Prevalence of autoimmune diseases in an admixed population of patients with type 1 diabetes: a multicenter study in Brazil.

BACKGROUND/OBJECTIVES: The primary aim of this study was to evaluate the prevalence of autoimmune diseases (AIDs) and its associated factors in an admixed Brazilian population of patients with type 1 diabetes (T1D). The secondary one was to determine the relationship between AIDs and the occurrence of diabetes-related chronic complications (DRCC). METHODS: This cross-sectional, nationwide survey was conducted in 13 public clinics in 11 Brazilian cities. Overall, 1,760 patients were included; 967 females (55.9%), 932 (54%) Caucasians, aged 29.9 ± 11.9 years, age at diagnosis 14.8 ± 8.9 years, diabetes duration 15.5 ± 9.3 years and 12.2 ± 3.8 years of school attendance. AIDs were retrieved from medical records or self-report and stratified as follows: absence of AIDs, only autoimmune thyroid disease (AITD), and other AIDs including the combination with AITD (hyper or hypothyroidism). RESULTS: The prevalence of AIDs was 19.5% being AITDs (16.1%), the most frequently found. A higher prevalence of hypertension, dyslipidemia and overweight or obesity was found in patients who had exclusively AITDs. A higher prevalence of diabetic retinopathy (DR) was observed in patients with AITDs and patients with other AIDs in combination with AITDs. Chronic kidney disease (CKD) was more prevalent in patients with only AITDs. Lower levels of HbA1C, were observed in patients with isolated AITDs or with other AIDs, regardless of the presence of AITD. Hierarchical multivariate analysis, showed that AIDs were associated with female gender, older age, and longer diabetes duration, self-reported color-race (White and Brown), geographic region (Brazilian North/Northeast region) and higher anti-TPO levels (≥ 35 UI/ml). CONCLUSIONS: In conclusion, Brazilian patients with T1D, belonging to a highly ethnically admixed population, had an important prevalence of AIDs, mostly AITDs, that was associated with female gender, self-reported color-race, older age and longer diabetes duration. Moreover, these patients also had a higher prevalence of DRCC. Even though we highlight the importance of investigating the presence of AIDs at diagnosis and at regular intervals, it is unclear whether screening and early detection of additional AIDs may improve the clinical outcomes in individuals with T1D. Future prospective studies are necessary to establish the interplay between T1D, AIDs and DRCC.

Prevalence of overweight/obesity and its relationship with metabolic syndrome and fatty liver index in adult patients with type 1 diabetes. A Brazilian multicenter study.

AIMS: To determine the prevalence of overweight/obesity and its relationship with metabolic syndrome (MS), fatty liver index (FLI), cardiovascular risk factors (CVRF), and diabetes-related chronic complications (DRCC) in adult patients with type 1 diabetes (T1D). METHODS: This study was conducted in 14 Brazilian public clinics in ten cities, with 1,390 patients: 802 females (57.7%), 779 (56.0%) Caucasians, aged 33.6 ± 10.8 years, age at diagnosis, 16.2 ± 9.2 years, diabetes duration, 17.4 ± 9.2 years, and HbA1c 8.8 ± 2.0%. RESULTS: Overall, 825 patients (59.4%) had normal weight, and 565 had overweight/obesity; ( 429 (30.9%) presented overweight and 136 (9.8%) presented obesity). After adjustments, overweight/obesity was associated with age, family history of overweight/obesity, total daily insulin dose, hypertension, adherence to diet, type of health care insurance, use of metformin, levels of C-reactive protein, triglycerides, uric acid and HDL-cholesterol. These patients also presented a higher prevalence of MS, FLI ≥ 60, and CVRF than patients without overweight/obesity. Overweight/obesity was not associated with DRCC and with HbA1c levels. CONCLUSIONS: Patients with T1D with overweight/obesity presented traditional risk factors for DRCC, cardiovascular diseases, MS, and non-alcoholic fatty liver disease; most of these risk factors are modifiable and can be avoided with interventions that prevent overweight/obesity.

Overweight/obesity in adolescents with type 1 diabetes belonging to an admixed population. A Brazilian multicenter study.

BACKGROUND: To determine the prevalence of overweight/obesity and associated risk factors in Brazilian adolescents with type 1 diabetes (T1D) and its association with diabetic retinopathy (DR) and chronic kidney disease (CKD). METHODS: This study was performed in 14 Brazilian public clinics in ten cities, with 1,760 patients. 367 were adolescents (20.9%):184 females (50.1%), 176 (48.0%) Caucasians, aged 16.4 ± 1.9 years, age at diagnosis 8.9 ± 4.3 years, diabetes duration 8.1 ± 4.3 years, school attendance 10.9 ± 2.5 years and HbA1c 9.6 ± 2.4%. RESULTS: 95 (25.9%) patients presented overweight/obesity, mostly females. These patients were older, had longer diabetes duration, higher levels of total and LDL-cholesterol, higher prevalence of family history of hypertension, hypertension, undesirable levels of LDL-cholesterol, and metabolic syndrome compared to eutrophic patients. No difference was found regarding ethnicity, HbA1c, uric acid, laboratorial markers of non-alcoholic fatty liver disease (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase). CONCLUSIONS: Almost one quarter of our patients presented overweight/obesity. These patients had higher prevalence of traditional risk factors for micro and macrovascular diabetes-related chronic complications such as diabetes duration, hypertension, high levels of LDL-cholesterol and metabolic syndrome. The majority of the patients with or without overweight/obesity presented inadequate glycemic control which is also an important risk factor for micro and macrovascular diabetes-related chronic complications. No association was found between overweight/obesity with diabetic CKD, DR and laboratorial markers of non-alcoholic fatty liver disease. The above-mentioned data point out that further prospective studies are urgently needed to establish the clinical prognosis of these young patients.

Human Leukocyte Antigens class II (HLA II) gene profile from an admixed population of patients with type 1 diabetes with severe diabetic retinopathy: a nested case-control study in Brazil.

BACKGROUND: Although the well-established role of the HLA genes on the predisposition of type 1 diabetes (T1D), its contribution to the development and progression of diabetic retinopathy is still unclear, especially in admixed populations. We aimed to study the relationship between HLA alleles and severe diabetic retinopathy in a highly admixed population of T1D patients. METHODS: This was a nested case-control study based on a cross-sectional, nationwide survey conducted in Brazil. We included 117 patients with severe diabetic retinopathy and 117 random controls composed of T1D patients without retinopathy, matched for diabetes duration. HLA-class II genes (HLA-DRB1, -DQA1, and -DQB1) were genotyped using the SSO and NGS methods. RESULTS: Haplotypes HLA-DRB1*04:05 ~ DQA1*03:01 g ~ DQB1*03:02 (OR 1.75, CI 0.97-3.16, p value 0.058) and HLA-DRB1*13:02 ~ DQA1*01:02 ~ DQB1*06:04 (OR 5.18, CI 1.12-23.09, p value 0.019) were more prevalent on the severe DR group but they did not present statistically difference after Bonferroni correction. The most frequent haplotype on both groups was HLA-DRB1*03:01 ~ DQA1*05:01 g ~ DQB1*02:01 (29.6% on severe DR and 33.33% on the control group). CONCLUSIONS: Our study showed no influence of HLA genes on the development of DR. Further longitudinal data is needed to better understand the role of genetic factors on this multifactorial significant microvascular complication.

Diabetes-related chronic complications in Brazilian adolescents with type 1 diabetes. A multicenter cross-sectional study.

AIMS: To investigate the prevalence of diabetes-related chronic complications (DRCCs) and its associated factors in Brazilian adolescents with type 1 diabetes (T1D). METHODS: This nationwide study was conducted in 14 public clinics in 10 cities, with 1,760 patients, 367 adolescents, with 328 eligible for this study. Evaluated DRCCs were retinopathy (DR), chronic kidney disease (CKD), peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). RESULTS: Among eligible patients, 184 were females (50.1%), age range 13-19 years, HbA1c 9.6% ± 2.4, aged 8.9 ± 4.3 years at diagnosis and diabetes duration of 8.1 ± 4.3 years. 103 (31.4%) patients presented any type of DRCC. CKD was found in 46 (14.0%), CAN in 41(12.5%), DR in 28 (8.5%) and DPN in 16 (4.9%) patients. One, two or three DRCCs were observed in 79 (24.1%), 19 (5.8%) and 5 (1.5%) patients, respectively, and were associated with longer diabetes duration, higher HbA1c and diastolic blood pressure levels (dBP), use of renin angiotensin inhibitors and lower adherence to diet. CONCLUSIONS: A high percentage of patients presented some kind of DRCC, associated with diabetes duration, glycemic control, dBP, adherence to diet. Educational programs should start from the diagnosis to avoid DRCCs in this young population.

Relationship between Proliferative Diabetic Retinopathy and Inflammatory Markers in Patients with Type 1 Diabetes in Brazil: A Nested Case Control Study.

INTRODUCTION: This study examined the relationship between proliferative diabetic retinopathy (PDR) and serum levels of C-reactive protein, VEGF, TNF-α, and IL-6 inflammatory biomarkers, related to the pathophysiology of diabetic retinopathy. METHODS: This cross-sectional, case control study comprised 240 patients with type 1 diabetes (80 cases with PDR and 160 controls without diabetic retinopathy) who were matched for gender and duration of diabetes. RESULTS: C-reactive protein was the only inflammatory biomarker that was positively related to PDR (OR 1.96; 95% CI 1.01-3.78, p = 0.0045). We also noted an association between high glycated hemoglobin levels, the use of angiotensin-converting enzyme inhibitor, low glomerular filtration rate, and PDR. CONCLUSION: Patients with higher levels of C-reactive protein are more likely to present with PDR. We did not find a link between serum levels of VEGF, TNF-α, or IL-6 and PDR. The function of inflammatory biomarkers in PDR must be addressed in further studies.

Genomic ancestry as a risk factor for diabetic retinopathy in patients with type 1 diabetes from an admixed population: a nested case-control study in Brazil.

AIMS: The influence of genetic factors on the development and progression of diabetic retinopathy is still unclear. Previous studies showed controversial results. We aimed to characterize the relationship between genomic ancestry and self-reported color/race with severe diabetic retinopathy in patients with type 1 diabetes belonging to a highly admixed population. METHODS: This study was a nested case-control based on data collected from a large cross-sectional, nationwide survey conducted in clinics from all five geographic regions of Brazil. For the present study, we included 414 individuals. Cases (n = 176) were considered if they had severe non-proliferative or proliferative diabetic retinopathy, and controls (n = 238) were type 1 diabetes patients without retinopathy, matched for diabetes duration by a range of 5 years. Indirect ophthalmoscopy was performed, and individual genomic ancestry was inferred using a panel of 46 ancestry informative markers. RESULTS: The backward stepwise logistic regression analysis showed that African genomic ancestry (OR 3.9, p = 0.045), HbA1c (OR 1.24, p = 0.001), glomerular filtration rate (OR 0.98, p < 0.001) and hypertension (OR 2.52, p < 0.001) were associated with severe diabetic retinopathy after adjusting for clinical and demographic data. Self-reported color/race was not statistically associated with diabetic retinopathy. CONCLUSIONS: Genomic ancestry, as well as clinical variables such as hypertension, impaired glomerular filtration rate and poor diabetes control (HbA1c), was important risk factor for the development of severe diabetic retinopathy. Further studies are needed, especially in highly admixed populations, to better understand the role of genomic ancestry and possible genes that might be associated with the development and/or progression of diabetic retinopathy.

Diabetic Retinopathy May Indicate an Increased Risk of Cardiovascular Disease in Patients With Type 1 Diabetes-A Nested Case-Control Study in Brazil.

Objective: Cardiovascular disease, the leading cause of death worldwide, and diabetic retinopathy, the main cause of blindness in economically active populations, share clinical risk factors, and pathophysiological features. The aim of this study is to examine the association between diabetic retinopathy, cardiovascular disease, and common risk factors in patients with type 1 diabetes. Design and Methods: This nested case-control study was performed in patients from the Brazilian Type 1 Diabetes Study Group, a nationwide survey that was conducted in Brazil and enrolled 1,760 patients with type 1 diabetes. A total of 342 patients were selected (57 cases with macrovascular disease and 285 controls who were matched for duration of diabetes and gender). Results: In the exploratory analysis, stratified by cardiovascular disease, the following variables were statistically significant: age (p=0.037), hypertension (p=0.035), high BMI (p = 0.046), diabetic retinopathy (p = 0.003), and chronic kidney disease (p = 0.026). By multivariate logistic regression, patients with diabetic retinopathy were more likely to develop cardiovascular disease (OR 2.16, 95% CI 1.16-4.02, p = 0.015). Although to a lesser extent than diabetic retinopathy, higher BMI levels were also related to an increase in the risk of cardiovascular disease of 1.08 (95% CI 1.01-1.15, p = 0.024). Conclusion: The presence of diabetic retinopathy indicates a greater risk for cardiovascular disease in Brazilian patients with type 1 diabetes. Further studies are warranted to determine whether a noninvasive exam, such as fundoscopy, could help identify patients who show an increased risk for cardiovascular disease.

Current epidemiology of diabetic retinopathy in patients with type 1 diabetes: a national multicenter study in Brazil.

BACKGROUND: Diabetic retinopathy is the leading cause of blindness in economically active populations. The aims of this study were to estimate the prevalence and to identify risk factors for diabetic retinopathy in patients with type 1 diabetes in Brazil. METHODS: This was a nationwide, cross-sectional study conducted between August 2010 and August 2014. The study included 1760 patients with type 1 diabetes. Patients underwent a standard questionnaire, clinical and laboratory analyses and were screened for diabetic retinopathy. To analyze the risk factors related to diabetic retinopathy, two models of logistic regression models were performed, one considering vision-threatening cases and the other with any diabetic retinopathy cases as dependent variables. The group with vision-threatening included patients with severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and macular edema. RESULTS: In total, 1644 patients (mean age, 30.1± 12.0 years; duration of diabetes, 15.3 ± 9.3 years; female, 55.8%) were studied. 35.7% presented diabetic retinopathy and 12% presented vision-threatening diabetic retinopathy. Three risk factors associated with diabetic retinopathy were in common to both groups: longer diabetes duration (OR 1.07; 95% CI, 1.05-1.09), higher levels of HbA1c (OR 1.24; CI, 1.17-1.32) and higher levels of serum uric acid (OR 1.22; CI, 1.13-1.31) (p < 0.001 for all comparisons). CONCLUSION: The higher rate of vision-threatening retinopathy found in our study highlights the need to improve access to eye care and screening programs for diabetic retinopathy in Brazil. In addition to traditional risk factors, we found an association between serum uric acid levels and diabetic retinopathy. Further studies are needed to address this association.

Regional differences in the prevalence of diabetic retinopathy: a multi center study in Brazil.

BACKGROUND: Diabetic retinopathy has a significant impact in every healthcare system. Despite that fact, there are few accurate estimates in the prevalence of DR in Brazil's different geographic regions, particularly proliferative DR and diabetic macular edema. This study aims to determine the prevalence of diabetic retinopathy in Brazil's five continental regions and its determinant factors. METHODS: This multi center, cross-sectional, observational study, conducted between August 2011 and December 2014, included patients with type 1 diabetes from the 5 Brazilian geographic regions (South, Southeast, North, Northeast and Midwest). During a clinical visit, a structured questionnaire was applied, blood sampling was collected and each patient underwent mydriatic binocular indirect ophthalmoscopy evaluation. RESULTS: Data was obtained from 1644 patients, aged 30.2 ± 12 years (56.1% female, 54.4% Caucasian), with a diabetes duration of 15.5 ± 9.3 years. The prevalence of diabetic retinopathy was 242 (36.1%) in the Southeast, 102 (42.9%) in the South, 183 (29.9%) in the North and Northeast and 54 (41.7%) in the Midwest. Multinomial regression showed no difference in the prevalence of non-proliferative diabetic retinopathy in each geographic region, although, prevalence of proliferative diabetic retinopathy (p = 0.022), and diabetic macular edema (p = 0.003) was higher in the Midwest. Stepwise analyses reviled duration of diabetes, level of HbA1c and hypertension as independent variables. CONCLUSIONS: The prevalence of non proliferative diabetic retinopathy in patients with type 1 diabetes was no different between each geographic region of Brazil. The Midwest presented higher prevalence of proliferative diabetic retinopathy and diabetic macular edema. Duration of DM and glycemic control is of central importance to all. Hypertension is another fundamental factor to every region, at special in the South and Southeast. Glycemic control and patients in social and economic vulnerability deserves special attention in the North and Northeast of Brazil.

Comparison between binocular indirect ophthalmoscopy and digital retinography for diabetic retinopathy screening: the multicenter Brazilian Type 1 Diabetes Study.

BACKGROUND: Diabetic retinopathy is the main cause of preventable blindness in the economically active population in western countries. Diabetic retinopathy screening is effective in preventing blindness and can be performed through various diagnostic methods. Our objective is to compare binocular indirect ophthalmoscopy (BIO) to telemedicine protocols of digital retinography for diabetic retinopathy screening in a large and heterogenous type 1 diabetes population in a developing country. METHODS: Data from 1266 Type 1 Diabetes Mellitus patients from a Brazilian multicenter study were analyzed. Patients underwent BIO and digital retinography, non-mydriatic and mydriatic. Images were sent to a reading center in a telemedicine protocol. Agreement between the different methods was calculated with kappa statistic for diabetic retinopathy and maculopathy classification. Clinical outcome was either observation or referral to specialist. RESULTS: Agreement between BIO and mydriatic retinography was substantial (kappa 0.67-0.74) for diabetic retinopathy observation vs referral classification. Agreement was fair to moderate (kappa 0.24-0.45) between retinography and BIO for maculopathy. Poor mydriasis was the main obstacle to image reading and classification, especially on the non-mydriatic strategy, occurring in 11.9 % of right eyes and 16.9 % of left eyes. CONCLUSION: Mydriatic retinography showed a substantial agreement to BIO for diabetic retinopathy observation vs referral classification. A significant amount of information was lost on the non-mydriatic technique because of poor mydriasis. We recommend a telemedicine-based diabetic retinopathy screening strategy with digital mydriatic retinography, preferably with 2 fields, and advise against non-mydriatic retinography in developing countries.

Clinical trials in Brazilian journals of ophthalmology: where we are.

PURPOSE: To compare clinical trials published in Brazilian journals of ophthalmology and in foreign journals of ophthalmology with respect to the number of citations and the quality of reporting [by applying the Consolidated Standards for Reporting Trials (CONSORT) statement writing standards]. METHODS: The sample of this systematic review comprised the two Brazilian journals of ophthalmology indexed at Science Citation Index Expanded and six of the foreign journals of ophthalmology with highest Impact Factor® according ISI. All clinical trials (CTs) published from January 2009 to December 2010 at the Brazilians journals and a 1:1 randomized sample of the foreign journals were included. The primary outcome was the number of citations through the end of 2011. Subgroup analysis included language. The secondary outcome included likelihood of citation (cited at least once versus no citation), and presence or absence of CONSORT statement indicators. RESULTS: The citation counts were statistically significantly higher (P<0.001) in the Foreign Group (10.50) compared with the Brazilian Group (0.45). The likelihood citation was statistically significantly higher (P<0.001) in the Foreign Group (20/20 - 100%) compared with the Brazilian Group (8/20 - 40%). The subgroup analysis of the language influence in Brazilian articles showed that the citation counts were statistically significantly higher in the papers published in English (P<0.04). Of 37 possible CONSORT items, the mean for the Foreign Group was 20.55 and for the Brazilian Group was 13.65 (P<0.003). CONCLUSION: The number of citations and the quality of reporting of clinical trials in Brazilian journals of ophthalmology still are low when compared with the foreign journals of ophthalmology with highest Impact Factor®.

Clinical trials in Brazilian journals of ophthalmology: where we are / Ensaios clínicos em periódicos brasileiros de oftalmologia: onde estamos

PURPOSE: To compare clinical trials published in Brazilian journals of ophthalmology and in foreign journals of ophthalmology with respect to the number of citations and the quality of reporting [by applying the Consolidated Standards for Reporting Trials (CONSORT) statement writing standards]. METHODS: The sample of this systematic review comprised the two Brazilian journals of ophthalmology indexed at Science Citation Index Expanded and six of the foreign journals of ophthalmology with highest Impact Factor® according ISI. All clinical trials (CTs) published from January 2009 to December 2010 at the Brazilians journals and a 1:1 randomized sample of the foreign journals were included. The primary outcome was the number of citations through the end of 2011. Subgroup analysis included language. The secondary outcome included likelihood of citation (cited at least once versus no citation), and presence or absence of CONSORT statement indicators. RESULTS: The citation counts were statistically significantly higher (P<0.001) in the Foreign Group (10.50) compared with the Brazilian Group (0.45). The likelihood citation was statistically significantly higher (P<0.001) in the Foreign Group (20/20 - 100%) compared with the Brazilian Group (8/20 - 40%). The subgroup analysis of the language influence in Brazilian articles showed that the citation counts were statistically significantly higher in the papers published in English (P<0.04). Of 37 possible CONSORT items, the mean for the Foreign Group was 20.55 and for the Brazilian Group was 13.65 (P<0.003). CONCLUSION: The number of citations and the quality of reporting of clinical trials in Brazilian journals of ophthalmology still are low when compared with the foreign journals of ophthalmology with highest Impact Factor®.

OBJETIVO: Comparar ensaios clínicos publicados em periódicos brasileiros de oftalmologia e em periódicos estrangeiros de oftalmologia em relação ao número de citações e à qualidade da informação [através da aplicação do Consolidated Standards for Reporting Trials (CONSORT) statement]. MÉTODOS: A amostra desta revisão sistemática abrangeu os dois periódicos brasileiras de oftalmologia indexaoas no Science Citation Index Expanded (Grupo Brasileiro) e seis dos periódicos estrangeiros de oftalmologia com maior fator de impacto de acordo com o ISI (Grupo Estrangeiro). Todos os ensaios clínicos, publicados entre janeiro de 2009 a dezembro de 2010, nos dois periódicos brasileiros e numa amostra aleatória 1:1 dos periódicos estrangeiros foram incluídos. O desfecho primário foi o número de citações até o final de 2011. A análise de subgrupos incluiu o idioma. O desfecho secundário incluiu a probabilidade de citação (citado ao menos uma vez versus não citado), e a presença ou ausência de indicadores da declaração CONSORT. RESULTADOS: O número de citações foi significativamente maior (P<0,001) no Grupo Estrangeiro (10,50) em comparação com o Grupo Brasileiro (0,45). A probabilidade de citação foi estatisticamente superior (P<0,001) no Grupo Estrangeiro (20/20-100%) comparado com o Grupo Brasileiro (8/20-41%). A análise de subgrupo sobre a influência da língua em artigos Brasileiros mostrou que o número de citações foi significativamente maior nos artigos publicados em Inglês (P<0,04). Dos 37 itens do CONSORT possíveis, a média para o Grupo Estrangeiro foi de 20,55 e para o Grupo Brasileiro foi 13,65 (P<0,003). CONCLUSÃO: O número de citações e a qualidade da redação dos ensaios clínicos em periódicos Brasileiros de oftalmologia ainda são baixos quando comparados com os periódicos estrangeiros de oftalmologia com mais alto fator de impacto.