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.

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.

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.

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.

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.

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.

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

ABSTRACT 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.

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.

Relationship among health-related quality of life and global ancestry, clinical and socioeconomic factors in type 1 diabetes in an admixed Brazilian population.

We aimed to evaluate the Health-related quality of life (HRQoL) of Type 1 diabetes mellitus (T1D) patients in an admixed Brazilian population. This is a cross-sectional study with 152 T1D patients. HRQoL information was obtained from two self-completed questionnaires: Short Form-6 dimensions and EuroQol-5 dimensions with visual analog scale. For inference of global ancestry, the panel of 46 autosomal informational insertion/deletion ancestry markers was used. Demographic and socioeconomic data, presence of chronic complications, glycemic control level, and type of treatment were obtained. Patients with good HRQoL were: male, under 18 years old, had health insurance, less than 5 years of diagnosis, practiced physical activity, without hypoglycemia in the last 30 days, absence of retinopathy and nephropathy, a participant in educational activities, used analogous insulin, monitoring blood glucose, observed maximum adherence to treatment and came from the secondary service. Global ancestry and self-reported color/race did not influence HRQoL indexes. Our study is the first to measure HRQoL, global ancestry and recognize the impact of T1D on the lives of patients in the State of Maranhão, Brazil. The results validate the need to provide T1D patients with continuous training on self-management and self-monitoring, aiming for better results in metabolic control and, subsequently, in the prevention of acute and chronic complications, in order to generate positive impacts on the quality of life of this population. We understand that global ancestry in a highly mixed population such as ours did not influence the HRQoL of these patients.

Early Markers of Cardiovascular Disease Associated with Clinical Data and Autosomal Ancestry in Patients with Type 1 Diabetes: A Cross-Sectional Study in an Admixed Brazilian Population.

Patients with type 1 diabetes (T1D) have a higher risk of developing cardiovascular disease (CVD), which is a major cause of death in this population. This study investigates early markers of CVD associated with clinical data and autosomal ancestry in T1D patients from an admixed Brazilian population. A cross-sectional study was conducted with 99 T1D patients. The mean age of the study sample was 27.6 years and the mean duration of T1D was 14.4 years. The frequencies of abnormalities of the early markers of CVD were 19.6% in the ankle-brachial index (ABI), 4.1% in the coronary artery calcium score (CACS), and 5% in the carotid Doppler. A significant percentage of agreement was observed for the comparison of the frequency of abnormalities between CACS and carotid Doppler (92.2%, p = 0.041). There was no significant association between the level of autosomal ancestry proportions and early markers of CVD. The ABI was useful in the early identification of CVD in asymptomatic young patients with T1D and with a short duration of disease. Although CACS and carotid Doppler are non-invasive tests, carotid Doppler is more cost-effective, and both have limitations in screening for CVD in young patients with a short duration of T1D. We did not find a statistically significant relationship between autosomal ancestry proportions and early CVD markers in an admixed Brazilian population.

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.

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.

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.

Genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in Type 1 Diabetes from an admixed Brazilian population.

This study aimed to investigate the relationship between genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in patients with Type 1 Diabetes from an admixed Brazilian population. Inference of autosomal ancestry; HLA-DRB1, -DQA1 and -DQB1 typifications; and Y chromosome analysis were performed. European autosomal ancestry was about 50%, followed by approximately 25% of African and Native American. The European Y chromosome was predominant. The HLA-DRB1*03 and DRB1*04 alleles presented risk association with T1D. When the Y chromosome was European, DRB1*03 and DRB1*04 homozygote and DRB1*03/DRB1*04 heterozygote genotypes were the most frequent. The results suggest that individuals from Maranhão have a European origin as their major component; and are patrilineal with greater frequency from the R1b haplogroup. The predominance of the HLA-DRB1*03 and DRB1*04 alleles conferring greater risk in our population and being more frequently related to the ancestry of the European Y chromosome suggests that in our population, the risk of T1D can be transmitted by European ancestors of our process miscegenation. However, the Y sample sizes of Africans and Native Americans were small, and further research should be conducted with large mixed sample sizes to clarify this possible association.

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.

Prevalence of non-alcoholic fatty liver disease and its associated factors in individuals with type 1 diabetes: a cross-sectional study in a tertiary care center in Brazil.

BACKGROUND: Data on non-alcoholic fatty liver disease (NAFLD) in individuals with type 1 diabetes (T1D) is controversial and so far, there are no published data on the Brazilian population. We investigated the prevalence of steatosis and hepatic fibrosis in a population with T1D from a tertiary care center in Brazil and its associated factors. METHODS: Ninety-five participants with T1D, aged 39 ± 13 years, with disease duration of 21 ± 9 years, being 55 (57.9%) females, from a university hospital in Rio de Janeiro, were screened for NAFLD with hepatic ultrasound (US) and transient elastography (TE). RESULTS: Prevalence of steatosis was, respectively, 12.6% and 16.8% when US and TE were used for diagnosis of NAFLD. Fibrosis was present in 8.4% of participants. A total of 31.6% of participants had at least one of the hepatic exams altered, which was associated with higher body mass index, waist circumference, hip circumference and waist-to-hip ratio,, presence of metabolic syndrome and higher triglycerides levels, even within the normal range. After multivariate analysis, presence of steatosis was only associated with metabolic syndrome and its component, triglycerides. CONCLUSION: In our study, prevalence of NAFLD in ultrasound approximates the one found with TE. Fibrosis was not frequent. Screening should be reserved for participants with T1D and metabolic syndrome, as this was the main factor associated with NAFLD. Triglycerides levels were the only component of metabolic syndrome associated with steatosis. Further studies are necessary to determine the best screening strategy for NAFLD in individuals with T1D. Also, predisposing factors for development in fibrosis in T1D should be further explored in prospective studies.

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.