Disorganization of the inner retinal layers in diabetic macular edema: systematic review / Desorganização das camadas internas da retina sem edema macular diabético: uma revisão sistemática

ABSTRACT The objective of this article was to review the disorganization of inner retinal layers as a biomarker in diabetic macular edema. A systematic search was conducted in PubMed®/MEDLINE®, Cochrane and Embase until August 2021. The keywords used were: "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" and "biomarkers". No restrictions were imposed on the types of study to be included. The studies selected for eligibility were those that included the diagnosis of diabetic macular edema (center involved, resolved), that were well documented with spectral domain optical coherence tomography, that included disorganization of inner retinal layers as one of the reported alterations, with a follow-up of at least 3 months, and those in which the best corrected visual acuity was evaluated pre and post. There were no limitations regarding the type of treatment established. References of identified studies were searched for additional relevant articles. Articles not published in peer review journals were excluded. All studies were evaluated by two investigators independently. When one of them was in doubt, it was assessed by a third evaluator. A total of seven studies were included. Four were retrospective, longitudinal cohort study and three cross-sectional observational. Regarding the population studied, 61.5% were men and 38.4% were women, most of them had diabetes mellitus type 2 (85.8%). Regarding the stage of diabetes, the percentage of patients with mild nonproliferative diabetic retinopathy was 28.2%, with moderate nonproliferative diabetic retinopathy was 28.5%, with severe nonproliferative diabetic retinopathy was 15.9% and with nonproliferative diabetic retinopathy was 27.4%. In 100% of the studies, the diagnosis of diabetic macular edema in the center involved was included by spectral domain optical coherence tomography (Heidelberg). In all the studies, the presence of disorganization of inner retinal layers was recorded and its association with best corrected visual acuity was evaluated. The measurement was carried out using the LogMAR scale. In all the studies, the presence or absence of disorganization of inner retinal layers was associated with the best corrected worse/better final visual acuity using p <0.05 as a statical significance. The disorganization of inner retinal layers as a biomarker and their presence have shown to be important predictors of visual acuity in the future in patients with diabetic macular edema. Histopathological studies are required to understand its mechanism of action.

RESUMO O objetivo deste artigo foi revisar sobre a desorganização das camadas internas da retina como biomarcador no edema macular diabético. Uma busca sistemática foi realizada no PubMed®/MEDLINE®, Cochrane e Embase até agosto de 2021. As palavras-chave utilizadas foram "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" e "biomarkers". Não foram impostas restrições quanto aos tipos de estudo a serem incluídos. Os estudos selecionados para elegibilidade foram aqueles que incluíram o diagnóstico de edema macular diabético (centro envolvido, resolvido), que foram bem documentados com tomografia de coerência óptica de domínio espectral, que incluíram a desorganização das camadas internas da retina como uma das alterações relatadas, com acompanhamento de pelo menos 3 meses, e aqueles em que a melhor acuidade visual corrigida foi avaliada pré e pós. Não houve limitações quanto ao tipo de tratamento estabelecido. Referências de estudos identificados foram pesquisadas para artigos relevantes adicionais. Foram excluídos os artigos não publicados em revistas de revisão por pares. Todos os estudos foram avaliados por dois investigadores de forma independente. Quando havia dúvida com algum deles, a mesma era avaliada por um terceiro avaliador. Um total de sete estudos foram incluídos. Quatro eram estudos de coorte retrospectivos longitudinais e três eram observacionais transversais. Em relação à população estudada, a proporção de homens foi de 61,5% e de mulheres, 38,4%, a maioria com diabetes mellitus tipo 2 (85,8%). Em relação ao estágio do diabetes, o percentual de pacientes com retinopatia diabética não proliferativa leve foi de 28,2%, retinopatia diabética não proliferativa moderada foi de 28,5%, de retinopatia diabética não proliferativa grave foi de 15,9% e de retinopatia diabética não proliferativa foi de 27,4%. Em 100% dos estudos, o diagnóstico de edema macular diabético no centro envolvido foi incluído pela tomografia de coerência óptica de domínio espectral (Heidelberg). Em todos os estudos, foi registrada a presença de desorganização das camadas internas da retina e avaliada sua associação com a melhor acuidade visual corrigida. A medição foi realizada usando a escala LogMAR. Em todos os estudos, a presença ou ausência de desorganização das camadas internas da retina foi associada a pior/melhor acuidade visual final melhor corrigida usando p<0,05 como significância estática. A desorganização das camadas internas da retina como biomarcador e sua presença têm se mostrado importantes como preditor da acuidade visual no futuro em pacientes com edema macular diabético. Estudos histopatológicos são necessários para entender seu mecanismo de ação.

Unilateral intravitreal dexamethasone implant for diabetic macular edema: effect in the contralateral eye / Implante de dexametasona intravítreo unilateral no edema macular diabético: efeito no olho contralateral

ABSTRACT We describe three patients who had previous heart diseases and nonproliferative diabetic retinopathy with clinically significant diabetic macular edema. They underwent unilateral dexamethasone intravitreal implantation. Without ophthalmological treatment in the fellow eye, patients showed marked bilateral improvement in best-corrected visual acuity, optical coherence images, and macular thickness values. These findings provide evidence of the bilateral effect of dexamethasone intravitreal implantation, which may be clinically useful in patients for whom the systemic effects of the drug may affect their general health.

RESUMO Descrevemos três pacientes que tiveram doenças cardíacas prévias e retinopatia diabética não proliferativa com edema macular diabético clinicamente significativo. Eles foram submetidos a implante intravítreo de dexametasona unilateral. Sem tratamento oftalmológico no olho contralateral, os pacien tes apresentaram uma melhora bilateral significativa na melhor acuidade visual corrigida, nas imagens de coerência óptica e nos valores da espessura macular. Esses achados fornecem evidências sobre o efeito bilateral do implante intravítreo de dexametasona, que pode ser clinicamente útil em pacientes para os quais os efeitos sistêmicos da droga possam afetar a saúde geral do paciente.

Comparative study between intravitreal ranibizumab and triamcinolone treatment of diabetic macular edema as regard to optical coherence tomography changes and visual acuity / Estudo comparativo entre o tratamento intravítreo com ranibizumabe e triancinolona do edema macular diabético quanto às alterações na tomografia de coerência óptica e na acuidade visual

Abstract Objectives: To compare the effect of intravitreal Ranibizumab (0.3mg) and Triamicinolone (4mg) on different parameters in spectral domain OCT and their relation to visual acuity of patients with diabetic macular edema. Methods: This study is designed as a prospective randomized study. Patients were randomly divided into 2 groups receiving either Pro re nata intravitreal Ranibizumab (0.3mg) or Triamicinolone acetonide (4mg), to whom Spectral Domain OCT was done as well as best corrected Log MAR visual acuity. Results: 40 patients were included in this study. Comparison and correlation of mean BCVA and mean CMT among and within treatment groups of our study revealed strong and significant relationship between both parameters and showing equal effect of both treatment types regarding them with the consideration that Triamicinolone acetonide treated group (Group B) showed statistically significant lower CMT compared to Ranibizumab treated group (Group A) at three and six months. Also both showed equal effectivity regarding improvement of the photoreceptors integrity and in turn the improvement of the BCVA. Meanwhile the association of CMT and IS/OS integrity was found to be significant only at six months in both groups (p =0.009 in Group A; p =0.031 in Group B). The fading initial effect of a single ranibizumab injection on macular edema can be augmented by following that one injection with two injections of the loading dose. Triamicinolone effect after single injection began to fade at 3 months. Conclusion: Both treatment types had good effect on reduction of CMT and improvement of BCVA and the IS/OS junction with difference in sustainability of their effects due to difference in their pharmacokinetics and need for repeated injections.

Resumo Objetivos: Comparar o efeito do ranibizumabe intravítreo (0,3mg) e triacmicinolona (4mg) em diferentes parâmetros do domínio espectral da OCT e sua relação com a acuidade visual de pacientes com edema macular diabético. Métodos: Este estudo foi concebido como um estudo prospectivo randomizado. Os pacientes foram divididos aleatoriamente em 2 grupos que receberam Ranibizumab Pro rata intravitreal (0,3mg) ou acetonido de Triamicinolona (4mg), a quem foi realizada a Spectral Domain OCT, bem como a melhor acuidade visual de Log MAR corrigida. Resultados: Quarenta pacientes foram incluídos neste estudo. A comparação e a correlação da acuidade visual média e CMT média entre e dentro de grupos de tratamento do nosso estudo revelaram uma relação forte e significativa entre ambos os parâmetros e mostrando um efeito igual de ambos os tipos de tratamento, considerando que o grupo tratado com acetonido Triamicinolona (Grupo B) apresentou significância estatística. menor CMT comparado ao grupo tratado com Ranibizumab (Grupo A) aos três e seis meses. Também ambos mostraram igual efetividade em relação à melhoria da integridade dos fotorreceptores e, por sua vez, a melhora do BCVA. Enquanto isso, a associação de CMT e IS / OS integridade foi significativa apenas aos seis meses em ambos os grupos (p = 0,009 no Grupo A; p = 0,031 no Grupo B). O efeito inicial enfraquecido de uma única injeção de ranibizumabe no edema macular pode ser aumentado seguindo-se aquela injeção com duas injeções da dose de ataque. O efeito triamicinolona após injeção única começou a diminuir aos 3 meses. Conclusão: Ambos os tipos de tratamento tiveram bom efeito na redução da CMT e melhora do BCVA e da junção IS / OS com a diferença na sustentabilidade de seus efeitos devido à diferença em sua farmacocinética e necessidade de injeções repetidas.

Frecuencia y severidad de retinopatía diabética en pacientes con diabetes mellitus tipo 2 en el Instituto Regional de Oftalmología / Frequency and severity of diabetic retinopathy in patients with type 2 diabetes mellitus at the Regional Institute of Ophthalmology

RESUMEN Para determinar la frecuencia y el grado de severidad de retinopatía diabética (RD) en pacientes con diabetes mellitus (DM) tipo 2 se realizó un estudio descriptivo transversal en 3239 pacientes del Instituto Regional de Oftalmología de la ciudad de Trujillo, región La Libertad, Perú. Previa dilatación pupilar, personal entrenado tomó dos fotografías de cada ojo, centrado en mácula y nervio óptico. La frecuencia de RD fue de 25,9 % con mayor proporción en varones con RD (28,2%) y en aquellos con más de 10 años de enfermedad por DM (49,0%). La mayoría de pacientes tuvieron retinopatía diabética no proliferativa (RDNP) leve a moderada (79,3%), el 10,1% tuvo RDNP severa y el 10,6 % RD proliferativa. Concluimos que la RD se presenta en uno de cada cuatro pacientes y alrededor del 20% en grados avanzados. Es preciso ampliar la cobertura de tamizaje desde el momento del diagnóstico de DM e implementar medidas preventivas como el control metabólico y el examen periódico del fondo de ojo.

ABSTRACT In order to determine the frequency and severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (MD), a cross-sectional descriptive study was conducted in 3,239 patients of the Regional Institute of Ophthalmology in the city of Trujillo, La Libertad region, Peru. After pupil dilation, trained personnel took two photographs of each eye, centered on macula and optic nerve. The frequency of DR was 25.9%, with a higher proportion in men with DR (28.2%) and in those with more than 10 years of MD disease (49.0%). Most patients had mild to moderate non-proliferative diabetic retinopathy (NPDR) (79.3%); 10.1% had severe NPDR, and 9.7% had proliferative DR. We conclude that DR occurs in one in four patients and about 20% in advanced degrees. There is a need to expand screening coverage from the time of diagnosis of DM and to implement preventive measures such as metabolic control and periodic ocular fundus exam.

Comparison between multi-spot laser and conventional laser in treatment of diabetic clinically significant macular edema / Comparação entre laser multi-spot e laser convencional no tratamento de edema macular diabético

Abstract Objectives: The purpose of this work is to assess the safety and the efficacy of multi-spot laser in comparison with the conventional laser in the treatment of non-proliferative diabetic retinopathy with CSME in relation to the visual outcome, central macular thickness by (OCT) and the presence of adverse events. Methods: prospective randomized study on total number of 50 eyes divided in two groups each one 25 patients . group A patients underwent focal, grid laser or modified grid macular laser photocoagulation using green laser 532nm GYC-1000. Group B underwent focal ,grid laser or modified grid macular laser photocoagulation multispot laser photocoagulation (VALON TT inclusion criteria was diabetes mellitus type II patients , clinically significant macular edema . patients were monitored by BCVA, OCT, IOP, adverse events pre and 1 week , one month , three months postoperative. Results: The mean preoperative BCVA in group A with conventional laser was 0.294 ± 0.1715 decimal and in group B with multispot laser (valon ) was 0.3040 ± 0.2140 . The mean BCVA 3 months post-laser in group A was 0.4820 ±0.244 decimal and in Group B was 0.5080 ± 0.1977. Central macular thickness of the patients was measured pre-laser and in the follow up periods of 1week, one month, three months. The mean preoperative CMT in Group A was 375.92 ± 65.69 um and in Group B was 361.0± 50.400 um. The mean CMT 3 months post-laser in Group A was 314.44 ±85.938 um and in Group B was 0322.668 ± 57.500 um. The multisport system parameters used higher power of mean 155 mW ± 90.1 more than the conventional laser 100 mW ± 19.4 to produce the same therapeutic visible effect. Conclusion: We found that multisport system is safe, rapid, effective in treatment of clinically significant macular edema in short term follow up periods and had short exposure time. Although the shorter pulse duration of the multisport system necessitates the use of a higher power, it is not associated with adverse effects.

Resumo Objetivos: O objetivo deste trabalho é avaliar a segurança e a eficácia do laser multi-spot em comparação com o laser convencional no tratamento da retinopatia diabética não proliferativa com CSME em relação ao resultado visual, à espessura macular central por (OCT) e à presença de eventos adversos. Métodos: estudo prospectivo randomizado sobre o número total de 50 olhos divididos em dois grupos, cada um de 25 pacientes. Os pacientes do grupo A foram submetidos a fotocoagulação focal, a laser de grade, ou de laser macular de grade modificada com a utilização do laser verde de 532nm GYC-1000. O grupo B foi submetido a fotocoagulação fotocoagulação focal, a laser de grade, ou de laser macular de grade modificada (os critérios de inclusão VALON TT foram pacientes com diabetes mellitus tipo II, edema macular clinicamente significativo). Os pacientes foram monitoradoss para BCVA, OCT, IOP, eventos adversos pré e uma semana, um mês, e três meses de pós-operatório. Resultados: O BCVA preoperatório médio no grupo A com laser convencional foi 0,294 ± 0,1715 decimal, e no grupo B com laser multispot (valon) foi 0,3040 ± 0,2140. O BCVA médio 3 meses após o laser no grupo A foi 0.4820 ± 0.244 decimal, e no grupo B foi 0.5080 ± 0.1977. A espessura macular central dos pacientes foi medida antes do laser e nos períodos de acompanhamento de 1 semana, um mês e três meses. O CMT médio pré-operatório no grupo A foi 375,92 ± 65,69 um, e no grupo B foi 361,0 ± 50,400 um. O CMT médio 3 meses após o laser no grupo A foi 314,44 ±85,938 um, e no grupo B foi 0322,668 ± 57,500 um. Os parâmetros do sistema multisport utilizaram uma potência media 155 mW ± 90,1 superior a do laser convencional de 100 mW ± 19,4 para produzir o mesmo efeito terapêutico visível. Conclusão: Descobrimos que o sistema multisport é seguro, rápido e eficaz no tratamento de edema macular clinicamente significativo em períodos de acompanhamento de curto prazo, e ele teve um curto tempo de exposição. Embora uma duração de pulso mais curta do sistema multisport necessite utilizar uma potência maior, ela não está associada aos efeitos adversos.

Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option?

Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.

The Effect of Pattern Scan Laser Photocoagulation on Peripapillary Retinal Nerve Fiber Layer Thickness and Optic Nerve Morphology in Diabetic Retinopathy

PURPOSE: To evaluate the effect of pattern scan laser (PASCAL) photocoagulation on peripapillary retinal nerve fiber layer (RNFL) thickness, central macular thickness (CMT), and optic nerve morphology in patients with diabetic retinopathy. METHODS: Subjects included 35 eyes for the PASCAL group and 49 eyes for a control group. Peripapillary RNFL thickness, cup-disc area ratio and CMT were measured before PASCAL photocoagulation and at 2 and 6 months after PASCAL photocoagulation in the PASCAL or control groups. RESULTS: The average RNFL thickness had increased by 0.84 microm two months after and decreased by 0.4 microm six months after PASCAL photocoagulation compared to baseline, but these changes were not significant (p = 0.83, 0.39). The cup-disc area ratio was unchanged after PASCAL photocoagulation. CMT increased by 18.11 microm (p = 0.048) at two months compared to baseline thickness, and partially recovered to 11.82 microm (p = 0.11) at six months in the PASCAL group. CONCLUSIONS: PASCAL photocoagulation may not cause significant change in the peripapillary RNFL thickness, CMT, and optic nerve morphology in patients with diabetic retinopathy.

Mean platelet volume is associated with glycaemic control and retinopathy in patients with Type 2 Diabetes Mellitus / Volumen medio de plaquetas está asociado con el control glucémico y la retinopatía en pacientes con Diabetes Mellitus Tipo 2

OBJECTIVES: To investigate the relationship between mean platelet volume (MPV) and glycometabolic indices, to compare MPV according to HbA1c levels, and to analyse the difference in MPV between patients with and without microvascular complications. METHODS: This retrospective study was conducted on 60 Type 2 diabetic patients and 50 age- and sex-matched non-diabetic controls. We obtained demographic, clinical and laboratory data including MPV, platelet count, fasting and postprandial blood glucose (FBG and PBG), haemoglobin A1c (HbA1c), lipid profile, creatinine, systolic and diastolic blood pressure (BP) in patient and control groups, and diabetic microvascular complications including nephropathy, neuropathy, and retinopathy in the patient group. All analyses were performed using SPSS version 15.0 for Windows. RESULTS: Mean platelet volume in the diabetic group was higher than in the control group (p = 0.001). Mean platelet volume was positively correlated with FBG and HbA1c levels (p = 0.03 and p < 0.001, respectively). It was also negatively related to platelet count (p < 0.001). Mean platelet volume in patients with HbA1c > 7% was significantly higher than those with HbA1c < 7% (p < 0.001). Mean platelet volume was significantly increased in patients with retinopathy compared to those without retinopathy (p = 0.04). CONCLUSION: This study has shown that an increased MPV is closely associated with poor glycaemic control, which may be a risk factor for diabetic retinopathy. Nonetheless, further prospective studies are needed to assess the relationship between MPV, glycaemic indices and microvascular complications.

OBJETIVOS: Investigar la relación entre el volumen medio de plaquetas (MPV) y los índices glicometabólicos, comparar el MPV según los niveles de HbA1c, y analizar la diferencia de MPV entre los pacientes con y sin complicaciones microvasculares. MÉTODOS: Este estudio retrospectivo se realizó en 60 pacientes diabéticos tipo 2, y 50 controles no diabéticos pareados por sexo y edad. Obtuvimos datos demográficos, clínicos y de laboratorio - incluyendo MPV, conteo de plaquetas, glucosa en sangre en ayunas (FBG) y postprandial (PBG), hemoglobina A1c (HbA1c), perfil lipídico, creatinina, presión arterial (BP) sistólica y diastólica en los grupos de pacientes y de control, así como complicaciones microvasculares diabéticas, incluyendo nefropatía, neuropatía y retinopatía en el grupo de pacientes. Todos los análisis se realizaron utilizando el SPSS versión 15.0para Windows. RESULTADOS: El volumen medio de plaquetas en el grupo diabético fue superior al del grupo control (p = 0,001). El volumen medio de plaquetas guardó una correlación positiva con el FBG y los niveles de HbAlc (p = 0.03 y p < 0.001, respectivamente). También se observó una correlación negativa con el conteo de plaquetas (p < 0.001). El volumen medio de plaquetas en los pacientes con HbA1c > 7% fue significativamente mayor que en aquellos con HbAlc < 7% (p < 0.001). El volumen medio de plaquetas aumentó significativamente en los pacientes con retinopatía en comparación con aquellos sin retinopatía (p = 0,04). CONCLUSIÓN: Este estudio mostró que el aumento de MPV está estrechamente relacionado con un control glicémico pobre, lo cual puede ser un factor de riesgo para la retinopatía diabética. Sin embargo, otros estudios prospectivos son necesarios para evaluar la relación entre MPV, los índices glicémicos, y las complicaciones microvasculares.

Early vitreous hemorrhage after vitrectomy with preoperative intravitreal bevacizumab for proliferative diabetic retinopathy

To evaluate the effect of preoperative intravitreal bevacizumab [IVB] on surgical] procedures, visual prognosis, and postoperative complications, especially postoperative vitreous hemorrhage, in cases with proliferative diabetic retinopathy [PDR]. Seventy-one eyes of 54 consecutive patients [23 eyes of 18 women, 48 eyes of 36 men] were investigated in this study. Twenty-five eyes received IVB one to 30 days before the vitrectomy [Bevacizumab Group] and the other 46 eyes had the vitrectomy alone [Control Group]. The surgical procedures, best-corrected visual acuities at baseline, 1, 3, and 6 months after the vitrectomy, and postoperative complications in the Bevacizumab Group were compared to the Control Group. The patients were significantly younger in the Bevacizumab Group compared to the Control Group [P = 0.008]. The incidence of preoperative vitreous hemorrhage, tractional retinal detachment, and iris neovascularization was significantly higher in the Bevacizumab Group than in the Control Group [P = 0.017, 0.041, and 0.018, respectively]. The surgical procedures performed and the visual acuity at all time points was not significantly different between groups [P> 0.05, all comparisons]. The incidence of early [<4 weeks] postoperative vitreous hemorrhage was significantly higher in the Bevacizumab Group [27%] than in the Control Group [7%; P = 0.027] although the rate of late [>4 weeks] postoperative vitreous hemorrhage was not significantly different between groups [P> 0.05]. Vitrectomy with preoperative IVB may have no detrimental effect on surgical procedures and achieves the surgical outcomes for repair of PDR equal to vitrectomy alone despite the obvious selection bias of the patients in this study. However, special monitoring is highly recommended for early postoperative vitreous hemorrhage because bevacizumab in the vitreous may be washed out during vitrectomy

Nephropathy following Type 2 diabetes mellitus in Tunisian population / Nefropatía tras la diabetes mellitus tipo 2 en la población Tunesina

OBJECTIVE: The purpose was to compare the characteristics of Tunisians with Type 2 diabetes mellitus (Type 2 DM) and nephropathy with those without nephropathy. This study assessed whether or not phenotypic characteristics can predict nephropathy development in Type 2 DM. The prevalence of nephropathy in Tunisian Type 2 DM patients, and their relationship with clinical and biochemical factors as well as chronic complications of the disease were determined. METHODS: This was a cross-sectional study of patients with diabetes diagnosed between January 2008 and December 2010. Altogether, 73 Type 2 DM and 42 healthy volunteers from the Basic Health Group of Sousse, were targeted for the study. Clinical, biochemical data, as well as complications of diabetes were collected. Kidney malfunction was defined by glomerular filtration rate (GFR). RESULTS: Diabetic patients were older. Diabetic women were more likely to have higher body mass index than men (p = 0.004). Obesity was more in women than men (60/23%). Complications including hypertension and dyslipidaemia were co-associated in women. Urinary creatinine clearance in Type 2 DM patients without nephropathy was significantly lower than in healthy participants (p < 0.0001). Microalbuminuria and urinary creatinine clearance were associated only in women with Type 2 DM with nephropathy (R² = 0.95); 1.5% of Type 2 DM patients without nephropathy had GFR < 60 mL/min/1.73m² and 76% had a GFR between 60 and 89 mL/min/1.73m². Glomerular filtration rate difference between Type 2 DM patients with/without nephropathy, as well as between Type 2 DM patients with nephropathy/Type 2 DM without nephropathy, and with retinopathy was not significant. CONCLUSIONS: By analysing factors associated with nephropathy in Type 2 DM Tunisian patients, this study demonstrated their susceptibility to nephropathy. In addition, retinopathy is potentially associated with incipient nephropathy in Type 2 DM Tunisian patients.

OBJETIVO: El propósito fue comparar las características de los tunesinos con diabetes mellitus tipo 2 (DMT2) y nefropatía, con aquéllos que no padecen nefropatía. Este estudio evaluó la posibilidad de saber si las características fenotípicas pueden predecir el desarrollo de una nefropatía en pacientes de DMT2. Se determinó la prevalencia de la nefropatía en los pacientes tunesinos con DMT2, y su relación con factores clínicos y bioquímicos, así como las complicaciones crónicas de la enfermedad. MÉTODOS: Se realizó un estudio transversal de pacientes con diabetes diagnosticada entre enero de 2008 y diciembre de 2010. En total, 73 voluntarios con DMT2 y 42 saludables del Grupo Básico de Salud de Sousse, fueron escogidos para el estudio. Se recogieron los datos clínicos y bioquímicos, así como las complicaciones por diabetes. El grado de mal funcionamiento renal fue determinado por la tasa de filtrado glomerular (GFR). RESULTADOS: Los pacientes diabéticos tenían más edad. Las mujeres diabéticas presentaban una mayor probabilidad de tener un índice de masa corporal más alto que los hombres (p = 0.004). Hubo mayor obesidad en las mujeres que en los hombres (60/23%). Las complicaciones - incluyendo hipertensión y dislipidemia - estuvieron co-asociadas en las mujeres. La depuración de la creatinina urinaria en los pacientes de DMT2 sin nefropatía fue significativamente más baja (p < 0.0001) que en los participantes saludables. La microalbuminuria y la depuración de la creatinina urinaria estuvieron asociadas en las mujeres con DMT2 con nefropatía (R² = 0.95); 1.5% de los pacientes con DMT2 sin nefropatía, tuvo una tasa GFR < 60 mL/min/1.73m² y 76% tuvo una GFR entre 60 y 89 mL/min/1.73m². La diferencia de la tasa de filtrado glomerular entre los pacientes de DMT2 con/sin nefropatía, así como entre los pacientes de DMT2 con nefropatía/DMT2 sin nefropatía, y con retinopatía, no fue significativa. CONCLUSIONES: Analizando factores asociados con la nefropatía en pacientes tunesinos con DMT2, este estudio demostró que estos últimos son susceptibles a la nefropatía. Además, la retinopatía se halla potencialmente asociada con la nefropatía incipiente en los pacientes tunesinos que padecen DMT2.

Correlation between central subfield thickness, visual acuity and structural changes in diabetic macular edema / Correlação entre a espessura do subcampo central, a acuidade visual e mudanças estruturais no edema macular diabético

PURPOSE: To correlate the central subfield thickness (CST) measured by CirrusTM SD-OCT with best-corrected visual acuity (BCVA) and structural changes in diabetic macular edema (DME). METHODS: The transversal study evaluated 200 patients with non-proliferative diabetic retinopathy (NPDR) and selected 55 eyes with DME between January, 2010 and April, 2011. Spectral domain OCT was performed in patients with type 2 diabetes and DME. CST and BCVA were correlated with the edema morphology and the ELM (external limiting membrane) integrity. Statistical tests were applied to validate the results. RESULTS: There was no difference between genders in the NPDR classification. 47.3% of the patients showed moderate NPDR. The CST average for male was of 393.58 µm and 434.16 µm for female, with no statistically significant difference. The patients with continuous ELM showed lower CST average (368.73 µm) than those with disrupted ELM (521.43 µm). There was a strong correlation between the macular volume and CST (59.63%), but poor correlation between age and CST (2.9%). Also, there was a significant difference between the average CST and the type of macular edema. Patients with serous detachment showed higher CST average (488.71 µm) than those with cystoid macular edema (CME) and diffuse edema. Patients with severe NPDR showed higher CST average (491.45 µm), if compared to mild and moderate NPDR. Cystoid macular edema was the most common type of edema (49.1%) and showed the worse VA. Patients with disrupted ELM showed worse BCVA. Patients with higher CST showed worse BCVA. There was a significant difference between the CST average of the case group (407.6 ± 113,1 µm) and the control group (diabetic patients without DME: 252 ± 12.5 µm). There was also a significant difference in the BCVA variables and macular volume between case and control groups. CONCLUSION: The study suggests that the CST of diabetic patients with edema is higher than the control group, the increase in CST of diabetic patients with edema leads to worsening of BCVA and macular volume. Continuous ELM showed lower CST average, and the serous detachment showed higher CST average. CirrusTM proved to be an important tool in the DME evaluation.

OBJETIVO: Correlacionar a espessura do subcampo central (ESCC) medida pelo CirrusTM SD-OCT com a acuidade visual (AV) e as mudanças estruturais no edema macular diabético (EMD). MÉTODOS: Um estudo transversal avaliou 200 pacientes com retinopatia diabética não proliferativa (RDNP) e selecionados 55 olhos com EMD entre janeiro de 2010 e abril de 2011. OCT spectral foi realizado em pacientes com diabetes tipo 2 e com edema macular diabético (EMD). A ESCC e a AV foram correlacionados com a morfologia do edema e a integridade da membrana limitante externa (MLE). Aplicaram-se testes estatísticos para validação dos resultados. RESULTADOS: Não houve diferença entre os sexos na classificação RDNP. 47,3% dos pacientes apresentou RDNP moderada. A média da ESCC no sexo masculino foi de 393,58 µm e no feminino de 434,16 µm, sem diferença estatística significativa. Pacientes com MLE íntegra apresentaram menor média da ESCC (368,73 µm) que aqueles com MLE descontínua (521,43 µm). Encontrou-se forte correlação entre o volume macular e a ESCC (59,63%), porém pequena correlação entre a idade e a ESCC (2,9%). Encontrou-se diferença significativa entre a média da ESCC e o tipo de edema macular, aqueles com descolamento seroso apresentaram maior média de ESCC (488,71 µm). Pacientes com RDNP grave apresentaram maior média da ESCC (491,45 µm), quando comparados à RDNP leve e moderada. O edema macular cistoide foi o tipo de edema mais frequente (49,1%) e apresentou pior AV. Pacientes com MLE íntegra apresentaram melhor AV. Pacientes com maior ESCC apresentaram pior AV. Houve diferença significativa entre a média da ESCC do grupo de casos (407,60 ± 113,05 µm) e controle (diabéticos sem edema macular: 252,0 ± 12,46 µm). Também houve diferença significativa nas variáveis AV e volume macular entre o grupo de casos e controle. CONCLUSÃO: O estudo sugere que a ESCC de diabéticos com edema é maior que o grupo controle; o aumento da ESCC de diabéticos com edema cursa com piora da AV e do volume macular. MLE contínua mostrou menor média da ESCC e o descolamento seroso mostrou maior média da ESCC. CirrusTM mostrou ser importante ferramenta na avaliação do EMD.

Factores de riesgo en el desarrollo de la retinopatía diabética / Risk factors in the development of diabetic retinopathy

OBJETIVO: Identificar los factores de riesgo que favorecen la aparición de la retinopatía diabética. MÉTODOS: Se efectuó un estudio observacional analítico de tipo caso-control en 153 diabéticos atendidos consecutivamente en el Centro de Atención al Diabético, entre julio y diciembre del año 2008. Se estudiaron: edad, sexo, color de piel, consumo de alcohol, hábito de fumar, tipo de diabetes mellitus, tratamiento y evolución, tipo de retinopatía diabética, factores sistémicos y oculares asociados. Se aplicó Odds Ratio para valorar la influencia de factores de riesgo en probabilidad de aparición de la complicación. RESULTADOS: Predominaron los diabéticos tipo 2 (72,5 por ciento en grupo estudio y 79,4 por ciento en grupo control), la retinopatía diabética no proliferativa moderada (31,4 por ciento), las mujeres (70,6 por ciento en grupo estudio y 61,8 por ciento en grupo control) mayores de 40 años y piel blanca. La hipertensión arterial (OR= 2,83, p= 0,003) se presentó en 52,9 y 28,4 por ciento, respectivamente. En el grupo estudio, el 43,1 por ciento eran fumadores (OR= 2,76, p= 0,005) y el 72,5 por ciento tenían más de 15 años de evolución de la diabetes (OR= 17,91, p= 0,000) mientras 62,8 por ciento del grupo control llevaban entre 5 y 15 años de diabéticos. Resultaron significativos el antecedente de oclusión venosa retiniana (OR= 4,92, p= 0,001), cirugía de catarata (OR= 2,85, p= 0,012), cicatriz coriorretiniana (OR= 0,12, p= 0,015) y glaucoma primario de ángulo abierto (OR= 0,18, p=0,013). CONCLUSIONES: Los factores de riesgo asociados fueron: tiempo de evolución de la diabetes mellitus en pacientes con tiempo de evolución de la enfermedad mayor de 15 años, la hipertensión arterial, el hábito de fumar, antecedentes de cirugía de catarata y oclusiones venosas. El glaucoma primario de ángulo abierto y cicatrices coriorretinianas parecen ser factores protectores significativos

OBJECTIVE: To identify the risk factors favoring the appearance of the diabetic retinopathy. METHODS: A case-control, analytical and observational study was conducted in 153 diabetic patients seen in the Diabetes Care Center from July to December, 2008. Variables included: age, sex, skin color, alcohol consumption, smoking, type of diabetes mellitus, treatment and evolution type of diabetic retinopathy, associated systemic and ocular factors. Odds Ratio was applied to assess the influence of risk factors on probability of appearance of the complication. RESULTS: There was predominance of type 2 diabetes (72.5 percent in study group and 79.4 percent in control group), moderate non-proliferative diabetic retinopathy (31.4 percent), women (70.6 percent) in study group and 61.8 percent in control group, over 40 years old and white skin. High blood pressure (OR = 2.83, p = 0.003) was present in the 52.9 and 28.4 percent, respectively. In the study group, the 43.1 percent were smokers (OR = 2.76, p= 0.005) and the 72.5 percent had more than 15 years of evolution of diabetes (OR= 17.91, p= 0.000) whereas the 62,8 percent of control group had 5 and 15 years to be diabetic. The retinal occlusion background (OR - 4.92, p= 0.001), cataract's surgery ( OR= 2.85, p= 0.012), chorioretinal scar (OR= 0.12, p = 0.015) and open angle primary glaucoma (OR= 0.18, p= 0.013). CONCLUSIONS: The associated risk factors were: evolution of the diabetes mellitus bigger than 15 years, arterial hypertension, smoking habit, antecedents of cataracts surgery and vein occlusions. Primary open angle glaucoma and corioretinal scars seem to be protective significant factors

Complicações microvasculares e disfunção autonômica cardíaca em pacientes com diabete melito tipo 1 / Microvascular complications and cardiac autonomic dysfunction in patients with diabetes mellitus type 1 / Complicaciones microvasculares y disfunción autonómica cardíaca en pacientes con diabetes mellittus tipo 1

FUNDAMENTO: A presença de neuropatia autonômica cardíaca (NAC) em pacientes com diabete melito (DM) está associada a aumento da mortalidade e a complicações crônicas microvasculares do diabete. OBJETIVO: Investigar uma possível associação entre achados sugestivos de NAC durante a realização do teste ergométrico (TE) e nefropatia e retinopatia em pacientes com DM tipo 1. MÉTODOS: Realizamos um estudo transversal com 84 pacientes com DM tipo 1. Todos os pacientes foram submetidos à avaliação clínica e laboratorial e realizaram TE, sendo que aqueles que apresentaram achados sugestivos de isquemia miocárdica foram excluídos da análise dos dados (n = 3). A avaliação de complicações microvasculares (retinopatia e nefropatia) foi realizada na amostra. RESULTADOS: Os pacientes com nefropatia e aqueles com retinopatia atingiram uma frequência cardíaca (FC) durante o pico de exercício (FC máxima) menor e apresentaram aumento menor da FC em relação ao repouso (ΔFC pico) quando comparados com aqueles sem estas complicações. Esses pacientes também apresentaram menor redução da FC no segundo e 4º minutos após o final do teste (ΔFC recuperação dois e 4 minutos). Após realização de análise multivariada com controle para os possíveis fatores de confusão, os ΔFC recuperação em dois e 4 minutos, FC máxima e o ΔFC pico permaneceram significativamente associados à retinopatia; e os ΔFC recuperação no segundo e 4º minutos permaneceram associados à presença de nefropatia. CONCLUSÃO: O TE pode ser considerado um instrumento adicional para a detecção precoce de NAC e para identificar pacientes em maior risco para complicações microvasculares do diabete.

BACKGROUND: The presence of cardiac autonomic neuropathy (CAN) in patients with diabetes mellitus (DM) is associated with increased mortality and chronic microvascular complications of diabetes. OBJECTIVE: To investigate a possible association between specific findings of CAN during exercise testing (ET) and nephropathy and retinopathy in patients with type 1 DM. METHODS: We conducted a cross-sectional study of 84 patients with type 1 DM. All patients underwent clinical laboratory evaluation and performed ET, and those who presented findings suggesting myocardial ischemia were excluded from data analysis (n = 3). The assessment of microvascular complications (retinopathy and nephropathy) was performed in the sample. RESULTS: Patients with nephropathy and those with retinopathy achieved a lower heart rate (HR) at peak exercise (HR max) and smaller increase in HR in relation to rest (Peak ΔHR) compared with those without these complications. These patients also had a smaller reduction in HR in the second and 4th minutes after the end of the test (ΔHR recovery 2 and 4 minutes). After performing a multivariate analysis with control for possible confounding factors, the ΔHR recovery in two and four minutes, maximum HR and Peak ΔHR remained significantly associated with retinopathy; and ΔHR recovery in the second and 4th minutes remained associated with the presence of nephropathy. CONCLUSION: The ET can be considered an additional tool for early detection of CAN and to identify patients at increased risk for microvascular complications of diabetes.

BACKGROUND: LA presencia de neuropatía autonómica cardíaca (NAC) en pacientes con diabetes mellittus (DM) está asociada a aumento de la mortalidad y a complicaciones crónicas microvasculares de diabetes. OBJECTIVE: Investigar una posible asociación entre hallazgos sugestivos de NAC durante la realización de la prueba ergométrica (PE) y nefropatía y retinopatía en pacientes con DM tipo 1. METHODS: Realizamos un estudio transversal con 84 pacientes con DM tipo 1. Todos los pacientes fueron sometidos a evaluación clínica y laboratorial y llevaron a cabo PE, siendo que aquellos que presentaron hallazgos sugestivos de isquemia miocárdica fueron excluidos del análisis de los datos (n = 3). La evaluación de complicaciones microvasculares (retinopatía y nefropatía) se realizó en la muestra. RESULTS: Los pacientes con nefropatía y aquellos con retinopatía alcanzaron una frecuencia cardíaca (FC) durante el nivel máximo de ejercicio (FC máxima) menor y presentaron aumento menor de FC con relación al reposo (ΔFC pico) cuando comparados con aquellos sin estas complicaciones. Estos pacientes también presentaron una menor reducción de la FC en el segundo y 4º minutos tras el final de la prueba (ΔFC recuperación 2 y 4 minutos). Tras la realización de análisis multivariado con control para los posibles factores de confusión, los ΔFC recuperación en dos y 4 minutos, FC máxima y el ΔFC pico permanecieron significativamente asociados a la retinopatía; y los ΔFC recuperación en el segundo y 4º minutos permanecieron asociados a la presencia de nefropatía. CONCLUSION: Se puede considerar la PE como un instrumento adicional para la detección precoz de NAC y para identificar pacientes en un mayor riesgo para complicaciones microvasculares de la diabetes.

Microalbuminuria and low hemoglobin as risk factors for the occurrence and increasing severity of diabetic retinopathy.

Aim: To assess the influence of urinary microalbuminuria and hemoglobin concentration on the occurrence and severity of diabetic retinopathy (DR), clinically significant macular edema (CSME) and hard exudate formation. Materials and Methods: In this prospective cross-sectional study carried out over a period of 2 years, type 2 diabetic patients seeking ocular evaluation for DR were assessed for presence and severity of DR, presence of hard exudates and CSME. Retinal findings were correlated to severity of microalbuminuria, hemoglobin concentration and other systemic risk factors using linear regression analysis. Results: Three hundred and six patients were included in the study. DR of any grade was seen in 132 (43%) patients, hard exudate formation in 93/306 (30.4%) patients, CSME in 50/306 (16.3%) patients and proliferative DR in 26/306 (8.5%) patients. Duration of diabetes (P <0.001), microalbuminuria (P <0.001) and low hemoglobin (P = 0.001) were found to be highly significant risk factors for the development and increasing severity of DR as well as for CSME and hard exudate formation. Conclusion: Microalbuminuria and low hemoglobin are strong predictors for DR, CSME and hard exudate formation in type 2 diabetics even after correcting for duration of diabetes and other systemic risk factors. Although not directly involved in the pathogenesis, microalbuminuria can help in identifying patients at risk for more severe diabetic eye disease. Microalbuminuria warrants intensive monitoring of both retinal and renal status. The hemoglobin levels should be monitored regularly in diabetic patients to detect and treat anemia, thereby reducing one risk factor for DR.

Pupil cycle time and contrast sensitivity in type II diabetes mellitus patients: A pilot study.

Context: Pupil cycle time (PCT) has been widely used for examination of ocular diabetic autonomic neuropathy (DAN). Aims: The primary aim of this study was to evaluate the difference of contrast sensitivity according to PCT results, and the secondary aim was to determine the factors associated with PCT difference for type II diabetes patients. Settings and Design: A clinical pilot study that included a total of 60 eyes of 60 type II diabetes patients. Materials and Methods: We divided all patients into three groups according to PCT results. Group A and Group C were composed of patients who had upper one third PCT and lower one third PCT, respectively. We analyzed difference of age, diabetes duration, hypertension duration, mean best corrected visual acuity (BCVA), mean spherical equivalent (SE), HbA1C, glomerular filtration rate (GFR), stage of diabetic retinopathy, and Cardiac Autonomic Function Score (CAFS). Contrast sensitivity and decrease of visual acuity by glare were also estimated and analyzed for 28 eyes of 28 non-proliferative diabetic retinopathy (NPDR) patients. Group [NPDR] A and Group [NPDR] C were defined as those who had lower one third PCT and upper one third PCT, respectively. Statistical Analysis: Statistical analysis was done using SPSS 17.0 software. Results and Conclusions: Each group contained 20 eyes. Significant differences between Group A and Group C were observed in duration of diabetes and CAFS (P ≤ 0.001 and P <0.001, respectively). Contrast sensitivity in Group [NPDR] A was significantly more than in Group [NPDR] C at all cpds (all P ≤ 0.001). We found that PCT can influence contrast sensitivity or glare in diabetes patients and also confirmed a significant correlation of PCT with CAFS and duration of diabetes.

Diabetes Mellitus tipo 2 no mundo: novas abordagens terapêuticas / Type 2 diabetes in the world: new therapeutic approaches

A Federação Internacional de Diabetes (/DF) publicou novos dados indicando a enormidade da epidemia mundial da doença. Esses dados demonstram que o diabetes afeta atualmente 246 milhões de pessoas em todo o mundo, sendo que 46% destes com idades entre 40 e 59 anos. Dados atuais predizem que, se nada for feito, o número total de portadores de diabetes ultrapassará 380 milhões de pessoas em 20 anos. O estilo de vida moderno trouxe inúmeras mudanças de hábito e comportamento, como menor tempo dedicado à prática de atividades físicas regulares, um cotidiano mais estressante, além da maior oferta de alimentos industrializados, ricos em carboidratos simples e gorduras, pobres em fibras, minerais e vitaminas. Atualmente dedica-se mais tempo a atividades em frente às telas de computadores e a jogos de videogame e programas de televisão. Como consequência, tem-se observado maior incidência de doenças metabólicas, tais como obesidade, diabetes mellitus tipo 2 (DM 2), hipertensão arterial sistêmica (HAS), dislipidemia e, portanto, doenças cardiovasculares (DCVs), gerando a necessidade crescente de pesquisas em busca de novas opções terapêuticas para estas doenças. O presente trabalho visa fazer uma breve revisão sobre os avanços terapêuticos do diabetes mellitus tipo 2.

The International Diabetes Federation (/DF) has published new data indicating the enormity of the diabetes epidemic in the globe. That data show that the disease now affects a staggering 246 million people worldwide, with 46% of a11 those affected in the 40-59 age group. The new data predict that the total number of people living with diabetes will skyrocket to 380 million within twenty years if nothing is done. The modern life style has brought many changes such as more variety of food rich in sugar, fat and poor in fiber, vitamins and minerals, less time to practice a regular physical activity and a more stressful lifestyle. Nowadays, people spend more time in front of their computers, playing video games and watching programs of TV. As a consequence, many metabolic diseases have been increasing such as obesity, type I1 diabetes mellitus, high blood pressure, hyperlipidemia and cardiovascular diseases, leading the growing necessity of researches for new therapeutic options to these diseases. This article is a short review of type II diabetes mellitus's new treatment.

Comparison of serum glycosylated hemoglobin levels in patients with diabetic cystoid macular edema with and without serous macular detachment.

Aim: A clinical comparative trial was conducted to compare the levels of glycosylated hemoglobin (HbA1c) in patients with diabetic cystoid macular edema (CME) with and without serous macula detachment (SMD). Materials and Methods: Thirty patients (group 1) with diabetic CME in both eyes, but without SMD, and 30 patients (group 2) with diabetic CME and SMD in both eyes documented by optical coherence tomography (OCT) and fundus fluorescein angiography (FFA), were included in the study. In addition to the measurement of central macular thickness by OCT and visual acuity (VA) (as logMAR) using the the early treatment diabetic retinopathy study (ETDRS) chart, the concentrations of HbA1c were measured by high performance liquid chromatography (HPLC). Statistical analysis was done by independent samples t test. Results: The mean logMAR VA was 0.8 ± 0.22 (1.0–0.5) in group 1and 0.7 ± 0.16 (1.0–0.6) in group 2. The mean central macular thickness, as determined by OCT, was 468.70 ± 70.44 μm (344–602 μm) in group 1 and 477.80 ± 73.34 μm (354–612 μm) in group 2. The difference between the groups was not statistically significant (P = 0.626). The mean HbA1c levels were 8.16 ± 0.99% in group 1 and 10.05 ± 1.66% in group 2. The difference between the groups was statistically significant (P < 0.001). Conclusions: The presence of SMD and high HbA1c levels in the patients with diabetic CME may be indirectly suggestive of retinal pigment epithelium dysfunction.

Increased levels of vascular endothelial growth factor in the aqueous humor of patients with diabetic retinopathy.

Purpose: This study aims to investigate the levels of aqueous vascular endothelial growth factor (VEGF) in diabetic patient groups in comparison to normal subjects, and to correlate elevated VEGF with the severity of diabetic retinopathy (DR). Materials and Methods: Aqueous samples were obtained from 78 eyes of 74 patients undergoing intraocular surgery and they were examined by the enzyme-linked immunosorbent assay. Color photographs, optical coherence tomography scans, and fluorescein angiography were used to evaluate patients preoperatively. Results: A strong statistical correlation was found to exist between the level of aqueous VEGF and the severity of DR (P < 0.001), whereas, the VEGF levels in a control group and a diabetic group without DR were not significantly different (P = 0.985). Aqueous VEGF levels were significantly elevated in patients with proliferative DR (PDR) as compared to the control group (P < 0.001), to diabetic patients without retinopathy (NDR) (P < 0.001), and to diabetic patients with nonproliferative DR (NPDR) (P < 0.001). The aqueous VEGF levels were significantly higher in patients with active PDR than in those with quiescent PDR (P = 0.001). On the other hand, a statistically insignificant (P = 0.065) correlation was found between elevated aqueous VEGF and the presence of macular edema in the NPDR group. Conclusions: VEGF was elevated in the aqueous humor of patients with DR compared to that in normal eyes. The aqueous VEGF level had a strong correlation with the severity of retinopathy along with a statistically insignificant difference in macular edema.

Fisiopatología de la retinopatía y nefropatía diabéticas / Pathophysiology of diabetic retinopathy and nephropathy

Despite the availability of multiple therapeutic approaches, diabetes mellitus with chronic hyperglycemia remains as the main cause of new cases of blindness and chronic renal failure in the western hemisphere. We herein review the molecular mechanisms by which chronic hyperglycemia causes retinopathy and nephropathy in type I and type 2 diabetic patients. Diabetic retinopathy develops silently along years or decades, producing symptoms only in its very ¡ate stages. Its slow development starts with the activation of aldose reducíase, shortly followed by the destruction of the retinal pericyte cells, and ends in sudden blindness when vitreous hemorrhage ensues. Nephropathy, on the other hand, centers its pathophysiology in the mesangial cell, that starts as a modified smooth-muscle cell, and turns itself into a myo-fibroblast, produces such amounts of cytoplasm and extracellular protein that strangulates the glomerular capillaries and causes renal failure. After a detailed review of the molecular mechanisms of the aforementioned complications, we conclude that, apart from directing our attention to the emerging medications that are being developed to block these molecular pathways, we should never abandon the struggle for improving the glycemic control of our diabetic patients.