Comparison of the effect of a compact vs a conventional, long-term education program on metabolic control in children and adolescents with type 1 diabetes: A pilot, randomized clinical trial.

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.

Prevalence of celiac disease in a large cohort of young patients with type 1 diabetes.

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.

Relationship between adherence to diet, glycemic control and cardiovascular risk factors in patients with type 1 diabetes: a nationwide survey in Brazil.

BACKGROUND: To determine the relationship between adherence to the diet reported by patients with type 1 diabetes under routine clinical care in Brazil, and demographic, socioeconomic status, glycemic control and cardiovascular risk factors. METHODS: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data was obtained from 3,180 patients, aged 22 ± 11.8 years (56.3% females, 57.4% Caucasians and 43.6% non-Caucasians). The mean time since diabetes diagnosis was 11.7 ± 8.1 years. RESULTS: Overall, 1,722 (54.2%) of the patients reported to be adherent to the diet without difference in gender, duration of diabetes and socioeconomic status. Patients who reported adherence to the diet had lower BMI, HbA1c, triglycerides, LDL-cholesterol, non HDL-cholesterol and diastolic blood pressure and had more HbA1c at goal, performed more frequently self-monitoring of blood glucose (p < 0.001), and reported less difficulties to follow specific schedules of diet plans (p < 0.001). Less patients who reported to be adherent were obese or overweight (p = 0.005). The quantity of food and time schedule of the meals were the most frequent complaints. Logistic regression analysis showed that ethnicity, (Caucasians, (OR 1.26 [1.09-1.47]), number of medical clinical visits in the last year (OR 1.10 [1.06-1.15]), carbohydrate counting, (OR 2.22 [1.49-3.30]) and diets recommended by diabetes societies', (OR 1.57 [1.02-2.41]) were related to greater patients' adherence (p < 0.05) and age, [adolescents (OR 0.60 [0.50-0.72]), high BMI (OR 0.58 [0.94-0.98]) and smoking (OR 0.58 [0.41-0.84]) with poor patients' adherence (p < 0.01). CONCLUSIONS: Our results suggest that it is necessary to rethink medical nutrition therapy in order to help patients to overcome barriers that impair an optimized adherence to the diet.

[Clinical Protocol of the Brazilian Ministry of Health on Parkinson's Disease: adherence and perception of the prescribing physician]. / Protocolo Clínico do Ministério da Saúde/Brasil para Doença de Parkinson: adesão e percepção do médico prescritor.

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.

Predictors of traffic events due to hypoglycemia in adults with type 1 diabetes: A Brazilian prospective cohort study.

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.

Superior Effects of High-Intensity Interval vs. Moderate-Intensity Continuous Training on Endothelial Function and Cardiorespiratory Fitness in Patients With Type 1 Diabetes: A Randomized Controlled Trial.

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.

Circulating miRNAs in diabetic kidney disease: case-control study and in silico analyses.

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.

Functional vascular endothelial growth factor -634G>C SNP is associated with proliferative diabetic retinopathy: a case-control study in a Brazilian population of European ancestry.

OBJECTIVE: The purpose of this study was to evaluate the effect of the single nucleotide polymorphism (SNP) -634G>C at the 5' regulatory region of the vascular endothelial growth factor (VEGF) in the risk of proliferative diabetic retinopathy (PDR) in the Brazilian population of European ancestry with type 2 diabetes. RESEARCH DESIGN AND METHODS: A case-control study was conducted in 501 type 2 diabetic patients of European ancestry. Patients underwent a standardized clinical, ophthalmological, and laboratory evaluation. Of these, 167 patients had PDR (case patients), and 334 were considered as control subjects (patients without PDR) for PDR. A reference population (110 individuals of European ancestry) was also evaluated. RESULTS: No evidence of association between -634G>C/VEGF and the presence of diabetic retinopathy or type 2 diabetes was observed (P > 0.05). However, CC homozygous for the SNP -634G>C was significantly more frequent in patients with PDR (37 of 167; 22.2%) than in the corresponding control group (40 of 334; 12%) in accordance with a recessive model (P = 0.003). This effect was further observed when creatinine, BMI, sex, duration of type 2 diabetes, HDL cholesterol, and systolic blood pressure were taken into account (odds ratio 1.9 [95% CI 1.01-3.79], P = 0.04). CONCLUSIONS: The presence of the allele -634C/VEGF in homozygosity is an independent risk factor for the development of PDR in type 2 diabetic patients of European ancestry.

Insulin Injection Technique Questionnaire: results of an international study comparing Brazil, Latin America and World data.

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.

MicroRNA expression profile in plasma from type 1 diabetic patients: Case-control study and bioinformatic analysis.

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.

Search for DQ2.5 and DQ8 alleles using a lower cost technique in patients with type 1 diabetes and celiac disease in a population of southern Brazil.

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.

Health-related quality of life and utility values associated to hypoglycemia in patients with type 1 diabetes mellitus treated in the Brazilian Public Health System: a multicenter study.

BACKGROUND: Hypoglycemia is a critical and limiting factor of a good metabolic control and can adversely affect the quality of life of diabetic patients. The aim of the study was to evaluate the health-related quality of life and calculate utilities values associated with hypoglycemia in patients with type 1 diabetes mellitus (T1DM). METHODS: A multicenter, cross-sectional and observational study with T1DM patients from reference centers of the Brazilian public health system was conducted in three cities. Demographic and clinical data were collected, besides details on the frequency and severity of hypoglycemia. Health-related quality of life was assessed using EQ-5D instrument and utility values generated. RESULTS: 221 patients (107 women, 114 men), aged 29.8 ± 11.6 and disease duration of 14.2 ± 9.1 years were included. Most patients (n = 214, 96.8%) reported at least one symptomatic hypoglycemia in the last three months, 68% (n = 150) reported nocturnal episodes and 34.8% (n = 77) reported severe episodes. High frequency (daily or weekly) was observed in 38.6 and 26% of those reporting nocturnal or severe hypoglycemia, respectively. The median visual analog scale was 70 [60-85] for all patients, with differences between those with and without severe hypoglycemia (70 [60-80] vs 80 [61-90]; p = 0.006) and those with high and low frequency (62.5 [50-72.25] vs 70 [60-80]; p = 0.007). The median utility values was 0.801 [0.756-1.000] for all patients, with difference between those with high and low frequency of severe episodes (0.737 [0.628-1.000] vs 0.801 [0.756-1.000]; p = 0.02). CONCLUSIONS: This study shows the high frequency of hypoglycemia in a sample of T1DM patients treated in three reference centers of the Brazilian public health system and the impact of severe episodes on health-related quality of life. Utility values were generated and can be used in economic analysis for treatments that could decrease hypoglycemia and consequently improve quality of life.

The catalase -262C/T promoter polymorphism and diabetic complications in Caucasians with type 2 diabetes.

Catalase is a central antioxidant enzyme constituting the primary defense against oxidative stress. In this study, we investigated whether the functional -262C/T polymorphism in the promoter of catalase gene is associated with the presence of diabetic retinopathy (DR), diabetic nephropathy (DN) and ischemic heart disease (IHD) in 520 Caucasian-Brazilians with type 2 diabetes. The -262C/T polymorphism was also examined in 100 Caucasian blood donors. Patients underwent a clinical and laboratory evaluation consisting of a questionnaire, physical examination, assessment of diabetic complications and laboratory tests. Genotype analysis was performed using the polymerase chain reaction followed by digestion with restriction enzyme. The genotype and allele frequencies of the -262C/T polymorphism in patients with type 2 diabetes were very similar to those of blood donors (T allele frequency=0.20 and 0.18, respectively). Likewise, there were no differences in either genotype or allele frequencies between type 2 diabetic patients with or without DR, DN or IHD. Thus, our results do not support the hypothesis that the -262C/T polymorphism is related to the development of DR, DN or IHD in patients with type 2 diabetes. Further studies are necessary to elucidate the role of catalase gene polymorphisms in the pathogenesis of diabetic complications.

Familial history of type 2 diabetes in patients from Southern Brazil and its influence on the clinical characteristics of this disease.

OBJECTIVE: To investigate the presence of maternal and paternal history of type 2 diabetes mellitus (DM) in relatives of 644 type 2 diabetic patients from Southern Brazil, and also to evaluate its influence on the clinical characteristics of this disease. PATIENTS AND METHODS: Familial history of type 2 DM was investigated by a questionnaire. The maternal and paternal history was investigated over two generations. Complete data sets on familial history were obtained from 396 patients. RESULTS: In general, 76.6% of the patients reported at least one first-degree affected relative. Besides, 31.6% of the patients reported a maternal history of type 2 DM and 12.6% reported a paternal history. Patients with maternal and/or paternal history presented a lower age at type 2 DM diagnosis when compared to patients without familial history. In addition, patients with only paternal history presented a higher frequency of hypertension than patients with no familial history. CONCLUSIONS: This study suggests that there is a significant maternal effect in the transmission of type 2 DM in Southern Brazil, and that most of the clinical characteristics of this disease do not differ between patients with or without familial history of type 2 DM.

Protocolo Clínico do Ministério da Saúde/Brasil para Doença de Parkinson: adesão e percepção do médico prescritor / Clinical Protocol of the Brazilian Ministry of Health on Parkinson's Disease: adherence and perception of the prescribing physician

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.

Relationship of p22phox C242T polymorphism with nephropathy in type 2 diabetic patients.

BACKGROUND: In this case-control study, we investigated the possible involvement of the p22phox C242T polymorphism in the development and progression of diabetic nephropathy (DN) in 535 Caucasian Brazilians with type 2 diabetes. We also evaluated the effects of the interaction of the C242T polymorphism with smoking and hypercholesterolemia on the susceptibility to nephropathy. METHODS: Genotype analysis was performed using polymerase chain reaction (PCR) followed by digestion with restriction enzyme. Logistic regression analysis was used to control for independent risk factors associated with nephropathy. RESULTS: The genotype frequencies in patients with overt DN (CC/CT/TT: 0.36/0.47/0.17) were not significantly different from those of diabetic individuals with normoalbuminuria (0.47/0.41/0.12) or microalbuminuria (0.42/0.48/0.10) (p=0.214). Likewise, there were no differences in the T allele frequency among patients with normoalbuminuria, microalbuminuria or overt DN (0.33, 0.34 and 0.40, respectively; p=0.111). However, the T allele was found to be more frequent among smokers with overt nephropathy (macroalbuminuria and/or in dialysis) than those who had normoalbuminuria (43 vs. 32%, p=0.045). The multiple logistic regression analysis confirmed that the CT+TT genotypes were independently associated with a higher risk of having overt nephropathy among smokers [odds ratio (OR)=6.76, 95% confidence interval (95% CI) 1.83-25.02]. CONCLUSIONS: Our study shows a gene-environment interaction associated with the increased risk of DN progression in Caucasian Brazilian smokers with type 2 diabetes. Further studies should be performed to clarify whether it exists, and to what extent there is a relationship between the p22phox C242T polymorphism and DN.

Health-related quality of life in patients with type 1 diabetes mellitus in the different geographical regions of Brazil: data from the Brazilian Type 1 Diabetes Study Group.

BACKGROUND: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. METHODS: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. RESULTS: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North-Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. CONCLUSIONS: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Diabetic retinopathy in Euro-Brazilian type 2 diabetic patients: relationship with polymorphisms in the aldose reductase, the plasminogen activator inhibitor-1 and the methylenetetrahydrofolate reductase genes.

We investigated the relationship between diabetic retinopathy (DR) and three polymorphisms, C(-106)T in the aldose reductase (ALR2) gene, 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene and C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, in 210 Euro-Brazilian type 2 diabetic patients. Retinopathy was evaluated by funduscopic examination and genotype analysis was performed using the polymerase chain reaction and allele-specific restriction. Retinopathy was detected in 47% of the patients. There were no significant differences in allele or genotype distributions between patients with or without retinopathy for all polymorphisms. Thus, the three polymorphisms are not related to the presence of DR in Euro-Brazilian type 2 diabetic patients.

[Prevalence of micro and macroangiopatic chronic complications and their risk factors in the care of out patients with type 2 diabetes mellitus]. / Prevalência de complicações micro e macrovasculares e de seus fatores de risco em pacientes com diabetes melito do tipo 2 em atendimento ambulatorial.

BACKGROUND: Type 2 diabetes (DM2) has been related to the development of macroangiopatic [coronary heart disease (CHD), peripheral vascular disease (PVD) and stroke] and microangiopatic [retinopathy, nephropathy, and distal sensory neuropathy (DSN)] complications. The aims of this study were to analyze prevalence of complications in DM2 patients and to estimate their associated risk factors. METHODS: Cross-sectional study, including 927 out patients with DM2 from three medical centers in Rio Grande do Sul: Hospital de Clinicas de Porto Alegre (n = 475), Grupo Hospitalar Conceicao (n = 229) and Hospital Sao Vicente de Paula (n = 223). Of the patients 42% were male, mean age was 59 +/- 10 years and the median known duration of DM2 was 11 (5-43) years. Retinopathy was identified by direct fundoscopy; CHD by WHO questionnaire and/or abnormal ECG and/or perfusion abnormalities on myocardial scintigraphy; DSN by compatible symptoms and absent sensation on 10 g monofilament and/or tune fork; PVD by the presence of claudication and absent foot pulses; stroke by presence of sequels and history; and nephropathy by the urinary albumin excretion rate (>20 microg/min). Hypertension was defined by blood pressure (>140/90 mmHg) and/or use of antihypertensive drugs. Body mass index (BMI, kg/m2) and waist-to-hip ratio (WHR) were calculated. RESULTS: CHD was present in 36% and PVD in 33% of the patients. Among the microvascular, 37% had nephropathy (12% with macroalbuminuria); 48% retinopathy (15% proliferative retinopathy). DSN was present in 36%. Seventy three percent of the patients presented arterial hypertension. Cholesterol levels were >200 mg/dl in 64% and BMI > 30 kg/m2 in 36%. Twenty two percent of patients were smokers and 21% ex-smokers. CONCLUSION: Diabetic complications are frequent among out patients referring to general hospitals. Almost all patients presented at least one risk factor for cardiovascular disease, justifying the efforts for identification and adequate control.

Initial experience and evaluation of reusable insulin pen devices among patients with diabetes in emerging countries.

BACKGROUND: Many individuals with type 2 diabetes in emerging countries are transitioning from vial-and-syringe insulin delivery to that of insulin pens (disposable or reusable). As with all insulin delivery methods, patient preferences and comfort are of utmost importance to optimize adherence to treatment. Patient-preferred characteristics for reusable insulin pens and barriers to appropriate injection, particularly in these regions, have not been widely reported in the clinical literature, highlighting a key information gap for clinicians considering these methods as part of a comprehensive diabetes management approach. METHODS: Face-to-face interviews were conducted with people with type 1/2 diabetes, including insulin-naïve and established insulin users. After moderator demonstration, participants were evaluated on their ability to perform a six-step process to inject a 10-unit dose into a pad with the AllStar(®) (AS; Sanofi, Mumbai, India), HumaPen Ergo II(®) (HE2; Eli Lilly, Indianapolis, USA), and NovoPen 4(®) (NP4; Novo Nordisk, Bagsværd, Denmark) pens. Local pens were also tested in India, China and Brazil. RESULTS: A total of 503 people from India, Malaysia, Brazil, Egypt, and China participated. Participants completed the six-step process in an average, 2-3 min per pen. Participants ranked ease of overall use and ease of self-injection and dialing/reading dose as most important features for new insulin pens. When using the pens, the most difficult step was priming/safety testing, with 7-12% failing and 28-40% having difficulty; 6%, 18%, and 22% failed to hold the injection button down for the required period of time using AS, NP4, and HE2, respectively. Participants ranked AS significantly higher for nine of 12 ease-of-use features including three of the top four features considered the most important for reusable pens, while HE2 was ranked higher for two features. Local pens were ranked lowest. CONCLUSIONS: Priming the pen and injecting the dose imparted most difficulty for people with diabetes in emerging countries. Most participants found AS easiest to use overall, with differences noted between pens for individual steps of dose delivery. Identifying characteristics most preferred by patients may assist in improving adherence to insulin therapy.