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To investigate the potential relationship between HLA alleles and haplotypes and the age at diagnosis of type 1 diabetes (T1DAgeD) in an admixed Brazilian population. This nationwide study was conducted in public clinics across 12 Brazilian cities. We collected demographic and genetic data from 1,600 patients with T1D. DNA samples were utilised to determine genomic ancestry (GA) and perform HLA typings for DRB1, DQA1 and DQB1. We explored allele and haplotype frequencies and GA in patients grouped by T1DAgeD categories (<6 years, ≥6–<11 years, ≥11–<19 years and ≥19 years) through univariate and multivariate analyses and primary component analyses. Additionally, we considered self‐reported colour–race and identified a familiar history of T1D in first‐degree relatives. The homozygosity index for DRB1~DQA1~DQB1 haplotypes exhibited the highest variation among T1DAgeD groups, and the percentages of Sub‐Saharan African and European ancestries showed opposite trends in principal component analysis (PCA) analyses. Regarding the association of alleles and haplotypes with T1DAgeD, risk alleles such as HLA‐DQB1*03:02g, ‐DQA1*03:01g, ‐02:01g, DRB1*04:05g and ‐04:02g were more frequently observed in heterozygosity or homozygosity in T1D patients with an early disease onset. Conversely, alleles such as DRB1*07:01g, ‐13:03g, DQB1*06:02g and DQA1*02:01 were more prevalent in older T1D patients. The combination DR3/DR4.5 was significantly associated with early disease onset. However, gender, GA, familiar history of T1D and self‐reported colour–race identity did not exhibit significant associations with the onset of T1D. It is worth noting that the very common risk haplotype DRB1*03:01g~DQA1*05:01g~DQB1*02:01g did not differentiate between T1DAgeD groups. In the admixed Brazilian population, the high‐risk haplotype DRB1*04:05~DQA1*03:01~DQB1*03:02 was more prevalent in individuals diagnosed before 6 years of age. In contrast, the protective alleles DQA1*01:02g, DQB1*06:02g, DRB1*07:01g and DRB1*13:03g and haplotypes DRB1*13:03g~DQA1*05:01g~DQB1*03:01g and DRB1*16:02g~DQA1*01:02g~DQB1*05:02g were more frequently observed in patients diagnosed in adulthood. Notably, these associations were independent of factors such as sex, economic status, GA, familiar history of T1D and region of birth in Brazil. These alleles and haplotypes contribute to our understanding of the disease onset heterogeneity and may have implications for early interventions when detected in association with well‐known genomic risk or protection factors for T1D. [ABSTRACT FROM AUTHOR]

We aimed to identify HLA-DRB1, -DQA1, and -DQB1 alleles/haplotypes associated with European, African, or Native American genomic ancestry (GA) in admixed Brazilian patients with type 1 diabetes (T1D). This exploratory nationwide study enrolled 1599 participants. GA percentage was inferred using a panel of 46 ancestry informative marker-insertion/deletion. Receiver operating characteristic curve analysis (ROC) was applied to identify HLA class II alleles related to European, African, or Native American GA, and showed significant (p < 0.05) accuracy for identifying HLA risk alleles related to European GA: for DRB1*03:01, the area under the curve was (AUC) 0.533; for DRB1*04:01 AUC = 0.558, for DRB1*04:02 AUC = 0.545. A better accuracy for identifying African GA was observed for the risk allele DRB1*09:01AUC = 0.679 and for the protective alleles DRB1*03:02 AUC = 0.649, DRB1*11:02 AUC = 0.636, and DRB1*15:03 AUC = 0.690. Higher percentage of European GA was observed in patients with risk haplotypes (p < 0.05). African GA percentage was higher in patients with protective haplotypes (p < 0.05). Risk alleles and haplotypes were related to European GA and protective alleles/haplotypes to African GA. Future studies with other ancestry markers are warranted to fill the gap in knowledge regarding the genetic origin of T1D in highly admixed populations such as that found in Brazil. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Patients with diabetes that are African-Americans or Asians have a higher chance of developing diabetic nephropathy than Caucasian. Our objective was to evaluate the association between self-reported color-race, genomic ancestry, and the presence of chronic kidney disease (CKD), assessed by glomerular filtration rate and albuminuria in patients with type 1 diabetes. Methods: This is a multicenter, observational, cross-sectional study with 1564 patients, conducted between August 2011 and August 2014 in 14 public clinics from 10 Brazilian cities. The ethnic aspects of the patients were evaluated using self-reported color-race and genomic ancestry (divided in European, African, and Amerindian). We divided the patients into groups: normal renal function and CKD. Results: More patients self-declared themselves as black and brown in the group with CKD. The multivariate logistic analysis revealed that self-reported color-race was not associated with CKD and that a higher African ancestry was also not associated with CKD (p=0.06). Patients with an African ancestry of 50% or higher had an association with CKD that did not persist after the multivariate analysis. Conclusion: In our patients, from an admixed, multi-ethnic population, we did not find an association between self-reported color-race, genomic ancestry and CKD. It is important to note that despite the fact that we did not find a significant p-value in the multivariate analysis concerning African ancestry and CKD, we found a narrow confidence interval (0.961–3.98) with an OR of 1.956. Further studies should be conducted to confirm the lack of association between African ancestry and CKD, especially from populations with higher African or Amerindian ancestries to better understand the association between self-reported color-race and genomic ancestry with CKD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to establish demographic and clinical data associated with the knowledge on diabetes management and its influence on glycemic control in patients with type 1 diabetes. Methods: This was a retrospective, observational, multicenter study conducted with 1,760 patients between August 2011 and August 2014 in 10 cities of Brazil. Results: Overall, 1,190 (67.6%) patients knew what glycated hemoglobin (HbA1c) means. These patients were older, had longer disease duration, longer follow-up in each center, reported lower frequency of self-reported hypoglycemia, and were more frequently Caucasians and at glycemic goal. Multivariate analysis showed that knowledge on what HbA1c means was related to more years of school attendance, self-reported ethnicity (Caucasians), severe hypoglycemia, economic status, follow-up time in each center, and participation on diabetes educational programs. Good glycemic control was related to older age, more years of school attendance, higher frequency of daily self-monitoring of blood glucose, higher adherence to diet, and knowledge on what HbA1c means. Conclusion: Patients with a knowledge on what HbA1c means had a better chance of reaching an adequate glycemic control that was not found in the majority of our patients. Diabetes care teams should rethink the approaches to patients and change them to more proactive schedules, reinforcing education, patients' skills, and empowerment to have positive attitudes toward reaching and maintaining a better glycemic control. Finally, the glucocentric approach to diabetes management should be changed to actions that include patients' psychosocial aspects aiming to reduce the stress of living with diabetes, improving glycemic control, and avoiding adverse outcomes. [ABSTRACT FROM AUTHOR]

The article highlights nationwide study in Brazil on Prevalence and risk factors for referable diabetic retinopathy (DR) in type 1 diabetes patients. Topics discussed include the DR screening assessed by mydriatic binocular indirect ophthalmoscopy; effects of cigarette smoking on hypoxia and endothelial damage; and mention about risk factors of DR are presence of hypertension and chronic kidney disease.

Obesity is increasing worldwide, affecting even patients with type 1 diabetes (T1D). A higher prevalence of associated comorbidities is expected, such as non-alcoholic fatty liver disease (NAFLD). This paper reports a cross-sectional multicenter study on a population with T1D ( n = 1662), which aimed to evaluate the prevalence of metabolic syndrome (MS), a known risk factor for NAFLD, and to investigate predisposing factors associated with MS, as well as factors associated with elevated alanine aminotransferase (ALT), as it correlates to liver fat content. Patients were from 14 public clinics of 10 cities from all geographical regions of Brazil. A high prevalence of MS was found, especially among adults (32.3%), and this was related to age, female gender, acid uric levels, and the presence of acanthosis nigricans. ALT above the normal range was associated with triglyceride levels (especially above 129.5 mg/dL), serum uric acid, age, male gender, HbA1c, and non-Caucasian ethnicity. Patients with T1D, metabolic syndrome, and the aforementioned factors may be at a higher risk of NAFLD and should be referred to ultrasound for NAFLD evaluation. Further studies are necessary to establish the prevalence of NAFLD in individuals with T1D and to determine the disease's progression in these patients., Competing Interests: All authors declare no conflict of interests. The founding sponsor (FAPERJ and CNPq) had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.