Pragmatic Clinic-Based Investigation of Glycemic Variability in Patients With Type 1 Diabetes in Routine Clinical Practice and Its Association With Cardiovascular Autonomic Neuropathy: A Pilot Study.

OBJECTIVE: To evaluate the relationship between markers of glycemic variability (GV), assessed by blinded continuous glucose monitoring (CGM), and cardiovascular autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D). METHODS: GV indices, such as SD and coefficient of variation were obtained by blinded CGM through an electrode inserted into the subcutaneous tissue for at least 3 consecutive days. CAN was assessed by cardiovascular reflex tests and HRV. RESULTS: Fifteen T1D patients were included: 7 (46.7%) women, aged 47.1 ± 11.6 years, with a diabetes duration of 26 years (20 to 29.5 years). Five patients (25%) were excluded from our study. The majority of our patients presented glycated hemoglobin (60%), SD (86.3%), and coefficient of variation (60%) above the established goals. Patients with defined CAN had a longer diabetes duration, higher glycated hemoglobin levels, lower glomerular filtration rate, lower prevalence of indices related to hypoglycemic stress, and short-term GV indices compared with patients without CAN. CONCLUSION: Our study showed an inverse association between GV and CAN. The most important risk factors associated with CAN were age, diabetes duration, and markers of chronic hyperglycemia. Furthermore, the difficulty in the interpretation of data extracted from the blinded CGM system, which also requires a minimum of 3 capillary blood glucose measurements for calibration, should be carefully analyzed to ensure the accuracy and usefulness of the blinded CGM system as a tool for diabetes management in developing countries. Further studies are necessary to establish the role of GV in the development of CAN in patients with T1D.

Reproducibility of methods used for the assessment of autonomous nervous system's function.

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 differences 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.

Regional differences in clinical care among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group.

BACKGROUND: To determine the characteristics of clinical care offered to type 1 diabetic patients across the four distinct regions of Brazil, with geographic and contrasting socioeconomic differences. Glycemic control, prevalence of cardiovascular risk factors, screening for chronic complications and the frequency that the recommended treatment goals were met using the American Diabetes Association guidelines were evaluated. METHODS: This was a cross-sectional, multicenter study conducted from December 2008 to December 2010 in 28 secondary and tertiary care public clinics in 20 Brazilian cities in north/northeast, mid-west, southeast and south regions. The data were obtained from 3,591 patients (56.0% females and 57.1% Caucasians) aged 21.2 ± 11.7 years with a disease duration of 9.6 ± 8.1 years (<1 to 50 years). RESULTS: Overall, 18.4% patients had HbA1c levels <7.0%, and 47.5% patients had HbA1c levels ≥ 9%. HbA1c levels were associated with lower economic status, female gender, age and the daily frequency of self-blood glucose monitoring (SBGM) but not with insulin regimen and geographic region. Hypertension was more frequent in the mid-west (32%) and north/northeast (25%) than in the southeast (19%) and south (17%) regions (p<0.001). More patients from the southeast region achieved LDL cholesterol goals and were treated with statins (p<0.001). Fewer patients from the north/northeast and mid-west regions were screened for retinopathy and nephropathy, compared with patients from the south and southeast. Patients from the south/southeast regions had more intensive insulin regimens than patients from the north/northeast and mid-west regions (p<0.001). The most common insulin therapy combination was intermediate-acting with regular human insulin, mainly in the north/northeast region (p<0.001). The combination of insulin glargine with lispro and glulisine was more frequently used in the mid-west region (p<0.001). Patients from the north/northeast region were younger, non-Caucasian, from lower economic status, used less continuous subcutaneous insulin infusion, performed less SBGM and were less overweight/obese (p<0.001). CONCLUSIONS: A majority of patients, mainly in the north/northeast and mid-west regions, did not meet metabolic control goals and were not screened for diabetes-related chronic complications. These results should guide governmental health policy decisions, specific to each geographic region, to improve diabetes care and decrease the negative impact diabetes has on the public health system.

[Evaluation of cardiovascular risk according to Framingham criteria in patients with type 2 diabetes]. / Avaliação do risco cardiovascular segundo os critérios de Framingham em pacientes com diabetes tipo 2.

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 University Hospital. The known diabetes duration was 12 (0-43) 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%. 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% (2-53) vs. 15% (1-27); 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.

[Early infancy onset of type 1A diabetes mellitus in dizygotic twins: association with genetic and environmental factors]. / Diabetes melito do tipo 1A na primeira infância de gêmeos dizigóticos: associação entre fatores genéticos e ambientais.

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.

Avaliação do risco cardiovascular segundo os critérios de Framingham em pacientes com diabetes tipo 2 / Evaluation of cardiovascular risk according to Framingham criteria in patients with type 2 diabetes

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 por cento e > 20 por cento de probabilidade de apresentar um evento CV. RESULTADOS: O RCV, em 10 anos na amostra estudada, foi de 18,7 ± 10,8 por cento, sendo maior no sexo masculino do que no feminino [20 por cento (2­53) vs. 15 por cento (1­27), p< 0,001]. A prevalência de risco > 20 por cento do escore de Framingham foi maior no sexo masculino (55,1 por cento) do que no feminino (38,6 por cento) (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...

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 percent and > 20 percent. 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 percent in the whole population, being higher in male than female [20 percent (2­53) vs. 15 percent (1­27); p< 0.001]. Fifty five percent of males and 38.6 percent of females had a CR > 20 percent 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...

Diabetes melito do tipo 1A na primeira infância de gêmeos dizigóticos: associação entre fatores genéticos e ambientais / Early infancy onset of type 1A diabetes mellitus in dizygotic twins: association with genetic and environmental factors

O Diabetes Mellitus tipo 1A diagnosticado antes do 1° 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 por cento 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 2° 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 por cento, assumem risco equivalente a monozigóticos (de 40 por cento) 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 percent 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 percent, they assume the equivalent risk as monozygotic (40 percent) 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.