HLA Genotypes and Type 1 Diabetes and Its Relationship to Reported Race/Skin Color in Their Relatives: A Brazilian Multicenter Study.

We aimed to investigate the relationship between HLA alleles in patients with type 1 diabetes from an admixed population and the reported race/skin color of their relatives. This cross-sectional, multicenter study was conducted in public clinics in nine Brazilian cities and included 662 patients with type 1 diabetes and their relatives. Demographic data for patients and information on the race/skin color and birthplace of their relatives were obtained. Typing of the HLA-DRB1, -DQA1, and -DQB1 genes was performed. Most studied patients reported having a White relative (95.17%), and the most frequently observed allele among them was DRB1*03:01. Increased odds of presenting this allele were found only in those patients who reported having all White relatives. Considering that most of the patients reported having a White relative and that the most frequent observed allele was DRB1*03:01 (probably a European-derived allele), regardless of the race/skin color of their relatives, we conclude that the type 1 diabetes genotype comes probably from European, Caucasian ethnicity. However, future studies with other ancestry markers are needed to fill the knowledge gap regarding the genetic origin of the type 1 diabetes genotype in admixed populations such as the Brazilian.

Genomic ancestry and glycemic control in adolescents with type 1 diabetes: A multicenter study in Brazil.

OBJECTIVE: To determine the influence of genomic ancestry (GA) and self-reportedcolor-race (SRCR) on glycemic control in adolescents with type 1 diabetes (T1D) in an admixed population. RESEARCH DESIGN AND METHODS: This multicenter nationwide study was conducted in 14 public clinics in 10 Brazilian cities. We estimated global and individual African, European, and Native Amerindian GA proportions using a panel of 46 AIM-INDEL markers. From 1760 patients, 367 were adolescents (20.9%): 184 female (50.1%), aged 16.4 ± 1.9 years, age at diagnosis 8.9 ± 4.3 years, duration of diabetes 8.1 ± 4.3 years, years of study 10.9 ± 2.5 and HbA1c of 9.6 ± 2.4%. RESULTS: Patients SRCR as White: 176 (48.0%), Brown: 159 (43.3%), Black: 19(5.2%), Asians: 5 (1.4%) and Amerindians: 8 (2.2%). The percentage of European GA prevailed in all groups: White (71.1), Brown (58.8), Black (49.6), Amerindians (46.1), and Asians (60.5). Univariate correlation was noted between A1c and African GA, r = 0.11, P = .03; years of study, r = -0.12 P = .010, and having both private and public health care insurance (r = -0.20, P < .001). After adjustments, the multivariate logistic analysis showed that SRCR or GA did not influence glycemic control. CONCLUSIONS: A high percentage of European GA was noted in our patients, even in those who self-reported as non-White, confirming the highly admixed ethnicity of the Brazilian population. Better glycemic control was associated with having both types of health care; however, there was no association between glycemic control with GA or SRCR. Future prospective studies with other admixed populations are necessary to confirm our findings.

Does knowledge on diabetes management influence glycemic control? A nationwide study in patients with type 1 diabetes in Brazil.

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

Microvascular Complications in Type 1 Diabetes: A Comparative Analysis of Patients Treated with Autologous Nonmyeloablative Hematopoietic Stem-Cell Transplantation and Conventional Medical Therapy.

OBJECTIVE: To explore the impact on microvascular complications, long-term preservation of residual B-cell function and glycemic control of patients with type 1 diabetes treated with autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST) compared with conventional medical therapy (CT). RESEARCH DESIGN AND METHODS: Cross-sectional data of patients treated with AHST were compared with patients who received conventional therapy from the Brazilian Type 1 Diabetes Study Group, the largest multicenter observational study in type 1 diabetes mellitus in Brazil. Both groups of patients had diabetes for 8 years on average. An assessment comparison was made on the presence of microvascular complications, residual function of B cell, A1c, and insulin dose of the patients. RESULTS: After a median of 8 years of diagnosis, none of the AHST-treated patients (n = 24) developed microvascular complications, while 21.5% (31/144) had at least one (p < 0.005) complication in the CT group (n = 144). Furthermore, no case of nephropathy was reported in the AHST group, while 13.8% of CT group (p < 0.005) developed nephropathy during the same period. With regard of residual B-cell function, the percentage of individuals with predicted higher C-peptide levels (IDAA1C ≤ 9) was about 10-fold higher in the AHST group compared with CT (75 vs. 8.3%) (p < 0.001) group. Among AHST patients, 54.1% (13/24) had the HbA1c < 7.0 compared with 13.1% in the CT (p < 0.001) group. CONCLUSION: Patients with newly diagnosed type 1 diabetes treated with AHST presented lower prevalence of microvascular complications, higher residual B-cell function, and better glycemic control compared with the CT group.

Cause-specific mortality in a cohort of Brazilian patients with type 1 diabetes.

AIMS: To assess cause-specific mortality in a cohort of patients with type 1 diabetes (T1D) followed at an university hospital (tertiary level, Rio de Janeiro city) and an outpatient clinic (secondary level, Bauru city) both in Brazil's southeast, and associations of survival with gender, age at diagnosis, self-reported ethnicity and diabetes duration. METHODS: Our study is based on a cohort of patients with T1D whose vital status was determined as of December 31, 2015. The causes of mortality were determined by death certificates and outpatient clinic records. RESULTS: Among 986 patients, (54.4%) females, (74.8%) Caucasians, 886 (89.9%) were alive, 62 (6.3%) had died, and in 38 (3.9%) the vital status was unknown. Median age at death [interquartile range] and diabetes duration until death were 30.0 [13] and 15.6 [10] years, respectively. Considering those who died (n = 62), most patients (about 70%) died from end-stage renal disease, macrovascular disease or acute complications of diabetes, mainly diabetic ketoacidosis. The other causes of mortality were infections, fatal accidents and non-diabetes-related. The standardized mortality ratio was 3.13 [2.35-4.08] in those aged under 40. In a multivariate Cox model, "age < 40 years" and "year of diagnosis" were the only significant variables with hazard ratios of 6.259 [(3.100-12.639), p < 0.001] and 0.915 [(0.880-0.951), p < 0.001], respectively. CONCLUSIONS: Our study shows that patients with T1D had a threefold increase in mortality. The specific causes of mortality were mainly diabetes-related chronic complications; however, acute complications, especially diabetic ketoacidosis, persisted as an important cause of mortality.

Relationship between adherence to diet, glycemic control and cardiovascular risk factors in patients with type 1 diabetes: a nationwide survey in Brazil.

BACKGROUND: To determine the relationship between adherence to the diet reported by patients with type 1 diabetes under routine clinical care in Brazil, and demographic, socioeconomic status, glycemic control and cardiovascular risk factors. METHODS: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data was obtained from 3,180 patients, aged 22 ± 11.8 years (56.3% females, 57.4% Caucasians and 43.6% non-Caucasians). The mean time since diabetes diagnosis was 11.7 ± 8.1 years. RESULTS: Overall, 1,722 (54.2%) of the patients reported to be adherent to the diet without difference in gender, duration of diabetes and socioeconomic status. Patients who reported adherence to the diet had lower BMI, HbA1c, triglycerides, LDL-cholesterol, non HDL-cholesterol and diastolic blood pressure and had more HbA1c at goal, performed more frequently self-monitoring of blood glucose (p < 0.001), and reported less difficulties to follow specific schedules of diet plans (p < 0.001). Less patients who reported to be adherent were obese or overweight (p = 0.005). The quantity of food and time schedule of the meals were the most frequent complaints. Logistic regression analysis showed that ethnicity, (Caucasians, (OR 1.26 [1.09-1.47]), number of medical clinical visits in the last year (OR 1.10 [1.06-1.15]), carbohydrate counting, (OR 2.22 [1.49-3.30]) and diets recommended by diabetes societies', (OR 1.57 [1.02-2.41]) were related to greater patients' adherence (p < 0.05) and age, [adolescents (OR 0.60 [0.50-0.72]), high BMI (OR 0.58 [0.94-0.98]) and smoking (OR 0.58 [0.41-0.84]) with poor patients' adherence (p < 0.01). CONCLUSIONS: Our results suggest that it is necessary to rethink medical nutrition therapy in order to help patients to overcome barriers that impair an optimized adherence to the diet.

Glargine vs. NPH insulin therapy in pregnancies complicated by diabetes: an observational cohort study.

AIMS: The effects of glargine insulin therapy in pregnancies are not well established. We compared maternal and neonatal outcomes of women with pregestational and gestational diabetes treated with glargine or NPH insulin. METHODS: A prospective cohort study was conducted analyzing outcomes from 56 women with pregestational and 82 with gestational diabetes treated with either insulin regimen. RESULTS: Comparisons were performed among 138 women: 56 with pregestational and 82 with gestational diabetes. In relation to maternal complications, worsening of retinopathy and nephropathy, preeclampsia, micro and macroalbuminuria, and all kinds of hypoglycemia were found higher in women with pregestational diabetes NPH-treated vs. glargine-treated. In women with gestational diabetes NPH-treated, it was observed increased incidence of prepregnancy and new-onset pregnancy hypertension, micro and macroalbuminuria, as well as mild and frequent hypoglycemia, compared to glargine-treated. Among the neonatal outcomes, 1-min Apgar score <7, necessity of intensive care unit and fetal death in pregestational, while jaundice and congenital malformations in gestational diabetes, respectively, were more frequently observed in infants born to NPH-treated, compared to glargine-treated. CONCLUSIONS: Glargine use during pregnancy from preconception through delivery, showed to be safe since it is associated with decreased maternal and neonatal adverse outcomes compared with NPH insulin-treated patients.

Association between different levels of dysglycemia and metabolic syndrome in pregnancy.

BACKGROUND: In this study, we sought to evaluate the prevalence of metabolic syndrome (MS) in a cohort of pregnant women with a wide range of glucose tolerance, prepregnancy risk factors for MS during pregnancy, and the effects of MS in the outcomes in the mother and in the newborn. METHODS: One hundred and thirty six women with positive screening for gestational diabetes mellitus (GDM) were classified by two diagnostic methods: glycemic profile and 100 g OGTT as normoglycemic, mild gestational hyperglycemic, GDM, and overt GDM. Markers of MS were measured between 2428th during the screening. RESULTS: The prevalence of MS was: 0%; 20.0%; 23.5% and 36.4% in normoglycemic, mild hyperglycemic, GDM, and overt GDM groups, respectively. Previous history of GDM with or without insulin use, BMI >/= 25, hypertension, family history of diabetes in first degree relatives, non-Caucasian ethnicity, history of prematurity and polihydramnios were statistically significant prepregnancy predictors for MS in the index pregnancy, that by its turn increased the adverse outcomes in the mother and in the newborn. CONCLUSION: The prevalence of MS increases with the worsening of glucose tolerance; impaired glycemic profile identifies pregnancies with important metabolic abnormalities even in the presence of a normal OGTT, in patients that are not classified as having GDM.

Influence of lower cutoff values for 100-g oral glucose tolerance test and glycemic profile for identification of pregnant women at excessive fetal growth risk.

OBJECTIVE: To evaluate data from patients with normal oral glucose tolerance test (OGTT) results and a normal or impaired glycemic profile (GP) to determine whether lower cutoff values for the OGTT and GP (alone or combined) could identify pregnant women at risk for excessive fetal growth. METHODS: We classified 701 pregnant women with positive screening for gestational diabetes mellitus (GDM) into 2 categories -- (1) normal 100-g OGTT and normal GP and (2) normal 100-g OGTT and impaired GP-to evaluate the influence of lower cutoff points in a 100-g OGTT and GP (alone or in combination) for identification of pregnant women at excessive fetal growth risk. The OGTT is considered impaired if 2 or more values are above the normal range, and the GP is impaired if the fasting glucose level or at least 1 postprandial glucose value is above the normal range. To establish the criteria for the OGTT (for fasting and 1, 2, and 3 hours after an oral glucose load, respectively), we considered the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL), mean plus 1 SD (85 mg/dL, 151 mg/dL, 133 mg/dL, and 118 mg/dL), and mean plus 2 SD (95 mg/dL, 182 mg/dL, 153 mg/dL, and 139 mg/dL); and for the GP, we considered the mean and mean plus 1 SD (78 mg/dL and 92 mg/dL for fasting glucose levels and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial glucose levels, respectively). RESULTS: Subsequently, the women were reclassified according to the new cutoff points for both tests (OGTT and GP). Consideration of values, in isolation or combination, yielded 6 new diagnostic criteria. Excessive fetal growth was the response variable for analysis of the new cutoff points. Odds ratios and their respective confidence intervals were estimated, as were the sensitivity and specificity related to diagnosis of excessive fetal growth for each criterion. The new cutoff points for the tests, when used independently rather than collectively, did not help to predict excessive fetal growth in the presence of mild hyperglycemia. CONCLUSION: Decreasing the cutoff point for the 100-g OGTT (for fasting and 1, 2, and 3 hours) to the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL) in association with the GP (mean or mean plus 1 SD-78 mg/dL and 92 mg/dL for the fasting state and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial values-increased the sensitivity and specificity, and both criteria had statistically significant predictive power for detection of excessive fetal growth.