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BACKGROUND: Individuals with type 1 diabetes (T1D) are exposed to an elevated risk of automobile accidents especially because of hypoglycemia that impairs physiological and defense responses. OBJECTIVES: To assess local risk factors for traffic events in T1D adult Brazilian patients. METHODS: This is a prospective study and 12-month follow-up to assess predictors for traffic events on a cohort of drivers with T1D (n = 168) in Brazil. The inclusion criteria for participants were Brazilian nationality, age ≥ 18 years-old, diagnosis of T1D for more than one year, driving license B, C or D categories (four-wheel vehicles), driving three-times per week or more, and checking blood glucose twice-daily or more. The primary outcome was hypoglycemia driving mishaps assessed by a seven-query questionnaire about the past 30 days. Secondary outcomes included driving mishaps not related to hypoglycemia. Statistical analysis was performed through Poisson regression models with robust variance estimarion, in which the measure of association is the relative risk. RESULTS: A total of 109 participants completed the 12-month follow-up. Most of them were men (66%) and 37 ± 11 years-old, and had a mean HbA1c of 8.2% (66 mmol/mol). In the follow up, the incidence of traffic events was high (70.6%); however, only a minority was attributed to hypoglycemia as the cause of the reported event (19.3%). The best predictors for new traffic events due to hypoglycemia were those related to driving characteristics. The best of them was a history of episodes of hypoglycemia while driving [RR 3.40 (1.22-9.43); p < 0.05]. CONCLUSIONS: We found that previous episodes of hypoglycemia while driving significantly increase the risk of new traffic events and are the best predictor for it. This highlights the need to assess the risks of traffic accidents especially in people who have had experienced episodes of hypoglycemia while driving.

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This study evaluated the adherence of physicians to the Clinical Protocol and Therapeutic Guidelines on Parkinson's Disease (CPTG-PD) within the scope of the Unified Health System (SUS). A descriptive analysis of 375 drug application documents sent to the Pharmaceutical Services of the Rio Grande do Sul State Public Health Department (AF/SES/RS) between March and September 2016, and a structured survey to evaluate the physician's perception about the protocol and barriers to its use was conducted. Only 5.33% of the requests analyzed presented all the necessary data, considering the criteria of the protocol. The requests from specialists had a higher percentage of adherence to the diagnostic and dose criteria (p<0.05). The main barriers to protocol use were the lack of awareness or familiarity with the protocol (48%) and the lack of time to complete the mandatory documents (52%). More recently qualified physicians tended to perceive fewer barriers to protocol use (p<0.05). The results indicate that actions are still necessary to implement the PCDT-DP in medical practice, focusing on care and management teams. Greater integration between pharmaceutical assistance and the healthcare network is needed.

Este estudo avaliou a adesão de médicos ao Protocolo Clínico e Diretrizes Terapêuticas para a Doença de Parkinson (PCDT-DP), no âmbito do SUS. Dois métodos complementares foram utilizados: avaliação descritiva de 375 solicitações de medicamentos encaminhadas à Assistência Farmacêutica da Secretaria de Estado da Saúde do Rio Grande do Sul, de março a setembro de 2016, e levantamento por meio de questionário estruturado aos prescritores para investigar a percepção de barreiras à utilização. Apenas 5,33% das solicitações analisadas apresentaram adesão completa às recomendações do protocolo. As solicitações oriundas de especialistas em DP tiveram maior adesão aos critérios para o diagnóstico (p<0,05) e dose do medicamento (p<0,05). Dentre as respostas ao questionário destacaram-se como principais barreiras a falta de tempo para preenchimento dos documentos obrigatórios (52%) e nenhum ou pouco conhecimento sobre o protocolo (48%). Médicos com menor tempo de exercício de profissão tendem a perceber menos barreiras para a utilização do protocolo (p<0,05). Os resultados indicam a necessidade de ações de implementação do PCDT-DP à prática médica, direcionadas às equipes assistenciais e de gestão, e maior integração da assistência farmacêutica com a rede de atenção.

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Resumo Este estudo avaliou a adesão de médicos ao Protocolo Clínico e Diretrizes Terapêuticas para a Doença de Parkinson (PCDT-DP), no âmbito do SUS. Dois métodos complementares foram utilizados: avaliação descritiva de 375 solicitações de medicamentos encaminhadas à Assistência Farmacêutica da Secretaria de Estado da Saúde do Rio Grande do Sul, de março a setembro de 2016, e levantamento por meio de questionário estruturado aos prescritores para investigar a percepção de barreiras à utilização. Apenas 5,33% das solicitações analisadas apresentaram adesão completa às recomendações do protocolo. As solicitações oriundas de especialistas em DP tiveram maior adesão aos critérios para o diagnóstico (p<0,05) e dose do medicamento (p<0,05). Dentre as respostas ao questionário destacaram-se como principais barreiras a falta de tempo para preenchimento dos documentos obrigatórios (52%) e nenhum ou pouco conhecimento sobre o protocolo (48%). Médicos com menor tempo de exercício de profissão tendem a perceber menos barreiras para a utilização do protocolo (p<0,05). Os resultados indicam a necessidade de ações de implementação do PCDT-DP à prática médica, direcionadas às equipes assistenciais e de gestão, e maior integração da assistência farmacêutica com a rede de atenção.

Abstract This study evaluated the adherence of physicians to the Clinical Protocol and Therapeutic Guidelines on Parkinson's Disease (CPTG-PD) within the scope of the Unified Health System (SUS). A descriptive analysis of 375 drug application documents sent to the Pharmaceutical Services of the Rio Grande do Sul State Public Health Department (AF/SES/RS) between March and September 2016, and a structured survey to evaluate the physician's perception about the protocol and barriers to its use was conducted. Only 5.33% of the requests analyzed presented all the necessary data, considering the criteria of the protocol. The requests from specialists had a higher percentage of adherence to the diagnostic and dose criteria (p<0.05). The main barriers to protocol use were the lack of awareness or familiarity with the protocol (48%) and the lack of time to complete the mandatory documents (52%). More recently qualified physicians tended to perceive fewer barriers to protocol use (p<0.05). The results indicate that actions are still necessary to implement the PCDT-DP in medical practice, focusing on care and management teams. Greater integration between pharmaceutical assistance and the healthcare network is needed.

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BACKGROUND: Effective education is considered essential for people with type 1 diabetes mellitus (T1DM) to adhere to a complex and long-term medical regimen and to delay or prevent the onset of diabetes-related complications. OBJECTIVE: We compared the effect of a compact, cost-effective, education program (CEPT1) vs a long-term program on the metabolic control of children and adolescents with T1DM. METHODS: Young people aged 8 to 21 years with T1DM were randomized to a short-term (experimental) or an extensive education program (control). The experimental group participated in three sessions of 90 minutes, with one session per week, containing five short videos. The control group attended an extended program delivered through 45-minute PowerPoint lectures, with one class every 3 months. The primary outcome was change in glycated hemoglobin A1c (HbA1c) levels from baseline to endpoint (baseline, 3, 6, 9, and 12 months). RESULTS: In total, 62 patients were randomized to the experimental (CEPT1) (n = 32) or control (n = 30) groups. Both groups showed comparable improvement in HbA1c levels at the end of 12 months (P = .183). In a per-protocol analysis, the mean HbA1c level reduction was -2.3% (-2.6, -2.0) in the experimental group and - 1.8% (-2.0, -1.5) in the control group (P = .008). CONCLUSION: CEPT1 was comparable with an extensive education program in reducing HbA1c levels. In a per-protocol analysis, the CEPT1 was more effective than the control program in reducing HbA1c levels. CEPT1 is a simple and cost-effective tool that can equally be used in settings with limited resources and specialized centers.

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This study aimed to compare the effect of high-intensity interval training (HIIT) with moderate-intensity continuous training (MCT) on endothelial function, oxidative stress and clinical fitness in patients with type 1 diabetes. Thirty-six type 1 diabetic patients (mean age 23.5 ± 6 years) were randomized into 3 groups: HIIT, MCT, and a non-exercising group (CON). Exercise was performed in a stationary cycle ergometers during 40 min, 3 times/week, for 8 weeks at 50-85% maximal heart rate (HRmax) in HIIT and 50% HRmax in MCT. Endothelial function was measured by flow-mediated dilation (FMD) [endothelium-dependent vasodilation (EDVD)], and smooth-muscle function by nitroglycerin-mediated dilation [endothelium-independent vasodilation (EIVD)]. Peak oxygen consumption (VO2peak) and oxidative stress markers were determined before and after training. Endothelial dysfunction was defined as an increase < 8% in vascular diameter after cuff release. The trial is registered at ClinicalTrials.gov, identifier: NCT03451201. Twenty-seven patients completed the 8-week protocol, 9 in each group (3 random dropouts per group). Mean baseline EDVD was similar in all groups. After training, mean absolute EDVD response improved from baseline in HIIT: + 5.5 ± 5.4%, (P = 0.0059), but remained unchanged in MCT: 0.2 ± 4.1% (P = 0.8593) and in CON: -2.6 ± 6.4% (P = 0.2635). EDVD increase was greater in HIIT vs. MCT (P = 0.0074) and CON (P = 0.0042) (ANOVA with Bonferroni). Baseline VO2peak was similar in all groups (P = 0.96). VO2peak increased 17.6% from baseline after HIIT (P = 0.0001), but only 3% after MCT (P = 0.055); no change was detected in CON (P = 0.63). EIVD was unchanged in all groups (P = 0.18). Glycemic control was similar in all groups. In patients with type 1 diabetes without microvascular complications, 8-week HIIT produced greater improvement in endothelial function and physical fitness than MCT at a similar glycemic control.

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BACKGROUND: Serological screening for celiac disease (CD) allows the identification of individuals genetically predisposed, as type 1 diabetes mellitus (T1DM). However, the diagnosis is confirmed by intestinal biopsy. The aim was to determine the prevalence of immunoglobulin-A anti-tissue transglutaminase antibodies (IgA-tTG) and CD in a large cohort of young T1DM patients. METHODS: Screening for CD was randomly conducted in 881 T1DM by IgA-tTG and total IgA. Individuals with positive antibodies were referred to endoscopy/duodenal biopsy. RESULTS: The age of the cohort at the screening was 14.3 ± 5.9 years and at T1DM onset was 7.9 ± 4.4 years. The prevalence of positive serology was 7.7%. Median IgA-tTG levels were 117.7 U/mL (interquartile range [IQR] 35.7-131.5 U/mL). Of the 62 duodenal biopsy, CD was diagnosed in 79.0%, yielding an overall prevalence of 5.6%. The mean age of CD patients was 15.6 ± 6.5 years and, at T1DM onset was 6.3 years (4.0-9.9 years). The modified Marsh-Oberhuber histological classification was 22.5% (3a), 36.7% (3b), and 40.8% (3c). In the biopsy-proven patients, T1DM onset occurred at slightly younger ages (6.3 vs 9.7 years, P = 0.1947), gastrointestinal (GI) manifestations, predominantly abdominal pain and distension, were more prevalent (71.4% vs 38.5%, P = 0.027) and higher IgA-tTG titers (128.0 vs 26.3 U/mL, P = 0.0003) were found than in those with negative-biopsies. CONCLUSION: Our results demonstrate the prevalence of 7.7% of IgA-tTG and 5.6% of CD in T1DM patients in South Brazil and, emphasize the importance of the screening in high-risk individuals. Furthermore, the presence of GI manifestations and higher IgA-tTG titers strongly suggest the diagnosis of CD.

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AIMS: The aim of this study was to investigate a miRNA expression profile in type 1 diabetes mellitus (T1DM) patients with DKD (cases) or without this complication (controls). METHODS: Expression of 48 miRNAs was screened in plasma of 58 T1DM patients (23 controls, 18 with moderate DKD, and 17 with severe DKD) using TaqMan Low Density Array cards (Thermo Fisher Scientific). Then, five of the dysregulated miRNAs were selected for validation in an independent sample of 10 T1DM controls and 19 patients with DKD (10 with moderate DKD and 9 with severe DKD), using RT-qPCR. Bioinformatic analyses were performed to explore the putative target genes and biological pathways regulated by the validated miRNAs. RESULTS: Among the 48 miRNAs investigated in the screening analysis, 9 miRNAs were differentially expressed between DKD cases and T1DM controls. Among them, the five most dysregulated miRNAs were chosen for validation in an independent sample. In the validation sample, miR-21-3p and miR-378-3p were confirmed to be upregulated in patients with severe DKD, while miR-16-5p and miR-29a-3p were downregulated in this group compared to T1DM controls and patients with moderate DKD. MiR-503-3p expression was not validated. Bioinformatic analyses indicate that the four validated miRNAs regulate genes from PI3K/Akt, fluid shear stress and atherosclerosis, AGE-RAGE, TGF-ß1, and relaxin signaling pathways. CONCLUSIONS: Our study found four miRNAs differentially expressed in patients with severe DKD, providing significant information about the biological pathways in which they are involved.

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BACKGROUND: In 2014-2015, the largest international survey of insulin injection technique in patients with diabetes taking insulin was conducted in 42 countries, totaling 13,289 participants. In Brazil, patients from five public health centers were included. This study aims to evaluate insulin injection technique in Brazilian patients and compare results with Latin America (LatAm) and World data. METHODS: The insulin Injection Technique Questionnaire (ITQ) survey consisted of an initial patient section (questions applied by an experienced nurse), followed by observation of injection technique and examination of the injection sites by the health care professional. RESULTS: In Brazil, 255 patients were evaluated: 25% had type 1 diabetes mellitus (T1DM) and 75% had T2DM. In this study, 79% of patients injected less than 4 times a day, and 17.3% used insulin pens, compared to 28% in LatAm and 86% worldwide. Syringes were used by 78% of patients in Brazil, compared to 65% in LatAm and 10% globally. Differences in needle length were substantial-nearly 64% in Brazil inject with 8 mm length needle compared to 48% in LatAm and 27% worldwide. Additionally, 48% of patients in Brazil skip doses, 80% reuse pen needles and 57% reuse syringes with 27% having lipohypertrophy by exam. CONCLUSION: Brazilian patients use syringes more and pens less, inject with larger needles and have more lipohypertrophy when compared to Latin America and World data. Their re-use of needles and syringes is also high. This study showed that in Brazil, teaching of proper injection technique has to be more widespread, and more intensive during diabetes educational sessions, and the type of delivered supplies must be updated to smaller, shorter needles preferred by patients, in order to facilitate adherence to treatment. From the ITQ, we conclude that there are many aspects of insulin injection technique that may be improved in Brazil.

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AIMS: To investigate a miRNA expression profile in plasma of type 1 diabetes (T1DM) patients and control subjects and analyze the putative pathways involved. METHODS: Expressions of 48 miRNAs were analyzed in plasma of 33 T1DM patients and 26 age-and-gender-matched controls using Stem-loop RT-PreAmp PCR and TaqMan Low Density Arrays (Thermo Fisher Scientific). Five dysregulated miRNAs were then chosen for validation in an independent sample of 27 T1DM patients and 14 controls, using RT-qPCR. Bioinformatic analyses were performed to determine in which pathways these miRNAs are involved. RESULTS: Nine miRNAs were differentially expressed between recently-diagnosed T1DM patients (<5 years of diagnosis) and controls. No differences were observed between patients with ≥5 years of diagnosis and controls. After validation in an independent sample of T1DM patients, miR-103a-3p, miR-155-5p, miR-200a-3p, and miR-210-3p were confirmed as being upregulated in recently-diagnosed T1DM patients compared with controls or patients with ≥5 years of diagnosis. Moreover, miR-146a-5p was downregulated in recently-diagnosed T1DM patients compared with the other groups. These five miRNAs regulate several genes from innate immune system-, MAPK-, apoptosis-, insulin- and cancer-related pathways. CONCLUSION: Five miRNAs are dysregulated in recently-diagnosed T1DM patients and target several genes involved in pathways related to T1DM pathogenesis, thus representing potential T1DM biomarkers.

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ABSTRACT Objective To evaluate the frequency of DQ2.5 and DQ8 alleles using the Tag-single-nucleotide polymorphism (Tag-SNP) technique in individuals with type 1 diabetes mellitus (T1DM) and celiac disease (CD) in southern Brazil. Materials and methods In a prospective design, we performed the search for DQA1*0501 and DQB1*0201 alleles for DQ2.5 and DQB1*0302 for DQ8 through Real-Time Polymerase Chain Reaction (RT-PCR) technique, using TaqMan Genotyping Assays (Applied Biosystems, USA). The diagnosis of CD was established by duodenal biopsy and genotypic determination performed by StepOne Software v2.3. Allelic and genotypic frequencies were compared between groups using Chi-square and Fisher's exact tests and the multiple comparisons using Finner's adjustment. Results Three hundred and sixty two patients with a median age of 14 years were divided into 3 groups: T1DM without CD (264); T1DM with CD (32) and CD without T1DM (66). In 97% of individuals with T1DM and CD and 76% of individuals with CD without T1DM, respectively, the alleles DQ2.5 and/or DQ8 were identified (p < 0.001). DQ2.5 was more common in individuals with CD (p = 0.004) and DQ8 was more common in individuals with type 1 diabetes (p = 0.008). Conclusions The evaluation of the alleles for DQ2.5 and DQ8 by Tag-SNP technique showed a high negative predictive value among those with T1DM, similar to that described by the conventional technique. The high frequency of DQ8 alleles in individuals with T1DM did not allow differentiating those at higher risk of developing T1DM.

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