Association Between Obesity and Microvascular Diseases in Patients With Type 2 Diabetes Mellitus

This study aimed to evaluate the association between obesity, evaluated by fat mass index (FMI) with the risk of microvascular diseases in patients with type 2 diabetes mellitus (T2DM) and compare the magnitude of associations of FMI, body mass index (BMI), and waist circumference (WC) with the risk of microvascular diseases. We performed a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes study. The primary microvascular outcomes of the present study included chronic kidney disease (CKD) progression, retinopathy, and neuropathy. Cox proportional-hazards models were performed to evaluate the association of FMI with microvascular diseases. A discordant analysis was performed to compare the magnitude of associations of FMI, BMI, and WC with the risk of microvascular diseases. Our study included 10,251 T2DM participants with a median of 5 years (interquartile range, 4.2–5.7) of follow-up. A total of 6,184 participants developed CKD progression, 896 participants had retinopathy, and 3,213 participants developed neuropathy (Michigan Neuropathy Screening Instrument, >2.0). After the confounding factors were adjusted for, patients in the highest FMI quartile had a higher risk of CKD progression (HR: 1.26, 95%CI: 1.16–1.36) and neuropathy (HR: 1.93, 95% CI: 1.74–2.15), except for retinopathy (HR: 1.17, 95% CI: 0.96–1.43), than those in the lowest quartile. Discordant analyses found that FMI and WC are better in identifying individuals with obesity-related risk of neuropathy, compared with BMI; neither is better in identifying individuals with obesity-related risk of CKD progression and retinopathy. Obesity is associated with CKD progression and neuropathy in T2DM participants. Further randomized trials are needed to test whether obesity control can improve the outcomes of T2DM participants with CKD or neuropathy. FMI and WC are more useful in identifying obesity-related risk of neuropathy compared with BMI in T2DM patients.Clinical Trial Registrationhttp://www.clinicaltrials.gov, NCT00000620.

Tibetan Medicines for the Treatment of Diabetic Nephropathy

As an important part of the traditional Chinese medicine system, Tibetan medicine has its unique treatment methods for diabetes mellitus and its complications. Diabetic nephropathy (DN) is one of the most serious diabetic microvascular diseases. Tibetan medicine believes that the occurrence of DN is closely related to renal function changes, and it can be effectively prevented and treated by improving renal lesions. In this paper, we consult ancient books of Tibetan medicine and summarize the medicines that treat kidney disease in the Tibetan medicine system. The Chinese name, English name, and Latin name of these drugs were searched as keywords in the online database. Thirty-four drugs were found for the treatment of DN. The most commonly used were Amomum kravanh, Terminalia chebula, and Tribulus terrestris, and we introduced the traditional uses and modern pharmacological activities of these drugs. The results indicate that Tibetan medicines for kidney disease could be used as potential candidate drugs for DN; they would expand the range of medications for DN and provide a new idea for the treatment of DN.

Aggressive course of central retinal vein branch occlusion in a young patient after COVID-19

Retinal vein occlusions are believed to have a more favorable prognosis in young patients (<50 years old) due to spontaneous regression. However, 20% of patients have a poor outcome with severe neovascular complications. The causal relationship of occlusion in this age group is still unclear in most cases. There are reports of the development of a clinical picture of retinal vein occlusion in patients with COVID-19, the formation of which is most likely due to hypercoagulation syndrome. Purpose. To present a clinical case of post thrombotic retinopathy in a young patient after COVID-19. Material and methods. A clinical example of post thrombotic retinopathy in a young patient with retinal vein occlusion. Conclusion. Management of patients with retinal vein occlusion, especially at a young age, requires a comprehensive diagnostic approach with an assessment of systemic risk factors and mandatory assessment of the initial degree of retinal ischemia according to fluorescein angiography or Optical coherence tomography angiography. The clinical criteria for the increase in retinal ischemia are a decrease in central visual acuity, macular edema, ischemic area increase, and at the later stages - retinal neovascularization and / or of the anterior segment of the eye. COVID-19 did not affect significantly the change in the parameters of the coagulogram indices. However, its effect as an aggravating factor in a patient with a genetic predisposition to vascular and microvascular diseases cannot be excluded. Key words: OCTA-angiography, retinal neovascularization, post thrombotic retinopathy.

Vascularized Microfluidics and Their Untapped Potential for Discovery in Diseases of the Microvasculature

Microengineering advances have enabled the development of perfusable, endothelialized models of the microvasculature that recapitulate the unique biological and biophysical conditions of the microcirculation in vivo. Indeed, at that size scale (<100 μm)—where blood no longer behaves as a simple continuum fluid; blood cells approximate the size of the vessels themselves; and complex interactions among blood cells, plasma molecules, and the endothelium constantly ensue—vascularized microfluidics are ideal tools to investigate these microvascular phenomena. Moreover, perfusable, endothelialized microfluidics offer unique opportunities for investigating microvascular diseases by enabling systematic dissection of both the blood and vascular components of the pathophysiology at hand. We review ( a) the state of the art in microvascular devices and ( b) the myriad of microvascular diseases and pressing challenges. The engineering community has unique opportunities to innovate with new microvascular devices and to partner with biomedical researchers to usher in a new era of understanding and discovery of microvascular diseases. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Processed foods drive intestinal barrier permeability and microvascular diseases

Intake of processed foods has increased markedly over the past decades, coinciding with increased microvascular diseases such as chronic kidney disease (CKD) and diabetes. Here, we show in rodent models that long-term consumption of a processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glycation pathway, which generates Maillard reaction products within foods upon thermal processing, reversed kidney injury. Consequently, a processed diet leads to innate immune complement activation and local kidney inflammation and injury via the potent proinflammatory effector molecule complement 5a (C5a). In a mouse model of diabetes, a high resistant starch fiber diet maintained gut barrier integrity and decreased severity of kidney injury via suppression of complement. These results demonstrate mechanisms by which processed foods cause inflammation that leads to chronic disease.

Effects of Rutin on Wound Healing in Hyperglycemic Rats

Long-term poor glycemic control negatively affects macrovascular and microvascular diseases, as well as wound restoration. Buckwheat is a good source of rutin (quercetin-3-O-rutoside) and has benefits in regulating blood sugar. This study was to evaluate the antioxidant and anti-inflammatory effects of rutin on wound healing in streptozotocin-induced hyperglycemic rats. Eighteen male Wistar rats were randomly divided into three groups: normal (NDM), hyperglycemic (DM), and hyperglycemic with rutin (DMR). After induction of hyperglycemia for 2 days, a 15 × 15 mm wound was induced on the back of each rat. Intraperitoneal injection of rutin significantly ameliorated diabetes-induced body weight loss and improved metabolic dysfunctions of hyperglycemic rats. Based on appearance and histopathological staining, rutin promotes wound healing and inhibits production of inflammatory cells. The immunoblotting data indicated that rutin promotes production of antioxidant enzymes induced by nuclear factor erythroid 2-related factor 2 (NRF2), inhibits the expression of matrix metalloproteinases (MMPs) regulated by NF-κB, and decreases the expression of vascular endothelial growth factor (VEGF). It also promotes the expression of neurogenic-related protein (UCH-L1). The aforementioned results indicated that rutin reduces oxidative stress and inflammatory response in hyperglycemic rats, promoting wound healing and subsequently reducing the risk of wound ulcers.

Eyeing the Extracellular Matrix in Vascular Development and Microvascular Diseases and Bridging the Divide between Vascular Mechanics and Function

The extracellular matrix (ECM) is critical in all aspects of vascular development and health: supporting cell anchorage, providing structure, organization and mechanical stability, and serving as a sink for growth factors and sustained survival signals. Abnormal changes in ECM protein expression, organization, and/or properties, and the ensuing changes in vascular compliance affect vasodilator responses, microvascular pressure transmission, and collateral perfusion. The changes in microvascular compliance are independent factors initiating, driving, and/or exacerbating a plethora of microvascular diseases of the eye including diabetic retinopathy (DR) and vitreoretinopathy, retinopathy of prematurity (ROP), wet age-related macular degeneration (AMD), and neovascular glaucoma. Congruently, one of the major challenges with most vascular regenerative therapies utilizing localized growth factor, endothelial progenitor, or genetically engineered cell delivery, is the regeneration of blood vessels with physiological compliance properties. Interestingly, vascular cells sense physical forces, including the stiffness of their ECM, through mechanosensitive integrins, their associated proteins and the actomyosin cytoskeleton, which generates biochemical signals that culminate in a rapid expression of matricellular proteins such as cellular communication network 1 (CCN1) and CCN2 (aka connective tissue growth factor or CTGF). Loss or gain of function of these proteins alters genetic programs of cell growth, ECM biosynthesis, and intercellular signaling, that culminate in changes in cell behavior, polarization, and barrier function. In particular, the function of the matricellular protein CCN2/CTGF is critical during retinal vessel development and regeneration wherein new blood vessels form and invest a preformed avascular neural retina following putative gradients of matrix stiffness. These observations underscore the need for further in-depth characterization of the ECM-derived cues that dictate structural and functional properties of the microvasculature, along with the development of new therapeutic strategies addressing the ECM-dependent regulation of pathophysiological stiffening of blood vessels in ischemic retinopathies.

Antidiabetic Properties of Medicinal Mushrooms with Special Reference to Phellinus Species: A Review

: Diabetes remains the major public health challenge to 21st century. It is strongly related to lifestyle changes. Most chronic complications of diabetes are macrovascular and microvascular diseases resulting from the existing hyperglycemic status. Failure of first line therapy which is based on diet modifications and exercise, conventional treatment using antihyperglycemic agents with different mechanisms of action will be implemented for type II diabetes in modern medicine. Higher Basidiomycetes mushrooms are highly praised for their nutritional value and pharmacological properties. They have long been used traditionally for the maintenance of health, prevention and treatment of various human ailments. Reports indicate the beneficial effects of medicinal mushrooms in diabetes treatments. However, scientific evidences are insufficient to make definitive conclusions on the efficacy of individual medicinal mushrooms. Mushrooms belong to the genera Phellinus such as Phellinus linteus, Phellinus ribis, Phellinus rimosus and Phellinus igniarius. They possess significant hypoglycemic effect in experimental diabetic models. However, well-designed controlled clinical trials are needed to establish their safety and bioactivity.

Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries

Microcirculatory obstruction is a hallmark of severe malaria, but mechanisms of parasite sequestration are only partially understood. Here, we developed a robust three-dimensional microvessel model that mimics the arteriole-capillary-venule (ACV) transition consisting of a narrow 5- to 10-μm-diameter capillary region flanked by arteriole- or venule-sized vessels. Using this platform, we investigated red blood cell (RBC) transit at the single cell and at physiological hematocrits. We showed normal RBCs deformed via in vivo–like stretching and tumbling with negligible interactions with the vessel wall. By comparison, Plasmodium falciparum–infected RBCs exhibited virtually no deformation and rapidly accumulated in the capillary-sized region. Comparison of wild-type parasites to those lacking either cytoadhesion ligands or membrane-stiffening knobs showed highly distinctive spatial and temporal kinetics of accumulation, linked to velocity transition in ACVs. Our findings shed light on mechanisms of microcirculatory obstruction in malaria and establish a new platform to study hematologic and microvascular diseases.