Diabetic retinopathy (DR) is the leading cause of visual impairment and preventable blindness and represents a significant socioeconomic cost for healthcare systems worldwide. In early stages of DR ...the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR (mainly blood glucose and blood pressure). The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. Therefore, new treatments for the early stages of DR are needed. However, in early stages of DR invasive treatments such as intravitreal injections are too aggressive, and topical treatment seems to be an emerging route. In the present review, therapeutic strategies based on the main pathogenic mechanisms involved in the development of DR are reviewed. The main gap in the clinical setting is the treatment of early stages of DR and, therefore, this review emphasizes in this issue by giving an overview of potential druggable targets. By understanding of disease-specific pathogenic mechanisms, biological heterogeneity and progression patterns in early and advanced DR a more personalised approach to patient treatment will be implemented.
Background
Bariatric surgery (BS) has a significant impact on body composition. The purpose of the study is to evaluate the usefulness of musculoskeletal ultrasound (MUS) to bioelectrical impedance ...(BIA) in the follow-up of patients undergoing BS in terms of body composition and quality of life (QoL).
Methods
This is a prospective pilot study including 32 subjects (75% female, mean age: 49.15 ± 1.9 years) who underwent BS. Fat mass (FM), lean mass (LM), and skeletal muscle index (SMI) were calculated by BIA. MUS measured subcutaneous fat (SF) and thigh muscle thickness (TMT) of the quadriceps. QoL was assessed by the Moorehead-Ardelt questionnaire. All these measurements were performed 1 month prior to BS and at 12-month follow-up.
Results
The mean BMI decreased by 6.63 ± 1.25 kg/m
2
(
p
=0.001). We observed significant reductions in FM (
p
=0.001) and SF (
p
=0.007) and in LM (
p
=0.001) but not in SMI and TMT. We found a correlation between the FM and SF (pre-surgical,
r
=0.42,
p
=0.01; post-surgical,
r
=0.52,
p
=0.003) and between SMI and TMT (pre-surgical,
r
=0.35,
p
=0.04; post-surgical,
r
=0.38,
p
=0.03). QoL test showed significant improvement (
p
=0.001). In addition, a correlation between the QoL questionnaire and TMT post-surgery (
r
=0.91,
p
=0.019) was observed. However, we did not find any statistically significant correlation between QoL assessment and SMI or LM.
Conclusions
Our results suggest that MUS can be complementary to BIA for the evaluation and the follow-up of body composition after BS. TMT of quadriceps can provide relevant information about regional sarcopenia and has a significant correlation with QoL.
Graphical Abstract
Diabetic retinopathy (DR) is the most frequent complication of diabetes. The main risk factors are disease duration, a poor glycemic control, and the presence of hypertension. However, there is an ...important variation in risk which indicates that other factors, such as genetic heritability or glycemic variability, play an important role in accounting for the susceptibility to DR development. Another important concept is that DR is an independent predictor of both microvascular and macrovascular complications. Thus, the presence of DR should be taken into account when evaluating the cardiovascular risk of a diabetic subject. Moreover, the evaluation of retinal neurodegeneration could help to identify those diabetic subjects at risk of cognitive impairment, an emerging complication of the type 2 diabetic population. When evaluating a diabetic subject, the awareness of the presence of DR has also therapeutic implications. In this regard, a worsening of DR could occur after a rapid improvement of blood glucose. In summary, a critical review on the importance of the presence of DR in the general management of subjects with diabetes is provided.
The etiology of diabetic retinopathy (DR) is complex, multifactorial and compromises all the elements of the retinal neurovascular unit (NVU). This diabetic complication has a chronic low-grade ...inflammatory component involving multiple inflammatory mediators and adhesion molecules. The diabetic milieu promotes reactive gliosis, pro-inflammatory cytokine production and leukocyte recruitment, which contribute to the disruption of the blood retinal barrier. The understanding and the continuous research of the mechanisms behind the strong inflammatory component of the disease allows the design of new therapeutic strategies to address this unmet medical need. In this context, the aim of this review article is to recapitulate the latest research on the role of inflammation in DR and to discuss the efficacy of currently administered anti-inflammatory treatments and those still under development.
Aims/hypothesis
The main aims of the present study were: (1) to assess the expression and content of dipeptidyl peptidase IV (DPP-IV) in human and
db/db
mouse retinas, and in human vitreous fluid; ...and (2) to determine whether the topical administration of the DPP-IV inhibitors (DPP-IVi) would prevent retinal neurodegeneration and vascular leakage in
db/db
mice by reducing endogenous glucagon-like peptide 1 (GLP-1) degradation.
Methods
To assess the expression and content of DPP-IV, human samples of vitreous fluid and retinas were obtained from participants with type 2 diabetes (
n
= 8) and age-matched non-diabetic individuals (
n
= 8), as well as from
db/db
(
n
= 72) and
db/+
(
n
= 28) mice. The interventional study, which included 72
db/db
mice, consisted of the topical administration (eye drops) of saxagliptin, sitagliptin or vehicle for 14 days. DPP-IV mRNA levels were assessed by RT-PCR, and protein content was measured by ELISA or western blotting. GLP-1 was assessed by immunofluorescence, and its downstream effector exchange protein activated by cAMP-1 (EPAC-1) was used as a measure of GLP-1 receptor activation. Retinal analyses were performed in vivo by electroretinography and ex vivo by RT-PCR
(Epac-1
,
Iba-1
also known as
Aif1
), western blotting (EPAC-1, glial fibrillar acidic protein GFAP, glutamate−aspartate transporter GLAST) and immunofluorescence measurements (GLP-1, GFAP, ionised calcium binding adaptor molecule 1 IBA-1, TUNEL, GLAST, albumin and collagen IV). Glutamate was quantified by HPLC. In addition, vascular leakage was examined by the Evans Blue method.
Results
DPP-IV was present in human vitreous fluid but in a range 100-fold less than in plasma. Both mRNA levels and protein content were much lower in the retina than in the liver or bowel, but were significantly higher in retinal pigment epithelium (RPE) from diabetic donors in comparison to non-diabetic donors (
p
< 0.05). Topical treatment with DPP-IVi prevented glial activation, apoptosis and vascular leakage induced by diabetes in
db/db
mice (
p
< 0.05). Moreover, it also significantly prevented diabetes-induced functional abnormalities in the electroretinogram. A significant increase of both GLP-1 and EPAC-1 was found after treatment with DPP-IVi (
p
< 0.05). Furthermore, GLAST downregulation induced by diabetes was prevented, resulting in a significant reduction of extracellular glutamate concentrations. All these effects were observed without any changes in blood glucose levels.
Conclusions/interpretation
The topical administration of DPP-IVi is effective in preventing neurodegeneration and vascular leakage in the diabetic retina. These effects can be attributed to an enhancement of GLP-1, but other mechanisms unrelated to the prevention of GLP-1 degradation cannot be ruled out.
The concept of diabetic retinopathy as a microvascular disease has evolved and is now considered a more complex diabetic complication in which neurovascular unit impairment plays an essential role ...and, therefore, can be considered as a main therapeutic target in the early stages of the disease. However, neurodegeneration is not always the apparent primary event in the natural story of diabetic retinopathy, and a phenotyping characterization is recommendable to identify those patients in whom neuroprotective treatment might be of benefit. In recent years, a myriad of treatments based on neuroprotection have been tested in experimental models, but more interestingly, there are drugs with a dual activity (neuroprotective and vasculotropic). In this review, the recent evidence concerning the therapeutic approaches targeting neurovascular unit impairment will be presented, along with a critical review of the scientific gaps and problems which remain to be overcome before our knowledge can be transferred to clinical practice.
Scope
Low sex hormone‐binding globulin (SHBG) levels are associated with higher risk of developing cardiovascular disease. Epidemiological studies have shown that red wine has beneficial effects on ...cardiovascular disease. In this work if resveratrol content in red wine increases SHBG levels is explored.
Methods and results
A pilot study aims at testing the effect of drinking for 14 days two types of red wine with different resveratrol content is conducted in 26 healthy volunteers. SHBG levels and several biochemical parameters are measured at the beginning and the end of every period. Results show that consumption of both wines does not change body mass index or biochemical markers of liver injury. The low resveratrol wine does not modify the lipid profile or SHBG levels. By contrast, red wine with high resveratrol content significantly reduces total cholesterol in both men and women. Finally, red wine with high resveratrol content increases circulating SHBG in women but not in men.
Conclusions
Red wine rich in resveratrol reduces total cholesterol in men and women and increases SHBG only in women. Further research aims at investigating the potential SHBG role enhancement mediated by resveratrol regarding cardiovascular protection that presents women in comparison with men seems warranted.
Low sex hormone‐binding globulin levels increase the risk of developing cardiovascular disease (CVD). Epidemiologically, red wine has benefits on CVD. A pilot study with volunteers to test the effect of drinking two red wines with different resveratrol content is performed. Red wine rich in resveratrol lowers total cholesterol in both men and women, but only increases SHBG in women.
Type 2 diabetes mellitus (T2D) and Alzheimer’s disease (AD) are two of the most common diseases of aging around the world. Given the frequency with which T2D and AD occur, the notion that people with ...T2D may be at increased risk for AD has large societal consequences, and understanding the mechanistic links between these diseases is imperative for the development of effective AD prevention and treatment strategies. Apart from being an accelerator of AD, T2D is associated with a progressive cognitive decline. Impaired insulin signaling, inflammation, the accumulation of advanced glycation end-products and oxidative stress all play an essential role in the pathogenesis of both AD and diabetic complications. Therefore, it is reasonable to postulate that these pathways are involved in the increased risk of dementia that occurs in the T2D population. The early diagnosis of cognitive impairment and the identification of the subset of patients at a higher risk of developing AD is a challenge for healthcare providers, and meeting it will permit us to implement a personalized medicine, which is an essential issue in diabetes care with significant therapeutic implications. The main gaps that should be filled to achieve this objective are examined.
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