Iron Overload in Diabetic Retinopathy: A Cause or a Consequence of Impaired Mechanisms?

Iron is an essential ion for life, playing a central role in many metabolic processes. The most important property of free iron is its capacity to be reversibly oxidized and reduced, but at same time this make it highly pro-oxidant molecule. In this regard, iron is able to generate powerful reactive oxygen species (ROS). For this reason, careful control on iron availability is central to the maintenance of normal cell function in the retina. In the diabetic eye there is an impairment of iron homeostasis, thus leading to iron overload. The mechanisms involved in this process include: (1) Destruction of heme molecules induced by hyperglycemia (2) Intraretinal and vitreal hemorrhages (3) Overexpression of the renin-angiotensin system. The main consequences of iron overload are the following: (1) Retinal neurodegeneration due to the increase of oxidative stress (2) Increase of AGE-RAGE binding (3) Defective phagocytosis of retinal pigment epithelium, which generates the accumulation of autoantigens and the synthesis of proinflammatory cytokines. Further studies addressed to explore not only the role of iron in the pathogenesis of diabetic retinopathy, but also to design novel therapeutic strategies based on the regulation of iron homeostasis are needed

New methods for the diagnosis and monitoring of cognitive function in patients with type 2 diabetes

Dementia; Retinal microperimetry; Type 2 diabetesDemencia; Microperimetría retiniana; Diabetes tipo 2Demència; Microperimetria retiniana; Diabetis tipus 2The presence of type 2 diabetes acts as an accelerator of cognitive impairment (mild cognitive impairment and later dementia), with a significant impact on the management of the disease and its complications. Therefore, it is recommended to perform an annual evaluation of cognitive function in patients with diabetes older than 65 years. Current guidelines still recommend the use of the Minimental State Evaluation Test (MMSE) as screening test, but it has a modest sensitivity and specificity for identifying mild cognitive impairment. This represents an important gap because patients with mild cognitive impairment are at risk of progressing to dementia. The neurocognitive diagnosis is based on complex neuropsychological tests, which require specifically trained personnel and are time consuming, making its routine incorporation into daily clinical practice unfeasible. Therefore, at present there are no reliable biomarkers to identify patients with type 2 diabetes at increased risk of developing cognitive impairment. Since the brain and the retina have a common embryological origin, our Research Group, has worked over the last 10 years evaluating the usefulness of the retina as a “window” to the brain. We provided evidence that retinal microperimetry is a simple, feasible and useful tool for screening and monitoring cognitive function in patients with type 2 diabetes. We propose a review of actual tests recommended for screening of cognitive impairment as well as an update of new emerging methods, such as retinal microperimetry

GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Physiology to Clinical Outcomes

GLP-1 receptor agonists; Diabetic kidney diseaseAgonistas del receptor de GLP-1; Enfermedad renal diabéticaAgonistes del receptor GLP-1; Malaltia renal diabèticaDiabetic kidney disease (DKD) is one of the most common complications in type 2 diabetes mellitus (T2D) and a major cause of morbidity and mortality in diabetes. Despite the widespread use of nephroprotective treatment of T2D, the incidence of DKD is increasing, and it is expected to become the fifth cause of death worldwide within 20 years. Previous studies have demonstrated that GLP-1 receptor agonists (GLP-1 RA) have improved macrovascular and microvascular outcomes independent of glycemic differences, including DKD. GLP-1Ras’ improvement on kidney physiology is mediated by natriuresis, reduction in hyperfiltration and renin-angiotensin-aldosterone system (RAAS) activity and anti-inflammatory properties. These findings translate into improved clinical outcomes such as an enhanced urine albumin-to-creatinine ratio (UACR) and a reduction in renal impairment and the need for renal replacement therapies (RRT). In this article, we review the role of GLP-1RAs on the mechanisms and effect in DKD and their clinical efficacy.This research received no external funding

Comparison of computed tomography and dual-energy X-ray absorptiometry in the evaluation of body composition in patients with obesity

Objectivea) To evaluate the accuracy of the pre-existing equations (based on cm2 provided by CT images), to estimate in kilograms (Kg) the body composition (BC) in patients with obesity (PwO), by comparison with Dual-energy X-ray absorptiometry (DXA). b) To evaluate the accuracy of a new approach (based on both cm2 and Hounsfield Unit parameters provided by CT images), using an automatic software and artificial intelligence to estimate the BC in PwO, by comparison with DXA.MethodsSingle-centre cross-sectional study including consecutive PwO, matched by gender with subjects with normal BMI. All the subjects underwent BC assessment by Dual-energy X-ray absorptiometry (DXA) and skeletal-CT at L3 vertebrae. CT images were processed using FocusedON-BC software. Three different models were tested. Model 1 and 2, based on the already existing equations, estimate the BC in Kg based on the tissue area (cm2) in the CT images. Model 3, developed in this study, includes as additional variables, the tissue percentage and its average Hounsfield unit.Results70 subjects (46 PwO and 24 with normal BMI) were recruited. Significant correlations for BC were obtained between the three models and DXA. Model 3 showed the strongest correlation with DXA (r= 0.926, CI95% [0.835-0.968], p<0.001) as well as the best agreement based on Bland – Altman plots.ConclusionThis is the first study showing that the BC assessment based on skeletal CT images analyzed by automatic software coupled with artificial intelligence, is accurate in PwO, by comparison with DXA. Furthermore, we propose a new equation that estimates both the tissue quantity and quality, that showed higher accuracy compared with those currently used, both in PwO and subjects with normal BMI

New methods for the diagnosis and monitoring of cognitive function in patients with type 2 diabetes

The presence of type 2 diabetes acts as an accelerator of cognitive impairment (mild cognitive impairment and later dementia), with a significant impact on the management of the disease and its complications. Therefore, it is recommended to perform an annual evaluation of cognitive function in patients with diabetes older than 65 years. Current guidelines still recommend the use of the Minimental State Evaluation Test (MMSE) as screening test, but it has a modest sensitivity and specificity for identifying mild cognitive impairment. This represents an important gap because patients with mild cognitive impairment are at risk of progressing to dementia. The neurocognitive diagnosis is based on complex neuropsychological tests, which require specifically trained personnel and are time consuming, making its routine incorporation into daily clinical practice unfeasible. Therefore, at present there are no reliable biomarkers to identify patients with type 2 diabetes at increased risk of developing cognitive impairment. Since the brain and the retina have a common embryological origin, our Research Group, has worked over the last 10 years evaluating the usefulness of the retina as a "window" to the brain. We provided evidence that retinal microperimetry is a simple, feasible and useful tool for screening and monitoring cognitive function in patients with type 2 diabetes. We propose a review of actual tests recommended for screening of cognitive impairment as well as an update of new emerging methods, such as retinal microperimetry

Analysis of Effectiveness and Psychological Techniques Implemented in mHealth Solutions for Middle-Aged and Elderly Adults with Type 2 Diabetes: A Narrative Review of the Literature

Diabetis; Gent gran; Tècniques psicològiquesDiabetes; Elderly; Psychological techniquesDiabetes; Ancianos; Técnicas psicológicaBackground: in diabetes, multiple mHealth solutions were produced and implemented for self-management behaviors. However, little research on the effectiveness of psychological techniques implemented within these mHealth solutions was carried out, and even less with the elderly population where technological barriers might exist. Reliable evidence generated through a comprehensive evaluation of mHealth interventions may accelerate its growth for successful long-term implementation and to help to experience mHealth benefits in an enhanced way in all ages. Objective: this study aimed to review mHealth solutions for diabetes self-management in older adults (adherence to treatments and glycemic control) by analyzing the effectiveness of specific psychological techniques implemented. Methods: a narrative review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed (Medline) and American Psychological Association (APA) PsycInfo databases were searched for published papers that addressed eHealth solutions’ effectiveness for diabetes self-management. Studies in English, Spanish, and/or German of any design were screened, with no time constraints regarding the year of publication. A qualitative analysis of the selected papers was conducted in several steps. Results: this review found 38 studies setting up and analyzing mHealth solutions for older adults. Most research showed improvements in HbA1c, self-management behaviors, and medication adherence in T2DM patients post intervention. However, different mid-to-long term effects were found across studies, specifically concerning the maintenance and adherence to healthy behaviors. The most employed psychological framework was CBT, including techniques such as self-monitoring of outcome behaviors (mostly targeting glycemia measurements and healthy habits as physical activity and/or diet), tailored motivational feedback from medical staff, and psychoeducation or health coaches. The most successful mHealth intervention combined the feature of tailored feedback messages, interactive communication with healthcare professionals, and multifaceted functions. Conclusions: there is a lack of elaborate and detailed information in the literature regarding the factors considered in the design and development of mHealth solutions used as interventions for T2DM self-management in the elderly. Documentation and inclusion of such vital information will foster a transparent and shared decision-making process that will ultimately lead to the development of useful and user-friendly self-management apps that can enhance the quality of life for diabetes patients. Further research adapting mHealth solutions to older adults’ sensory deficits is necessary.This research received no external funding

Molecular Implications of the PPARs in the Diabetic Eye

Diabetic retinopathy (DR) remains as the leading cause of blindness among working age individuals in developed countries. Current treatments for DR (laser photocoagulation, intravitreal corticosteroids, intravitreal anti-VEGF agents, and vitreoretinal surgery) are applicable only at advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of the disease are needed. Emerging evidence indicates that peroxisome proliferator-activator receptors (PPARs) agonists (in particular PPAR α ) are useful for the treatment of DR. However, the underlying molecular mechanisms are far from being elucidated. This paper mainly focuses on PPARs expression in the diabetic eye, its molecular implications, and the effect of PPAR agonists as a new approach for the treatment of DR. The availability of this new strategy will not only be beneficial in treating DR but may also result in a shift towards treating earlier stages of diabetic retinopathy, thus easing the burden of this devastating disease (Cheung et al. (2010))

Usefulness of eye fixation assessment for identifying type 2 diabetic subjects at risk of dementia

Type 2 diabetic (T2D) subjects have a significantly higher risk of developing mild cognitive impairment (MCI) and dementia than age-matched non-diabetic individuals. However, the accurate evaluation of cognitive status is based on complex neuropsychological tests, which makes their incorporation into the current standard of care for the T2D population infeasible. Given that the ability to maintain visual gaze on a single location (fixation) is hampered in Alzheimer's disease (AD), the aim of the present study was: (1) To assess whether the evaluation of gaze fixation during fundus-driven microperimetry correlated with cognitive status in T2D subjects; (2) to examine whether the addition of fixational parameters to the assessment of retinal sensitivity increased the predictive value of retinal microperimetry in identifying T2D subjects with MCI. For this purpose, fixation parameters and retinal sensitivity were compared in three age-matched groups of T2D subjects: normocognitive (n = 34), MCI (n = 33), and AD (n = 33). Our results showed that fixation is significantly more unstable in MCI subjects than normocognitive subjects, and even more altered in those affected by AD (ANOVA; p < 0.01). Moreover, adding fixation parameters to retinal sensitivity significantly increases the predictive value in identifying those subjects with MCI: ROC (Receiver Operating Characteristic) Area 0.68 with retinal sensitivity alone vs. ROC Area 0.86 when parameters of fixation are added to retinal sensitivity (p < 0.01). In conclusion, our results suggest that fixational eye movement parameters assessed by fundus-microperimetry represent a new tool for identifying T2D subjects at risk of dementia

Prevalence and risk factors accounting for true silent myocardial ischemia: a pilot case-control study comparing type 2 diabetic with non-diabetic control subjects

<p>Abstract</p> <p>Background</p> <p>Given the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, the need to screen asymptomatic diabetic patients for CAD assumes increasing importante. The aims of the study were to assess prospectively the prevalence and risk factor predictors of true silent myocardial ischemia (myocardial perfusion defects in the absence of both angina and ST-segment depression) in asymptomatic type 2 diabetic patients.</p> <p>Methods</p> <p>Stress myocardial perfusion gated SPECT (Single Photon Emission Computed Tomography) was carried out in 41 type 2 diabetic patients without history of cardiovascular disease (CVD) and 41 nondiabetic patients matched by age and gender.</p> <p>Results</p> <p>There were no significant differences between the two groups regarding either the classic CVD risk factors or left ventricular function. True silent ischemia was detected in 21.9% of diabetic patients but only in 2.4% of controls (p < 0.01). The presence of myocardial perfusion defects was independently associated with male gender and the presence of diabetic retinopathy (DR). The probability of having myocardial perfusion defects in an asymptomatic diabetic patient with DR in comparison with diabetic patients without DR was 11.7 [IC95%: 3.7-37].</p> <p>Conclusions</p> <p>True silent myocardial ischemia is a high prevalent condition in asymptomatic type 2 diabetic patients. Male gender and the presence of DR are the risk factors related to its development.</p