Hemodynamics In Type Research Articles

69 - Assessment of Renal Parenchymal Fat Deposition and Hemodynamics in Type 2 Diabetes Mellitus using Functional MRI

69 - Assessment of Renal Parenchymal Fat Deposition and Hemodynamics in Type 2 Diabetes Mellitus using Functional MRI

Hemodynamic effects of entry and exit tear size in aortic dissection evaluated with in vitro magnetic resonance imaging and fluid–structure interaction simulation

Understanding the complex interplay between morphologic and hemodynamic features in aortic dissection is critical for risk stratification and for the development of individualized therapy. This work evaluates the effects of entry and exit tear size on the hemodynamics in type B aortic dissection by comparing fluid–structure interaction (FSI) simulations with in vitro 4D-flow magnetic resonance imaging (MRI). A baseline patient-specific 3D-printed model and two variants with modified tear size (smaller entry tear, smaller exit tear) were embedded into a flow- and pressure-controlled setup to perform MRI as well as 12-point catheter-based pressure measurements. The same models defined the wall and fluid domains for FSI simulations, for which boundary conditions were matched with measured data. Results showed exceptionally well matched complex flow patterns between 4D-flow MRI and FSI simulations. Compared to the baseline model, false lumen flow volume decreased with either a smaller entry tear (− 17.8 and − 18.5%, for FSI simulation and 4D-flow MRI, respectively) or smaller exit tear (− 16.0 and − 17.3%). True to false lumen pressure difference (initially 11.0 and 7.9 mmHg, for FSI simulation and catheter-based pressure measurements, respectively) increased with a smaller entry tear (28.9 and 14.6 mmHg), and became negative with a smaller exit tear (− 20.6 and − 13.2 mmHg). This work establishes quantitative and qualitative effects of entry or exit tear size on hemodynamics in aortic dissection, with particularly notable impact observed on FL pressurization. FSI simulations demonstrate acceptable qualitative and quantitative agreement with flow imaging, supporting its deployment in clinical studies.

In Vitro Studies on Hemodynamics of Type B Aortic Dissection: Accuracy and Reliability.

1. Hemodynamic of TBAD is important to improve the long-term outcome of TEVAR.2. This review provides an overview of the in-vitro for the hemodynamic study of TBAD.3. The accuracy and validity of in-vitro TBAD experiments should be further studied.

887-P: Renal Benefit of Dapagliflozin Therapy in Hyperfiltering Type 2 Diabetes Patients

Aim: To investigate the benefits of dapagliflozin [DAPA] on renal hemodynamics in type 2 diabetes patients [T2D] with glomerular hyperfiltration. Design and Methods: 24 T2D with elevated [HYPER] and normal [NORMO] GFR, measured by Iohexol, randomized to either DAPA, 10mg/day [DAPA/HYPER, n=6; DAPA/NORMO, n=6] or metformin+glipizide [CON/HYPER, n=6; CON/NORMO, n=6] for 4 months. Hyperfiltration was defined as GFR>125ml/min/1.73m2. Renal plasma (blood) flow [RP(B)F] measured with PAH divided by (1-Hct), mean arterial pressure [MAP], filtration fraction [FF] and renal vascular resistance [RVR] were determined before and after treatment. Results: A1c[%] decreased similarly in DAPA/HYPER (8.3±0.2 vs. 6.8±0.2), CON/HYPER (8.7±0.3 vs. 7.2±0.1), DAPA/NORMO (8.6±0.3 vs. 7.3±0.2) and CON/NORMO (8.2±0.3 vs. 7.4±0.2). Body weight[Kg] was reduced in DAPA/HYPER (89±4 vs. 84±4) and DAPA/NORMO (90±3 vs. 87±2) but not in CON/HYPER (86±4 vs. 87±3) and CON/NORMO (87±4 vs. 91±3) (p<0.05). GFR declined by 17% in DAPA/HYPER and by 8% in DAPA/NORMO (both, p<0.05) but did not change in CON. FF and RVR fell in DAPA but not in CON. Renal hemodynamics at baseline [PRE-Tx] and after 4 months [POST-Tx] are shown in the table. Conclusion These results indicate that dapagliflozin, but not metformin+glipizide therapy, normalizes glomerular hyperfiltration and reduces renal vascular resistance in hyperfiltering type 2 diabetes patients. Disclosure G.Baskoy: None. Y.Qin: None. E.Cersosimo: None. C.Solis-herrera: None. J.M.Adams: None. R.A.Defronzo: Advisory Panel; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Novo Nordisk, Research Support; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc., Speaker's Bureau; AstraZeneca. C.L.Triplitt: Speaker's Bureau; Novo Nordisk. Funding AstraZeneca; Texas Diabetes Institute

Association of triglyceride-glucose with cardiac hemodynamics in type 2 diabetes

PurposeTriglyceride-glucose (TyG) index is a reliable and inexpensive alternative indicator of insulin resistance. Previous studies have shown that elevated TyG index increases the risk of diabetes, coronary heart disease, and other diseases, but the relationship between TyG index and cardiac hemodynamics in patients with type 2 diabetes mellitus (T2DM) is not clear. This study was conducted in patients with T2DM to assess the relationship between TyG and cardiac hemodynamics and its predictive ability for T2DM.MethodsA total of 647 individuals (348 males and 299 females) were enrolled in this study, including 446 T2DM patients and 201 healthy controls. The clinical data and related laboratory variables were assessed and recorded, and TyG index was calculated. Cardiac hemodynamics was measured by echocardiography. Pearson or Spearman correlation analysis and linear regression analysis were conducted to explore the association between TyG and cardiac hemodynamics. The receiver operating characteristics (ROC) curve was used to evaluate the efficacy of TyG index in the diagnosis of T2DM.ResultsCompared with healthy controls, the systolic blood pressure (SBP), body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), HOMA-IR, and TyG levels were higher in patients with T2DM. With the increase of TyG, the levels of left ventricular mass index (LVMI), left ventricular mass (LVM), left ventricular end diastolic diameter (LVDd), posterior wall thickness (PWT), and interventricular septum thickness (IVST) were also increased in T2DM individuals. Multivariate linear regression analysis showed that TyG was an independent determinant of LVEF, PWT, IVST, and ejection time (ET) after adjusting for confounding factors. In addition, individuals with visceral obesity had higher TyG and TyG can be used as a predictor of T2DM with an AUC of 0.903 (95% CI:0.879–0.927).ConclusionsThe increase of TyG index is closely related to cardiac hemodynamics of T2DM patients, which is expected to be a simple and practical biological index to predict the changes of cardiac function in patients with T2DM.

CHIVA cure and sclerotherapy

Sclerotherapy is, by definition, a destructive treatment and, as such, it is conceptually long far away from the basic principles of the conservative hemodynamic cure for venous insufficiency (CHIVA cure). Accordingly, Phlebologists and Vascular Surgeons who practice the CHIVA cure at most acknowledge the use of sclerotherapy after the CHIVA cure for the aesthetical refinement or for the control over time of small calibre recurrences. However, intraoperative sclerotherapy can be used in association with the CHIVA cure in those cases in which the surgical gesture foreseen by the CHIVA cure would not be able to flush disconnect escape points at the level of the deep venous system and, as a consequence, it would leave non-draining stumps, which are a source of recurrences. Further, under some particular circumstances, sclerotherapy can be used instead of the CHIVA cure for the treatment of type II shunts or as the 1st step of the CHIVA 2 strategy for the treatment of type III shunts. This paper describes the use of intraoperative sclerotherapy for the treatment of escape points from the deep venous system difficult to treat by surgery, such as perforator veins, some anatomic presentations of the saphenous-popliteal junction and some pelvic shunts. This paper also describes the use of sclerotherapy alone for the treatment of type II shunts or for modelling saphenous hemodynamics in type III shunts before completing the treatment by surgery.

Abstract 14372: Identification of the Genes That Are Involved in Severe Pulmonary Hypertension in Type 2 Diabetic Mice

Pulmonary hypertension (PH) is a progressive disease characterized by increased pulmonary vascular resistance. Increasing evidence shows that diabetes increases the risks of PH, and diabetic priming leads to severe PH. However, the molecular mechanism by which preconditioning of diabetes results in severe PH is still unknown. It has been shown that endothelium serves as a key regulator of vascular tone, and endothelial cell dysfunction is implicated in the development of PH and diabetes-related vascular complications. Therefore, we identified the genes that contribute to the development of severe PH in diabetic mice with a focus on endothelial function. We first determined the effect of chronic hypoxia (10% O 2 , 4 weeks) on hemodynamics in type 2 diabetic (T2D) mice. We used inducible T2D mice (generated by high-fat diet and a low-dose streptozotocin injection) and spontaneous T2D mice (TALLYHO/Jng). Diabetic mice exhibited a slight increase in right ventricular systolic pressure (RVSP), and chronic hypoxia led to a further rise in RVSP in both inducible and spontaneous T2D mice. We isolated pulmonary endothelial cells (MPEC) from normoxia-exposed control mice (CN), hypoxia-exposed control mice (CH), normoxia-exposed diabetic mice (DN), and hypoxia-exposed diabetic mice (DH) to examine the levels of 92 genes using real-time PCR. Nighty two genes were selected based on their functions, which are significantly related to endothelial function. We found that 27 genes were significantly changed among 4 groups. We then examined the protein levels of genes that were related to apoptosis and glycolysis. Western Blot data indicated that the protein level of GAPDH was significantly increased in CH and DH compared to CN and DN. In addition, hypoxic exposure in diabetic mice (DH) significantly increased HK2 protein level compare to hypoxia-exposed control mice (CH). These data suggest that precondition of diabetes increases susceptibility to developing PH due partly to altering gene expression of HK2 and Gapdh in MPECs. Since HK2 and GAPDH are a crucial regulator of glycolysis, alteration of glycolysis is expected in hypoxia-exposed diabetic mice. Our study revealed the key molecules which could be used for treating severe PH in diabetes.

Visceral Fat Area, Not Subcutaneous Fat Area, is Associated with Cardiac Hemodynamics in Type 2 Diabetes.

BackgroundThis study was conducted in patients with type 2 diabetes mellitus (T2DM) to assess the association between visceral fat area (VFA) and cardiac hemodynamics.MethodsA total of 568 patients with type 2 diabetes (mean age 54±12 years; 40.8% of women) were enrolled. Visceral fat area (VFA, m2) and subcutaneous fat area (SFA, m2) were evaluated by a bioelectrical impedance analyzer. Cardiac hemodynamics were measured by echocardiography, and other clinical and laboratory variables were also assessed and recorded. Patients were divided into those with VFA ≤ 100 (n=369) and those with VFA > 100 (n=199).ResultsVFA, SFA, LVMI (left ventricular mass index), left atrial diameter, left ventricular diastolic diameter (LvDd), interventricular septal thickness (IVST), left ventricular systolic diameter (LvSd), and posterior wall thickness (PWT) levels in high-V groups were significantly higher than those in low-V groups. Correlation analysis showed that VFA was positively correlated with LVMI (r=0.120, p=0.004), LVM (r=0.249, p<0.0001), left atrial diameter (r=0.375, p<0.0001), aortic root diameter (r=0.243, p<0.0001), left ventricular systolic diameter (LvSd) (r=0.211, p<0.0001) and negatively correlated with LVEF (r=−0.107, p=0.011). In multivariate linear regression analysis, VFA was the strongest independent determinant of LVMI (β=0.04, p=0.016), LVEF (β=−0.01, p=0.023), and left atrial diameter (β=0.035, p<0.0001), Internal diameter of the aortic root (β=0.014, p<0.0001) and LvSd (β=0.017, p<0.0001). In addition, the VFA also better predicted cardiovascular disease risk with AUC of 0.609 (95% CI:0.563–0.656), compared with SFA, waist–hip ratio (WHR), in a statistically significant manner.ConclusionWe found a significant correlation between VFA (but not SFA) and cardiac hemodynamic parameters. The VFA has advantages as a predictor of visceral obesity and is significantly associated with the development of cardiovascular risk factors (CVD) in T2DM patients.

Fetal cardiovascular hemodynamics in type 1 diabetic pregnancies at near-term gestation.

Poor glycemic control in maternal type 1 diabetes mellitus during pregnancy can affect fetal cardiac and placental function. However, studies concerning fetal central hemodynamics have revealed conflicting results. We hypothesized that in pregnancies complicated by maternal type 1 diabetes, fetal cardiovascular and placental hemodynamics are comparable to the control fetuses at near-term gestation. In addition, we investigated the relation between newborn serum biomarkers of cardiac function and fetal cardiovascular and placental hemodynamics. Furthermore, we studied whether maternal diabetes is associated with placental inflammation. In this prospective case-control study, fetal central and peripheral hemodynamics were assessed by ultrasonography in 33 women with type 1 diabetes and in 67 controls with singleton pregnancies between 34+2 and 40+2 gestational weeks. Newborn umbilical cord serum was collected to analyze cardiac natriuretic peptides (atrial and B-type natriuretic peptides) and troponin T concentrations. Placental tissue samples were obtained for cytokine analyses. Fetal ventricular wall thicknesses were greater and weight-adjusted stroke volumes and cardiac outputs were lower in the type 1 diabetes group than in the control group. Pulsatility in the aortic isthmus and inferior vena cava blood flow velocity waveforms was greater in the type 1 diabetes group fetuses than in the controls. A positive correlation was found between branch pulmonary artery and aortic isthmus pulsatility index values. Umbilical artery pulsatility indices were comparable between the groups. Umbilical cord serum natriuretic peptide and troponin T concentrations were elevated in the type 1 diabetes fetuses. These cardiac biomarkers correlated significantly with cardiovascular hemodynamics. Placental cytokine levels were not different between the groups. In maternal type 1 diabetes pregnancies, fetal cardiovascular hemodynamics is impaired. Maternal type 1 diabetes does not seem to alter placental vascular impedance or induce placental inflammation.

SO022EVALUATION OF GLOMERULAR HEMODYNAMIC CHANGES BY SGLT2 INHIBITION IN TYPE 2 DIABETIC RATS USING IN VIVO IMAGING TECHNIQUES

Abstract Background and Aims In recent clinical trials, the SGLT2 inhibitor (SGLT2i) slowed the progression of kidney disease compared with the placebo in patients with type 2 diabetes. Improvement of glomerular hyperfiltration via tubuloglomerular feedback (TGF) is considered to be one of the possible pathways for renal protection with SGLT2 inhibition (SGLT2i) in diabetic kidney disease (DKD). We have successfully developed the novel method to measure single-nephron GFR (SNGFR) in mice using multiphoton laser microscopy and demonstrated that the adenosine/adenosine A1 receptor (A1aR) pathway plays a pivotal role in the TGF mechanism in the type 1 diabetic model, Akita mice (Kengo Kidokoro, David Z. I. Cherney et al. Circulation. 2019). It has been suggested that the mechanism of improvement effects in glomerular hyperfiltration by SGLT2i is different in type 1 diabetes and type 2 diabetes. However, the detailed regulatory mechanism of GFR by SGLT2i is not fully understood in type 2 diabetes. This study aims to clarify the effects of SGLT2i on glomerular hemodynamics in type 2 diabetic rats. Method Zucker lean (ZL) rats and Zucker diabetic fatty (ZDF) rats were used. In the first experiment, SNGFR and diameters of glomerular afferent/efferent arterioles were measured in both groups. Next, we examined the change of SNGFR and diameters of glomerular afferent/efferent arterioles, as well as urinary excretions of glucose and sodium in ZDF after a single-dose administration of SGLT2i (luseogliflozin; 10mg/kg, gavage) for 120 minutes, which generated the following three groups: SGLT2i group, SGLT2i + adenosine A1 receptor (A1aR) antagonist (8-cyclopentyl-1,3-dipropylxanthine, 1mg/kg) group, and insulin group. Results SNGFR in the ZDF group was significantly higher than in the ZL group. The diameter of the afferent arteriole and efferent arteriole was also wider in ZDF rats than in ZL rats. The SNGFR and diameter of the afferent arteriole were significantly decreased after a single-dose administration of SGLT2i in ZDF. However, there was no significant diameter change in the efferent arteriole. Moreover, a decrease of SNGFR was not observed in the A1aR antagonist group after SGLT2i administration. Urinary excretions of glucose and sodium showed a similar pattern in the SGLT2i and SGLT2i+ A1aR antagonist groups. Conclusion The adenosine/A1aR pathway plays an important role in the regulation of the tonus of the afferent arteriole and is involved in the suppression of glomerular hyperfiltration by SGLT2 inhibition in type 2 diabetes.

Renal sinus fat and renal hemodynamics: a cross-sectional analysis

ObjectivesIncreased renal sinus fat (RSF) is associated with hypertension and chronic kidney disease, but underlying mechanisms are incompletely understood. We evaluated relations between RSF and gold-standard measures of renal hemodynamics in type 2 diabetes (T2D) patients.MethodsFifty-one T2D patients [age 63 ± 7 years; BMI 31 (28–34) kg/m2; GFR 83 ± 16 mL/min/1.73 m2] underwent MRI-scanning to quantify RSF volume, and subcutaneous and visceral adipose tissue compartments (SAT and VAT, respectively). GFR and effective renal plasma flow (ERPF) were determined by inulin and PAH clearances, respectively. Effective renal vascular resistance (ERVR) was calculated.ResultsRSF correlated negatively with GFR (r = − 0.38; p = 0.006) and ERPF (r = − 0.38; p = 0.006) and positively with mean arterial pressure (MAP) (r = 0.29; p = 0.039) and ERVR (r = 0.45, p = 0.001), which persisted after adjustment for VAT, MAP, sex, and BMI. After correction for age, ERVR remained significantly related to RSF.ConclusionsIn T2D patients, higher RSF volume was negatively associated to GFR. In addition, RSF volume was positively associated with increased renal vascular resistance, which may mediate hypertension and CKD development. Further research is needed to investigate how RSF may alter the (afferent) vascular resistance of the renal vasculature.

4-D Flow MRI-Based Computational Analysis of Blood Flow in Patient-Specific Aortic Dissection.

Computational hemodynamic studies of aortic dissections usually combine patient-specific geometries with idealized or generic boundary conditions. In this study, we present a comprehensive methodology for the simulation of hemodynamics in type B aortic dissection (TBAD), based on fully patient-specific boundary conditions. Pre-operative four-dimensional (4-D) flow magnetic resonance imaging (MRI) and Doppler-wire pressure measurements (pre- and post-operative) were acquired from a TBAD patient. These data were used to derive boundary conditions for computational modeling of flow before and after thoracic endovascular repair (TEVAR). Validations of the computational results were performed by comparing predicted flow patterns with pre-TEVAR 4-D flow MRI, as well as pressures with in vivo measurements. Comparison of instantaneous velocity streamlines showed a good qualitative agreement with 4-D flow MRI. Quantitative comparison of predicted pressures with pressure measurements revealed a maximum difference of 11 mmHg (-9.7%). Furthermore, our model correctly predicted the reduction of true lumen pressure from 74/115 mmHg pre-TEVAR to 64/107 mmHg post-TEVAR (diastolic/systolic pressures at entry tear level), compared to the corresponding measurements of 72/118 mmHg and 64/114 mmHg. This demonstrates that pre-TEVAR 4D flow MRI can be used to tune boundary conditions for post-TEVAR hemodynamic analyses.

Regional Patterns of Retinal Oxygen Saturation and Microvascular Hemodynamic Parameters Preceding Retinopathy in Patients With Type II Diabetes.

Alterations in retinal oxygen metabolism and retinal microcirculation are signs of impending diabetic retinopathy (DR). However, if specific retinal regions are primarily affected is so far unknown. The purpose of this study was to investigate if retinal oxygen saturation (SO2) and microvascular hemodynamic parameters follow a distinct regional pattern in patients with diabetes but no DR. Patients with type II diabetes without clinically apparent DR were imaged as follows: SO2 in peripapillary vessels was assessed with dual-wavelength oximetry. Optical coherence tomography angiography (OCTA) scans were acquired with a prototype system using a swept-source laser with an effective 400 kHz A-scan rate and 16° field of view. Regional flow indices termed "flux" were calculated for the peripapillary microvasculature. Parafoveal capillary density was evaluated with the commercially available AngioVue OCTA. Twenty-nine eyes of 16 consecutive patients (59 ± 10 years, 6 females) were included in this study. SO2 differed significantly between quadrants (P < 0.001), with a decreasing pattern from the upper nasal through the lower nasal, the upper temporal and the lower temporal quadrant in arterioles and venules. In contrast, peripapillary flux followed an increasing trend from nasally to temporally. Peripapillary and parafoveal microvascular hemodynamic parameters demonstrated no significant regional variability as observed for retinal oxygenation. Metabolic imaging identified regional differences in retinal SO2 without an associated topographic variance in microvascular hemodynamics in type II diabetes without DR. Future studies should focus on the mechanisms causing this heterogeneity in metabolic demand.

Abstract 11562: Computational Fluid Dynamics in Type B Aortic Dissection: A Systematic Review

Introduction: Computational fluid dynamics (CFD) has been increasingly used to analyse cardiovascular hemodynamics through simulations to predict the behaviour of blood flow in the cardiovascular system. Hypothesis: It is hypothesized that CFD modelling assists in clinical decision-making by providing detailed analysis of flow patterns in patients with aortic dissection. Methods: A search of biomedical database for English literature was performed to identify studies investigating the CFD applications in type B aortic dissection. Only studies dealing with patient’s data were included, while reports based on phantom studies were excluded from the analysis. Results: Twelve studies were found to meet selection criteria and were included in the analysis. CFD simulations were based on a selected CT or MRI imaging data in 8 studies, while in the remaining four studies, CFD simulations were derived from 3 cases in two studies, and 4 and 8 cases in one study, respectively. CFD models and simulations were found to successfully capture the complex regions of hemodynamic flow by demonstrating low velocities in the false lumen and high velocities in the true lumen. In the true lumen, high time-averaged wall shear stress (TAWSS) was seen in the regions around the tear, while in the false lumen, TAWSS was less uniform due to recirculating flow in the dilated region (Figure). Presence of an additional re-entry tear was shown to provide an extra return path for blood back to the true lumen during systole, and an extra flow path into the false lumen during diastole. Following endovascular stent grafting, large WSS magnitudes were eliminated in the true lumen, while in the false lumen, the maximum WSS was reported to be reduced by more than a factor of 2. Conclusions: CFD offers insight into the hemodynamic factors such as velocity field and wall shear stress, and CFD models and simulations improve understanding of hemodynamics in type B aortic dissection.

PS9 - 4. Changes in Circadian Haemodynamics and Autonomic Nervous System Balance in Non- Hypertensive Uncomplicated Type 2 Diabetes

Conflicting results exist regarding circadian haemodynamics in type 2 diabetes mellitus (T2DM). Inasmuch T2DM is associated with an altered cardiac autonomic nervous system (ANS) balance, we investigated circadian haemodynamic and ANS rhythms and their interrelationship in 12 non-hypertensive male patients with uncomplicated T2DM and 15 age- and gender-matched healthy controls.

Effects of the DPP-4 inhibitor saxagliptin on early vascular changes in the retinal and systemic circulation

In type-2 diabetes early vascular changes (among others) are hyperperfusion in the retinal circulation (like in the kidney) and increased pulse wave reflection leading to increased aortic pressure. We analyzed whether the DPP4-inhibitor saxagliptin reverses early vascular and haemodynamic changes in type-2 diabetes. In this double-blind randomized controlled clinical cross-over trial 42 patients with type-2 diabetes (age 60.3, 13 were females, BMI 30.6 kg/m2, mean duration of diabetes 4 years, HbA1c 7.0%, blood pressure 132/79 mmHg) were consecutively [PB1] included and randomized to placebo or saxagliptin 5 mg for 6 weeks each. Retinal capillary flow (RCF) was assessed at baseline and after flickerlight exposure (as a vasodilatory test) by scanning laser Doppler flowmetry. Central (aortic) systolic blood pressure (SBP), central pulse pressure (PP), augmentation index and pulse wave velocity were determined with the SphygmoCor device. Following treatment with saxagliptin (as opposed to placebo) saxagliptin effected a better glycemic control, a reduced retinal capillary flow (p=0.033) and, in parallel, reduced central systolic augmentation and pulse pressure (see table). In accordance, Flicker light induced increment of RCF (indicative of vasodilatory capacity of the retinal circulation) was numerically 2-fold greater, although not significant. View this table: Table 1 Our data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central haemodynamics in type 2 diabetes.

Orthopedic trauma reduces renal hemodynamics in the STZ‐induced diabetic rat

Diabetes is an independent risk factor for the development of acute renal dysfunction following orthopedic trauma (OT). Whether OT affects renal hemodynamics has yet to be investigated. The hypothesis tested in this study was that OT reduces renal hemodynamics in type 1 diabetes.Male lean Zucker rats (12 wks) were divided into 4 treatment groups (n=4/gp): non‐diabetic without trauma (ND‐NT), non‐diabetic with trauma (ND‐T), STZ‐induced diabetic without trauma (D‐NT) and STZ‐induced diabetic with trauma (D‐T). Four wks after induction of diabetes, animals were implanted with catheters and OT was induced by soft tissue injury and local injection of bone components in both hind limbs. Animals were placed in metabolic cages for 12hrs to collect urine and urine albumin excretion (UAE) was measured by ELISA. 24 hrs post‐trauma, glomerular filtration rate (GFR) was measured in conscious rats. Our results show that diabetes after 4 wks causes a reduction in GFR compared to controls. However, OT caused a greater reduction in GFR in diabetics than controls. Our data suggest that OT compromises renal function in the setting of type 1 diabetes. Group Body Weight (g) Glucose (mg/dL) UAE (mg/day) GFR/KW (ml/min/g) ND‐NT 396±25 81±6 0.5±0.1 1.37±0.09 ND‐T 415±20 85±4 1.2±0.7 1.52±0.08 D‐NT 298±12*# 358±27*# 3.3±0.6*# 1.17±0.08# D‐T 330±14*# 366±15*# 4.6±0.3*# 1.06±0.07*# Avg±SEM; P&lt;0.05 vs. ND‐NT; P&lt;0.05 vs. ND‐T

The association between high‐sensitive c‐reactive protein and retinal hemodynamics in type 1 diabetes patients with non‐proliferative diabetic retinopathy

Abstract Purpose There is evidence that low‐grade inflammatory processes play a role in the pathogenesis of microvascular complications in diabetes mellitus. In addition, various studies have shown that retinal vascular reactivity is reduced in diabetes, whereas retinal leukocyte velocity is increased. The aim of the present study was to investigate correlations between levels of the inflammation biomarker C‐reactive protein (CRP) and measures of retinal vascular function and perfusion in type 1 diabetes patients with non‐proliferative diabetic retinopathy. Methods 25 type 1 diabetes patients with non‐proliferative diabetic retinopathy were included in this cross‐sectional study. Blood samples were collected to measure glucose, HbA1C and blood cell count. Serum CRP was determined by high sensitivity enzyme immunoassay. The reaction of retinal vessel diameters to flickering light was measured using the Retinal Vessel Analyzer. Perifoveal leucocyte blood flow was assessed using the blue‐field entoptic technique. Results Elevated CRP was found in 12 patients. There was no correlation found between white blood cell velocity or flow and CRP. Flicker‐induced vasodilatation also showed no correlation with CRP levels. However, reactivity of retinal veins was negatively correlated to HbA1C (r = ‐0.4, p = 0.049). Conclusion The results indicate that in our sample of type 1 diabetes patients with diagnosed non‐proliferative retinopathy, serum levels of CRP, a biomarker for inflammation, are not associated with perifoveal leukocyte blood flow or with retinal vessel reactivity. Further investigations are necessary in larger patient groups and with additional inflammatory markers.

The relationship between retinal hemodynamics and systemic markers of endothelial function and inflammation in type 2 diabetes

Abstract Purpose The aim of the study was to investigate the associations, if any, between retinal hemodynamics and systemic markers of endothelial function and inflammation in patients with type 2 diabetes and non‐proliferative diabetic retinopathy (NPDR). Methods Retinal blood flow measurements and blood serum samples were obtained from 9 healthy controls (Group 1, mean age 53.8 yrs, SD 11.7), 23 patients with mild‐to‐moderate NPDR (Group 2, mean age 61.4 yrs, SD 8.5; duration 9.9 yrs, SD 8.8) and 14 patients with moderate‐to‐severe NPDR (Group 3, mean age 60.3 yrs, SD 9.9; duration 17.0 yrs, SD 9.4). Retinal blood flow was measured in the supero‐temporal arteriole using the Canon Laser Blood Flowmeter. Blood samples were collected to derive levels of intercellular adhesion molecule (ICAM‐1), vascular adhesion molecule (VCAM‐1), E‐selectin and von Willebrand factor (vWF). Results Diameter, velocity, maximum‐to‐minimum velocity ratio and flow were the same across the groups and did not change over a 6 month follow‐up. A1c and ICAM‐1 were significantly elevated across the groups (p=0.001 and p=0.030, resp., ANOVA). VCAM‐1 (r =0.325, p=0.046) and vWF (r =0.334, p=0.050) showed relatively weak associations with baseline max:min velocity ratio. vWF showed moderate associations with change in velocity (r = 0.571, p=0.007) and change blood flow (r = 0.455, p=0.038). Conclusion The relationship between endothelial dysfunction and inflammation markers and retinal hemodynamics in type 2 diabetes is complex since not all markers show an association. This work is on‐going.

Roles of Insulin Receptor Substrates (IRS) in renal function and renal hemodynamics.

We have reported previously that renal hemodynamic abnormalities exist in the prediabetic stage of type II diabetic rats. At this stage these rats have insulin resistance. It is well known that insulin resistance is frequently associated with renal abnormalities, but the mechanism underlying this association has remained speculative. Although insulin is known to modify renal hemodynamics, little is known about the roles of insulin receptor substrates (IRS1, IRS2) in the renal actions of insulin. To address this issue, we investigated in wild type (WT), IRS1‐deficient (IRS1‐/‐), and IRS2‐deficient (IRS2‐/‐) mice. IRS2‐/‐ mice had elevated blood pressure and glucose level as expected. 24‐h urine collections revealed that creatinine clearance did not significantly differ between these groups. Fractional excretion of sodium was significantly lower in IRS1‐/‐ and IRS2‐/‐ compared to WT mice. Albuminuria was found in IRS1‐/‐ and IRS2‐/‐ groups. We assessed autoregulatory responses of total renal blood flow (RBF), and of superficial (SBF) and deep renal cortical blood flow (DBF) to stepwise reductions of renal perfusion pressure (RPP) induced by a manual clamp on the abdominal aorta. RBF, SBF and DBF fell significantly more in IRS1‐/‐ and IRS2‐/‐ than in WT mice. These results indicate that IRS plays a major role in the stimulation of renal functions and renal hemodynamics in type II diabetes.