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.

Preperitoneal fat as a non-invasive marker of increased risk of severe non-alcoholic fatty liver disease in patients with type 2 diabetes.

BACKGROUND AND AIM: Fat distribution may have prognostic value in the evaluation of non-alcoholic fatty liver disease. This study was conducted to evaluate associations of magnetic resonance imaging-measured abdominal fat areas with steatosis, steatohepatitis, and fibrosis, assessed histopathologically, in patients with type 2 diabetes. METHODS: This prospective study included 66 patients with type 2 diabetes (12 males, 54 females, age 26-68 years), without chronic liver disease of other causes. Axial dual-echo magnetic resonance images were acquired. Visceral, subcutaneous, and preperitoneal fat areas were measured using Osirix software. Liver biopsy specimens were obtained from all patients and examined histopathologically to evaluate steatosis, steatohepatitis, and fibrosis. Linear (for steatosis) and logistic (for steatohepatitis and fibrosis) regression models were fitted for the outcomes. R2 was used as a measure of how much model variance the predictors explained and to compare different predictors of the same outcome. RESULTS: Visceral and preperitoneal fat areas correlated well with histopathologically determined liver steatosis grade (both P = 0.004) and liver fibrosis (P = 0.008 and P = 0.037, respectively). All fat areas correlated well with steatohepatitis (P ≤ 0.002). Preperitoneal and visceral fat areas were the best predictors of steatohepatitis (R2 = 0.379) and fibrosis (R2 = 0.181), respectively. CONCLUSIONS: Visceral fat area was the best predictor of fibrosis in patients with type 2 diabetes. Preperitoneal fat area was the best predictor of steatohepatitis and is a potential new non-invasive marker for use in the screening of these patients to detect more aggressive forms of non-alcoholic fatty liver 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.

Health-related quality of life in people with type 1 Diabetes Mellitus: data from the Brazilian Type 1 Diabetes Study Group.

BACKGROUND: Type 1 Diabetes Mellitus (Type 1 DM) affects the psychological and emotional well-being of patients and their families. This study aims to evaluate the health- related quality of life (HRQoL) of people with Type 1 DM in Brazil, a country of continental proportions, using the EuroQol questionnaires. METHODS: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group, by analyzing EuroQol scores from 3,005 participants with Type 1 DM, in 28 public clinics in Brazil. Data on demography, economical status, chronic complications, glycemic control and lipid profile were also collected. RESULTS: The assessment of HRQoL by the EuroQol showed that the average score assigned to general health in Brazil is markedly lower than those found in two other Type 1 DM population-based studies conducted in Europe (EQ-VAS from the Netherlands, the United Kingdom and Brazil were 80.8 ± 15.2, 75.1 ± 18.4 and 72.5 ± 22, respectively). Additionally, our data suggest that a better glycemic control could positively impact the HRQoL of people with Type 1 DM, implying that each 1 % reduction in glycated haemoglobin might lead to an increase of 1.5 points in general health status assessed by the EuroQol. CONCLUSIONS: This is a population-based study evaluating the HRQoL of people with Type 1 DM in Brazil. Our data indicate a worse quality of health of people with Type 1 DM in Brazil in comparison to Europe, and suggest that a better glycemic control could positively impact the HRQoL of these individuals. However, this study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of these people.

Retirement due to disabilities in patients with type 1 diabetes a nationwide multicenter survey in Brazil.

BACKGROUND: There is scarcity of data concerning retirement and workforce loss exclusively in patients with type 1 diabetes. The aim of this study was to evaluate the prevalence, causes, and predictors of retirement in patients with type 1 diabetes in Brazil. METHODS: This was a multicenter cross-sectional study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,180 patients aged 22 ± 11.7 years; 56.3% of the participants were female, and 57.4% were Caucasians. The mean time since diabetes diagnosis was 10.3 ± 8.1 years. Patients' information (clinical factors and retirement data) was obtained through a questionnaire and a chart review. Patients were retired by diabetes according to the Brazilian Institute of Social Security's criteria that takes in account the presence of diabetes-related chronic complications certified by a doctor, excluding any personal reason or another health condition besides diabetes. Both quantitative and qualitative tests were employed, and a multivariate logistic regression model was performed to identify the factors associated with retirement due to disabilities in patients with type 1 diabetes. RESULTS: The overall frequency of retirement was 4.2%, with no difference between genders. The mean age of retirement was 35.5 ± 9.3 years, resulting in 17.5 ± 9.1 years of workforce losses. These patients had a significantly higher prevalence of severe hypoglycemia, proliferative and non-proliferative retinopathy, foot disorders, chronic or end-stage renal disease requiring dialysis or transplantation, cataracts, glaucoma, psychological disorders, hypertension, and overweight/obesity than did the employed patients. Multivariate logistic regression analysis with retirement as the dependent variable showed adjusted odds ratios (ORs) of 4.87 (2.66-8.78) for the presence of microvascular complications and 3.7 (2.04-6.70) for macrovascular complications. CONCLUSIONS: Retirement due to disabilities occurred in 4.2% of Brazilian patients with type 1 diabetes at an early age and is strongly associated with diabetes-related chronic complications. Health care workers should thus reevaluate the quality of care given to these patients.

Plant-Based Food for the Prevention of Type 2 Diabetes: Scoping Review.

Type 2 Diabetes Mellitus (T2DM) is a chronic condition with growing worldwide prevalence. Besides genetic factors, a sedentary lifestyle, excess weight, and inadequate eating habits, characterized by an excess intake of refined carbohydrates and ultra-processed foods, are contributing factors for the development of the disease. In this scenario, promoting a plant-based diet, and limiting animal product consumption while increasing the intake of vegetables, concurrently with healthy lifestyle habits, is a promising strategy to prevent T2DM. This scoping review, carried out between 2017 and 2022, aimed to gather evidence substantiating the benefits of a plant-based diet in T2DM prevention, considering different eating patterns, such as vegetarian, vegan, Mediterranean, and DASH diets. Several studies demonstrate a significant reduction in T2DM incidence among individuals adopting plant-based eating patterns or emphasizing healthy plant-based food alongside decreased intake or exclusion of animal-based foods. There are still no robust data regarding plant-based diets and the prevention of diabetes without loss in body weight. Hence, prospective studies in plant-based diets with weight control are needed. Nevertheless, adopting plant-based diets appears to induce significant weight loss, which is crucial in an obesity-endemic context. Thus, embracing plant-based diets, along with healthy habits, emerges as a relevant strategy in obesity and T2DM prevention.

Prevalence of cardiovascular autonomic neuropathy in an admixed population of patients with type 1 diabetes. Lessons from a pioneer multicentre study in Brazil.

AIMS: To evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) and its associated factors in Brazilian patients with type 1 diabetes (T1D). METHODS: This cross-sectional, multicentre study was conducted in 14 public clinics in ten Brazilian cities. From 1760 patients, 1712 were included (97.3 %): 953 females (55.7 %), 930 (54.3 %) Caucasians, aged 29.9 ±11.9 years and with diabetes duration of 15.4 ± 9.2 years. CAN was evaluated using cardiovascular autonomic reflex tests. RESULTS: The prevalence of CAN was 23.4 %. Multivariable hierarchical logistic regression showed CAN associated with age, smoking, lower socioeconomic status, higher yearly medical appointments, insulin therapeutic regimens, higher levels of HbA1c, total cholesterol, uric acid, diastolic blood pressure and heart rate, presence of retinopathy, diabetic kidney disease and a tendency to be associated with severe hypoglycemia. Lower health-related quality of life was also found in univariate analysis in these patients. CONCLUSIONS: Patients with T1D presented an important prevalence of CAN that was associated with other diabetes-related chronic complications, and also with demographic, clinical and laboratorial traditional risk factors. Considering lack of formal policy, our data could be used for guiding public health approach to awareness and CAN's screening, diagnosis and clinical management in patients with T1D in Brazil.

A pilot study of mitochondrial genomic ancestry in admixed Brazilian patients with type 1 diabetes.

Interactions between multiple genes and environmental factors could be related to the pathogenesis of type 1 diabetes (T1D). The Brazilian population results from different historical miscegenation events, resulting in a highly diverse genetic pool. This study aimed to analyze the mtDNA of patients with T1D and to investigate whether there is a relationship between maternal ancestry, self-reported color and the presence of T1D. The mtDNA control region of 204 patients with T1D residing in three geographic regions of Brazil was sequenced following the International Society for Forensic Genetics (ISFG) recommendations. We obtained a frequency of Native American matrilineal origin (43.6%), African origin (38.2%), and European origin (18.1%). For self-declared color, 42.6% of the patients with diabetes reported that they were White, 50.9% were Brown, and 5.4% were Black. Finally, when we compared the self-declaration data with maternal ancestral origin, we found that for the self-declared White group, there was a greater percentage of haplogroups of Native American origin (50.6%); for the self-declared Black group, there was a greater percentage of African haplogroups (90.9%); and for the Brown group, there was a similar percentage of Native American and African haplogroups (42.3% and 45.2%, respectively). The Brazilian population with diabetic has a maternal heritage of more than 80% Native American and African origin, corroborating the country's colonization history.

Type 1 Diabetes Brazilian patients exhibit reduced frequency of recent thymic emigrants in regulatory CD4+CD25+Foxp3+T cells.

To control immune responses, regulatory CD4+CD25+Foxp3+ T cells (Treg) maintain their wide and diverse repertoire through continuous arrival of recent thymic emigrants (RTE). However, during puberty, the activity of RTE starts to decline as a natural process of thymic involution, introducing consequences, not completely described, to the repertoire. Type 1 diabetes (T1D) patients show quantitative and qualitative impairments on the Treg cells. Our aim was to evaluate peripheral Treg and RTE cell frequencies, in T1D patients from two distinct age groups (young and adults) and verify if HLA phenotypes are concomitant associated. To this, blood samples from Brazilian twenty established T1D patients (12 young and 8 adults) and twenty-one healthy controls (11 young and 10 adults) were analyzed, by flow cytometry, to verify the percentages of CD4, Treg (CD4+CD25+Foxp3+) and the subsets of CD45RA+ (naive) and CD31+(RTE) within then. Furthermore, the HLA typing was also set. We observed that the young established T1D patients feature decreased frequencies in total Treg cells and naive RTE within Treg cells. Significant prevalence of HLA alleles, associated with risk, in T1D patients, was also identified. Performing a multivariate analysis, we confirmed that the cellular changes described offers significant variables that distinct T1D patients from the controls. Our data collectively highlight relevant aspects about homeostasis imbalances in the Treg cells of T1D patients, especially in young, and disease prognosis; that might contribute for future therapeutic strategies involving Treg cells manipulation.

Association between HLA alleles and haplotypes with age at diagnosis of type 1 diabetes in an admixed Brazilian population: A nationwide study.

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.

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.

The cost of type 1 diabetes: a nationwide multicentre study in Brazil.

OBJECTIVE: To determine the direct medical costs of type 1 diabetes mellitus (T1DM) to the National Brazilian Health-Care System (NBHCS) and quantify the contribution of each individual component to the total cost. METHODS: A retrospective, cross-sectional, nationwide multicentre study was conducted between 2008 and 2010 in 28 public clinics in 20 Brazilian cities. The study included 3180 patients with T1DM (mean age 22 years ± 11.8) who were surveyed while receiving health care from the NBHCS. The mean duration of their diabetes was 10.3 years (± 8.0). The costs of tests and medical procedures, insulin pumps, and supplies for administration, and supplies for self-monitoring of blood glucose (SMBG) were obtained from national and local health system sources for 2010-2011. Annual direct medical costs were derived by adding the costs of medications, supplies, tests, medical consultations, procedures and hospitalizations over the year preceding the interview. FINDINGS: The average annual direct medical cost per capita was 1319.15 United States dollars (US$). Treatment-related expenditure - US$ 1216.33 per patient per year - represented 92.20% of total direct medical costs. Insulin administration supplies and SMBG (US$ 696.78 per patient per year) accounted for 52.82% of these total costs. Together, medical procedures and haemodialysis accounted for 5.73% (US$ 75.64 per patient per year) of direct medical costs. Consultations accounted for 1.94% of direct medical costs (US$ 25.62 per patient per year). CONCLUSION: Health technologies accounted for most direct medical costs of T1DM. These data can serve to reassess the distribution of resources for managing T1DM in Brazil's public health-care system.

Pragmatic clinic-based investigation of echocardiogram parameters in asymptomatic patients with type 2 diabetes in routine clinical practice and its association with suggestive coronary artery disease: a pilot study.

BACKGROUND: Patients with diabetes mellitus (DM) have cardiovascular diseases (CVD) as a major cause of mortality and morbidity. The primary purpose of this study was to assess the echocardiographic parameters that showed alterations in patients with type 2 diabetes mellitus(T2DM) with suggestive coronary artery disease (CAD) determined by electrocardiography and the secondary was to assess the relationship of these alterations with established cardiovascular risk factors. METHODS: This cross-sectional, observational pilot study included 152 consecutive patients with T2DM who attended a tertiary DM outpatient care center. All patients underwent clinical examination and history, anthropometric measurements, demographic survey, determination of the Framingham global risk score, laboratory evaluation, basal electrocardiogram, echocardiogram, and measurement of carotid intima-media thickness (CIMT). RESULTS: From the overall sample, 134 (88.1%) patients underwent an electrocardiogram. They were divided into two groups: patients with electrocardiograms suggestive of CAD (n = 11 [8.2%]) and those with normal or non-ischemic alterations on electrocardiogram (n = 123 [91.79%]). In the hierarchical multivariable logistic model examining all selected independent factors that entered into the model, sex, high triglycerides levels, and presence of diabetic retinopathy were associated with CAD in the final model. No echocardiographic parameters were significant in multivariate analysis. The level of serum triglycerides (threshold) related to an increased risk of CAD was ≥ 184.5 mg/dl (AUC = 0.70, 95% IC [0.51-0.890]; p = 0.026. CONCLUSION: Our pilot study demonstrated that no echocardiogram parameters could predict or determine CAD. The combination of CIMT and Framingham risk score is ideal to determine risk factors in asymptomatic patients with T2DM. Patients with diabetic retinopathy and hypertriglyceridemia need further investigation for CAD. Further prospective studies with larger sample sizes are needed to confirm our results.

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.

Association between HLA Class II Alleles/Haplotypes and Genomic Ancestry in Brazilian Patients with Type 1 Diabetes: A Nationwide Exploratory Study.

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.

Healthy lifestyle and genomic ancestry related to good glycemic control in type 1 diabetes patients from Northeastern Brazil: a hierarchical analysis.

Introduction: This study aimed to investigate the sociodemographic factors, dietary adherence, regular physical activity, and genomic ancestry percentage associated with good glycemic control in Brazilian patients with type 1 diabetes (T1D) using a hierarchical approach. Methods: A cross-sectional study was conducted in 152 T1D patients. Glycated hemoglobin (HbA1C) levels were measured to evaluate the glycemic control status (good, moderate, or poor). Independent factors included sex, age, self-reported skin color, educational level, family income, dietary patterns, and physical activity. The percentage of genomic ancestry (Native American, European, and African) was influenced by a panel of 46 autosomal insertion/deletion ancestry markers. Statistical analyses included receiver operating characteristic curves, and hierarchical logistic regression analysis. Results: The hierarchical analysis, patients who had high dietary adherence showed a positive association with good glycemic control (adjustedOR = 2.56, 95% CI:1.18-5.59, P = 0.016). Thus, age greater than 40 years was associated with good glycemic control compared to the children and adolescents group (adjustedOR = 4.55, 95% CI:1.14-18.1, P = 0.031). Males were associated with good glycemic control (adjustedOR = 2.00, 95% CI:1.01-4.00, P =0.047). Conclusion: The study findings suggest that consistent adherence to dietary regimens is associated with good glycemic control after adjusting for sociodemographic and genomic ancestry factors in an admixed population of T1D patients from Northeast Brazil.

Epidemiology and risk factors of hypoglycemia in subjects with type 1 diabetes in Brazil: a cross-sectional, multicenter study.

Objective: The aim of this study was to investigate the factors associated with hypoglycemia and severe hypoglycemia (SH) in individuals with type 1 diabetes mellitus (T1D) in Brazil. Materials and Methods: This multicenter, cross-sectional study was conducted between August 2011 and August 2014 across 10 Brazilian cities. The data were obtained from 1,760 individuals with T1D. Sociodemographic and clinical characteristics related to hypoglycemic events in the previous 4 weeks were evaluated. Results: Of 1,760 individuals evaluated, 1,319 (74.9%) reported at least one episode of hypoglycemia in the previous 4 weeks. The main factors associated with hypoglycemia were lower hemoglobin A1c (HbA1c) level, better adherence to self-monitoring of blood glucose (SMBG), and higher education level. Episodes of SH were reported by 251 (19%) individuals who, compared with subjects with nonsevere hypoglycemia, received lower doses of prandial insulin and higher doses of basal insulin, in addition to reporting less frequent use of long-acting basal insulin analogs. The percentage of SH episodes was evenly distributed across all ranges of HbA1c levels, and there were no correlations between the mean number of nonsevere or severe hypoglycemic events and HbA1c values. Higher alcohol consumption and more frequent hospitalizations were independently associated with SH. Conclusion: Although individuals presenting with hypoglycemia had lower HbA1c values than those not presenting hypoglycemia, there were no correlations between the number of nonsevere hypoglycemia or SH and HbA1c values. Also, the frequency of SH was evenly distributed across all ranges of HbA1c values. Better adherence to SMBG and higher education level were associated with hypoglycemia, while alcohol consumption, higher doses of basal insulin, and more frequent hospitalizations in the previous year were associated with SH.

Biochemical and clinical markers of endothelial dysfunction do not outweigh traditional risk factors for the presence of diabetic retinopathy in patients with type 1 diabetes.

BACKGROUND: This study aimed to evaluate whether soluble vascular cytoadhesive molecule-1 (sVCAM-1), intracellular cytoadhesive molecule-1 (sICAM-1), and endothelial function as assessed by EndoPat outweighed traditional risk factors for the presence of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D). METHODS: Patients aged ≥ 12 years completed a clinical-epidemiological questionnaire. Fasting venous blood samples were obtained (lipid profile, glycemic control, and C-reactive protein levels). Vascular reactivity was assessed via peripheral arterial tonometry performed by supplying the reactive hyperemia index (RHI) through the EndoPAT device. sVCAM-1 and sICAM-1 levels were measured using multiplex assays. RESULTS: Data were obtained from 187 patients (51.3% female), aged 32 ± 13 years with a disease duration of 14 (6-15) years and mean hemoglobin A1c (HbA1c) of 9.1% ± 2.1%. After adjustments were made, age, HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function were found to be associated with DR. No association was noted with sVCAM-1 and sICAM-1 levels and RHI. CONCLUSIONS: In our sample, sVCAM-1, sICAM and EndoPAT did not outweigh the traditional DR risk factors, such as age, high HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function and are significantly associated with DR. Further prospective studies should evaluate if markers of endothelial dysfunction could predict diabetes-related micro and macrovascular complications in T1D.

Screening of latent tuberculosis infection among patients with diabetes mellitus from a high-burden area in Brazil.

Although several cohort studies have raised the important association between diabetes mellitus (DM) and latent tuberculosis infection (LTBI), evidences are limited and controversial. Furthermore, it is well documented that the poor glycemic control may exacerbate the risk for active TB. Thus, the monitoring of diabetic patients living in high-incidence areas for TB is an important concern in views of available diagnostic tests for LTBI. In this cross-sectional study, we estimate the association of DM and LTBI among diabetic patients classified as type-1 DM (T1D) or type-2 DM (T2D) living in Rio de Janeiro, RJ, Brazil - considered a high TB burden region of these country. Non-DM volunteers were included as endemic area healthy controls. All participants were screened for DM using glycosylated-hemoglobin (HbA1c) and for LTBI using the QuantiFERON-TB Gold in Tube (QFT-GIT). Demographic, socioeconomic, clinical and laboratorial data were also assessed. Among 553 included participants, 88 (15.9%) had QFT-GIT positive test, of which 18 (20.5%) were non-DM, 30 (34.1%) T1D and 40 (45.4%) T2D. After adjustments for potential baseline confounders, age, self-reported non-white skin color and an active TB case in the family were significantly associated with LTBI among the studied population by using a hierarchical multivariate logistic regression analysis. Additionally, we verified that T2D patients were able to produce significant increased interferon-gamma (IFN-γ) plasma levels in response to Mycobacterium tuberculosis-specific antigens, when compared to non-DM individuals. Altogether, our data showed an increased prevalence of LTBI among DM patients, albeit non-statistically significant, and point out to important independent factors associated with LTBI, which deserve attention in monitoring patients with DM. Moreover, QFT-GIT test seems to be a good tool to screening LTBI in this population, even in a high TB burden area.

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.