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FUNDAMENTO: Em pacientes com diabetes tipo 2, a presença de retinopatia está associada a doença cardiovascular aumentada, independentemente dos fatores de risco conhecidos para a doença vascular. OBJETIVO: Investigar a associação da retinopatia diabética (RD) e seus graus com a presença de aterosclerose coronariana subclínica em pacientes com diabetes tipo 1. MÉTODOS: Um estudo transversal foi conduzido com 150 pacientes com diabetes tipo 1, assintomáticos para doença arterial coronariana. Foram submetidos à avaliação clínica para verificar complicações microvasculares e avaliação para a presença de calcificação arterial coronariana (CAC). RESULTADOS: Formas graves de RD (RD grave não proliferativa - RDNP - e RD proliferativa - RDP) foram associadas à CAC (RC: 3,98; IC de 95%; 1,13-13,9, p = 0,03), de maneira independente dos fatores de risco conhecidos para a doença cardiovascular (idade, A1C, hipertensão, dislipidemia e sexo masculino). CONCLUSÃO: Os pacientes com formas graves de RD estão em risco de presença de doença arterial coronariana, de maneira independente dos tradicionais fatores de risco cardiovascular. BACKGROUND: In patients with type 2 diabetes, the presence of retinopathy is associated with increased cardiovascular disease, regardless of known risk factors for vascular disease. OBJECTIVE: To investigate the association of diabetic retinopathy (DR) and its grades with the presence of subclinical coronary atherosclerosis in patients with type 1 diabetes. METHODS: A cross-sectional study was conducted with 150 type 1 diabetes individuals asymptomatic for coronary artery disease. They underwent clinical evaluation for microvascular complications and for the presence of coronary artery calcification (CAC). RESULTS: Severe forms of DR (severe non-proliferative DR and proliferative DR) were associated with CAC (OR: 3.98 95% CI 1.13-13.9, p = 0.03), regardless of known risk factors for cardiovascular disease (age, A1C, hypertension, dyslipidemia and male gender). CONCLUSION: Patients with severe forms of DR are at risk for the presence of coronary artery disease regardless of traditional cardiovascular risk factors.

To analyze the prevalence of masked hypertension and its possible association with microvascular complications in patients with type 1 diabetes (T1D).A cross-sectional study was conducted in 188 consecutive normotensive patients at the office with T1D without renal replacement therapy or previous renal transplant. All patients were assessed regarding the presence of diabetic retinopathy (DR) (direct and indirect fundoscopy), urinary albumin excretion rate (immunoturbidimetry), and ambulatory blood pressure monitoring (ABPM) (Spacelabs 90207).Masked hypertension was observed in 14 (13.6%) out of 103 clinical normotensive patients and in 7.4% of the entire cohort. Twenty-three percent of patients with clinical normotension had masked nocturnal hypertension. DR was associated with night systolic and diastolic BP [OR of each 5mmHg change 1.41 (95%CI: 1.09-1.83, P=0.009) and 1.40 (95%CI: 1.02-1.93, P=0.04), respectively] and with masked nocturnal hypertension [OR: 3.23 (95%CI: 1.29-8.11, P=0.01)].In T1D patients with clinic BP130/80mmHg, masked hypertension and especially masked nocturnal hypertension are present. Normotensive patients with nocturnal BP120/70mmHg have higher presence of DR, and only will be identified through ABPM.

Aims To evaluate the prevalence of cataract and the possible factors associated with cataract in young type 1 diabetes mellitus (DM). Methods 293 patients were evaluated. The association of cataract with diabetic retinopathy (DR), retinal laser treatment, hypertension, body mass index, peripheral neuropathy, lipid profile, glycemic control, serum creatinine and albuminuria was evaluated. Results Cataract was present in 19.8% ( n =58) of the sample. Patients with cataracts were older, had a higher frequency of history of retina photocoagulation treatment, higher serum creatinine values and higher prevalence of arterial hypertension. There was a progressive increase in cataract frequency according to the number of risk factors, starting to rise with two or more. In logistic regression model cataract was associated with mild/moderate DR (odd ratio (OR) 4.28 95% CI 1.63–11.29), severe DR (OR 4.07 95% CI 1.63–10.23) and macroalbuminuria (OR 2.34 95% CI 1.06–5.16). Conclusion These data indicate a high prevalence of cataract in subjects with type 1 DM attending a general hospital in Southern Brazil and suggest that the more severe the disease process the greater is the risk of having this diabetic complication. Cataract should be suspected in young patients with two or more risk factors.

Objetivo: Avaliar a prevalência de catarata e seus fatores de risco em uma população portadora de diabetes mellitus tipo 1 (DM1). Métodos: Estudo de casos e controles de um banco de dados de 181 pacientes (362 olhos) com diagnóstico de diabetes mellitus tipo 1. Os pacientes foram classificados como casos quando apresentavam diagnóstico de catarata. As variáveis estudadas foram a presença ou não de retinopatia diabética, tratamento com panfotocoagulação, presença de hipertensão arterial sistêmica e neuropatia periférica, colesterol total, triglicerídios séricos, HDL, LDL, índice de massa corporal, creatinina sérica, albuminúria, hemoglobina glicosilada e glicemia de jejum. Resultados: A prevalência de catarata foi de 19,9%. Na análise univariada foi encontrada associação estatisticamente significativa (p

A retinopatia diabética (RD) acomete cerca de 95% dos pacientes com diabetes melito tipo 1 (DM1) e 60% dos pacientes com diabetes melito tipo 2 (DM2), sendo a principal causa de cegueira legal em adultos. O objetivo desse manuscrito foi revisar os principais fatores de risco para RD. Os fatores de risco ambientais mais importantes são a hiperglicemia sustentada, os valores elevados de pressão arterial e a longa duração de DM. Entretanto, nem todos os pacientes desenvolvem RD, o que sugere a presença de fatores genéticos, em especial para as formas graves de RD. Diferentes estratégias têm sido utilizadas para avaliar o papel da genética na RD. Estudos de famílias demonstraram agregação familiar de RD. Genes candidatos têm sido estudados (RAGE; VEGF; PPAR-δ; ICAM-1; ECA; ENPP 1; eNOS), observando-se associações positivas ou negativas com a RD. Também alguns cromossomos, em populações selecionadas, foram associados à RD. Finalmente, estudos de expressão genética reforçam a associação de genes candidatos, ou determinam a participação de outros, com a presença da RD. A RD é uma complicação freqüente do DM e junto com os fatores não-genéticos ou ambientais, a identificação de genes relacionados à RD poderá resultar tratamentos mais específicos e eficazes para a RD. Diabetic Retinopathy Risk Factors. Diabetic retinopathy (DR) occurs in about 95% of patients with type 1 diabetes mellitus (DM) and in 60% of type 2 DM patients and it is the main cause of legal blindness in adult people. The aim of this manuscript was to review the main risk factors for DR. The major environmental risk factors are hyperglycemia, high blood pressure levels, and long-term duration of DM. However, not all patients will not develop DR, suggesting the presence of a genetic predisposition to DR, especially for severe forms of DR. Special strategies has been used to evaluate the genetic role in DR. Family studies shown that there is a familial aggregation of DR. Candidates genes have been studied (RAGE; VEGF; PPAR-δ; ICAM-1; ECA; ENPP 1; eNOS) and positive or negative associations with DR were demonstrated. Some chromosomes were also associated to DR in selected populations. Finally, genetic expression studies reinforce the association of candidate genes, or participation of others genes, with the presence of DR. DR is a common complication of DM and, along with nongenetic or environmental risk factors, the identification of genes related to DR could result in more specific and efficient DR treatment.

The main risk factors for the development and progression of diabetic retinopathy (DR) are chronic hyperglycemia, disease duration and systemic blood pressure. So far chronic hyperglycemia is the strongest evidence concerning the risk of developing DR. However there are some patients with poor metabolic control who never develop this diabetic complication. We present a case of a 73-year-old woman with type 1 diabetes mellitus, diagnosed 69 years ago. The patient is 73 years old, with no evidence of DR, despite poor glycemic control and several risk factors for DR. This case suggests the presence of a possible protection factor, which could be genetic.

Objetivos. Determinar a prevalência de RD e seus fatores de risco em pacientes com DM tipo 1 atendidos em um hospital geral. Métodos. Foi realizado um estudo transversal com 437 pacientes (50,3% homens, 82,4% brancos). RD foi agrupada em: 1) ausente; 2) não proliferativa leve e moderada (RDNP leve/moderada); 3) não prolifetiva grave e RD proliferativa (RD avançada). Edema de mácula clinicamente significativo (EMCS) também foi registrado. Resultados. Qualquer grau de RD esteve presente em 44,4% dos pacientes. Na análise multivariada, duração do DM, pressão arterial sistólica e teste A1C foram associados com a RD leve/moderada (P

Diabetic macular edema (DME) affects up to 29% of patients with diabetic retinopathy (DR) and is the most frequent cause of visual impairment in these patients (Klein, Klein, Moss, Davis, & DeMets, 1984). However, risk factors for DME have not been fully established. Recently, Romero et al. (2007) prospectively studied 112 type 1 diabetes mellitus (DM) patients (age 39.9±10.5 years; DM duration 23.4±7.5 years; 48.2% males) to evaluate risk factors for DME. After 15 years, the incidence of DME was 20.5%. In logistic multivariate regression models, adjusted for gender and age, A1c test and low-density lipoprotein (LDL) cholesterol levels, arterial hypertension, macroangiopathy, severity of retinopathy, and macroalbuminuria were the recognized risk factors for DME. In a cross-sectional study, we evaluated 224 Type 1 DM patients aged 33.3±13.9 years, with 16.5±9.6 years of DM duration (105 males) regularly attending the DM outpatient clinic at Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. A complete clinical evaluation was performed as previously described (Leitao et al., 2007). DME was defined as one or more of the following: any retinal thickening within 500 μm of the center of the macula, with or without loss of retinal transparency; hard exudates associated with retinal thickening within 500 μm of the center of the macula; or one disc area of thickening within one disc diameter of the center of the macula (ETDRS, 1985). Twenty-four percent of the patients had nonproliferative DR (mild, n=38; moderate, n=9; severe, n=7), and 20.7 % (n=46) proliferative DR. The prevalence of DME was 9.4% (n=21). In univariate analysis, patients with DME had higher levels of urinary albumin excretion (UAE) [26.2 mg/dl (0.1–1105) vs. 8.7 (0.1– 71110), P=.049] than those without it. DM duration, body mass index, blood pressure levels, glycemic (A1c test) and lipid profile (total, LDL, and high-density lipoprotein cholesterol and triglycerides) did not differ between groups. Current or former smoking habit (50% vs. 25%; P=.034) and diabetic nephropathy (micro- and macroalbuminuria) (58.8% vs. 29.5%; P=.026) were more frequent in patients with than those without DME. The severity of DR was also associated with DME (P for trend .027). In logistic multivariate regression analysis, with the presence of DME as the dependent variable and DM duration, smoking habit, systolic blood pressure, A1c test, and UAE as independent ones, only the smoking habit was associated with DME (OR 2.02, 95%CI 1.01–4.00; P=.04). Differences between our results and those of Romero et al., besides study design, could be explained by the younger age and shorter DM duration of our patients: a difference of about 6 years of age [6.6 years (95% CI 3.6–9.5; Pb.0001)] and of 7 years of DM duration [6.9 years (95% CI 4.7-8.9; Pb.0001)]. The present data demonstrated that, besides glycemic, lipid, and blood pressure control, the smoking habit, a nontraditional DME risk factor, should also be taken into account in order to prevent it. To our knowledge, this is the first report of this association.

To investigate the relationship between diabetic retinopathy (DR) and 24-h ambulatory blood pressure (ABP) in a cohort of normotensive, normoalbuminuric type 1 diabetic patients. This is a 6.1+/-3.3 year prospective study of 44 normotensive, normoalbuminuric type 1 diabetic patients. ABP was measured at the beginning and at the end of the study. Measurements of urinary albumin excretion rate (UAER) and direct and indirect ophthalmoscopy after mydriasis were performed at the start and end of the study and at least once a year. DR was observed in 12 patients at baseline. At the end of the study, eight of these patients had progressed to more advanced stages of retinopathy. Four patients developed retinopathy after the study began. These patients were grouped and classified as progressors. At baseline, progressors were older, had longer duration of diabetes, higher levels of UAER, and higher 24-h diastolic (P=0.03) and diurnal diastolic blood pressure (P=0.03). UAER and diastolic blood pressure (24h or day) remained significantly associated with development and progression of DR after multivariate analysis. High normal ABP was associated with the development or progression of DR in this cohort of normotensive, normoalbuminuric type 1 diabetic patients. Abnormalities in blood pressure homeostasis could indicate higher susceptibility to DR.

PURPOSE Uncoupling protein 1 (UCP1) reduces mitochondrial production of reactive oxygen species (ROS). ROS overproduction is related to diabetic retinopathy (DR), a chronic complication of diabetes mellitus (DM). Therefore, deleterious polymorphisms in the UCP1 gene are candidate risk factors for DR. We investigated the relationships between the UCP1 -3826A/G polymorphism and risk of DR and UCP1 gene expression in human retina. Considering that superoxide dismutase-2 (MnSOD2) enzyme is the first line of defense against oxidative stress in mitochondria, we also analyzed MnSOD2 gene expression in retinal samples according to different UCP1 -3826A/G genotypes. METHODS In a case-control study, frequencies of -3826A/G polymorphisms were analyzed in 257 type 1 DM patients (154 cases with DR and 103 controls without DR). In a cross-sectional study comprising cadaveric cornea donors, UCP1 and MnSOD2 gene expressions were evaluated in 107 retinal samples differentiated according to different -3826A/G genotypes. RESULTS In the type 1 DM group, multivariate analysis confirmed that the G/G genotype was an independent risk factor for DR (OR = 3.503; P = 0.043). In cornea donors, G allele carriers had higher UCP1 cDNA and protein concentrations than A/A carriers (P = 0.034 and P = 0.039, respectively). Interestingly, G allele carriers exhibited increased MnSOD2 expression (P = 0.001). CONCLUSIONS This study suggests that the -3826A/G polymorphism is associated with DR in type 1 DM patients. This is the first report demonstrating UCP1 gene expression in human retinas and indicates that the -3826A/G polymorphism influences its expression. In addition, the -3826G allele was associated with increased MnSOD2 expression; thus, suggesting that this allele could be a marker of oxidative stress.