Podocytopathies associated with familial partial lipodystrophy due to LMNA variants: report of two cases

SUMMARY Lipodystrophies are characterized by complete or selective loss of adipose tissue and can be acquired or inherited. Familial partial lipodystrophy (FPLD) is a hereditary lipodystrophy commonly caused by mutations in the LMNA gene. Herein, we report two cases of FPLD associated with podocytopathies. Patient 1 was diagnosed with FPLD associated with the heterozygous p.Arg482Trp variant in LMNA and had normal glucose tolerance and hyperinsulinemia. During follow-up, she developed nephrotic-range proteinuria. Renal biopsy was consistent with minimal change disease. Patient 2 was diagnosed with FPLD associated with a de novo heterozygous p.Arg349Trp variant in LMNA. Microalbuminuria progressed to macroalbuminuria within 6 years and to nephrotic range proteinuria in the last year. He remained without diabetes and with hyperinsulinemia. Renal biopsy revealed focal segmental glomerulosclerosis not otherwise specified. This report provides further evidence of variable features of lipodystrophy associated with LMNA variants and the importance of long-term follow-up with evaluation of kidney dysfunction.

Association between neck circumference and glucose tolerance levels at 2-6 months postpartum in women with and without gestational diabetes

ABSTRACT Objective: To evaluate the association between neck circumference (NC) measured during pregnancy and markers of glucose metabolism measured 2-6 months postpartum in women with overweight/obesity with and without gestational diabetes (GDM). Subjects and methods: This prospective study enrolled 100 pregnant women (including 50 with GDM) with pregestational body mass index (BMI) ≥ 25 kg and < 40 kg/m². The cohort was stratified according to NC tertiles during pregnancy. Glucose metabolism was assessed in the postpartum period. The association between NC during pregnancy and markers of glucose metabolism postpartum was tested using linear regression analysis. Results: Participants with NC in the third tertile, compared with those with NC in the second and first tertiles, had higher levels of glycated hemoglobin (HbA1c; 5.6 ± 0.4% versus 5.4 ± 0.3% versus 5.3 ± 0.2%, respectively, p = 0.006), fasting insulin (13.2 ± 6.6 µIU/mL versus 11.1 ± 5.8 µIU/mL versus 9.5 ± 4.9 µIU/mL, respectively, p = 0.035), homeostasis model for insulin resistance (HOMA-IR; 3.1 ± 1.7 versus 2.5 ± 1.3 versus 2.1 ± 1.2, respectively, p = 0.035) and triglyceride-glucose index (TyG; 4.6 ± 0.2 versus 4.5 ± 0.2 versus 4.5 ± 0.3, respectively, p = 0.010). In crude linear regression analysis, NC measured during pregnancy was significantly associated with levels of fasting plasma glucose, 2-hour glucose, HbA1c, log HOMA-IR, and TyG index. The association remained after adjustment for age, family history of diabetes, and number of pregnancies. When adjusted for pregestational BMI and gestational weight gain, NC remained independently associated with fasting plasma glucose and HbA1c levels. Conclusion: The NC measured during pregnancy was positively associated with worse glucose metabolic profile in the postpartum among women with obesity/overweight with and without GDM. The NC measurement may be a feasible tool for early identification of women at a higher risk of developing type 2 diabetes mellitus.

Maternal-fetal outcomes of pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections during pregnancy - A Brazilian health care referral center cohort study

ABSTRACT Objective: Pregnant women with type 1 diabetes (T1D) have an increased risk of maternal-fetal complications. Regarding treatment, continuous subcutaneous insulin infusion (CSII) has advantages compared to multiple daily injections (MDI), but data about the best option during pregnancy are limited. This study's aim was to compare maternal-fetal outcomes among T1D patients treated with CSII or MDI during pregnancy. Subjects and methods: This study evaluated 174 pregnancies of T1D patients. Variables of interest were compared between the groups (CSII versus MDI), and logistic regression analysis was performed (p < 0.05). Results: Of the 174 included pregnancies, CSII was used in 21.3% (37) and MDI were used in 78.7% (137). HbA1c values improved throughout gestation in both groups, with no difference in the first and third trimesters. The frequency of cesarean section was significantly higher in the CSII group [94.1 vs. 75.4%, p = 0.017], but there was no significant difference in the frequency of other complications, such as miscarriage, premature delivery and preeclampsia. The mean birth weight and occurrence of neonatal complications were also similar, except for the proportion of congenital malformations, which was significantly lower in the CSII group [2.9 vs. 15.6%, p = 0.048]. In regression analysis, the association of CSII with cesarean section and malformations lost significance after adjusting for HbA1c and other covariates of interest. Conclusion: In this study, we observed a higher frequency of cesarean section and a lower occurrence of congenital malformations in the CSII group, but the adjusted results might indicate that these associations are influenced by glycemic control.

Neck circumference as a predictor of gestational diabetes and risk of adverse outcomes in pregnancy of Brazilian woman with overweight and obesity

ABSTRACT Objective: To evaluate the association of neck circumference (NC) with gestational diabetes (GDM) and adverse outcomes in women with overweight and obesity. Subjects and methods: This prospective study included 132 (BMI > 25 kg/m2) pregnant women without and with GDM. Standardized questionnaire and biochemical/physical evaluation were performed during the 1st to 3rd trimester. Fifth-five women were evaluated regarding hypertension in pregnancy, type of delivery and neonatal complications (death, intensive care unit admission and hypoglycemia). Results: Women with (n = 61) and without (n = 71) GDM had similar mean (SD) pre-gestational BMI [30.3 (4.0) vs. 29.4 (3.5) kg/m2, p = 0.16]. Women with GDM were older [32 (6) vs. 28 (6) yrs, p < 0.001] and had greater NC [36.0 (2.7) vs. 34.5 (1.8) cm, p < 0.001]. NC was similar in women with GDM diagnosed in first or third trimester [p = 0.4] and was correlated with FPG [r 0.29, p = 0.01] and systolic [r 0.28, p = 0.001] and diastolic [r 0.25, p = 0.004] blood pressure. NC was associated with GDM [OR 1.25, 95%CI 1.03-1.52] adjusted for age, physical activity, education and familiar history of diabetes. In ROC analysis, the area under the curve was 0.655 and the cut-off value of 34.5 cm had 0.70 of sensitivity and 0.51 of specificity for GDM. Women who had NC ≥ 34.5 vs. < 34.5 cm had higher frequencies of hypertension [32.3 vs. 4.2%, p = 0.01]. Conclusions: In a group of pregnant women with overweight or obesity, NC can be a useful tool for identifying risk of GDM and obstetric adverse outcomes.

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

ABSTRACT Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Materials and methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 x 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusions: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.

Relationship between short and long-term glycemic variability and oxidative stress in type 1 diabetes mellitus under daily life insulin treatment

ABSTRACT Objectives: The purpose of this study was to investigate the heterogeneity of the association between glycemic variability and oxidative stress markers in T1DM patients under daily life insulin treatment. Subjects and methods: We studied, in a cross-sectional analysis, 76 T1DM patients without clinical chronic diabetes complications and 22 healthy individuals. Were evaluated the short-term glycemic variability (STGV), long-term glycemic variability (LTGV), oxidative stress markers [8-isoprostaglandin-F2α (Ur-8-iso-PGF2α), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and erythrocytes reduced/oxidized glutathione (GSH/GSSG)] and biochemical dosages (glycaemia, HbA1c, lipidogram, albuminuria). Results: Plasmatic NO was positively associated with LTGV (last year average of HbA1c) (8.7 ± 1.6% or 71 ± 18 mmol) (rS: 0.278; p: 0.042). Plasmatic TBARS, erythrocytes GSH/GSSH and Ur-8-iso-PGF-2α didn't show correlation with glycemic variability. GSH/GSSG was inversely correlated with LDL-cholesterol (rS: - 0.417; p: 0.047) and triglycerides (rS: −0.521; p: 0.013). Albuminuria was positive correlated with age (rS: 0.340; p: 0.002), plasmatic NO (rS: 0.267; p 0.049) and TBARS (rS: 0.327; p: 0.015). Conclusion: In daily life insulin treatment, young T1DM patients have higher plasmatic NO than healthy subjects. However, the correlation between glycemic variability and oxidative stress markers is heterogeneous. Lipid profile and albuminuria are associated with different oxidative stress markers. These data collaborate to explain the controversial results in this issue.

Serum leveis of inflammatory markers in type 2 diabetes patients with chronic periodontitis

Diabetes has been associated with periodontitis, but the mechanisms through which periodontal diseases affect the metabolic control remain unclear. Objective: This study aimed to evaluate serum leveis of inflammatory markers, IL-8, IL-6 and monocyte chemoattractant protein 1 (MCP-1), in type 2 diabetic patients in the presence of chronic periodontitis. Material and Methods: Forty two individuals were enrolled in this study and assigned to one of five groups: diabetes mellitus with inadequate glycemic control and periodontitis (DMI+P, n = 10), diabetes mellitus with adequate glycemic control and periodontitis (DMA+P, n = 10), diabetes mellitus without periodontitis (DM, n = 10), periodontitis without diabetes (P, n=6), and neither diabetes nor periodontitis (H, n = 6). Periodontal clinical examination included visible plaque index (PL), gingival bleeding index (GB), probing depth (PD), attachment level (AL) and bleeding on probing (BP). Glycemic control was evaluated by serum concentration of glycated hemoglobin (HbAlc). Inflammatory serum markers IL-8, IL-6 and (MCP-1) were measured by ELISA. Results: DMI+P and DMA+P groups presented higher PD (p=0.025) and AL (p=0.003) values when compared to the P group. There were no significant differences among groups for IL-6, IL-8 and MCP-1 serum levels. Conclusions: Although periodontitis was more severe in diabetic patients, the serum levels of the investigated inflammatory markers did not differ among the groups. .

Vitamin D and diabetes mellitus: an update 2013 / Vitamin D e diabetes melito: uma atualização 2013

Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association of vitamin D deficiency and increased risk of chronic diseases, such as cancer, cardiovascular disease, type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-α-hydroxilase expression in pancreatic beta cells, in cells of the immune system, and in various others tissues, besides the bone system support the role of vitamin D in the pathogenesis of type 2 diabetes. Observational studies have revealed an association between 25(OH) D deficiency and the prevalence of type 1 diabetes in children and adolescents. This review will focus on the concept of vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk of diabetes mellitus and cardiovascular diseases.

A deficiência de vitamina D e o diabetes melito são enfermidades comuns na população e são altamente prevalentes em todas as raças, idades, regiões geográficas e situação socioeconômica. Estudos epidemiológicos mostram uma associação entre hipovitaminose D com o aumento do risco de doenças crônicas, tais como câncer, doença cardiovascular, diabetes melito do tipo 2 e doenças autoimunes como a esclerose múltipla e o diabetes mellitus do tipo 1. A identificação de receptores da 1,25(OH)2 D e da expressão da 1 α-hidroxilase nas células betapancreáticas, em células do sistema imunológico e em uma variedade de células do organismo além do tecido ósseo, suporta o papel da vitamina D na patogênese do diabetes tipo 2 e do tipo 1. Esta revisão apresenta e discute o conceito de deficiência de vitamina D, sua prevalência e seu papel na patogênese e no risco de desenvolvimento do diabetes melito e doenças cardiovasculares.

Optimal cutoff points for body mass index, waist circumference and HOMA-IR to identify a cluster of cardiometabolic abnormalities in normal glucose-tolerant Brazilian children and adolescents / Valores de corte ótimos do índice de massa corporal, circunferência abdominal e HOMA-IR para a identificação de um conjunto de anormalidades cardiometabólicas em crianças e adolescentes brasileiros com tolerância normal à glicose

OBJECTIVE: The aim of this study was to establish the best cutoff values for waist circumference (WC), body mass index (BMI) and HOMA-IR (HR) to identify a cluster (> 3) of cardiovascular risk factors (CVRF) in normal glucose-tolerant (NGT) Brazilian children and adolescents. SUBJECTS AND METHODS: Cross-sectional study of 319 individuals (aged 10 to 19y) from a southern Brazilian city. Gender-specific receiver-operating characteristics (ROC) curves were constructed to assess cutoffs values of BMI (kg/m², WC (cm), and HR. RESULTS: The areas under the ROC curves to detect a cluster of CVRF were 0.92, 0.93 and 0.68 (females), and 0.93, 0.93 and 0.89 (males), for WC, BMI and HR, respectively. The cutoff values were 83.0 and 80.5 cm (WC), 22.7 and 20.4 kg/m2 (BMI), and 1.65 and 1.95 (HR), for females and males, respectively, to detect the cluster of CVRF. CONCLUSION: These values of BMI, WC-) and (HR) detected a high proportion of NGTt Brazilian children and adolescents with a cluster of CVRF.

OBJETIVO: O objetivo deste estudo foi estabelecer os melhores valores de corte para circunferência abdominal (CA), índice de massa corpórea (IMC) e HOMA-IR (HR) para identificação da concomitância de um conjunto de fatores de risco cardiovascular (> 3) em crianças e adolescentes brasileiros com tolerância normal à glicose (TNG). SUJEITOS E MÉTODOS: Estudo transversal realizado em uma cidade do sudeste do Brasil com 319 indivíduos de 10 a 19 anos de idade. Curva ROC para cada gênero foi utilizada para estabelecimento dos valores de IMC (kg/m²), CA (cm) e HRR. RESULTADOS: As áreas sob as curvas ROC para detectar o conjunto de fatores cardiovascular foram 0,92, 0,93 e 0,68 (meninas) e 0,93, 0,93 e 0,89 (meninos) para CA, IMC e HR, respectivamente. Os valores de corte foram 83,0 e 80,5 cm (CA), 22,7 e 20,4 kg/m² (IMC) e 1,65 e 1,95 (HR), para meninas e meninos, respectivamente, para detecção do grupo de fatores de risco cardiovascular. CONCLUSÃO: Esses valores de IMC,CA e HR detectaram uma porcentagem significativa de crianças e adolescentes brasileiros com TNG e elevado risco cardiovascular.

Heterogeneidade clínica e coexistência das neuropatias diabéticas: diferenças e semelhanças entre diabetes melito tipos 1 e 2 / Clinical heterogeneity and coexistence of diabetic neuropathies: difference and similarities between types 1 and 2 diabetes mellitus

OBJETIVO: Estudar a heterogeneidade e a coexistência das neuropatias no diabetes melito tipos 1 (DMT1) e 2 (DMT2). MÉTODOS: Foram avaliados 74 DMT2 e 20 DMT1 em relação à idade (anos), tempo de diagnóstico do DM (TDDM, em anos), índice de massa corpórea (IMC, kg/m²), HbA1c e tipo de neuropatia (critérios da American Diabetes Association). RESULTADOS: DMT1 era mais jovem (32,7 ± 11 versus 56,9 ± 10,3; p = 0,0001), com maior TDDM (17,1 ± 9,7 versus 10,4 ± 6,8; p = 0,003) e menor IMC (23,6 ± 3,8 versus 28,4 ± 5,3; p = 0,0005). A neuropatia autonômica cardiovascular (NAC) (60 por cento versus 32,4 por cento; p = 0,02) e a coexistência desta com polineuropatia (PND) (62,5 por cento versus 33,3 por cento; p = 0,03) foram mais prevalentes no DMT1; a PND dolorosa crônica (PNDDC) (60,8 por cento versus 30,0 por cento; p = 0,009) o foi no DMT2. A HbA1c (p = 0,04) foi preditiva de PND em ambos os grupos. O TDDM (p = 0,03) e a PNDDC (p = 0,003) foram preditivos de NAC no DMT1. A idade (p = 0,0004) teve valor preditivo para PNDDC no DMT2. CONCLUSÕES: As neuropatias apresentam distribuição heterogênea no DMT1 e no DMT2. Com exceção do controle glicêmico, os fatores relacionados a essa complicação diferem de acordo com o tipo de diabetes.

OBJECTIVE: To evaluate the heterogeneity and the coexistence of diabetic neuropathy (DNP) in type 1 (T1DM) and 2 (T2DM) diabetes mellitus. METHODS: 74 T2DM and 20 T1DM patients were evaluated according to age (years), time from diagnosis of diabetes (TDD, years), body mass index (BMI, kg/m²), HbA1c and DNP type (American Diabetes Association criteria). RESULTS: T1DM was younger (32.7 ± 11.0 versus 56.9 ± 10.3; p = 0.0001), leaner (BMI: 23.6 ± 3.85 versus 28.4 ± 5.3; p = 0.0005) and they had longer TDD (17.1 ± 9.7 versus 10.4 ± 6.8; p = 0.003). Cardiovascular autonomic neuropathy (CAN) (60 percent versus 32.4 percent; p = 0.02) and its coexistence with polyneuropathy (PN) (62.5 percent versus 33.3 percent; p = 0.03) were more common in T1DM. Chronic painful polyneuropathy (CPP) was more prevalent in T2DM (60.8 percent versus 30.0 percent; p = 0.009). Logistic regression showed HbA1c as an independent variable related to PN (p = 0.04) in both groups. TDD (p = 0.03) and CPP (p = 0.003) were related to CAN in T1DM. Age (p = 0.0004) was related to CPP in T2DM. CONCLUSIONS: The DNP have shown a heterogeneity distribution in type 1 and type 2 diabetes mellitus. The related factors to different phenotypes of this complication, apart from hyperglycemia, may be variable between these two types of diabetes mellitus.

Efeito da freqüência do exercício físico no controle glicêmico e composição corporal de diabéticos tipo 2 / El efecto de la frecuencia del ejercicio físico en el control glucémico y composición corporal de diabéticos tipo 2 / Effect of frequency of physical exercise on glycemic control and body composition in type 2 diabetic patients

FUNDAMENTO: O diabete e a doença cardiovascular emergiram como ameaças principais à saúde humana, e o risco está aumentado nos indivíduos com obesidade visceral. É consenso que o exercício físico deve fazer parte do tratamento do diabete melito (DM). OBJETIVO: Comparar a influência de programas de exercício físico orientados e estruturados (PEOE) com freqüência de três e cinco vezes por semana, no período de 20 semanas, no controle glicêmico e composição corporal de diabéticos tipo 2 (DM2). MÉTODOS: A pesquisa realizou-se na Universidade Federal de São Paulo. Grupo Controle (GC), n=17, idade (Mi: 55,8 anos), recebeu incentivo, na consulta médica, para o exercício físico. Grupo 3x (G3), n=14, idade (Mi: 57,4 anos), uma hora de exercício físico, 3x/semana. Grupo 5x (G5), n=9, idade (Mi: 58,8 anos), mesmo protocolo, mas 5x/semana. Tempo de diagnóstico: Mi: 5 anos, em todos os grupos. Aula constava de 5 min aquecimento, 30 min caminhada (esteira) a 70 por cento da freqüência cardíaca máxima e 10 min relaxamento. IMC, cintura, porcentual de gordura (PG), glicemia capilar (Gcap), glicemia de jejum (GJ), hemoglobina glicada (HbA1c) foram avaliados. RESULTADOS: Realizou-se uma comparação entre o instante Basal (B) e 20ª semana (20ª). IMC no G3(B: 29,5±2,9 vs 20ª: 28,3±2,2 kg/m², p=0,005) e G5 (B: 29,7±4,4 vs 20ª: 29,1±4,3 kg/m², p=0,025); cintura G5 (B: 100,5±11,9 vs 20ª: 933±11,7 cm, p=0,001); PG no G3 (B: 31±5,1 vs 20ª: 26±5 por cento, p=0,001) e G5 (B: 32,4±5,4 vs 20ª: 30,3±6,9 por cento, p=0,001); GJ, G5 (B: 150,8±47,5 vs 20ª: 109,2±30,5 mg/dl, p=0,034), apresentaram diferenças estatisticamente significativas. GC não apresentou diferenças estatisticamente significativas, nessas variáveis. Gcap apresentou uma tendência de queda no pós-exercício físico no G5. HbA1c não apresentou diferenças estatisticamente significativas nos três grupos. CONCLUSÃO: O G5 foi melhor que o G3, na maioria dos parâmetros avaliados. Porém, os resultados não apresentaram...

BACKGROUND: Diabetes and cardiovascular disease have emerged as key threats to human health, and the risk is increased in individuals with visceral obesity. The consensus is that physical exercise should be part of the treatment of diabetes mellitus (DM). OBJECTIVE: To compare the influence of guided and structured physical exercise programs (SPEP), three to five times per week, during a period of 20 weeks, on glycemic control and body composition of type 2 diabetic patients (DM2). METHODS: The research was conducted at the Universidade Federal de São Paulo (Federal University School of Medicine in São Paulo). At the clinical visit, patients from the Control Group (CG) n=17, mean age 55.8 years, were encouraged to engage in a physical exercise program. Patients from Group 3x (G3), n=14, mean age 57.4 years, were to engage in 1 hour of physical exercise, 3x/week, and Group 5x (G5), n=9, mean age 58.8 years, followed the same protocol but 5x/week. Mean of 5 years since diagnosis in all groups. Classes consisted of a 5-minute warm-up, 30-minute treadmill walk at 70 percent of maximum heart rate, and 10-minute relaxation. BMI, abdominal circumference (AC), percentage of body fat (BF), capillary glycemia (CG), fasting glycemia (FG), and glycated hemoglobin (HbA1c) were assessed. RESULTS: A comparison was made between the baseline time point (B) and the 20th week (20th). BMI in G3 (B:29.5±2.9 vs. 20th: 28.3 ± 2.2 Kg/sqm, p=0.005) and G5 (B:29.7±4.4 vs. 20th: 29.1 ± 4.3 Kg/sqm, p=0.025); abdominal circumference in G5 (B:100.5±11.9 vs. 20th: 933 ± 11.7 cm, p=0.001); BF in G3 (B:31±5.1 vs 20th: 26±5 percent, p=0.001) and G5 (B:32.4 ± 5.4 vs. 20th: 30.3 ± 6.9 percent, p=0.001); FG, G5 (B:150.8 ± 47.5 vs. 20th: 109.2± 30.5 mg/dL, p=0.034), showed statistically significant differences. CG did not show statistically significant differences for these variables. CG showed a tendency to drop after physical exercise in G5. HbA1c showed no statistically...

FUNDAMENTO: La diabetes y la enfermedad cardiovascular surgieron como principales amenazas a la salud humana, y el riesgo crece en los individuos con obesidad visceral. Es un consenso que el ejercicio físico debe formar parte del tratamiento de la diabetes mellitus (DM). OBJETIVO: Comparar la influencia de programas de ejercicio físico orientados y estructurados (PEOE) con frecuencia de tres y cinco veces por semana, en el período de 20 semanas, en el control glucémico y la composición corporal de diabéticos tipo 2 (DM2). MÉTODOS: La investigación se realizó en la Universidad Federal de São Paulo. Grupo Control (GC), n=17, edad (edad promedio (EP): 55,8 años), recibió incentivo en la consulta médica para la realización de ejercicio físico. Grupo 3x (G3), n=14, edad (EP: 57,4 años), una hora de ejercicio físico, 3x/semana. Grupo 5x (G5), n=9, edad (EP: 58,8 años), mismo protocolo, pero 5x/semana. Tiempo de diagnóstico: EP: 5 años, en todos los grupos. La clase constaba de 5 min calentamiento, 30 min caminata en estera rodante hasta el 70 por ciento de la frecuencia cardiaca máxima y 10 min relajamiento. Se analizó IMC, cintura, porcentual de grasa (PG), glucemia capilar (GCap), glucemia de ayuno (GA), hemoglobina glucosilada (HbA1c). RESULTADOS: Se realizó una comparación entre el instante Basal (B) y la 20ª semana (20ª). Presentaron diferencias estadísticamente significativas: IMC en el G3(B: 29,5±2,9 vs 20ª: 28,3±2,2 kg/m², p=0,005) y el G5 (B: 29,7±4,4 vs 20ª: 29,1±4,3 kg/m², p=0,025); cintura G5 (B: 100,5±11,9 vs 20ª: 933±11,7 cm, p=0,001); PG en el G3 (B: 31±5,1 vs 20ª: 26±5 por ciento, p=0,001) y G5 (B: 32,4±5,4 vs 20ª: 30,3±6,9 por ciento, p=0,001); GA, G5 (B: 150,8±47,5 vs 20ª: 109,2±30,5 mg/dl, p=0,034). El GC no presentó diferencias estadísticamente significativas, en estas variables. La GCap presentó una tendencia de caída en el post ejercicio físico en G5. La HbA1c no presentó diferencias estadísticamente significativas en...

Neuropatia autonômica cardiovascular diabética: fatores de risco, impacto clínico e diagnóstico precoce / Diabetic cardiovascular autonomic neuropathy: risk factors, clinical impact and early diagnosis

A neuropatia autonômica cardiovascular (NAC) constitui uma das complicações de maior repercussão clínica do diabete melito (DM) e, ao mesmo tempo, está entre as menos diagnosticadas. Nesta revisão, são discutidos os principais fatores de risco para o desenvolvimento e a progressão da NAC nos pacientes com DM, a história natural da neuropatia autonômica e seu impacto na doença cardiovascular do DM, bem como os testes para o diagnóstico precoce e o estadiamento da NAC na prática clínica. A pesquisa bibliográfica teve como base dois bancos de dados: Medline e Tripdatabase, com os seguintes descritores: diabetic cardiovascular autonomic neuropathy e cardiovascular autonomic neuropathy and diabetes. Os artigos de 1998 a 2007 em inglês e alemão foram selecionados. A NAC em estágios iniciais (precoce e intermediária) pode ser diagnosticada e revertida, porém, nos casos avançados (estágio grave), resta apenas o tratamento sintomático. A NAC está associada a um maior índice de morbidade e mortalidade cardiovasculares e pior qualidade de vida nos indivíduos diabéticos

Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus (DM), but one of the least frequently diagnosed. In this review, we discuss the major risk factors for the development and progression of CAN in patients with DM, the natural history of autonomic neuropathy and its impact on cardiovascular disease in DM, as well as the tests for the early diagnosis and staging of CAN in the clinical practice. The bibliographic research was based on two databases: Medline and Tripdatabase, with the following descriptors: diabetic cardiovascular autonomic neuropathy and cardiovascular autonomic neuropathy and diabetes. We selected English and German articles, written between 1998 and 2007. In its initial stages (early and intermediate), CAN may be diagnosed and reversed. However, in advanced cases (severe stage), the only treatment that remains is a symptomatic one. CAN is associated with higher cardiovascular morbidity and mortality rates and poor quality of life in diabetic individuals.

Heterogeneidade do diabetes melito tipo 1 / Heterogeneity of type 1 diabetes mellitus

O diabetes melito tipo 1 (DM1) caracteriza-se pela deficiência de insulina por causa da destruição das células-beta pancreáticas. O DM1 atualmente é classificado em dois subtipos: um auto-imune (DM1A) e outro não auto-imune (DM1B). O DM1A poligênico (isolado ou associado a outras doenças auto-imunes) é a forma mais prevalente. O DM1A pode fazer parte de síndromes raras em virtude de alterações monogênicas [gene regulador da auto-imunidade (AIRE)] e mutações no gene FOX-p3. O DM1B corresponde de 4 por cento a 7 por cento do DM1 e pode incluir formas não clássicas, como o diabetes fulminante e o DATC. Jovens com DM1A e sinais de resistência à insulina associados têm sido denominados de diabetes duplo (DD), tipo 1 e tipo 2. Nessa revisão são discutidas as patofisiologias e as características clínicas das formas raras de DM1A, o DM1B, as formas atípicas de DM1 não auto-imune e as inter-relações entre a inflamação subclínica da obesidade e o processo auto-imune do DM1A no DD. Em resumo, apresentamos o conceito de heterogeneidade do DM1.

Type 1 diabetes (T1D) comprises all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to absolute insulin deficiency. The etiological heterogeneity of T1D has been recognized for the last decades, but it has been divided into only two subtypes so far: autoimmune (T1D)A and non-autoimmune (T1D)B mediated. Polygenic T1DA (isolated or associated to other autoimmune diseases) is the most prevalent type of T1D. T1DA might be part of rare monogenic syndromes related to mutations in the autoimmune regulator gene (AIRE) and FOXp3. Non-autoimmune forms of T1D correspond to approximately 4 to 7 percent of newly diagnosed T1D and include T1DB, as well as other types of atypical diabetes, for example fulminant type 1 diabetes and adult ketosis-prone diabetes. A new expression of diabetes in young with insulin resistance and obesity, along with the presence of pancreatic autoimmunity markers, namely auto-antibodies to islet cell antigens, is called double diabetes (DD), T1DA plus type 2 diabetes. Evidence has been collected concerning the potential effect of obesity-linked cytokines in amplifying the autoimmune response in DD. Therefore all these issues are presented and discussed in this review as the concept of heterogeneity of Type 1 Diabetes.

Obesidade / Obesity

A obesidade é atualmente um dos mais graves problemas de saúde pública. A prevalência da obesidade tem crescido acentuadamente nas últimas décadas, tanto nos países desenvolvidos como nos em desenvolvimento. Estes dados a levaram à condição de epidemia global(1).Os estudos epidemiológicos em populações latino-americanas têm revelado dados preocupantes nesse sentido. Entre as camadas mais pobres da população, à medida que se consegue erradicar a miséria, a obesidade desponta como um problema mais freqüente e mais grave que a desnutrição. É o fenômeno denominado de transição nutricional.Entre as complicações médicas associadas com a obesidade podemos citar as doenças cardiovasculares, hipertensão arterial, dislipidemias, diabetes mellitus, esteatose hepática, calculose de vesícula biliar, osteoartrite e diversos tipos de câncer. Estas doenças são responsáveis por uma demanda crescente no nosso sistema de saúde(2). É provável que 200.000 pessoas morram anualmente em decorrência destas complicações na América Latina.A abordagem atual da obesidade, entretanto, continua produzindo resultados insatisfatórios, em grande parte por estratégias equivocadas e pelo mau uso dos recursos terapêuticos disponíveis. Além da procura de planos terapêuticos mais eficazes, faz-se necessário, também, que sejam adotadas medidas de prevenção para conter a crescente demanda.A obesidade é definida como uma doença crônica que se caracteriza pelo acúmulo excessivo de gordura e comprometimento da saúde. Deve ser considerado que existe diferença na distribuição regional de gordura corpórea(3). O acúmulo de gordura abdominal (gordura visceral) é considerado um fator de risco maior para o desenvolvimento das doenças decorrentes da obesidade(4).Os compartimentos corpóreos sofrem variações fisiológicas em relação á idade e ao sexo. O compartimento aquoso tem uma relação inversa com a idade, já os compartimentos muscular e adiposo apresentam relação direta com a faixa etária. Durante a infância e a adolescência ocorrem as maiores flutuações entre estes compartimentos. É importante lembrar que as diferenças entre os gêneros se acentuam a partir da puberdade, sendo o compartimento adiposo maior na mulher do que no homem(5).

Glycemic control in adult type 1 diabetes patients from a brazilian country city: comparison between a multidisciplinary and a routine endocrinological approach / Controle glicêmico em pacientes adultos com diabetes do tipo 1 em uma cidade brasileira: comparação entre abordagem multidisciplinar e endocrinológica de rotina

OBJECTIVE: To evaluate the metabolic control of a cohort of adult type 1 diabetes mellitus (T1DM) patients assisted in a public Diabetes Center (DC) that follows the rules of a national diabetes society. METHODS: We compared for one year the metabolic control and the characteristics of 175 T1DM patients attended by a multidisciplinary team in a DC (test group) with 30 patients assisted only by endocrinologists at a public endocrinology outpatient center (control group). RESULTS: The test group presented a larger proportion of well-controlled patients (p= 0.002). The proportions (test x control group) were as follows: 51.4 percent x 16.7 percent in the subgroup with A1C < 7 percent; 21.7 percent x 36.7 percent in the subgroup with A1C between 7.1 percent and 8.0 percent; and 26.9 percent x 46.7 percent in the subgroup with A1C > 8 percent. Patients assisted in the DC presented a likelihood 4.38 times higher of reaching levels of A1C up to 7 percent. CONCLUSIONS: This study shows the effectiveness of a DC and emphasizes the importance of education, adherence and multidisciplinarity as cornerstones for the treatment, showing that in developing countries it is possible to treat T1DM with satisfactory results.

OBJETIVO: Avaliar o controle metabólico de uma coorte de pacientes adultos com diabetes do tipo 1 (DM1) atendidos em um Centro de Diabetes (CD) que segue as normas da Sociedade Brasileira de Diabetes. MÉTODOS: Foram comparados o controle glicêmico e as características de 175 pacientes com DM1 atendidos por uma equipe multidisciplinar em um CD (grupo teste) com 30 pacientes assistidos em um ambulatório de endocrinologia geral (grupo controle) durante um ano. RESULTADOS: O grupo teste apresentou uma maior proporção de pacientes bem controlados (p= 0,002). As proporções (grupo teste x grupo controle) foram: 51,4 por cento x 16,7 por cento no subgrupo com A1C < 7 por cento; 21,7 por cento x 36,7 por cento no subgrupo com A1C entre 7,1 por cento e 8,0 por cento; e 26,9 por cento x 46,7 por cento no subgrupo com A1C > 8 por cento. Os pacientes atendidos no CD apresentaram probabilidade 4,38 vezes maior de atingir níveis de A1C até 7 por cento. CONCLUSÃO: O estudo mostra a efetividade do CD e enfatiza a importância da educação, aderência e da multidisciplinaridade como pedras angulares do tratamento, mostrando ser possível tratar o DM1 nos países em desenvolvimento com resultados satisfatórios.

Resistência à insulina e síndrome metabólica no diabetes melito do tipo 1 / Insulin resistance and metabolic syndrome in type 1 diabetes mellitus

A resistência à insulina (RI) pode desempenhar um papel, na história natural do diabetes melito do tipo 1 (DM1), maior do que o habitualmente reconhecido. Nas últimas décadas, este papel se tornou mais evidente com o aumento da obesidade e da diminuição da atividade física nos jovens. Esta revisão tem como objetivo apresentar e discutir a RI nas diferentes fases do DM1, bem como a prevalência da Síndrome Metabólica (SM) nessa condição. O aumento na RI, concomitante a uma diminuição da massa de células beta, pode alterar o equilíbrio entre a sensibilidade à insulina e a secreção de insulina, e precipitar a hiperglicemia nos indivíduos com pré-DM1. A RI poderia refletir uma forma mais agressiva de doença autoimune, mediada por fatores imuno-inflamatórios, comuns a ambos os processos, que também mediassem a destruição das células beta (TNF-alfa e IL-6). Estes conceitos fazem parte da "Hipótese Aceleradora". A história familiar de DM2 e a hiperglicemia crônica (glicotoxicidade), durante a fase clínica do DM1, estão associadas a uma diminuição da captação periférica de glicose. A nefropatia diabética (ND), através da inflamação subclínica e do aumento no estresse oxidativo, contribui para a RI e o desenvolvimento da SM. A prevalência da SM no DM1 varia entre 12 a 40 por cento, sendo mais freqüente nos pacientes com ND e controle glicêmico insatisfatório. Estes achados possuem implicações na terapêutica e no prognóstico cardiovascular dos pacientes com DM1.

Insulin resistance (IR) plays a larger role in the type 1 diabetes mellitus (T1DM) disease process than commonly recognized. Overweight and physical inactivity have increased steadily for the last 20-30 years in children and adolescents in many populations, concurrently with a rising incidence of T1DM. The role of IR in T1DM has only recently been gaining acceptance. This review will focus on how IR influences our current understanding of disease development and metabolic syndrome (MS) in T1DM. Increases in IR by weight gain and sedentarism, associated to decreased beta cell mass by autoimmune process, may disrupt normoglycemia in pre-T1DM individuals. IR may reflect a more aggressive form of autoimmune disease mediated by immuno-inflammatory factors that also mediate beta cell destruction (TNF-alpha and IL-6). These concepts are included in the "accelerator hypothesis". Moreover, family history of T2DM and chronic hyperglycemia (glucotoxicity), occurring after T1DM diagnosis, contribute to decrease peripheral glucose uptake. The onset of diabetic nephropathy (DN) might also contribute to IR and metabolic syndrome (MS) via low-grade inflammation and increased oxidative stress. MS is found between 12 to 40 percent in T1DM, especially in patients with advanced DN and poor glycemic control. These findings have therapeutic and cardiovascular prognostic implications as children make the transition toward adolescence and young adulthood T1DM.