A predisposição genética para o desenvolvimento da microangiopatia no DM1: [revisão] / Genetic susceptibility to microangiopathy development in Type 1 diabetes mellitus: [review]

Acredita-se que o controle glicêmico e a duração do diabetes sejam os fatores de risco mais importantes para o desenvolvimento das microangiopatias diabéticas, contudo, as velocidades de progressão da nefropatia, da retinoaptia e da polineuropatia variam consideravelmente entre os pacientes. Além da presença de fatores de risco, como a hipertensão arterial, a dislipidemia e o fumo, existem evidências sugerindo que uma predisposição genética desempenha um papel na susceptibilidade para as complicações microvasculares. Com base na patogênese dessas complicações crônicas do diabetes, polimorfismos de vários genes candidatos que atuam em diferentes vias desse processo têm sido investigados, como os genes relacionados aos mecanismos dos danos induzidos pela hiperglicemia (os produtos finais de glicação avançada, o aumento na formação de espécies reativas de oxigênio e a atividade aumentada da via da aldose-redutase), os genes relacionados ao sistema renina-angiotensina; os genes que codificam a síntese das citoquinas, dos fatores de crescimento e dos seus receptores e dos transportadores de glicose entre muitos outros. Este artigo discute alguns estudos que corroboram com a importância da predisposição genética no desenvolvimento da microangiopatia diabética.

Glycemic control and diabetes duration are believed to be the most important risk factors for the development of diabetic microangiopathy; however, the rate of progression of nephropathy, retinopathy and polyneuropathy varies considerably among patients. Besides the presence of risk factors such as hypertension, dyslipidaemia and smoking, there is evidence suggesting that genetic predisposition plays a role in the susceptibility to microvascular complications. Based on underlying pathogenesis, polymorphisms of several candidate genes belonging to multiple pathways have been investigated, like the genes related to mechanisms of hyperglycaemia-induced damage (such as advanced glycation end-products and reactive oxygen species increased formation, augmented activity of the aldose reductase pathway); genes related to the renin-angiotensin system; genes coding for cytokines, growth factors and its receptors, glucose transporter; among many others. This article reviews some studies that corroborate the importance of the genetic background in the development of diabetic microangiopathy.

Adiponectin gene and cardiovascular risk in type 2 diabetic patients: a review of evidences

Diabetic patients have a 3-fold higher risk of developing atherosclerosis and its clinical complications as compared to non-diabetic individuals. Part of the cardiovascular risk associated with diabetes is probably due to genetic determinants influencing both glucose homeostasis and the development of atherosclerosis. However, type 2 diabetes frequently coexists with other cardiovascular risk factors like arterial hypertension, central obesity and dyslipidemia. Genetic variability affecting many areas such as lipid and energy metabolisms, hypertension and haemodynamic mechanisms, blood clotting homeostasis, inflammation, and matrix turnover in the vascular wall will have an impact on the development of macrovascular complications in diabetic patients. Adiponectin is abundantly secreted by adipocytes. It plays important roles in lipid and glucose metabolisms and has direct anti-inflammatory and anti-atherogenic effects. In this review, we summarize recent data from the literature suggesting an implication of allelic variations of the adiponectin gene (ADIPOQ) in the genetic determinants of cardiovascular disease in diabetic subjects.

Os pacientes com diabetes apresentam risco três vezes maior de desenvolverem aterosclerose e suas complicações quando comparados a indivíduos sem hiperglicemia. Parte desse risco associado ao diabetes é provavelmente relacionado a determinantes genéticos que influenciam tanto a homeostase glicídica quanto o desenvolvimento da aterosclerose. Entretanto, o diabetes tipo 2 freqüentemente coexiste com outros fatores de risco cardiovascular, tais como hipertensão arterial, obesidade central e dislipidemia. A variabilidade genética interfere em várias áreas tais como o metabolismo lipídico, o metabolismo energético, hipertensão, mecanismos hemodinâmicos, mecanismos de coagulação, inflamação e na formação da matriz na parede vascular, que podem estar envolvidos nas complicações macrovasculares dos pacientes com diabetes. A adiponectina é secretada com abundância pelos adipócitos. Apresenta importante papel no metabolismo lipídico e glicídico, tendo ação direta tanto antiinflamatória quanto anti-aterogênica. Na atual revisão, nós resumimos os dados recentes da literatura que sugerem uma implicação de variantes alélicas do gene da adiponectina (ADIPOQ) que podem estar envolvidos na determinação genética da doença cardiovascular em indivíduos com diabetes.

Absence of association between serum homocysteine levels and coronary artery disease in south Indian males.

BACKGROUND: Asian Indians are reported to have a very high prevalence of premature coronary artery disease. However, traditional risk factors do not explain this excess of coronary artery disease. Elevated levels of homocysteine are reported to be associated with coronary artery disease among Europeans. This study looked at the association of serum homocysteine levels with coronary artery disease in South Indians. METHODS AND RESULTS: Four groups of patients were studied: Group 1 consisted of healthy nondiabetic subjects without coronary artery disease (n=18): Group 2 consisted of nondiabetic subjects with coronary artery disease (n=21); Group 3 consisted of type 2 diabetic patients without coronary artery disease (n=18) and Group 4 consisted of type 2 diabetic patients with coronary artery disease (n=20). The mean homocysteine value was 12.4+/-3.4 micromol/L in Group 1; 12.6+/-4.6 micromol/L in Group 2; 10.1+/-4.4 micromol/L in Group 3; and 10.4+/-3.9 micromol/ L in Group 4. There was no significant difference in the homocysteine levels between the groups studied. The prevalence of hyperhomocysteinemia, defined as a level of 17.1 micromol/L (the 95th percentile for serum homocysteine in the control group) was not significantly different among the groups. CONCLUSIONS: Elevated serum homocysteine levels are not associated with coronary artery disease in South Indian male subjects with or without diabetes. However, the results must be interpreted with caution because of the small numbers studied.

Macroangiopatía en la diabetes mellitus no insulinodependiente / Macroangiopathy in non insulin-dependent diabetes mellitus

La diabetes mellitus cursa con una alta prevalencia de complicaciones macrovasculares, las que afectan principalmente a las arterias coronarias, cerebrales y meimbros inferiores. La lesión ateromatosa que aparece en los diabéticos es desde el punto de vista anátomo-patológico, similar a la observada en individuos no diabéticos y sólo se disntingue por desarrollarse de manera rápida, extensa y precoz. Dada la alta morbilidad y mortalidad provocada por esta patología en los diabéticos no insulinodependiente, es indispensable estudiar los mecanismos que conducen a las complicaciones vasculares, así como la identificación de los marcadores de riesgo, para evitar la aparición y progresión de la macroangiopatía diabética