Comprehensive retinal vascular measurements: a novel association with renal function in type 2 diabetic patients in China.
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ABSTRACT:
SUBMITTER: Xu X
PROVIDER: S-EPMC7426409 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Comprehensive retinal vascular measurements: a novel association with renal function in type 2 diabetic patients in China.
Xu Xiayu X Sun Fei F Wang Qiong Q Zhang Maiye M Ding Wenxiang W Yang Aili A Gao Bin B
Scientific reports 20200813 1
To examine the association between various retinal vascular measurements and microalbuminuria in patients with type 2 diabetes in a northwestern China study. Data from 911 patients with type 2 diabetes were analyzed. Novel retinal vascular measurements from the whole vascular tree were extracted using a validated fully automatic computer program. Retinal vascular measurements were analyzed continuously and categorically for associations with microalbuminuria using multiple logistic regressions, ...[more]
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Project description:BackgroundType 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob) mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.Methods and resultsIn this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.ConclusionIn parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.
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Project description:ContextCognitive dysfunction is a growing and understudied public health issue in the aging type 1 diabetic population and is difficult and time-consuming to diagnose. Studies in long duration type 1 diabetes have reported the presence of proliferative diabetic retinopathy was associated with cognitive dysfunction.ObjectiveThis study assessed whether structural and vascular abnormalities of the retina, representing an extension of the central nervous system, are associated with cognitive impairment and other complications of type 1 diabetes.MethodsAn observational cross-sectional study of individuals with 50 or more years of type 1 diabetes (Joslin Medalist Study) was conducted at a university hospital in the United States. The study included 129 participants with complete cognitive testing. Validated cognitive testing measures included psychomotor speed, and immediate, and delayed memory. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed to obtain neural retinal layer thicknesses and vascular density for superficial (SCP) and deep retinal capillary plexus (DCP). Multivariable modeling was adjusted for potential confounders associated with outcomes in unadjusted analyses.ResultsDecreased vessel density of the SCP and DCP was associated with worse delayed memory (DCP: P = .002) and dominant hand psychomotor speed (SCP: P = .01). Thinning of the retinal outer nuclear layer was associated with worse psychomotor speed both in nondominant and dominant hands (P = .01 and P = .05, respectively). Outer plexiform layer thickness was associated with delayed memory (P = .04).ConclusionThese findings suggest that noninvasive retinal imaging using OCT and OCTA may assist in estimating the risks for cognitive dysfunction in people with type 1 diabetes.
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Project description:Advanced glycation end products (AGEs) and the renin-angiotensin system (RAS) are both implicated in the development of diabetic retinopathy. How these pathways interact to promote retinal vasculopathy is not fully understood. Glyoxalase-I (GLO-I) is an enzyme critical for the detoxification of AGEs and retinal vascular cell survival. We hypothesized that, in retina, angiotensin II (Ang II) downregulates GLO-I, which leads to an increase in methylglyoxal-AGE formation. The angiotensin type 1 receptor blocker, candesartan, rectifies this imbalance and protects against retinal vasculopathy.Cultured bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRP) were incubated with Ang II (100 nmol/l) or Ang II+candesartan (1 ?mol/l). Transgenic Ren-2 rats that overexpress the RAS were randomized to be nondiabetic, diabetic, or diabetic+candesartan (5 mg/kg/day) and studied over 20 weeks. Comparisons were made with diabetic Sprague-Dawley rats.In BREC and BRP, Ang II induced apoptosis and reduced GLO-I activity and mRNA, with a concomitant increase in nitric oxide (NO(•)), the latter being a known negative regulator of GLO-I in BRP. In BREC and BRP, candesartan restored GLO-I and reduced NO(•). Similar events occurred in vivo, with the elevated RAS of the diabetic Ren-2 rat, but not the diabetic Sprague-Dawley rat, reducing retinal GLO-I. In diabetic Ren-2 rats, candesartan reduced retinal acellular capillaries, inflammation, and inducible nitric oxide synthase and NO(•), and restored GLO-I.We have identified a novel mechanism by which candesartan improves diabetic retinopathy through the restoration of GLO-I.
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Project description:The objective of this paper is to study the effect of aliskiren on metabolic parameters and micro- and macrovascular reactivity in individuals diagnosed with or at high risk for developing type 2 diabetes mellitus (T2DM).We studied 47 T2DM and 41 at-risk individuals in a randomized, double-blinded, placebo-controlled trial. All subjects were treated with 150 mg aliskiren or placebo daily for 12 weeks. Twenty-six (55%) of T2DM and four (8%) at-risk subjects were also treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers.Aliskiren treatment was associated with improvement in systolic and diastolic blood pressure and endothelium-independent vasodilation at the skin microcirculation in those with T2DM but not in those at risk. There were no incidences of hypotension and no significant changes in serum potassium or creatinine levels with aliskiren treatment in either study group.Aliskiren improves blood pressure and vascular smooth muscle function in the skin microcirculation of T2DM patients.
| S-EPMC5287335 | biostudies-literature
Project description:The Early Treatment Diabetic Retinopathy Study (ETDRS) and other standardized classification schemes have laid a foundation for tremendous advances in the understanding and management of diabetic retinopathy (DR). However, technological advances in optics and image analysis, especially optical coherence tomography (OCT), OCT angiography (OCTa), and ultra-widefield imaging, as well as new discoveries in diabetic retinal neuropathy (DRN), are exposing the limitations of ETDRS and other classification systems to completely characterize retinal changes in diabetes, which we term diabetic retinal disease (DRD). While it may be most straightforward to add axes to existing classification schemes, as diabetic macular edema (DME) was added as an axis to earlier DR classifications, doing so may make these classifications increasingly complicated and thus clinically intractable. Therefore, we propose future research efforts to develop a new, comprehensive, and clinically useful classification system that will identify multimodal biomarkers to reflect the complex pathophysiology of DRD and accelerate the development of therapies to prevent vision-threatening DRD.
| S-EPMC5786342 | biostudies-literature
Project description:Diabetic retinopathy (DR) is the leading cause of vision loss in working age adults. Understanding the retinal metabolic response to circulating high glucose levels in diabetic patients is critical for development of new therapeutics to treat DR. Measuring retinal metabolic function using the Seahorse analyzer is a promising technique to investigate the effect of hyperglycemia on retinal glycolysis and mitochondrial respiration. Here, we analyzed the retinal metabolic function in young and old diabetic and control mice. We also compared the expression of key glycolytic enzymes between the two groups. The Seahorse XF analyzer was used to measure the metabolic function of retina explants from young and old type 1 diabetic Akita (Ins2Akita ) mice and their control littermates. Rate-limiting glycolytic enzymes were analyzed in retina lysates from the two age groups by Western blotting. Retinas from young adult Akita mice showed a decreased glycolytic response as compared to control littermates. However, this was not observed in the older mice. Western blotting analysis showed decreased expression of the glycolytic enzyme PFKFB3 in the young Akita mice retinas. Measurement of the oxygen consumption rate showed no difference in retinal mitochondrial respiration between Akita and WT littermates under normal glucose conditions ex vivo despite mitochondrial fragmentation in the Akita retinas as examined by electron microscopy. However, Akita mice retinas showed decreased mitochondrial respiration under glucose-free conditions. In conclusion, diabetic retinas display a decreased glycolytic response during the early course of diabetes which is accompanied by a reduction in PFKFB3. Diabetic retinas exhibit decreased mitochondrial respiration under glucose deprivation.
| S-EPMC9201036 | biostudies-literature
Project description:To measure the effect of nonproliferative diabetic retinopathy (NPDR) on retinal branching. To compare vascular branching in healthy and diabetic subjects with established biophysical models.Vascular bifurcations in arteries and veins were imaged in 17 NPDR and 26 healthy subjects with the Indiana adaptive optics scanning laser ophthalmoscope (AOSLO). Vessel measurements were grouped according to parent vessel diameters into large (?50 ? <100 ?m) and small (?20 ? <50 ?m) sizes. Vessel diameters and bifurcation angles were measured manually. Vascular diameters were compared with predictions of Murray's law using curve fitting. For analysis of bifurcation angles, two models from Zamir were compared: one based on the power required for blood pumping, the other based on drag force between blood and vascular wall.For normal larger vessels, the exponent relating the parent and daughter branching diameters was significantly less than the value of 3 predicted by Murray's law (arteries: 2.59; veins: 1.95). In NPDR, the best-fit exponent was close to 3 for arteries but close to 2 in healthy subjects in veins, (arteries: 3.09; veins: 2.16). For both small arteries and veins, diabetics' exponent differed from healthy subjects (P < 0.01). Bifurcation angles in the healthy subjects (78° ± with a standard error (SE) of 0.9°) were not much different than in NPDR (79° ± SE 1.3°). The model based on minimizing pumping power predicted the measurements better than the one minimizing the vascular drag and lumen surface area.The relation between parent and daughter branch diameters changes in diabetes, but the branching angles do not.
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Project description:ObjectiveDiabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (?-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ?-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM).DesignMale leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks-26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ?-3 or ?-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet.ResultsThe ?-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ?-6PUFA-rich diet. There was also an enhanced ability of ?-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ?-3PUFAs.ConclusionThis study identifies beneficial effects of dietary ?-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ?-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ?-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM.
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Project description:ObjectiveIt is believed that Meniere's disease (MD) is associated with vascular disorders, but few studies have reported the relationship between retinal vascular disorders and MD. We evaluated and compared the retinal vascular calibres in patients with MD with healthy subjects matched for age, sex and vascular risk factors using retinal photographs to explore the association between MD and retinal vascular calibre.Study designA prospective study.SettingTertiary referral centre.ParticipantsSixty patients with MD and 62 healthy subjects matched for age, sex and vascular risk factors were enrolled in this study. Twenty-four patients with MD had migraines, and 36 patients with MD did not have migraines.Main outcome measureRetinal vascular calibres were calculated and compared not only between patients with MD and healthy subjects but also between subgroups of patients with MD.ResultsCompared with healthy subjects, patients with MD had a slightly larger retinal artery calibre (126.30±10.45vs 119.61±15.86, p=0.006) and a higher retinal artery/vein ratio (0.79±0.09vs 0.75±0.10, p=0.005). Among patients with MD, those with migraines had a larger retinal artery calibre (130.73±11.55vs 123.35±8.61, p=0.006) than those without migraines. Moreover, the presence of migraines and the high frequency of vertigo attacks appeared to increase the retinal artery calibre.ConclusionsOur study suggests that a relationship exists between retinal vascular calibre and MD. Although the pathophysiological relationship between migraine and MD remains unclear, the presence of migraine attacks may aggravate endolymphatic hydrops (EH) and accelerate the outflow of EH in patients with MD. More extensive studies are required to explore the association between retinal vascular calibre and MD.
| S-EPMC6169750 | biostudies-literature
Project description:BACKGROUND:Albuminuria is the early manifestation of the pathogenesis of diabetic nephropathy (DN). The current study was to investigate the relationship of pulmonary function with albuminuria in type 2 diabetic patients with preserved renal function to evaluate the role of pulmonary function in the early stage of DN. METHODS:A total of 326 patients with type 2 diabetes mellitus (T2DM) including 270 without albuminuria and 56 with albuminuria, and 265 non-diabetic patients were enrolled. The patients' general information, and the parameters of pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1?s (FEV1), FEV1/FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide of lung (DLCO) were compared between T2DM and control groups, as well as T2DM patients with and without albuminuria groups. All pulmonary function parameters were expressed as a percentage of those predicted (%pred). Logistic regression models were constructed to test the association of albuminuria and pulmonary function. RESULTS:The values of FVC%pred, FEV1%pred, TLC%pred and DLCO%pred were lower, and the proportion of subjects with FVC%pred <?80, FEV1%pred <?80, and DLCOc%pred <?80 was higher in T2DM subjects than controls (all P?<?0.05). Subgroup analysis of diabetic patients showed that the values of FVC%pred, FEV1%pred, TLC%pred, and DLCOc%pred (97.18?±?13.45, 93.95?±?14.51, 90.64?±?9.97, 87.27?±?13.13, respectively) were significantly lower in T2DM subjects with albuminuria than those without albuminuria (103.94?±?14.12, 99.20?±?14.25, 93.79?±?10.36, 92.62?±?13.45, all P?<?0.05). There was a significantly negative correlation between the urine albumin-to-creatinine ratio (UACR) and DLCOc%pred (r =?-?0.143, P =?0.010) in spearman linear correlation test. In logistic regression analysis, the FVC%pred (OR 0.965, 95%CI 0.944-0.988), FEV1%pred (OR 0.975, 95%CI 0.954-0.996), and DLCOc%pred (OR 0.974, 95%CI 0.951-0.998) were independently associated with albuminuria after adjustments for smoking index, duration, HbA1c, FBG, and TG. CONCLUSION:Our results demonstrated albuminuria is associated with a restrictive pulmonary function as well as pulmonary diffusion function in T2DM with preserved renal function, which remind us to be alert of the pulmonary function decline even in the early stage of DN.
| S-EPMC7379808 | biostudies-literature