Tratamento Medicamentoso da Hiperglicemia no Diabetes Melito Tipo 2

O diabetes melito tipo 2 (DM2) decorre de alteração na ação e secreção de insulina. A longo prazo, a elevação da glicemia promove dano microvascular, neuropatia e dano macrovascular, com consequente aumento da morbi-mortalidade destes pacientes. Nas últimas décadas, diversos ensaios clínicos clássicos demonstraram que intervenções terapêuticas específicas para corrigir a hiperglicemia e hipertensão arterial são capazes de prevenir ou retardar o avanço das complicações crônicas. Neste sentido, tratamento efetivo e da forma mais precoce possível deve ser oferecido a todos os pacientes com DM2. Fármacos antiobesidade e agentes orais, como a metformina, sulfonilureias, glinidas, tiazolidinedionas, inibidores da alfa-glicosidase, e os mais recentes fármacos incretinomiméticos e amilinomiméticos são apresentados nessa revisão, nos aspectos de mecanismos de ação, efeitos colaterais e contraindicações

Low-dose aspirin does not affect the renal function of microalbuminuric type 2 Diabetic patients

BACKGROUND: Low-grade inflammation has been implicated in the pathogenesis of diabetic nephropathy, and anti-inflammatory drugs could be potentially useful as a therapeutic tool. The aim of this study was to analyze the effect of low-dose aspirin (300 mg/d) on urinary albumin excretion (UAE) and glomerular filtration rate (GFR) levels of microalbuminuric type 2 DM patients.METHODS: In this randomized, double-blind, crossover, placebo-controlled study, 18 microalbuminuric (UAE=30-300 mg/24 h) type 2 DM patients received aspirin (300 mg/d) or identical placebo for 8 weeks, with a 6-week washout period. The patients were aged 56±9 years, had a diabetes duration of 16±7.5 years; 11 (61%) were female, and they were all using enalapril 10 mg bid. GFR was measured by 51Cr-EDTA single-injection method and UAE by immunoturbidimetry. The sample-size calculation showed that 17 patients were needed to detect a 30% change in UAE (α= 0.05 and β= 0.20).RESULTS: After 8 weeks of treatment, there were no significant differences between placebo and aspirin, respectively, regarding UAE [57.7 (8.9-420.0) vs. 63 (8.2-272.0) mg/24 h; P=0.45] and GFR (108±34 vs. 111±47 ml/min/1.73 m2; P=0.90). C-reactive protein levels [2.72 (0.34-10.3) vs. 2.03 (0.25-10.3) μg/l; P=0.21] were comparable after placebo and aspirin, respectively. There were no period (P=0.41) or carry-over effects (P=0.49).CONCLUSION: Low-dose aspirin did not affect GFR and UAE levels of microalbuminuric type 2 DM. It seems that the putative low-grade inflammation of diabetic nephropathy does not respond to these low doses of the drug

Vitamin D deficiency increases the risk of adverse neonatal otcomes in gestational diabetes

Background: Gestational diabetes mellitus (GDM) and vitamin D deficiency have been associated with increased risk of adverse perinatal outcomes but the consequences of both conditions simultaneously present in pregnancy have not yet been evaluated. Our objective was to study the influence of vitamin D deficiency in neonatal outcomes of pregnancies with GDM. Methods: 184 pregnant women with GDM referred to specialized prenatal monitoring were included in this cohort and had blood sampled for 25-hydroxyvitamin D measurement. Vitamin D was measured by chemiluminescence and deficiency was defined as < 20 ng/mL. Participants were followed until puerperium and adverse neonatal outcomes were evaluated. Results: Newborns of women with vitamin D deficiency had higher incidences of hospitalization in intensive care units (ICU) (32 vs 19%, P = 0.048), of hypoglycemia (any, 17.3 vs 7.1%, P = 0.039 requiring ICU, 15.3 vs 3.6%, P = 0.008), and were more frequently small for gestational age (SGA) (17.3 vs 5.9%, P = 0.017). After adjustment, relative risk (RR) for hypoglycemia requiring ICU was 3.63 (95%CI 1.09±12.11) and for SGA was 4.32 (95%CI 1.75± 10.66). The incidence of prematurity, jaundice and shoulder dystocia was no statistically different between groups. Conclusions: In this cohort of pregnant women with GDM, vitamin D deficiency was associated with a major increase in the incidence of adverse neonatal outcomes such as SGA newborns and neonatal hypoglycemia

Diabetes e Gestação: Perfil Clínico e Laboratorial em Pré-Natal de Alto Risco

Introdução: O diabetes é complicação clínica frequente na gestação e sua prevalência vem aumentando nos últimos anos.Objetivo: Analisar a frequência dos tipos de diabetes na gestação, as características clínicas das gestantes e alguns desfechos materno-fetais, em pré-natal de alto risco.Método: Estudo retrospectivo de revisão dos prontuários eletrônicos de mulheres com diabetes e gestação atendidas no período de janeiro 2009 a junho 2010 no Hospital de Clínicas de Porto Alegre (HCPA).Resultados: Nesse período, 173 gestantes foram atendidas no ambulatório de gestação e diabetes, no total de 1459 consultas. O diabetes gestacional ocorreu em 84% das gestantes, 8% apresentaram diabetes tipo 2, 6%, diabetes tipo 1 e 2%, outros tipos. As mulheres com diabetes gestacional apresentaram HbA1c inferior às demais. A maioria das pacientes iniciou o pré-natal após o primeiro trimestre. A taxa geral de cesariana foi de 56%, tendo sido mais frequente no diabetes tipo 1. O recém-nascido foi considerado pequeno para a idade gestacional em 9% dos casos, e grande em 13%, sem diferença entre os tipos de diabetes. Nas mulheres com diabetes gestacional, o peso do recém-nascido correlacionou-se positivamente com o índice de massa corporal, glicemia de jejum ao diagnóstico e HbA1c da mãe.Conclusão: O diabetes associado à gestação é motivo frequente de atendimento no pré-natal especializado do HCPA, sendo a maioria diabetes gestacional. Nesses casos, obesidade e pior controle glicêmico associaram-se com o peso fetal aumentado. As gestantes chegam tardiamente ao centro de tratamento, com controle metabólico aquém do recomendado

Losartan-Induced Acute Interstitial Nephritis

Nefrite intersticial aguda é uma causa comum de perda aguda de função renal. Exposição a drogas é o fator desencadeante mais freqüentemente relatado, porém auto-imunidade e infecções também estão associadas. Os inibidores da enzima de conversão da angiotensina têm sido relatados como possíveis agentes, porém não há relato na literatura de nefrite intersticial com uso de losartan. Descrevemos então, o caso de perda aguda de função renal após exposição a losartan, em paciente com dano renal prévio por nefropatia diabética, cuja biópsia renal diagnosticou nefrite intersticial aguda.Acute interstitial nephritis is an important cause of acute renal failure. The majority of cases results from exposure to drugs. How-ever imune-mediated injury and infection are common causes. The angiotensin-converting enzyme inhibitors have been implicated as possible etiologic agents, but we could not find previous data of acute intestitial nephritis associated with losartan exposure. We report a case of acute renal failure after losartan exposure, in a patient with diabetic nephropathy. The final diagnosis was confirmed by renal biopsy: acute interstitial nephritis

Losartan-induced acute interstitial nephritis

Nefrite intersticial aguda é uma causa comum de perda aguda de função renal. Exposição a drogas é o fator desencadeante mais freqüentemente relatado, porém auto-imunidade e infecções também estão associadas. Os inibidores da enzima de conversão da angiotensina têm sido relatados como possíveis agentes, porém não há relato na literatura de nefrite intersticial com uso de losartan. Descrevemos o caso de perda aguda de função renal após exposição a losartan, em paciente com dano renal prévio por nefropatia diabética, cuja biópsia renal diagnosticou nefrite intersticial aguda.Acute interstitial nephritis is an important cause of acute renal failure. The majority of cases results from exposure to drugs. However imune-mediated injury and infection are common causes. The angiotensin-converting enzyme inhibitors have been implicated as possible etiologic agents, but we could not find previous data of acute intestitial nephritis associated with losartan exposure. We report a case of acute renal failure after losartan exposure, in a patient with diabetic nephropathy. The final diagnosis was confirmed by renal biopsy: acute interstitial nephritis

Targeted sequencing identifies novel variants in common and rare MODY genes

Background: Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY-X). Methods: We conducted a next-generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY-GCK and 76 were non-GCK MODY. Results: After excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY-PDX1/HNF1B. Conclusion: A multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY-X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes