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.

Prevalence of chronic kidney disease in an admixed population of patients with type 1 diabetes. A multicenter study in Brazil.

AIMS: To evaluate diagnosis, prevalence and associated factors of CKD in Brazilian patients with type 1 diabetes. METHODS: This cross-sectional, multicenter study was conducted in 14 public clinics in 10 Brazilian cities. From 1760 patients, 1736 were included (98.6%): 977 females (56.3%), 932 (54%) Caucasians, aged 29.9 ± 11.9 years, age at diagnosis 14.7 ± 8.9 years, diabetes duration 15.5 ± 9.3 years and 12.2 ± 3.8 years of school attendance. CKD was determined by using estimated glomerular filtration rate and by the presence of albuminuria in two out of three morning urine samples. RESULTS: The prevalence of CKD was 33.7%. Overall, 28.1% of the patients could not be classified due to insufficient number of urine samples for albuminuria determination. Multivariable analysis showed that female gender, diabetes duration, high levels of HbA1c and uric acid, use of renin-angiotensin system inhibitors, retinopathy, high systolic blood pressure, and economic status (medium, low and very low) were associated with CKD. CONCLUSIONS: Although a high prevalence of CKD, associated comorbidities and retinopathy was observed in our study, a large number of patients are still undiagnosed, making CKD a challenge in routine clinical practice in admixed populations with T1D in a developing country like Brazil.

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.

Health literacy and glycemic control in patients with diabetes: a tertiary care center study in Brazil.

BACKGROUND: The primary objective of our study was to determine which factors influence health literacy (HL) in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D), and the secondary one was to evaluate the influence of HL on glycemic control. METHODS: This was an observational, cross-sectional study with 347 patients (144 with T1D and 203 with T2D), conducted between December 2014/December 2017. Data were obtained from medical records and/or questionnaire. The short test of Functional Health Literacy (S-TOFHLA) was used to evaluate HL. RESULTS: Age and years of school attendance were the most important variables associated with better performance in S-TOFHLA mainly in patients with T1D. A correlation between age and years of school attendance with S-TOFHLA score was observed in both groups of patients. After an unadjusted analysis, more patients with T1D presented adequate HL [119 (82.6%) vs 87 (44.8%, p < 0.001)]. Patients with T1D had higher scores than patients with T2D (84.4 ± 21.4 vs 61.6 ± 26.8 points, p < 0.001), respectively. This difference did not persist after adjustment for age and years of school attendance (73.04 ± 2.14 ± vs 70.04 ± 1.76 points) respectively, p = 0.348). No difference was found in HbA1c levels according to S-TOFHLA. All patients with T1D and HbA1c levels < 7.0% (53 mmol/mol) had adequate HL. CONCLUSIONS: A considerable number of patients with either T1D or T2D did not have adequate HL. Overall, age and years of school attendance were the most important variables associated with better performance of S-TOFHLA. Although no difference was found in HbA1c levels according to S-TOFHLA, patients with T1D who self-reported as White, with more years of school attendance, and higher HL score reached more frequently a good glycemic control. Finally, in addition to therapeutic regimens, approaches on diabetes management should also include patients' HL evaluation along with psychological and social aspects.

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.

Influence of genomic ancestry and self-reported color-race in CKD in a nationwide admixed sample of Brazilian patients with type 1 diabetes.

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.

Relationship between health care insurance status, social determinants and prevalence of diabetes-related microvascular complications in patients with type 1 diabetes: a nationwide survey in Brazil.

AIMS: To evaluate the relationship between social determinants, health care insurance status and occurrence of diabetes-related chronic complications (DRCC) in Brazilian patients with type 1 diabetes. METHODS: A multicenter cross-sectional study conducted between August 2011 and August 2014 in 14 public clinics in 10 Brazilian cities. Data were obtained from 1760 patients, aged 29.9 ± 11.9 years, with diabetes duration of 15.5 ± 9.3 years; 55.9% female, 54.5% Caucasians, 69.7% were attended exclusively by the public Brazilian National Health Care System (BNHCS) and 30.3% had also private health care insurance. Patients' information was obtained through a questionnaire and a chart review form. RESULTS: The social determinants associated with having both private and public health care insurance were being employed, belonging to medium or high socioeconomic status, having more years of school attendance and having younger age. Regarding DRCC, patients that had private and public health care had lower rates of diabetic retinopathy and of any other DRCC. Chronic kidney disease was not associated with health care coverage status after adjusting for classical clinical risk factors. CONCLUSIONS: Brazilian patients with type 1 diabetes had better clinical control and lower rates of DRCC, mainly retinopathy, when also having private health care insurance. These patients presented less frequently predictors of chronic complications such as high levels of HbA1c and blood pressure. BNHCS should change the approach for screening DRCC such as diabetic retinopathy, using methods such as telemedicine that would lead to earlier diagnosis, better outcomes and will be cost-effective sometime after its implementation.

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.

Serum uric acid and renal function in patients with type 1 diabetes: a nationwide study in Brazil.

BACKGROUND: Diabetes nephropathy is a microvascular complication associated with high morbidity and mortality in patients with type 1 diabetes, and its pathogenesis is not fully understood. Our aim was to evaluate the association between levels of serum uric acid and renal function assessed by glomerular filtration rate (GFR) and albuminuria in patients with type 1 diabetes. METHODS: This is a multicenter, cross-sectional, observational study with 1686 patients, conducted between August 2011 and August 2014 in 14 public clinics from ten Brazilian cities. Renal function was estimated by CKD-EPI (adults) and by Schwartz (adolescents). RESULTS: We analyzed 1686 patients, aged 30.1 ± 12.0, with 15.4 ± 9.3 years of duration of diabetes; 55.8% were female and 54.0% were Caucasians. Serum uric acid was related to renal function, with a mean of 4.8 ± 1.4 (in the normal renal function group) vs 5.2 ± 2.0 (GFR ≥ 60 ml/min and albuminuria) vs 6.5 ± 2.6 mg/dl (GFR < 60 ml/min). In the pooled group, multivariate analysis showed an inverse correlation between serum uric acid and GFR (r = - 0.316, p < 0.001) with a decrease of 4.11 ml/min in the GFR for every increase of 1 mg/dl in serum uric acid. Considering only patients with normal renal function (n = 1170), a decrease of 2.04 ml/min in the GFR for every increase of 1 mg/dl in Serum uric acid was noted using multivariate analysis. CONCLUSIONS: Patients with higher levels of serum uric acid have worse renal function, independently of HbA1c or duration of diabetes, which persisted even in patients with normal renal function. Further prospective studies are necessary to establish if patients with higher serum uric acid may have an elevated risk for developing chronic kidney disease.

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.

Type 1 Diabetes and Non-Alcoholic Fatty Liver Disease: When Should We Be Concerned? A Nationwide Study in Brazil.

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.

Aspectos atuais no diagnóstico do edema macular diabético: [revisão] / Recent aspects on diagnosis of diabetic macular edema: [review]

O diagnóstico do edema macular diabético deve ser feito precocemente, a fim de evitar perda visual significativa. Para tal, contamos com exames complementares cada vez mais desenvolvidos e específicos. Os autores fazem uma revisão dos principais métodos existentes para diagnosticar a retinopatia diabética.

Diabetic macular edema must be assessed as early as possible, to avoid significant vision loss. To achieve this goal, there are many specific diagnostic tests that can be performed. The authors review the most common methods in diagnosing diabetic retinopathy.

Aspectos atuais na fisiopatologia do edema macular diabético: [revisão] / Recent aspects on physiopathology of diabetic macular edema: [review]

O edema macular é a principal causa de baixa visual em pacientes diabéticos. Seu mecanismo de formação é complexo e envolve alterações bioquímicas e estruturais. Os autores fazem uma revisão e atualização dos conceitos fisiopatológicos envolvidos na maculopatia diabética.

Macular edema is the leading cause of poor vision in diabetic patients.The mechanism of edema formation is complex and involves biochemical and structural changes. The authors review and update the physiopathologic concepts related to diabetic maculopathy.