los pacientes respectivamente, un 4% no presentó AAPs. El 95,6% de los pacientes presentaron al menos un AAPs positivo. La frecuencia de IAA en el grupo en debut fue mayor en menores de 5 años. En el grupo en seguimiento el 75,2% resultaron GADA positivo (85,7% en mujeres y 62,8% en varones) p<0,05. IA-2A y ZnT8A fueron positivos en 45 y 51.7% respectivamente. El 91% presentaron al menos un AAP positivo. En este grupo se evidenció una menor positividad en función del tiempo de evolución. Se pudo determinar la frecuencia de presentación de los AAPs en un grupo en debut y la relación con la edad, sexo y tiempo de evolución en pacientes en seguimiento. La determinación de APPs facilita la correcta clasificación y elección de la terapia adecuada (AU)

In type 1 diabetes (DM1) the loss of pancreatic ß-cells is a consequence of an autoimmune process that results in the presence of pancreatic anti-islet autoantibodies (PAAs). PAAs are useful markers for the classification of the disease. The frequency of presentation of GADA, IA-2A, ZnT8A, and IAA in a group with recent debut seen between January 2018 and August 2021 (n= 90) was analyzed in a tertiary pediatric center. In addition, we investigated the frequency of presentation and association of PAAs with age, sex, and time of evolution in patients in follow-up (n= 240). In the debut group, GADA, IA2A, ZnT8A, and IAA positivity was found in 77.8, 60, 62, and 47.8% of patients, respectively; no PAAs were observed in 4% of the patients. Overall, 95.6% presented at least one positive PAA. The frequency of IAA in the debut group was higher in children younger than 5 years. In the follow-up group, 75.2% were GADA positive (85.7% of females and 62.8% of males) p<0.05. IA-2A and ZnT8A were positive in 45 and 51.7% respectively. Ninety-one percent presented with at least one positive PAA. In this group, a lower positivity was evidenced as a function of the time of evolution. The frequency of presentation of PAAs in a debut group and the relationship with age, sex, and time of evolution in patients in follow-up was demonstrated. The assessment of PAAs facilitates the correct classification and choice of adequate therapy (AU)

Different amounts of moderate to vigorous physical activity and change in glycemic variability in adolescents with type 1 diabetes: is there dose-response relationship?

ABSTRACT Objective To identify the level of physical activity and glycemic variability of adolescents with type 1 diabetes mellitus and to compare glycemic variability on days with different amounts of moderate to vigorous physical activity (MVPA). Subjects and methods A sample of 34 subjects aged 10 to 15 years, 18 (52.94%) female; age: 13.04 ± 1.94; HbA1c: 9.76 ± 1.51. Physical activity was measured by wGT3X accelerometer. The glucose data were obtained using continuous glucose monitoring, and the following glycemic variability measures were calculated: standard deviation (SD), low blood glucose index (LBGI), high blood glucose index (HBGI), mean amplitude of glycemic excursions (MAGE), glycemic risk assessment in diabetes equation (GRADE) and coefficient of variation (CV). The most and least active days (the days with greater and lesser time dedicated to physical activities of moderate to vigorous intensity, respectively) were identified. In addition, based on the whole period of accelerometer use, daily means of time spent in MVPA were identified among participants, who were then divided into three groups: up to 100 minutes; from 101 to 200 minutes and above 201 minutes. Then, the measures of glycemic variability were compared among the most and least active days and among the groups too. Results The amount of MVPA was significantly different between the days evaluated (237.49 ± 93.29 vs. 125.21 ± 58.10 minutes), but glycemic variability measures did not present a significant difference. Conclusion Despite the significant differences in the amount of MVPA between the two days evaluated, the glycemic variability did not change significantly. Arch Endocrinol Metab. 2020;64(3):312-8

Asociación entre síntomas depresivos de las madres y control metabólico en adolescentes con Diabetes Mellitus tipo 1 / Association between depressive symptoms in mothers and metabolic control in adolescents with type 1 diabetes

Resumen: Introducción: Un mal control metabólico en pacientes con Diabetes Mellitus tipo 1 (DM1) se asocia a complica ciones a corto y largo plazo. Los adolescentes con Diabetes tipo 1 presentan peor control metabólico comparado con pacientes de otros grupos etarios. Escasos estudios han demostrado una asociación entre síntomas depresivos de las madres con el control metabólico de sus hijos adolescente. Objetivo: Evaluar la asociación entre síntomas depresivos maternos y control metabólico de adolescentes con DM1. Sujetos y Método: Estudio observacional transversal realizado en adolescentes, edades 10 a 18 años, con diagnóstico de DM1 de más de un año de evolución y sus madres. Se aplicó test de Beck II, cuestionario de depresión infantil, cuestionario SALUFAM y cuestionario de datos sociodemográficos. Se realizó hemoglobina glicosilada capilar, como marcador de control metabólico. Resultados: Se estudiaron 86 parejas (madre-hijo adolescente), adolescentes de edad media 14.04 años y 5.95 años de evolución de DM1. El 25.6% (n 22) de las madres presentó síntomas depresivos, asociándose a peor control metabólico en sus hijos (HbA1c: 7.66% y 8.91%, p < 0.001). El 17.9% de adolescentes presentó síntomas depresivos, no asociándose a síntomas depresivos maternos ni a peor control metabólico. Los síntomas depresivos maternos se asociaron a menor nivel educacional materno y pater no, mayor número de hijos en la familia, presencia de otros hermanos con enfermedades crónicas y a mayor vulnerabilidad en salud (SALUFAM). Conclusiones: La presencia de síntomas depresivos maternos se asocia a peor control metabólico en el adolescente con DM1, siendo fundamental un enfoque multidisciplinario familiar para obtener mejores resultados metabólicos en los adolescentes.

Abstract: Introduction: Poor metabolic control in patients with Type 1 Diabetes Mellitus (T1DM) is associated with short- and long-term complications. Adolescents with T1DM present poorer metabolic control than patients of other age groups. Few studies have shown an association between mothers with depressive symptoms and the metabolic control of their adolescent children. Objective: To evaluate the associa tion between maternal depressive symptoms and metabolic control of their adolescents with T1DM. Subjects and Method: Cross-sectional observational study carried out with adolescents aged between 10 and 18 years, with T1DM diagnosis of at least 1 year ago and their mothers. The Beck Depression Inventory-II and the SALUFAM questionnaire were applied, and sociodemographic data were co llected. Glycosylated hemoglobin from capillary blood was used as a marker of metabolic control. Results: 86 couples (mother-adolescent children) were studied. The average age of the adolescents was 14.04 years and the average evolution time of T1DM was 5.95 years. 27.325.6% of mothers had depressive symptoms, which was associated with worse metabolic control of their children (HbA1c of 7.66% and 8.91%, p-value <0.001). 17.9% of adolescents had depressive symptoms, which was not associated with maternal depressive symptoms or worse metabolic control. Maternal depressive symptoms were also associated with lower maternal and paternal educational levels, high number of children in the family, presence of other siblings with chronic illnesses, and high health vulnera bility (SALUFAM). Conclusions: The mother's depressive symptoms can be associated with worst metabolic control in T1MD adolescents. It is fundamental a multidisciplinary family approach to get better metabolic controls in T1DM adolescents.

Hypertriglyceridemic waist and associated factors in children and adolescents with type 1 diabetes mellitus / Cintura hipertrigliceridêmica e fatores associados em crianças e adolescentes portadores de diabetes melito tipo 1

ABSTRACT Objective: To assess the frequency of the hypertriglyceridemic waist phenotype and its associated factors in children and adolescents with type 1 diabetes mellitus. Methods: This is an observational analytical study with individuals with type 1 diabetes mellitus, aged 5 to 18 years, of both genders, followed in a university hospital in the Brazilian Northeast. Weight, height, and waist circumference were measured, and the lipid profile and glycated hemoglobin were analyzed. The hypertriglyceridemic waist phenotype was defined by the simultaneous presence of increased waist circumference (≥90th percentile for age and gender) and elevated serum triglyceride levels (≥75 mg/dL for children and ≥90 mg/dL for adolescents). We also investigated the family history of cardiovascular diseases and diabetes, as well as sociodemographic and behavioral variables. In the statistical inference tests, the proportions were compared by Pearson's chi-square test ­and/­or Fisher's exact test, being significant p<0.05. Results: A total of 102 patients were evaluated, most of them females (54.9%) and adolescents (66.7%). The frequency of hypertriglyceridemic waist was 23.5%, which was associated with females (p=0.043), overweight (p=0.023), hypercholesterolemia (p=0.002), high LDL (p=0.001), and borderline VLDL (<0.001). Conclusions: The frequency of the hypertriglyceridemic waist phenotype was associated with females, atherogenic lipid profile, and overweight, indicating the importance of the nutritional monitoring of this population, aiming at reducing future cardiovascular diseases.

RESUMO Objetivo: Avaliar a frequência do fenótipo cintura hipertrigliceridêmica e analisar seus fatores associados em crianças e adolescentes portadores de diabetes melito tipo 1. Métodos: Trata-se de um estudo observacional analítico com indivíduos com diabetes melito tipo 1, de cinco a 18 anos de idade, de ambos os sexos, acompanhados em um hospital universitário do Nordeste brasileiro. Foram realizadas medidas de peso, altura e circunferência da cintura, além da análise do perfil lipídico e da hemoglobina glicada. O fenótipo cintura hipertrigliceridêmica foi definido pela presença simultânea da circunferência da cintura aumentada (≥percentil 90 por idade e sexo) e dos níveis séricos de triglicerídeos elevados (≥75 mg/dL para crianças e ≥90 mg/dL para adolescentes). Investigaram-se, ainda, os antecedentes familiares para doenças cardiovasculares e diabetes, e também variáveis sociodemográficas e comportamentais. Nos testes de inferência estatística, as proporções foram comparadas pelo teste do qui-quadrado de Pearson e/ou exato de Fisher, sendo significante p<0,05. Resultados: Foram avaliados 102 pacientes, com predomínio do sexo feminino (54,9%) e de adolescentes (66,7%). A frequência de cintura hipertrigliceridêmica foi de 23,5%; a qual apresentou associação com o sexo feminino (p=0,043), excesso de peso (p=0,023), hipercolesterolemia (p=0,002), LDL elevado (p=0,001) e VLDL em valores limítrofes (<0,001). Conclusões: A frequência do fenótipo cintura hipertrigliceridêmica foi associada ao sexo feminino, ao perfil lipídico aterogênico e ao excesso ponderal, evidenciando a importância do acompanhamento nutricional dessa população, visando à redução de agravos cardiovasculares futuros.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes / Estado antioxidante da coenzima Q10 e da vitamina E em crianças com diabetes tipo 1

Abstract Objective: The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. Method: This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Results: Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p < 0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p < 0.05). The platelet redox status showed a negative correlation with the A1c % levels (r = −0.31; p = 0.022) and the duration of type 1 diabetes (r = −0.35, p = 0.012). Conclusion: Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress.

Resumo Objetivo: Avaliar o estado antioxidante da vitamina E no plasma e da coenzima Q10 no plasma e intracelular em crianças com diabetes tipo 1. Método: Este estudo caso-controle realizado em com 72 crianças com diabetes tipo 1 comparadas por idade, sexo e etnia de 58 crianças saudáveis. As crianças diabéticas foram divididas em dois grupos de acordo com sua hemoglobina glicosilada (A1c %): grupos de controle glicêmico bom e baixo. Todas as crianças foram submetidas a anamnese total, exame clínico e laboratorial para hemograma completo, A1c %, colesterol no plasma, triglicerídeos e níveis de vitamina E e níveis de coenzima Q10 no plasma, eritrócitos e plaquetas. Resultados: As crianças com baixo controle glicêmico mostraram nível de vitamina E no plasma significativamente maior, coenzima Q10, triglicerídeos, lipoproteína de baixa densidade, proporção da circunferência da cintura/estatura e níveis de colesterol e menor nível de lipoproteína de alta densidade e estado redox da coenzima Q10 em comparação aos com bom controle glicêmico e com o grupo de controle (p < 0,05). A coenzima Q10 no plasma mostrou correlação positiva com a duração da diabetes tipo 1, triglicerídeos, colesterol, vitamina E e A1c % e correlação negativa com a idade do grupo diabético (p < 0,05). O estado redox das plaquetas mostrou correlação negativa com os níveis de A1c % (r = -0,31; p = 0,022) e a duração da diabetes tipo 1 (r = -0,35, p = 0,012). Conclusão: Os pacientes com diabetes tipo 1, principalmente mal controlados, apresentaram aumento nos níveis de vitamina E no plasma e coenzima Q10 e redução no estado redox das plaquetas da coenzima Q10 que podem indicar aumento do estresse oxidativo.

Influence of socioeconomic and psychological factors in glycemic control in young children with type 1 diabetes mellitus / Influência dos fatores socioeconômicos e psicológicos no controle glicêmico em crianças jovens com diabetes mellitus tipo 1

Abstract Objective: To evaluate the influence of socioeconomic and psychological factors on glycemic control in young children with type 1 diabetes mellitus. Methods: This was a cross-sectional study assessing prepubertal children with type 1 diabetes mellitus. The authors analyzed the socioeconomic status using the Brazil Economic Classification Criterion (Critério de Classificação Econômica Brasil [CCEB]) and psychological conditions through the Brazilian version of the Problem Areas in Diabetes, associated with glycemic control, measured by glycated hemoglobin (HbA1c). Descriptive analysis was used. The variables were assessed by bivariate and multivariate robust Poisson regression model, as well as Fisher's exact and Pearson's chi-squared tests to obtain the ratios of gross and adjusted prevalence ratio, with confidence interval being estimated at 95%. Results: A total of 68 children with type 1 diabetes mellitus were included in the study. A negative association between glycemic control (glycated hemoglobin levels), socioeconomic status (Brazil Economic Classification Criterion), and psychological condition (Brazilian version of the Problem Areas in Diabetes) was observed. Among the study participants, 73.5% (n = 50) of the children had an unfavorable socioeconomic status; these participants were 1.4 times more likely to present altered glycated hemoglobin values. In relation to individuals with compromised psychological status, 26 (38.2%) had a score above 70, thus being classified with psychological stress; these children were 1.68 times more likely (95% confidence interval: 1.101, 1.301) to have higher glycated hemoglobin levels. Conclusions: The socioeconomic conditions and psychological characteristics of the study participants were negatively associated with glycated hemoglobin results. These data reinforce the importance of the studied variables as predictors of glycemic control.

Resumo Objetivo: Avaliar a influência dos fatores socioeconômicos e psicológicos no controle glicêmico de crianças pequenas portadoras de diabetes mellitus tipo 1. Métodos: Estudo de corte transversal, avaliou crianças pré-púberes, com diabetes mellitus tipo 1. Foram analisados os fatores socioeconômicos com o Critério de Classificação Econômica Brasil e as condições psicológicas através da versão brasileira do Problem Areas in Diabetes (B-Paid), associado ao controle glicêmico, mensurado pela hemoglobina glicada. Foi utilizada análise descritiva. As variáveis foram avaliadas bivariada e multivariantemente pelo modelo de regressão de Poisson robusto, os testes Exato de Fisher e Qui-Quadrado de Pearson para as razões de prevalência bruta e ajustada, sendo o intervalo de confiança estimado em 95%. Resultados: Foram incluídas no estudo 68 crianças com diabetes mellitus tipo 1. Foi observada uma associação negativa entre controle glicêmico (níveis de hemoglobina glicada), status socioeconômico (Critério de Classificação Econômica Brasil) e condição psicológica (versão brasileira do Problem Areas in Diabetes). Entre os participantes do estudo, 73,5% (n = 50) das crianças apresentaram status socioeconômico desfavorável, esses participantes apresentaram 1,4 vezes mais chances de apresentar valores alterados de hemoglobina glicada. Em relação a indivíduos com estado psicológico comprometido, houve uma prevalência de 26 (38,2%) apresentou uma pontuação acima de 70, sendo assim classificada com estresse psicológico, essas crianças foram 1,68 vezes mais prováveis (intervalo de confiança 95%: 1,101, 1,301) de apresentar níveis mais elevados de hemoglobina glicada. Conclusão: As condições socioeconômicas e as características psicológicas dos participantes do estudo foram negativamente associadas aos resultados da hemoglobina glicada. Esses dados reforçam a importância das variáveis estudadas como preditores de controle glicêmico.

Insulina degludec en pacientes diabéticos tipo 1: observación a 18 meses / Degludec insulin in type 1 diabetic patients: 18 months of observation

Antecedentes: En el tratamiento de la diabetes se buscan insulinas de acción más prolongada y con menores tasas de hipoglicemias. Objetivo. Uso del análogo de insulina de acción ultralenta degludec en diabéticos tipo 1 (DM1) tratados previamente con glargina. Pacientes y método: Se observaron 230 DM1 durante 18 meses, promedio de edad 34 años y de diagnóstico 14 años, registrándose parámetros clínicos, bioquímicos, hipoglicemias y requerimientos de insulina (U/kg/peso), en régimen basal/bolo, con degludec y ultra-rápida precomidas. Degludec se ajustó quincenalmente. Resultados: A los 3 meses, la glicemia de ayunas disminuyó de 253mg/dl (243-270) a 180 mg/dl (172- 240), (p< 0,05); a los 6 meses a 156 mg/dl (137-180) (p< 0,05), a los 12 meses a 151 mg/dl (50-328) (p< 0,001) y a los 18 meses 150 (50-321) (p<0,001). La HbA1c, inicialmente de 10,6% (10,3-12,2) bajó a los 3 meses a 8,7% (8,2-11,1) (p< 0,05), a 6 meses a 8,3% (8,0-9,6) (p<0,05), a los 12 meses subió 9,0% (5,9-14,5) (p<0,001) y a los 18 meses 9,0% (5,9-14,6) (p<0,001). La dosis de degludec fue 0,5 U/kg/peso a los 18 meses. Hubo reducción de hipoglicemias: a los 3 meses 14 leves, 4 moderados 1 grave; a los 6 meses 8 leves, 2 moderados y ninguna grave; a los 12 meses 1 leve, y a los 18 meses 2 leves, 1 moderado y ninguna grave. Un 7,8% no presentó hipoglicemias. Conclusión: Degludec en DM1 mostró reducir las glicemias de ayunas y HbA1c, y menor número de hipoglicemias.

Background: In the treatment of diabetes, longer-acting insulins with lower rates of hypoglycaemia are sought. Objective. Use of ultralow-acting insulin analog degludec in type 1 diabetic patients (T1D) previously treated with glargine. Patients and method: 230 T1D patients were observed during 18 months, average of age 34 years and of diagnosis 14 years, registering clinical, biochemical, hypoglycemia and insulin requirements (U / kg / weight), in basal / bolus regimen, with degludec and ultra-fast pre-meals. Degludec adjusted himself fortnightly. Results: At 3 months, the fasting glycemia decreased from 253 mg / dl (243-270) to 180 mg / dl (172 - 240), (p <0.05); at 6 months at 156 mg / dl (137-180) (p <0.05), at 12 months at 151 mg / dl (50-328) (p <0.001) and at 18 months 150 (50-321) ;(p <0.001). HbA1c, initially of 10.6% (10.3-12.2), decreased after 3 months to 8.7% (8.2 - 11.1) (p <0.05), to 6 months to 8 months, 3% (8.0-9.6) (p <0.05), at 12 months it rose 9.0% (5.9-14.5) (p <0.001) and at 18 months 9.0 % (5.9-14.6) (p <0.001). The dose of degludec was 0.5 U / kg / weight at 18 months. There was reduction of hypoglycemia: at 3 months, 14 mild, 4 moderate, 1 severe; at 6 months 8 mild, 2 moderate and none serious; at 12 months 1 mild, and at 18 months 2 mild, 1 moderate and none serious. 7.8% did not present hypoglycemia. Conclusion: Degludec in T1D patients showed to reduce fasting glycemia and HbA1c, and lower number of hypoglycemia.

The characteristics of blood glucose fluctuations in patients with fulminant type 1 diabetes mellitus in the stable stage

ABSTRACT Objective: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). Subjects and methods: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. Results: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. Conclusion: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.

Expression of miR-155, miR-146a, and miR-326 in T1D patients from Chile: relationship with autoimmunity and inflammatory markers

ABSTRACT Objective The aim of this research was to analyze the expression profile of miR-155, miR-146a, and miR-326 in peripheral blood mononuclear cells (PBMC) of 47 patients with type 1 diabetes mellitus (T1D) and 39 control subjects, as well as the possible association with autoimmune or inflammatory markers. Subjects and methods Expression profile of miRs by means of qPCR using TaqMan probes. Autoantibodies and inflammatory markers by ELISA. Statistical analysis using bivariate correlation. Results The analysis of the results shows an increase in the expression of miR-155 in T1D patients in basal conditions compared to the controls (p < 0.001) and a decreased expression level of miR-326 (p < 0.01) and miR-146a (p < 0.05) compared T1D patients to the controls. miR-155 was the only miRs associated with autoinmmunity (ZnT8) and inflammatory status (vCAM). Conclusion Our data show a possible role of miR-155 related to autoimmunity and inflammation in Chilean patients with T1D.

Association of different biomarkers of renal function with D-dimer levels in patients with type 1 diabetes mellitus (renal biomarkers and D-dimer in diabetes)

ABSTRACT Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8-25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2-12.9), 8.4 (2.5-25.4), 9.1 (2.6-31.4) and 3.5 (1.4-8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies.

Effects of a structured education program on glycemic control in type 1 diabetes

ABSTRACT Objective Diabetes mellitus is associated with significant morbidity and mortality, and education is known to play a key role in managing this disease. This study addresses the effects of a structured education program (SEP) on self-care in subjects with type 1 diabetes mellitus (T1DM). The aim was to evaluate the effect of a SEP on glycemic control, knowledge, and skills associated with diabetes care in subjects with T1DM. Subjects and methods A total of 47 adults with T1DM were followed up for 20 months (32 participated in the SEP and 15 served as a control group). The SEP consisted of workshops, individualized care, 24-hour distant support, and a questionnaire assessing knowledge of diabetes care. Glycosylated hemoglobin (HbA1c) levels were measured before and after the SEP implementation. Results Compared with pre-SEP levels, the mean HbA1c levels decreased by approximately 20% (21 mmol/mol) at 1 year, with a further 11% reduction (10 mmol/mol) observed 8 months later (p < 0.001). Knowledge about diabetes care increased by 37% between the pre-SEP and post-SEP questionnaires (p < 0.005). Conclusion Relevant improvements occurred after SEP activities. The sustained decrease in HbA1c levels and the overall increase in knowledge and confidence regarding diabetes care reinforce the importance, necessity, and positive outcomes of a SEP intervention in T1DM.

Decrease in Mandibular Cortical in Patients With Type 1 Diabetes Mellitus Combined with Poor Glycemic Control

Abstract In this study we analyzed the mandibular cortical bone of patients with type 1 diabetes mellitus (T1DM) and non-diabetic. Fifty patients with T1DM and 100 non-diabetic ones paired by age and gender were analyzed. Two double-blinded observers evaluated 150 digital panoramic images of both groups. The mandibular cortical bone was analyzed using the Mandibular Cortical Index (MCI), Mental Index (MI), Gonial Index (GI), Antegonial Index (AI) and Upper and Lower Panoramic Mandibular Indexes (UPMI and LPMI), with the aid of RADIOIMP® software. Influence of T1DM in the morphology of the mandibular cortical bone was studied based on obtaining data related to T1DM diagnosis time, blood glucose level, T1DM control and the presence of chronic complications. Collected data were submitted to descriptive (mean and standard deviation) and inferential analyzes (Pearson's chi-squared test and Fisher's exact test) (p≤0.05). According to the MCI, individuals with T1DM had higher frequencies of mandibular cortical alterations, in both sexes and all age groups (p<0.01). For quantitative indexes, MI, GI, AI, UPMI and LPMI, female patients showed statistically significant differences for GI and AI, while male patients had statistically significant differences for all indexes (p<0.05), presenting the individuals with TDM1 inferior measures. Individuals with poor T1DM control showed significantly higher frequency of mandibular cortical alteration (92.3%), with lower means for MI, GI, AI and LPMI (p≤0.05). In conclusion, patients with T1DM showed decrease in the mandibular cortical bone when compared to non-diabetic ones, indicating that poor disease control is associated with these alterations.

Resumo Neste estudo, nós analisamos a cortical óssea mandibular de pacientes com Diabetes Mellitus tipo 1 (DM1) e não diabéticos. Foram analisados ​​50 pacientes com DM1 e 100 não diabéticos, pareados por idade e sexo. Dois observadores com duplo-mascaramento avaliaram 150 imagens panorâmicas digitais de ambos os grupos. A cortical óssea mandibular foi analisada por meio do Índice Cortical Mandibular (ICM), Índice Mental (IM), Índice Goníaco (IG), Índice Antegoníaco (IA) e os Índices Panorâmicos Mandibulares Superior (IPMS) e Inferior (IPMI), com o auxílio do software RADIOIMP®. A influência do DM1 na morfologia da cortical óssea mandibular foi analisada com base na obtenção de dados relacionados ao tempo de diagnóstico do DM1, nível de glicemia, controle do DM1 e presença de complicações crônicas. Os dados coletados foram submetidos a análises descritivas (média e desvio-padrão) e inferenciais (teste de Qui-quadrado de Pearson e teste exato de Fisher) (p ≤0,05). De acordo com o ICM, indivíduos com DM1 apresentaram maiores frequências de alterações corticais mandibulares, em ambos os sexos e todas faixas etárias (p <0,01). Para os índices quantitativos, IM, IG, IA, IPMS e IPMI, pacientes do sexo feminino apresentaram diferença estatisticamente significativa para os IG e IA, enquanto os pacientes do sexo masculino mostraram diferenças estatisticamente significativas para todos os índices (p <0,05), tendo os indivíduos com DM1 medidas inferiores. Indivíduos com controle ruim do DM1 apresentaram frequência de alteração na cortical mandibular significativamente maior (92,3%), com menores médias para o IM, IG, IA e IPMI (p ≤0,05). Em conclusão, pacientes com DM1 apresentaram diminuição na cortical óssea mandibular quando comparados aos não diabéticos, indicando que o controle ruim da doença está associado a essas alterações.

Correlation between parameters of self-monitoring of blood glucose and the perception of health-related quality of life in patients with type 1 diabetes mellitus

ABSTRACT Objective The aim of this study was to evaluate how different parameters of short-term glycemic control would correlate with the perception of health-related quality of life (HRQoL) in patients with type 1 diabetes mellitus (T1D). Subjects and methods A total of 50 T1D patients aged 18 to 50 years were evaluated with the questionnaires Problem Areas in Diabetes (PAID) scale and Diabetes Quality of Life (DQOL) measure after 30 days of self-monitoring of blood glucose (SMBG). Glycemic control was evaluated using glycated hemoglobin (HbA1c), mean glucose levels (MGL) in the prior month's data from SMBG (Accu-Check 360o), number of hypoglycemic episodes (< 70 mg/dL and < 50 mg/dL), and glycemic variability (GV). Results PAID correlated positively with MGL (r = 0.52; p < 0.001) and HbA1c (r = 0.36; p < 0.0097), but not with GV (r = 0.17; p = 0.23) or number of hypoglycemic episodes (r = 0.15; p = 0.17 for glucose < 70 mg/dL and r = 0.02; p = 0.85 for glucose < 50 mg/dL). After multiple linear regression, only MGL remained independently related to PAID scores. DQOL scores had a positive correlation with MGL (r = 0.45; p = 0.001), but not with HbA1c (r = 0.23; p = 0.09), GV (r = 0.20; p = 0.16), or number of hypoglycemic episodes (r = 0.06 p = 0.68). Conclusion In T1D patients, MGL, but not HbA1c or number hypoglycemic episodes, was the glycemic control parameter that best correlated with short-term perception of HRQoL.

Cetosis normoglicémica en adolescente con diabetes tipo 1 recibiendo insulina y dapaglifozina: Reporte de un caso / Euglycemic ketosis in an adolescent with type 1 diabetes on insulin and dapaglifozin: Case report

Dapaglifozina, un inhibidor del cotransportador de sodio-glucosa 2 (I-SGLT2) induce glucosuria y reduce la glicemia en adultos con diabetes tipo 2. Objetivo: Presentar una cetosis diabética “normoglicémica” en una adolescente con diabetes tipo 1 (DM1) que recibía dapaglifozina y alertar sobre el riesgo del uso I-SGLT2 que parece promisorio, pero no está aprobado en niños ni en DM1. Caso clínico: Paciente de 17 años sin cetosis durante 9 años con DM1, inició dapaglifozina 10 mg/día para reducir la insulina y el peso. Durante 11 meses de tratamiento tuvo cetonas capilares indetectables, redujo el índice de masa corporal 23,9 a 21,1 kg/m², la insulina basal 40 a 17 U, la hemoglobina glicosilada 8,3 a 7,5%, la glicemia capilar 175 a 161 mg/dl y la variabilidad de la glucosa (desvío estándar 85 a 77). Inesperadamente aparecieron náuseas y vómitos. La paciente portaba bomba de insulina con monitorización continua de glucosa, bien calibrada (glucosas intersticiales concordantes con glicemias), que mostraba glucosa estable bajo 200 mg/dl. Recibió insulina pero los vómitos persistieron; en tres horas, aparecieron deshidratación y desmayos, con cetonas 4,6 nmol/l y glicemia 224 mg/dl. Recibió suero fisiológico, ondansetrón, carbohidratos y varias dosis de insulina con pronta recuperación del estado general e hidratación, sin embargo, la cetosis continuó durante 24 horas. Cabe destacar que la bomba estaba funcionando bien y no se cambió la cánula. Al superar la cetosis, continuó con la misma cánula con buen control metabólico. Conclusión: Es importante sospechar la cetosis diabética normoglicémica por ser de riesgo vital.

Dapagliflozin, an insulin-independent sodium-glucose cotransporter 2 inhibitor (SGLT2-I) induces glycosuria and reduces hyperglycemia in adults with type 2 diabetes. Objective: To present an “euglycemic” diabetic ketosis in an adolescent with type 1 diabetes (T1D) receiving dapagliflozin, to alert about the risk of a drug not approved in children nor in T1D. Case report: A 17 years old adolescent with T1D during 9 years, was started on dapagliflozin 10 mg / day to reduce insulin dose and weight. During 11 months on treatment, capillaries ketones were undetectable and she exhibited a reduction in body mass index 23.9 to 21.1 kg/m2, basal insulin 40 to 17 U, glycated hemoglobin 8.3 to 7.5%, capillary glucose 175 to 161 mg/dl and glucose variability (standard deviation) 85 to 77. Suddenly nausea and vomits appeared. The patient was on an insulin pump and well calibrated continuous glucose monitoring, showing stable glucose levels under 200 mg/dl, and an insulin bolus was delivered. Vomiting without hyperglycemia persisted; three hours later, she was severely dehydrated and fainting, with ketones 4.6 nmol/l and glucose 224 mg/dl. She received IV saline fluids, ondansetron, carbohydrates and several insulin boluses. Hydration and general condition improved soon, however despite several insulin doses, ketosis continued for 24 hours. It is remarkable that the pump was working well and the cannula was not changed. After the ketosis was resolved, she continued using the same cannula with good metabolic control. Conclusion: Euglycemic ketosis is a life-threatening condition that must be suspected.

Control metabólico y rendimiento escolar en niños con diabetes tipo 1 / Metabolic control and school performance in children with type 1 diabetes

El impacto de la diabetes tipo 1 (DM1) en el rendimiento escolar es controversial. Objetivo: Evaluar la relación entre rendimiento escolar y control metabólico en niños con DM1 (N-DM1) y comparar sus resultados con niños de la población general (N-PG). Pacientes y Método: Se revisaron datos clínicos de 66 N-DM1. Se compararon las calificaciones de N-DM1 según Hemoglobina Glicosilada (HbA1c) < 7,5% y ≥ 7,5% con N-PG del mismo nivel, comuna, tipo de colegio (municipal, particular subvencionado y particular pagado) y localidad. Para la comparación de los grupos se utilizó la regresión lineal simple y el test de suma de los rangos de Wilcoxon (Mann y Whitney) previa comprobación de incumplimiento de normalidad con el test de Shapiro-Wilk según el caso. Se consideró un valor de p < 0,05 como estadísticamente significativo con una confiabilidad del 95%. Resultados: La edad fue 13,4 ± 2,9 años, tiempo de evolución DM1 5,3 ± 3,2 años, HbA1c 8,6 ± 1,9% y controles de glicemia capilar 3,2 ± 1,2 veces por día. Las calificaciones no mostraron correlación con HbA1c, duración de DM1, hipotiroidismo, problemas de salud mental, antecedentes de hipoglicemia ni de cetoacidosis. N-DM1 de educación básica mostraron calificaciones inferiores a N-PG del mismo nivel 5,6 ± 0,7 vs 6,0 ± 0,2 (p = 0,0002). Las calificaciones se correlacionaron con el número de controles diarios de glicemia capilar, coeficiente de correlación de Pearson (r) de 0,25, 0,41, 0,52 y 0,58 con el promedio general, matemática, lenguaje e historia respectivamente (p < 0,05). Un 6,1% de N-DM1 y 4,8% de N-PG no fue promovido de curso (p = 0,65). La deserción escolar fue 10,5% en N-DM1 y 7,7% en N-PG (p = 0,47). Conclusión: N-DM1que cursaban educación básica tuvieron calificaciones inferiores a N-PG y los pacientes que controlaban su glicemia capilar con mayor frecuencia mostraron mejores calificaciones. La DM1 puede tener un impacto deletéreo en el rendimiento escolar.

The impact of type 1 diabetes (T1D) on school performance is controversial. Objective: To study the relationship between school performance and metabolic control in children with T1D (Ch-T1D), comparing their school grades to general population children (Ch-GP). Patients and Method: Clinical data for 66 Ch-T1D was reviewed, school grades were compared in Ch-T1D with Glycated Haemoglobin (HbA1c) HbA1c < 7.5% and ≥ 7.5%. School marks were also compared between Ch-T1D and Ch-GP from the same level, community and school type (public, private o chartered). Simple linear regression analysis and Mann Whitney test were used to compare groups. A p < 0.05 was considered significant. Results: Ch-T1D were: 13.4 ± 2.9 years old, T1D duration: 5.3 ± 3.2 years, HbA1c was 8.6 ± 1.9% and capillary blood glucose was measured 3.2 ± 1.2 times per day. Grade averages showed no correlation with HbA1c, diabetes duration, hypothyroidism, mental health issues, neither with hypoglycemia or ketoacidosis records. However, primary education Ch-T1D showed lower grades than Ch-GP 5.6 ± 0.7 and 6.0 ± 0.2 (p = 0,0002). School grades correlated with the number of capillary blood glucose readings per day, Pearson correlation coefficient (r) 0.25, 0.41, 0.52 and 0.58 with general grade point average, math, language, and history average respectively (p < 0.05). School non-pass rate was 6.1% in Ch-T1D and 4.8% in Ch-GP (p = 0.65) and school dropout rate was 10.5% in Ch-T1D and 7.7% in Ch-GP (p = 0.47). Conclusion: Ch-T1D attending primary school showed lower school grades than Ch-GP, and patients who more frequently checked capillary blood glucose showed better school grades. T1D may have a deleterious impact on school performance.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

ABSTRACT Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.

Evaluation of creatinine-based and cystatin C-based equations for estimation of glomerular filtration rate in type 1 diabetic patients

ABSTRACT Objective Several formulas based in different biomarkers may be used to estimate glomerular filtration rate (GRF). However, all of them have some limitations, and it is very important to evaluate their performances in different groups of patients. Therefore, we compared GFR, as estimated by creatinine-based and cystatin C-based equations, according to albuminuria, in type 1 diabetes (T1DM), in an observational case-control study. Subjects and methods T1DM patients were classified according to albuminuria: normoalbuminuric (n = 63), microalbuminuric (n = 30), macroalbuminuric (n = 32). GFR was calculated using creatinine-based and cystatin C-based (aMDRD, CKD-EPIcr, CKD-EPIcys, MacIsaac, Tan and CKD-EPIcrcys) equations. Spearman Correlation was used to evaluate the correlation of GFR estimated by the formulas with albuminuria. ROC curves were constructed to compare AUCs of GFR estimated by equations, in reference to macroalbuminuria. Sensibility, specificity and accuracy were calculated for a cut-off < 60 mL/min/1.73 m2. Results GFR estimated by creatinine-based and cystatin C-based equations significantly differed among normoalbuminuric, microalbuminuric and macroalbuminuric patients. Spearman correlation and AUCs of GFR estimated by creatinine-based and cystatin C-based formulas were very similar to each other, though cystatin C-based equations presented better correlation with albuminuria and higher AUCs than the creatinine-based ones, and the best accuracy to detect macroalbuminuric patients. Conclusion Although GFR estimated by all creatinine-based and cystatin C-based equations permitted the differentiation between T1DM patients, according to albuminuria, cystatin C-based equations presented best accuracy to detect macroalbuminuria in T1DM patients and should be considered in the clinical routine in order to increase the possibility of early diagnostic of chronic renal disease.

Frequency of ABO/Rhesus blood groups in patients with diabetes mellitus

The correlation between ABO/Rh blood groups and diabetes mellitus is still controversial. The aim of this study was to determine the relationship between ABO/Rhesus blood groups and diabetes in Turkish population. This cross-sectional study was conducted in Istanbul Medeniyet University Goztepe Education and Training Hospital's Diabetes Units. The study group was composed of 421 patients with type-1 diabetes, 484 patients with type-2 diabetes and 432 controls. Blood samples were collected and tested for ABO/Rhesus blood groups. Data was analyzed by SPSS version 17.0. A significant association was found between blood groups and diabetes mellitus. The frequency of AB blood group was significantly higher in type-1 diabetics; and A blood group was significantly higher in type-2 diabetics. Furthermore, Rh negativity were significantly more frequent in type-2 diabetics

The influence of glycemic control on the oral health of children and adolescents with diabetes mellitus type 1

ABSTRACT Objective To evaluate the influence of disease control, expressed by the mean values of glycated hemoglobin (HbA1c), in the oral health of children and adolescents with diabetes mellitus type 1 (T1DM). Subjects and methods A cross sectional study involving 87 children and adolescents (59 girls), 10 ± 2.6 years old. The participants were divided into three groups: HbA1c ≤ 8%, 8% < HbA1c ≤ 10% and HbA1c > 10%. The duration of the disease, age and average HbA1c were obtained from their medical records. Oral health was evaluated according to the following indexes: Simplified Oral Hygiene Index (OHI-S); Community Periodontal Index (CPI); Decayed, Missing or Filled Teeth Index (DMFT/dmft) for permanent and deciduous teeth; and the stimulated salivary flow rate (SSFR). Results The median SSFR was 1.1 mL/min in the group with HbA1c ≤ 8%, 0.7 mL/min in the intermediary group and 0.6 mL/min in the HbA1c > 10% group. A significant decrease in salivary flow was observed with an increase in HbA1c (p = 0.007). The DMFT/dmft and CPI indexes were higher in individuals with higher HbA1c values. More caries-free individuals were found in the group with HbA1c ≤ 8% compared to those with HbA1c > 10%. The group with HbA1c > 10% exhibited more caries and bleeding gums than the other groups. HbA1c values in girls were higher than in boys. Conclusion Children and adolescents with unsatisfactory glycemic control, represented by higher HbA1c concentrations, exhibited a higher frequency of caries and gingivitis, and a reduction in salivary flow. Arch Endocrinol Metab. 2015;59(6):535-40.

Bombas de insulina (BI) / Insulin pumps (IP)

En la década pasada, el conocimiento sobre la historia natural y fisiopatogenia de la diabetes tipo 1 tuvo un importante crecimiento, particularmente en relación con predicción, heterogeneidad, patología pancreática y su epidemiología. Las mejoras tecnológicas específicamente en el desarrollo de bombas de insulina y sensores continuos de glucosa ayudan a los pacientes con diabetes tipo 1 en el desafío de la administración de insulina a largo plazo. A pesar de grandes inversiones sobre distintos aspectos de la enfermedad (financiación de proyectos, organizativos, educacionales, etc.) no existe hasta el momento la prevención ni la cura para la diabetes tipo 1, y sumado a esto la calidad sobre el manejo de la enfermedad es muy heterogéneo. Como el control glucémico mejora con un tratamiento intensificado (múltiples inyecciones de insulina), el número y frecuencia de eventos hipoglucémicos tienden a incrementarse. La hipoglucemia es generadora de cuadros de estrés, ansiedad y deterioro de la calidad de vida en los pacientes con diabetes. Una de las razones por las cuales existe gran dificultad de alcanzar los objetivos glucémicos en pacientes con diabetes tipo 1 es la variabilidad en la absorción de la insulina inyectada en forma subcutánea, la que conlleva mayor e impredecible variabilidad en la concentración glucémica y todo esto en general se relaciona con valores elevados de hemoglobina glicosilada e hipoglucemia. La terapia con bomba de insulina se inició hace más de 30 años con el objetivo de mejorar el control en pacientes con diabetes tipo 1. El objetivo de esta revisión es actualizar las herramientas tecnológicas en el tratamiento de la diabetes. (AU)

Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly with regard to disease prediction and heterogeneity, pancreatic pathology, and epidemiology. Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage the challenge of lifelong insulin administration. Agents that show promise for averting debilitating disease-associated complications have also been identified. However, despite broad organisational, intellectual, and fiscal investments, no means for preventing or curing type 1 diabetes exists, and , globally, the quality of diabetes management remains uneven. As glycemic control improves with intensified insulin regimens, the frequency of hypoglycemia tends to increase. Hypoglycemia is the cause of considerable stress and anxiety, impaired well-being, and poor quality of life in patients with type diabetes. One reason for continued poor glycemic control in patients with type 1 diabetes is the erratic absorption and action of subcutaneously injected insulin, which lead to unpredictable swings in blood glucose concentrations, and those swings, in themselves, are associated with elevated glycated hemoglobin levels and hypoglycemia. Insulinpump therapy, or continuous subcutaneous insulin infusion, was introduced more than 30 years ago as a procedure for improving glycemic control in patients with type 1 diabetes. The primary goal is to perform an up date about the new technological tools in diabetes treatment. (AU)