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Objectives: To evaluate the alternate use of flash glucose monitoring (FGM) with self-monitoring blood glucose (SMBG), in patients with type 1 diabetes (T1D). Materials and methods: Two weeks of open FGM (P2), both preceded (P1) and followed by 2 weeks (P3) of SMBG with a blinded FGM system. Mean absolute relative difference (MARD) was calculated by (|FGMi − SMBGi|) / SMBGi, where it was a paired data sample. Results: In total, 34 patients were evaluated. Time in range (TIR) did not change between P1 and P2. In 12 patients (35.3%), TIR increased from 40% at P1 to 52% at P2 (p = 0.002) and in 22 (64.7%), TIR decreased or did not change. FGM use resulted in decreased % time spent in hypoglycemia (180 mg/dL) (44.5% to 51%; p = 0.046) with no significant change in % TIR. The proportion of patients who reached sensor-estimated glycated hemoglobin (eA1c) < 7% decreased from 23.5% at P1 to 12.9% at P2, p = 0.028. For the whole sample, the MARD between the two methods was 15.5% (95% CI 14.5-16.6%). For normal glucose range, hyperglycemic levels and hypoglycemic levels MARD were 16.0% (95% CI 15.0-17.0%), 13.3% (95% CI 11.5-15.2%) and 23.4% [95% CI 20.5-26.3%)], respectively. Conclusion: FGM after usual SMBG decreased the % time spent in hypoglycemia concomitant with an undesired increase in % time spent in hyperglycemia. Lower accuracy of FGM regarding hypoglycemia levels could result in overcorrection of hypoglycemia.

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.

O Diabetes Mellitus tipo 1A diagnosticado antes do 1º ano de vida é uma condição rara, podendo haver uma associação entre fatores genéticos e ambientais (infecção) que explique tal precocidade. Foi descrita a presença do genoma do Citomegalovírus (CMV) nos linfócitos, em cerca de 15% de novos casos de DM1. Relatamos os casos de desenvolvimento do diabetes em gêmeos dizigóticos do sexo masculino, nos primeiros 9 meses de idade com identidade nos alelos HLA (DR3/DR4) e história de infecção pelo CMV em ambos, comprovada por IgG+ e PCR urinária. Apenas o 2º gemelar apresentava o anticorpo anti-GAD positivo (9,6 UI/mL). Apesar de tratar-se de gêmeos dizigóticos, cuja taxa de concordância para diabetes, na literatura, é de 3,8%, assumem risco equivalente a monozigóticos (de 40%) por apresentarem HLA de alto risco para o diabetes. Acreditamos que tanto a concordância temporal como o início precoce do diabetes são decorrentes da associação entre infecção por CMV e forte suscetibilidade genética. The onset of type 1A diabetes before the first year of age is a rare condition and is probably due to an interaction between genetic and environmental factors (infection), which, together, may explain such an early event. Studies say that about 15% of newly diagnosed type 1 diabetic patients had human Cytomegalovirus (CMV) specific viral genome in their lymphocytes. We report two cases of dizygotic twins with type 1 diabetes onset in their first 9 months of age, with genetic homogeneity (for HLA DR3/DR4 alleles), a history of CMV infection (positive IgG and urinary PCR) and positive antibody anti-GAD (9.6 UI/ml), present only in the second twin. Although they were dizygotic twins, which concordance rate is 3.8%, they assume the equivalent risk as monozygotic (40%) as they have similar high risk genotype (HLA) for type 1 diabetes. We believe that both time concordance and also the early onset of diabetes are due to an association between infection and the high genetic liability.

A neuropatia autonomica cardiovascular (NAC), apesar de ser considerada uma complicacao cronica comum no paciente com diabetes mellitus (DM) e associada com o aumento de morbimortalidade cardiovascular (CV), ainda permanece subdiagnosticada. A presente revisao tem o objetivo de descrever os criterios diagnosticos da NAC, os fatores clinicolaboratoriais relacionados com a sua presenca e as estrategias terapeuticas disponiveis. A NAC esta presente em 25% dos pacientes com DM tipo 1 (DM1) e em 34% dos pacientes com DM tipo 2 (DM2). Encontra-se associada a neuropatia periferica, assim como a presenca de hipertensao arterial sistemica (HAS), dislipidemia, nefropatia, retinopatia diabeticas, doenca vascular periferica (DVP) e os principais fatores de risco sao idade, duracao do DM e presenca de controle glicemico inadequado. A NAC pode se manifestar atraves de taquicardia de repouso, hipotensao postural, intolerância a atividade fisica, isquemia miocardica silenciosa, aumento do intervalo QT, cardiomiopatia diabetica e ausencia de descenso noturno de pressao arterial sistolica (PAS). Os sinais e sintomas associados a presenca da NAC surgem tardiamente na evolucao da doenca, tornando necessaria a utilizacao de testes reflexos CV para identificacao precoce da NAC (teste da respiracao profunda, teste de Valsalva, teste do ortostatismo e pesquisa de hipotensao ortostatica). De acordo com as recomendacoes atuais, e necessaria a presenca de pelo menos dois testes reflexos CV alterados para o diagnostico definitivo de NAC. As estrategias terapeuticas disponiveis sao tratamento dos fatores de RCV (HAS, dislipidemia e diabetes), alem da pratica de exercicios fisicos, uso de betabloqueadores, inibidores da enzima conversora de angiotensina (iECA) e acido alfalipoico. A NAC ainda permanece subdiagnosticada. O rastreamento e recomendado para o diagnostico de pacientes com DM2 e apos cinco anos do diagnostico de pacientes com DM1 para permitir o diagnostico precoce tratamento adequado e prevencao e reversao das alteracoes autonomicas de CV. Descritores: Diabetes mellitus ; Risco; Doencas cardiovasculares; Neuropatias diabeticas; Angiopatias diabeticas.

Background: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. Methods: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. Results: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North- Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. Conclusions: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 1 diabetes (T1D). The cardiovascular autonomic neuropathy (CAN), although considered as an independent risk factor for CVD, remains underdiagnosed. The aim of this paper was to determine the prevalence, predictors of CAN in patients with T1D and its association with other chronic complications of diabetes. Patients with T1D underwent a clinical-epidemiological survey, had blood and urinary samples collected, performed ophthalmoscopic and clinical neurological examination and cardiovascular reflex tests. One hundred and fifty one patients with T1D, 53.6% female, 45.7% Caucasian, mean age of 33.4 ± 13 years, diabetes duration of 16.3 ± 9.5 years, and glycated hemoglobin levels of 9.1 ± 2% were evaluated. The prevalence of CAN in the studied population was 30.5%. CAN was associated with age (p = 0.01), diabetes duration (p = 0.036), hypertension (p = 0.001), resting heart rate (HR) (p = 0.000), HbA1c (p = 0.048), urea (p = 0.000), creatinine (p = 0.008), glomerular filtration rate (p = 0.000), urinary albumin concentration (p = 0.000), LDL (p = 0.048), free T4 (p = 0.023), hemoglobin (p = 0.01) and presence of retinopathy (p = 0.000), nephropathy (p = 0.000) and diabetic neuropathy (p = 0.000), the following symptoms syncope (p = 0.000), post prandial nausea (p = 0.042), early satiety (p = 0.031), sexual dysfunction (p = 0.049), and gustatory sweating (p = 0.018). In logistic regression model, it was observed that only resting HR, diabetic neuropathy, and retinopathy were independent associated with CAN. In conclusion, CAN is a common chronic complication of T1D affecting about 30% of the studied population and is associated with the presence of other chronic complications. Indicators of CAN included age, diabetes duration, hypertension, resting HR, diabetic neuropathy and retinopathy, and symptoms suggestive of autonomic neuropathy. This study confirms the importance of systematic and early screening for CAN.

Background: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.

Background and aims Regional differences in the clinical care of Type 1 diabetes (T1D) in Brazil have been recently described. This study aimed to estimate the costs of T1D from the public health care system’s perspective across the regions of Brazil and to determine the components that influence these costs. Methods This was a retrospective, cross-sectional and nationwide multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The study included 3,180 T1D subjects receiving healthcare from the National Brazilian Healthcare System (NBHCS) with a follow-up of at least one year. The direct medical costs were derived from the costs of medications, supplies, examinations, visits to the center, medical procedures and hospitalizations that occurred during the previous year. Clinical and demographic factors that determined the differences in the cost across four geographic regions (southeast, south, north/northeast and mid-west) were investigated. Results The per capita mean annual direct medical costs of T1D in US$ were 1,466.36, 1,252.83, 1,148.09 and 1,396.30 in southeast, south, north/northeast and mid-west regions, respectively. The costs of T1D in the southeast region were higher compared to south (p < 0.001) and north/northeast regions (p = < 0.001), but not to the mid-west (p = 0.146) region. The frequency of self-monitoring of blood glucose (SMBG) was different across the regions as well as the daily number of SMBG, use of insulin pumps or basal or prandial insulin analogs. Age, ethnicity, duration of diabetes, level of care, socioeconomic status and the prevalence of chronic diabetic complications differed among the regions. In a regression model the determinants of the costs were the presence of microvascular diabetes-related complications (p

Cardiovascular diseases are the most prevalent cause of morbidity and mortality among patients with type 1 or type 2 diabetes. The proposed mechanisms that can link accelerated atherosclerosis and increased cardiovascular risk in this population are poorly understood. It has been suggested that an association between hyperglycemia and intracellular metabolic changes can result in oxidative stress, low-grade inflammation, and endothelial dysfunction. Recently, epigenetic factors by different types of reactions are known to be responsible for the interaction between genes and environment and for this reason can also account for the association between diabetes and cardiovascular disease. The impact of clinical factors that may coexist with diabetes such as obesity, dyslipidemia, and hypertension are also discussed. Furthermore, evidence that justify screening for subclinical atherosclerosis in asymptomatic patients is controversial and is also matter of this review. The purpose of this paper is to describe the association between poor glycemic control, oxidative stress, markers of insulin resistance, and of low-grade inflammation that have been suggested as putative factors linking diabetes and cardiovascular disease.

Objective. This study evaluated the prevalence, awareness, and type of treatment for hypertension in Brazil in patients with type 1 diabetes (T1D).Methods. This was a cross-sectional, multicenter study that was conducted from December 2008 to December 2010 in 28 public clinics located in 20 Brazilian cities.Results. A total of 3,591 patients were studied, 56% female, average age21.2±11.7years, with a median duration of diabetes9.6±8.1years. Blood pressure levels were available for a total of 3,323 patients and 689 (19.2%) patients were hypertensive. Hypertensive patients were older, exhibited longer duration of diabetes, and had higher body mass index (BMI), total cholesterol, triglycerides, and LDL-C values (P<0.001, for all comparisons), but only 370 (53.7%) received treatment. Patient awareness of hypertension was documented in 453 (65.5%) patients. However, only 76 (22.9%) of the treated patients attained the target systolic (sBP) and diastolic blood pressures (dBP).Conclusions. Our results demonstrate that a large number of T1D patients with hypertension do not receive appropriate treatment; few of the treated T1D patients achieved the target sBP and dBP values. Greater attention should be paid to blood pressure evaluation, hypertension diagnosis, and treatment of T1D patients in Brazil.

OBJETIVO: Avaliar o risco cardiovascular (RCV) em pacientes com diabetes tipo 2 (DM2) de acordo com os critérios de Framingham, e sua associação com outros fatores não incluídos no escore de Framingham. DESENHO DO ESTUDO E MÉTODOS: Foram avaliados, em corte transverso, 333 pacientes DM2 (215 do sexo feminino) com média de idade de 59,6 ± 9,7 anos, acompanhados no Serviço de Diabetes e Metabologia do HUPE no período de março de 2004 a fevereiro de 2005. A duração conhecida do diabetes foi de 12 (0 a 43) anos. Foi aplicado o escore de Framingham em todos os pacientes para determinação do risco de morte por doença coronariana. Os pacientes foram estratificados em grupos quanto ao RCV em 10 anos: < 20% e > 20% de probabilidade de apresentar um evento CV. RESULTADOS: O RCV, em 10 anos na amostra estudada, foi de 18,7 ± 10,8%, sendo maior no sexo masculino do que no feminino [20% (253) vs. 15% (127), p< 0,001]. A prevalência de risco > 20% do escore de Framingham foi maior no sexo masculino (55,1%) do que no feminino (38,6%) (p= 0,003). O RCV foi correlacionado à duração conhecida do DM, níveis de triglicerídeos (TGs), creatinina, glicemia pós-prandial e circunferência abdominal (CA). Houve associação do RCV com a CA, pela classificação da IDF (International Diabetes Federation) (p< 0,001) e Organização Mundial de Saúde (OMS) (p= 0,003). Na regressão múltipla em stepwise, encontramos correlação significativa e independente do RCV com as seguintes variáveis: sexo masculino, duração conhecida do DM, creatinina plasmática, CA e TGs (p< 0,001). CONCLUSÕES: A população diabética estudada apresentou alto risco para eventos cardiovasculares segundo os critérios de Framingham, principalmente os pacientes do sexo masculino. Considerando-se o elevado custo das investigações cardiológicas para o sistema de saúde público, estudos posteriores poderão ratificar se a aplicação rotineira deste escore, prático e não-invasivo, permitiria um melhor direcionamento na solicitação destas investigações. Isto poderia resultar na adoção de medidas de intervenção mais precoces e intensivas nos pacientes, no sentido de reduzir ou controlar o risco coronariano. OBJECTIVE: The aim of our study was to evaluate cardiovascular risk (CR) in type 2 diabetic (T2DM) patients according to Framingham criteria and its possible relationship with other risk factors not included in the Framingham score. PATIENTS AND METHODS: We evaluated 333 T2DM outpatients (215 females), aged 56.9 ± 9.7 years followed regularly from March 2004 to February 2005 in the Diabetes Unit in our Universitary Hospital. The known diabetes duration was 12 (043) years. In order to determinate the risk of death from coronary artery disease (CAD), we applied the Framingham score. Patients were classified in two groups, according to their probability of having a cardiovascular event in ten years: < 20% and > 20%. We intended to establish a correlation between the CR verified in this population and other variables probably related to CR not included on Framingham score. RESULTS: The CR in ten years was 18.7 ± 10.8% in the whole population, being higher in male than female [20% (253) vs. 15% (127); p< 0.001]. Fifty five percent of males and 38.6% of females had a CR > 20% according to Framingham score (p= 0.003). The CR was related to diabetes duration, triglycerides (TG), creatinine and 2-hour postprandial plasma glucose (2G) levels and abdominal circumference (AC) either according to International Diabetes Federation (p< 0.001) or World Health Organization (p= 0.003) criteria. In the stepwise multivariate analyses we found an independent and significant correlation of CR with the following variables: gender (male), diabetes duration, plasma creatinine levels, AC and TG (p< 0.001). CONCLUSION: Our T2DM patients represent a high-risk population for cardiovascular events according to the Framingham score, mainly males. Routine use of Framingham score, which is feasible and noninvasive, could identify such patients and institute precocious and intensive measures in order to reduce their cardiovascular risk.

article i nfo Objective: The objective of this study is to investigate the influence of the day-to-day variability of the measures of heart rate variability (HRV) on the sample size calculation for the study of cardiac autonomic neuropathy. Material and methods: We analyzed HRV in the frequency domain (very low (VLF), low (LF), and high frequency (HF) bands) and in the time domain (the root mean squared of successive RR intervals differences (RMSSD); the mean RR intervals (RRNN); the standard deviation of RR intervals (SDNN) and the coefficient of variation (CV)) during a 5-min electrocardiogram record. We also analyzed the heart rate response to deep breathing (expiration:inspiration ratio), to the Valsalva maneuver and to standing (maximum:minimum ratio) and the blood pressure response to standing. The day-to-day variability was assessed by calculating the within-subject standard deviations (WSSD), limits of agreement, typical errors and the ratio of the WSSD to the mean values obtained on days 1 and 2 (WSSD/GM). Results: Sixty-seven healthy subjects (45 females), aged 27 (19-39) years, were recruited. The RMSSD, CV, VLF, LF, HF and blood pressure response to standing showed marked variability (WSDD/GM (%) = 237.7, 455.1, 69.9, 126.5, 81.3 and 380.5, respectively), while the RRNN, SDNN, Valsalva, expiration:inspiration and maximum:minimum ratio showed less variability (WSSD/GM (%) = 6.4, 24.5, 18.6, 11.0 and 14.1, respectively). The minimum differ- ences expected to be statistically significant for the autonomic measurements were calculated. Conclusion: Some tests that assess HRV showed adequate reproducibility. This study allows the determination of a sample size calculation for longitudinal or drug-testing studies.

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