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The research presented in this thesis focuses on the receptivity to surface roughness of swept wing boundary layers dominated by crossflow instabilities (CFI), providing insights into how surface roughness can be used to passively control the developing instabilities. Discrete roughness elements (DRE) arrays and distributed randomized roughness patches (DRP) are employed to investigate the physical phenomena governing receptivity and their impact on CFI onset. The supporting data combine numerical solutions of linear and non-linear stability theory with advanced experimental flow diagnostics. This booklet is divided into three main parts. The first part investigates the flow mechanisms dominating the receptivity of stationary CFI to the amplitude and location of DRE arrays. The relation between the external forcing configuration and the initial instability amplitude is investigated, along with scaling principles allowing for the up-scaled reproduction of the swept wing leading-edge configurations, which provide experimentally observable configuration. The second part of this research explores the stationary CFI receptivity to specific up-scaled roughness configurations, including both isolated discrete roughness elements and DRE arrays. These roughness elements are applied at relatively downstream chord locations to enhance the experimental resolution of the near-roughness flow field. The isolated discrete roughness elements ensure strong boundary layer forcing, which helps to outline the relation between the near-element instability onset and the rapid transitional process. In contrast, the applied DRE arrays configurations provide boundary layers dominated by the development of CFI. In such scenarios, high-magnification tomographic particle tracking velocimetry identifies the dominant near-element stationary instabilities precursor to CFI. Specifically, the presence of transient growth and decay mechanisms in the near-roughness flow regi, Aerodynamics

This work presents the first experimental characterization of the flow field in the vicinity of periodically spaced discrete roughness elements (DRE) in a swept wing boundary layer. The time-averaged velocity fields are acquired in a volumetric domain by high-resolution dual-pulse tomographic particle tracking velocimetry. Investigation of the stationary flow topology indicates that the near-element flow region is dominated by high- and low-speed streaks. The boundary layer spectral content is inferred by spatial fast Fourier transform (FFT) analysis of the spanwise velocity signal, characterizing the chordwise behaviour of individual disturbance modes. The two signature features of transient growth, namely algebraic growth and exponential decay, are identified in the chordwise evolution of the disturbance energy associated with higher harmonics of the primary stationary mode. A transient decay process is instead identified in the near-wake region just aft of each DRE, similar to the wake relaxation effect previously observed in two-dimensional boundary layer flows. The transient decay regime is found to condition the onset and initial amplitude of modal crossflow instabilities. Within the critical DRE amplitude range (i.e. affecting boundary layer transition without causing flow tripping) the transient disturbances are strongly receptive to the spanwise spacing and diameter of the elements, which drive the modal energy distribution within the spatial spectra. In the super-critical amplitude forcing (i.e. causing flow tripping) the near-element stationary flow topology is dominated by the development of a high-speed and strongly fluctuating region closely aligned with the DRE wake. Therefore, elevated shears and unsteady disturbances affect the near-element flow development. Combined with the harmonic modes transient growth these instabilities initiate a laminar streak structure breakdown and a bypass transition process., Aerodynamics, Wind Energy

The present work details the steady and unsteady flow topology in the vicinity of an array of periodically spaced super-critical (i.e. causing flow tripping) discrete roughness elements (DRE) applied in a swept wing boundary layer. The stationary flow field is acquired by means of high-magnification dual-pulse tomographic particle tracking velocimetry (3D-PTV), while the unsteady instabilities are investigated through high-resolution hot wire anemometry (HWA). The 3D-PTV time-averaged velocity fields, indicate that the near-element flow region is dominated by the alternation of high- and low-speed streaks. A high-speed region substitutes the wake development shortly downstream of the DRE location, due to the high-speed streaks merging. This initiates a region of strong unsteady fluctuations that expands in the spanwise and wall-normal directions, ultimately leading to the boundary layer transition to turbulence. The spectral content of the stationary flow structures is investigated through a spanwise spatial Fourier transform. The extracted spectra and instability amplitudes, indicate the presence of non-modal mechanisms in the near-element stationary wake region. Nonetheless, the temporal spectral analysis of the HWA velocity signal, identifies the presence of strongly tonal shedding mechanisms initiating and the unsteady instabilities the element vicinity. Their rapid downstream growth and evolution retains a fundamental role in the transitional process., Aerodynamics, Wind Energy

The effect of discrete roughness elements on the development and breakdown of stationary crossflow instability on a swept wing is explored. Receptivity to various element heights and chordwise locations is explored using a combination of experimental and theoretical tools. Forcing configurations, determined based on linear stability predictions, are manufactured and applied on the wing in a low turbulence facility. Measurements are performed using infrared thermography, quantifying the transition front location, and planar particle image velocimetry, providing a reconstruction of stationary crossflow instabilities and their associated growth. Measurements are corroborated with simulations based on nonlinear parabolised stability equations. Results confirm the efficacy of discrete roughness elements in introducing and conditioning stationary crossflow instabilities. Primary instability amplitudes and resulting laminar-turbulent transition location are found to strongly depend on both roughness amplitude and chordwise location. The Reynolds number based on element height is found to satisfactorily approximate the initial forcing amplitude, revealing the importance of local velocity effects in non-zero-pressure gradient flows. Direct estimation of initial perturbation amplitudes from nonlinear simulations suggests the existence of pertinent flow mechanisms in the element vicinity, active in conditioning the onset of modal instabilities. Dedicated velocimetry planes, elucidate the development of a momentum deficit wake which rapidly decays downstream of the element followed by mild growth, representing the first experimental evidence of transient behaviour in swept wing boundary layers. The outcome of this work identifies a strong scalability of the transition dynamics to roughness amplitude and location, warranting the upscaling of roughness elements to more accessible, measurable and spatially resolved configurations in future experiments., Aerodynamics, Wind Energy

The application of an isolated roughness element in the laminar boundary layer developing on the surface of a wing, introduces flow instabilities that eventually lead to the breakdown of the laminar flow structures and the formation of a turbulent wedge. The present work, investigates the instabilities and transition process initiated by an isolated roughness element applied in a swept wing boundary layer. Specifically, the perturbations induced by a cylindrical element are analysed, providing relevant insights regarding the nature of the instabilities developing in the flow field. The global flow features are measured through infrared thermography, while local information on the stationary and unsteady disturbances are provided by hot-wire anemometry. The collected results, prove that the main instabilities responsible for the wedge origin and evolution are related to the shedding process initiated in the wake of the roughness element. Additionally, the dominant flow features identified in the present work, show significant similarities with those pertaining to 2D boundary layer transition initiated by isolated roughness elements., Aerodynamics, Wind Energy

This work presents the first reported experimental characterization of the flow field in the direct vicinity of discrete roughness elements (DRE), in a swept wing boundary layer. High magnification tomographic Particle Tracking Velocimetry (3D-PTV) measurements are used to acquire time-averaged velocity and standard deviation fields in a 3D volume directly aft of the DRE elements. The collected data detail the near-element flow topology, providing information on the developing wake and emerging flow structures, their organization and amplitude evolution. A transient growth behaviour is identified in the element wake, while onset and growth of crossflow instabilities is observed further downstream. As such, the near element flow is confirmed to be a fundamental part of the receptivity process, contributing in setting the initial amplitudes for the crossflow instability evolution., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Aerodynamics, Wind Energy

The presented work introduces a cancellation technique, based on the linear superposition of stationary crossflow instabilities (CFIs) through the application of a streamwise series of optimally positioned discrete roughness element (DRE) arrays on a swept wing surface. The DRE arrays are designed and arranged with suitable amplitude and phase shift to induce velocity disturbance systems that destructively interact, ultimately damping the developing CFIs. The robustness of this technique is investigated for a smooth wing surface as well as in the presence of enhanced distributed surface roughness. The resulting flow fields are measured with infrared thermography and particle tracking velocimetry, allowing for the extraction of the laminar-to-turbulent transition front location and for the characterization of the local boundary layer development. The acquired data show that the superposition of suitably arranged DRE arrays can successfully suppress monochromatic CFIs, reducing their amplitude and growth and delaying the boundary layer transition to turbulence when applied on a smooth wing surface. However, the presence of elevated background roughness significantly reduces the effectiveness of the proposed method., Aerodynamics, Wind Energy

The present work is dedicated to the investigation of the effect of an isolated roughness element on a swept wing boundary layer. In particular, the flow modifications incurred by a single cylindrical element applied on a swept wing model are measured, toward describing the nature of the perturbations introduced in the flow field, their development in the near and far wake region, as well as their eventual breakdown. The measurements are performed using infrared thermography, to achieve a general overview of the element wake origin and spatial spreading. Local quantitative characterization of the stationary and unsteady disturbances evolving in the flow is instead acquired through hot wire anemometry. When present in an undisturbed laminar boundary layer, isolated roughness elements are found to introduce flow disturbances, which lead to the formation of a turbulent wedge. As it develops downstream, the wedge undergoes rapid spanwise expansion, affecting the adjacent laminar flow regions. The wedge origin and development is mostly associated with the instabilities introduced by the shedding process initiated in the roughness element wake, comparably to the dominant flow features characterizing the transition of two-dimensional boundary layers conditioned by an isolated roughness element. Nonetheless, the presence of the crossflow velocity component in the boundary layer baseflow notably affects the overall flow development, introducing an asymmetric evolution of the main flow features., Aerodynamics, Wind Energy

Background: Resistant hypertension is independently associated with an increased risk of death in the general hypertensive population. We assessed whether resistant hypertension is an independent predictor of all-cause mortality in individuals with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. Methods: On 31 October 2015, vital status information was retrieved for 15,656 of the 15,773 participants enrolled in 2006-2008. Based on baseline blood pressure (BP) values and treatment, participants were categorized as normotensive, untreated hypertensive, controlled hypertensive (i.e., on-target with < 3 drugs), uncontrolled hypertensive (i.e., not on-target with 1-2 drugs), or resistant hypertensive (i.e., uncontrolled with > 3 drugs or controlled with > 4 drugs). Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the association with all-cause mortality. Results: Using the 130/80 mmHg targets for categorization, crude mortality rates and Kaplan-Meier estimates were highest among resistant hypertension participants, especially those with controlled resistant hypertension. As compared with resistant hypertension, risk for all-cause mortality was significantly lower for all the other groups, including individuals with controlled hypertension (hazard ratio 0.81 [95% confidence interval 0.74-0.89], P < 0.0001), but became progressively similar between resistant and controlled hypertension after adjustment for cardiovascular risk factors and complications/comorbidities. Also when compared with controlled resistant hypertension, mortality risk was significantly lower for all the other groups, including controlled hypertension, even after adjusting for cardiovascular risk factors (0.77 [0.63-0.95], P = 0.012), but not for complications/comorbidities (0.88 [0.72-1.08], P = 0.216). BP was well below target in the controlled hypertensive groups (resistant and non-resistant) and values < 120/7

An experimental parametric study of the effect of discrete roughness elements (DRE) on the development and breakdown of stationary crossflow instability on a swept wing is presented. A systematic investigation of the receptivity to various elements height and chord locations is carried out in a crossflow dominated flow. The flow is globally and locally investigated through simultaneous infra-red (IR) and planar particle image velocimetry (PIV) acquisitions that correlate the extracted transition location and the developing flow feature with the applied forcing configuration, providing insights on the physical mechanisms governing receptivity. The presented results show how a downstream shift in the DRE array location is accompanied by a transition delay, while an increase of the elements height leads to a transition advancement. Moreover, the entire set of PIV measurements allows to compare the instabilities development between different forcing cases, providing insights on the dominant physical mechanisms governing receptivity of stationary CFI to discrete roughness and possible scaling rules. In fact, an up-scaled forcing configuration replicating the instabilities strength and evolution would allow to investigate the near-flow features in a set-up easier to measure experimentally., Virtual/online event due to COVID-19, Aerodynamics, Wind Energy

A dielectric barrier discharge actuator (DBD) is considered and studied as a stall recovery device. The DBD is installed on the nose of a NACA0015 airfoil with chord × span 300 × 930 mm. The geometry of the exposed electrode has periodic triangular tips purposely designed for the case under study. Wind tunnel tests have been carried out over a range of airspeeds up to 35 m/s with a Reynolds number of 700 k. The flow morphology has been characterized by means of the particle image velocimetry technique, obtaining velocity fields and pressure coefficients. By exploring different planes along the model span, the three-dimensional effect of the DBD has been reconstructed, identifying the flow region mainly sensitive to the plasma actuation. Finally, the actuator effectiveness has been quantified accounting for the power consumption data, leading to defining further design improvements in view of a better efficiency., Aerodynamics

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50–75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2–3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15–45 mg) or a sulfonylurea (5–15 mg glibenclamide, 2–6 mg glimepiride, or 30–120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 p

Objective Atherogenic dyslipidemia seems to play a major role in microvascular complications and in residual microvascular risk after statin therapy, which reduces triglycerides up to 40%. We assessed whether raised TG levels are associated with an increased burden from microvascular complications in patients with type 2 diabetes. Methods Subjects from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study (n= 15,773) were divided in 4 groups depending on whether they had plasma triglycerides below (NTG, 67.8%) or above (HTG, 32.2%) 1.7 mmol/L and were (42.4%) or not on (57.6%) statin therapy. Estimated GFR (eGFR) was calculated from serum creatinine, albuminuria was measured by immunonephelometry or immunoturbidimetry, and retinopathy was evaluated by fundus examination. Results HTG subjects, either with or without statin, had higher prevalence of albuminuria, reduced eGFR and chronic kidney disease (CKD), especially the albuminuric forms, but not of retinopathy, than NTG subjects. In contrast, cardiovascular disease and advanced DR were more prevalent in subjects on statin than in those not, independently of triglyceride levels. Logistic regression analysis confirmed that HTG, without or with statin, was independently associated with micro and macroalbuminuria, mildly to severely reduced eGFR, and all CKD phenotypes, but not with retinopathy. The adjusted odd ratios for CKD increased linearly for every 0.26 mmol/L increase (approximately one decile) in triglyceride levels. The increase was higher with increasing severity of albuminuria, eGFR loss and CKD phenotype as well as in subjects receiving than in those not receiving statin treatment. Conclusions Triglycerides are associated with CKD, but not retinopathy in subjects with type 2 diabetes, independently of statin treatment. These data point to a possible role of hypertriglyceridemia in the development of CKD, though it remains to be demonstrated that diabetic individuals might ben

Aims Within the normoalbuminuric range, low albuminuria (LA, 10-29 mg/24 h) is associated with higher adverse cardiovascular and renal outcomes than normal albuminuria (NA, < 10 mg/24 h). This cross-sectional analysis of the cohort from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study was aimed at assessing the independent correlates of LA versus NA in patients with type 2 diabetes. Methods This analysis involved 11,538 normoalbuminuric patients (73.2 % of the entire RIACE cohort): 6023 (52.2 %) with NA and 5515 (47.8 %) with LA. Binary logistic regression analysis with backward conditional variable selection was applied to assess the independent correlates of LA versus NA. Results Compared with NA subjects, LA patients were more frequently males, older and with family history of hypertension, had longer diabetes duration, lower HDL cholesterol, and higher haemoglobin (Hb) A(1c), triglycerides, and blood pressure (BP), use of anti-hyperglycaemic and anti-hypertensive drugs, and prevalence of metabolic syndrome, retinopathy, chronic kidney disease, any cardiovascular disease, myocardial infarction, and coronary and peripheral events. Men with LA were also more frequently current or former smokers and had higher body mass index, waist circumference, and non-HDL cholesterol. Independent correlates of LA were age (OR 1.018), family history of hypertension (OR 1.321), smoking status (former, OR 1.158; current, OR 1.237), HbA(1c) (OR 1.062), waist circumference (OR 1.050), triglycerides (OR 1.001), and diastolic BP (OR 1.014), together with use of anti-hyperglycaemic and anti-hypertensive agents. Conclusions Several risk factors are associated with increased albuminuria within the normoalbuminuric range. As most of these factors are potentially modifiable, treating them aggressively might reduce the excess risk associated with LA.

Objective: The phenotype of resistant hypertension in patients with type 2 diabetes has been poorly characterized. This cross-sectional analysis of the large cohort from the Renal Insufficiency and Cardiovascular Events (RIACE) study was aimed at assessing the clinical correlates and association with complications of resistant hypertension in patients with type 2 diabetes. Methods: The RIACE study enrolled 15 773 patients consecutively visiting 19 diabetes clinics during the years 2007-2008. Resistant hypertension, defined as BP values not on target (i.e. >130/80 mmHg, respectively) with three antihypertensive agents, was detected in 2363 individuals (15% of the whole RIACE cohort, 17.4% of hypertensive individuals, and 21.2% of treated hypertensive patients). Patients without resistant hypertension [nonresistant hypertension (NRH)], that is on target with one (n = 1569), two (n = 1369), and three (n = 803) drugs, and individuals with uncontrolled hypertension, that is untreated or not on target with less than three drugs (n = 7440), served as controls. Results: As compared with NRH and uncontrolled hypertension patients, patients with resistant hypertension were older and more frequently women and had significantly higher waist circumference, albuminuria, and serum creatinine, and lower glomerular filtration rate. Prevalence values of chronic kidney disease and advanced retinopathy were significantly higher in resistant hypertension than in both nonresistant hypertension and uncontrolled hypertension individuals, whereas cardiovascular disease was more frequent in resistant hypertension versus uncontrolled hypertension, but not nonresistant hypertension patients, especially those on 2-3 drugs. Conclusions: Resistant hypertension is relatively common in patients with type 2 diabetes. In these individuals, age, female sex and waist circumference are independent correlates of resistant hypertension, which is strongly associated with microvascular (especially renal)

Background: Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study.Methods: Serial (3-5) HbA1c values obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine.Results: HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P<0.0001) in subjects with history of any CVD (n. 2,133, 25.7%) than in those without CVD (n. 6,157, 74.3%). Median and interquartile range were 7.78 (7.04-8.56) and 7.49 (6.81-8.31), respectively, for HbA1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke

OBJECTIVE - To evaluate the rate and determinants of concordance between advanced diabetic retinopathy (DR) and chronic kidney disease (CKD), as assessed by both albuminuria and estimated glomerular fi ltration rate (eGFR), in the large cohort of the Renal Insuf ficiency And Cardiovascular Events (RIACE) Italian multicenter study. RESEARCH DESIGN AND METHODS - Patients with type 2 diabetes (n = 15,773) visiting consecutively 19 hospital -based diabetes clinics in years 2007 and 2008 were examined. DR was assessed by dilated fundoscopy. CKD was de fined based on albuminuria and eGFR. RESULTS - CKD was present in 58.64%of subjects with advanced DR, whereas advanced DR was detectable only in 15.28%of individuals with any CKD and correlated with the albuminuric CKD phenotypes more than with the nonalbuminuric phenotype. Age, male sex, diabetes duration, hemoglobin A 1c, hypertension, triglycerides, previous cardiovascular disease, and, inversely, HDL-cholesterol correlated independently with the presence of any CKD in individuals with advanced DR; correlates differed according to the presence of albuminuria, reduced eGFR, or both. Conversely, factors associated with the presence of advanced DR in subjects with any CKD were diabetes treatment, previous cardiovascular disease, albuminuria, and, inversely, smoking, eGFR, and age at diagnosis. CONCLUSIONS - Concordance of CKD with advanced DR is low in subjects with type 2 diabetes, and CKD without advanced DR ismore frequent than isolated advanced DR, at variance with type 1 diabetes. Factors independently associated with the presence of any CKD in individuals with advanced DR differ, at least in part, from those correlating with the presence of advanced DR in subjects with any CKD and by CKD phenotype.

OBJECTIVE - Data on cardiac function in patients with nonalcoholic fatty liver disease (NAFLD) are limited and conflicting. We assessed whether NAFLD is associated with abnormalities in cardiac function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - We studied 50 consecutive type 2 diabetic individuals without a history of ischemic heart disease, hepatic diseases, or excessive alcohol consumption, in whom NAFLD was diagnosed by ultrasonography. A tissue Doppler echocardiography with myocardial strain measurement was performed in all patients. RESULTS - Thirty-two patients (64%) had NAFLD, and when compared with the other 18 patients, age, sex, BMI, waist circumference, hypertension, smoking, diabetes duration, microvascular complication status, and medication use were not significantly different. In addition, the left ventricular (LV) mass and volumes, ejection fraction, systemic vascular resistance, arterial elasticity, and compliance were also not different. NAFLD patients had lower e′ (8.2 ± 1.5 vs. 9.9 ± 1.9 cm/s, P < 0.005) tissue velocity, higher E-to-e′ ratio (7.90 ± 1.3 vs. 5.59 ± 1.1, P < 0.0001), a higher time constant of isovolumic relaxation (43.1 ± 10.1 vs. 33.2 ± 12.9 ms, P < 0.01), higher LV-end diastolic pressure (EDP) (16.5 ± 1.1 vs. 15.1 ± 1.0 mmHg, P < 0.0001), and higher LV EDP/end diastolic volume (0.20 ± 0.03 vs. 0.18 ± 0.02 mmHg, P < 0.05) than those without steatosis. Among the measurements of LV global longitudinal strain and strain rate, those with NAFLD also had higher E/global longitudinal diastolic strain rate during the early phase of diastole (E/SR E). All of these differences remained significant after adjustment for hypertension and other cardiometabolic risk factors. CONCLUSIONS - Our data show that in patients with type 2 diabetes and NAFLD, even if the LV morphology and systolic function are preserved, early features of LV diastolic dysfunction may be detected. © 2012 by the American Diabetes Association

Nonalcoholic fatty liver disease (NAFLD), comprising its whole spectrum of conditions ranging from simple steatosis to steatohepatitis (nonalcoholic steatohepatitis; NASH) and cirrhosis, is the most frequent liver disease in developed countries and is now regarded as the liver manifestation of the metabolic syndrome. Several studies indicate that NAFLD, especially in its necro-inflammatory form (NASH), is associated with a systemic proinflammatory/prothrombotic state, independently of shared metabolic risk factors. This suggests that NAFLD/NASH is not simply a marker of the proinflammatory/ prothrombotic state in the metabolic syndrome but is actively involved in its pathogenesis, possibly through the systemic release of proinflammatory and procoagulant factors from the steatotic liver (C-reactive protein, plasminogen activator inhibitor-1, interleukin-6, fibrinogen, and other proinflammatory cytokines). The clinical impact of NAFLD on the proinflammatory/prothrombotic risk profile deserves particular attention in view of the implications for screening and surveillance strategies in the growing number of patients with NAFLD. Copyright © 2009 by Thieme Medical Publishers, Inc.