The Associations between Kidney Function and Sexual Dysfunction among Males and Females with Type 2 Diabetes Mellitus.

Background and Objectives: Diabetic kidney disease (DKD), expressed either as albuminuria, low estimated glomerular filtration rate (eGFR) or both, and sexual dysfunction (SD), are common complications among type 2 diabetes mellitus (T2DM) patients. This study aims to assess whether an association exists between DKD and SD, erectile dysfunction (ED) or female sexual dysfunction (FSD) in a T2DM population. Materials and Methods: A cross-sectional study was designed and conducted among T2DM patients. The presence of SD was assessed using the International Index of Erectile Function and the Female Sexual Function Index questionnaires for males and females, respectively, and patients were evaluated for DKD. Results: Overall, 80 patients, 50 males and 30 females, agreed to participate. Sexual dysfunction was present in 80% of the study population. Among the participants, 45% had DKD, 38.5% had albuminuria and/or proteinuria and 24.1% had an eGFR below 60 mL/min/1.73 m2. The eGFR was associated with SD, ED and FSD. Moreover, SD and ED were proven as significant determinants for lower eGFR values in multiple linear regression analyses. DKD was associated with lower lubrication scores and eGFR was associated with lower desire, arousal, lubrication and total scores; however, the multivariate linear regression analyses showed no significant associations between them. Older age resulted in significantly lower arousal, lubrication, orgasm and total FSFI scores. Conclusions: SD is commonly encountered in older T2DM patients and DKD affects almost half of them. The eGFR has been significantly associated with SD, ED and FSD, while SD and ED were proven to be significant determinants for the eGFR levels.

The role of asymmetric dimethylarginine in endothelial dysfunction and abnormal nitric oxide metabolism in systemic sclerosis: results from a pilot study.

INTRODUCTION/OBJECTIVES: Systemic sclerosis (SSc) is characterized by generalized vasculopathy affecting mainly small vessels while macrovascular involvement is less investigated. The aim of this study was to examine associations between asymmetric dimethylarginine (ADMA) - a biomarker of atherosclerosis - and assessments of macrovascular endothelial function in patients with SSc. METHODS: This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA measurement in serum samples was based on an enzyme immunoassay technique. Participants underwent blood pressure measurement according to 2018 ESC/ESH Guidelines, applanation tonometry for the evaluation of arterial stiffness, and carotid ultrasound for the measurement of the intima-media thickness (cIMT). RESULTS: Eighty-one Caucasians (82.3% female) SSc individuals with mean age 55.44 ± 13.4 years were included in this analysis. The correlation analysis of ADMA levels (unadjusted and adjusted values) with functional and morphological parameters of atherosclerosis revealed no statistically significant associations. Subgroup analysis based on disease duration (≤ 4 years), immunologic profile (SCL-70 and ACA antibodies), disease type (limited, diffuse), and inflammatory status (erythrocyte sedimentation rate [ESR] > 25 mm/h and C-reactive protein [CRP] > 5 mg/L) showed no associations, except from a significant positive correlation between ADMA levels and cΙΜΤmean (r = 0.370, p = 0.044) in individuals with early SSc. CONCLUSIONS: The results of the study suggest that ADMA may be related with accelerated atherosclerosis in early stages of the disease. However, the lack of association between other morphological and functional parameters of endothelial dysfunction may suggest that other regulators of nitric oxide metabolism may contribute to macrovascular injury in SSc in various phases of the disease. Key Points • ADMA is a biomarker of atherosclerosis and has been linked with microvascular complications of SSc. •ADMA was not correlated with morphological and functional parameters of atherosclerosis in the population of the study. •The demonstrated association between ADMA and cIMT in patients with early SSc may suggest a role of NO/ADMA pathway in the initiation of macrovascular injury in SSc.

Right ventricular performance in patients with heart failure with mildly reduced ejection fraction: the forgotten ventricle.

Right ventricular (RV) function is a major determinant of prognosis and adverse outcomes in patients with heart failure (HF). It is largely unknown if HF with mildly reduced ejection fraction (HFmrEF) patients have some special characteristics in RV function (RVF) that may distinguish them from HF with reduced or preserved ejection fraction (HFrEF or HFpEF) patients. Standard echocardiography was performed to estimate RVF [tricuspid annular systolic velocity (TDSV), plane systolic excursion (TAPSE), TAPSE to pulmonary artery systolic pressure (TAPSE/PASP) and RV myocardial performance index (MPI-TEI index)] in a cross-sectional study. In 306 participants, the RV systolic function evaluated with TAPSE and TDSV was impaired in 39.1 and 24.2%, respectively. TAPSE, TAPSE/PASP and TDSV were lower in HFmrEF compared with HFpEF and higher compared with HFrEF (p < 0.001 for among-groups comparison). RV diastolic dysfunction varied between 12.6 and 43.8% depending on the echocardiographic parameter. Diastolic RVF determined by tricuspid inflow E/A wave ratio (Et/At) was impaired in less patients with HFmrEF compared with those with HFpEF or HFrEF (25.9% vs 48.4% vs 56.3%; p = 0.030, respectively). RV diastolic dysfunction by et'/at' (tissue Doppler tricuspid valve annulus e' and a' waves) was impaired in less patients with HFmrEF compared with HFrEF (11.8% vs 33.3%; p = 0.019). A multivariate regression analysis revealed a significant association between RV and LV systolic dysfunction. The present study shows a high prevalence of RV dysfunction in HFmrEF patients. Study findings provides some new insights on RV and LV systolic dysfunction coupling whereas RV diastolic dysfunction was not dependent on LV systolic dysfunction.

Effect of Empagliflozin and Dapagliflozin on Ambulatory Arterial Stiffness in Patients with Type 2 Diabetes Mellitus and Cardiovascular Co-Morbidities: A Prospective, Observational Study.

Background and Objectives: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease. Arterial stiffness is an independent prognostic marker for cardiovascular disease development. We aimed at determining the effect of two different sodium-glucose co-transporter-2 (SGLT-2) inhibitors on ambulatory arterial stiffness in individuals with T2DM. Materials and Methods: In this single-center, single-arm, prospective study performed from January 2020 to August 2021, we planned to enroll adult subjects with T2DM and stable antidiabetic and antihypertensive treatment, assigned either to empagliflozin or dapagliflozin for 6 months. All eligible subjects underwent ambulatory blood pressure monitoring. We set as the primary efficacy outcome the change in ambulatory pulse wave velocity (PWV) from baseline to week 24. Results: We finally enrolled 46 diabetic subjects, with a mean age of 62.89 (8.53) years and mean T2DM duration of 9.72 (6.37) years. Thirty patients received dapagliflozin, while sixteen patients received empagliflozin. Due to COVID-19 pandemic restrictive measures during the study, the mean follow-up period extended from 6 months to 9.98 (3.27) months. Regarding the prespecified primary efficacy outcome, we found that the SGLT-2 inhibitor treatment did not have a significant effect on PWV (p = 0.65). Prior history of cardiovascular disease did not significantly affect the observed effects. Other indices of arterial stiffness, such as augmentation index and central pulse pressure, were not significantly affected, neither by empagliflozin nor by dapagliflozin. Conclusions: SGLT-2 inhibitor treatment with empagliflozin or dapagliflozin in subjects with T2DM failed to improve ambulatory PWV over a mean follow-up of 10 months. Registration number: ISRCTN88851713.

Effect of sodium-glucose co-transporter-2 inhibitors on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). METHODS: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. RESULTS: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. CONCLUSION: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

Cardiovascular Outcomes with Finerenone According to Glycemic Status at Baseline and Prior Treatment with Newer Antidiabetics among Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) and cardiovascular disease are closely interconnected. We sought to determine the cardioprotective action of finerenone according to prior treatment with newer antidiabetics and glycemic status. We searched PubMed and Cochrane Library from inception to October 1, 2021 for randomized controlled trials (RCTs) assessing the effect of finerenone on major adverse cardiovascular outcomes in patients with T2DM. We set the primary endpoint as major adverse cardiovascular events (MACE), defined as the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. We finally included two RCTs in our quantitative synthesis. Compared to placebo, finerenone induced a 23% risk reduction for the composite cardiovascular endpoint, regardless of prior glycemia. We also showed that finerenone provided significant cardiovascular benefit for obese patients with T2DM compared to placebo, although this benefit was diminished for subjects with a body mass index lower than 30 kg/m2. Finally, the combination of finerenone with sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists did not produce a significant risk reduction for MACE. We conclude that finerenone provides significant cardiovascular benefits for patients with T2DM, especially for those who are obese, while glycemic status or treatment with newer antidiabetics at baseline does not affect the observed cardioprotective action.

Serum adipokine levels in patients with type 1 diabetes are associated with degree of obesity but only resistin is independently associated with atherosclerosis markers.

PURPOSE: The role of adipokines in causing inflammation and insulin resistance in normal weight and obese patients is generally well studied. However, there are often conflicting results regarding their levels in type 1 diabetes mellitus (T1DM) patients and their relationship to micro- and macrovascular disease. We therefore investigated which serum adipokine levels are independently associated with markers of early atherosclerosis and microvascular complications in patients with T1DM. METHODS: A cross-sectional study was performed in the Diabetes Outpatient Clinic of Hippokrateion General Hospital, Thessaloniki, Greece. Sixty T1DM patients (30 females, mean age 38.8 ± 10.6 years, mean diabetes duration 17.4 ± 9.9 years) were included. Plasma adiponectin, leptin, and resistin, carotid artery intima media thickness (cIMT), and arterial stiffness (pulse wave velocity, PWV/SpygmoCor CP System and Mobil-O-Graph 24 h PWA) were assessed. RESULTS: Leptin and resistin levels were significantly higher in overweight and obese patients (p = 0.002 and p = 0.039, respectively). Adiponectin was the only adipokine negatively correlated with BMI (rs = - 0.41, p = 0.001). We report a bivariate association between serum adiponectin levels and retinopathy (p = 0.007). Resistin was the only adipokine that showed significant correlation with systolic (rs = 0.42, p = 0.001) and diastolic (rs = 0.29, p = 0.024) hypertension and PWV (p = 0.035). CONCLUSIONS: Serum adipokine levels demonstrate similar bivariate associations with anthropometric variables in patients with T1DM to those in normal weight subjects. Although microvascular complications are associated with serum adipokine levels by bivariate analysis, only resistin, an inflammatory marker, is independently associated with arterial stiffness in patients with T1DM.

Arterial Stiffness as a Cardiovascular Risk Factor for the Development of Preeclampsia and Pharmacopreventive Options.

Arterial Stiffness (AS) describes the rigidity of the arterial walls. Epidemiological studies have shown that increased AS is an independent predictive marker of Cardiovascular (CV) morbidity and mortality in both pregnant and non-pregnant women. Preeclampsia (PE), a form of pregnancy-induced hypertension, affects approximately 5% of pregnancies worldwide. Preeclamptic women have a higher risk of CV Disease (CVD), mainly because PE damages the heart's ability to relax between contractions. Different pharmacological approaches for the prevention of PE have been tested in clinical trials (e.g., aspirin, enoxaparin, metformin, pravastatin, and sildenafil citrate). In current clinical practice, only low-dose aspirin is used for PE pharmacoprevention. However, low-dose aspirin does not prevent term PE, which is the most common form of PE. Compromised vascular integrity precedes the onset of PE and therefore, AS assessment may constitute a promising predictive marker of PE. Several non-invasive techniques have been developed to assess AS. Compared with normotensive pregnancies, both Carotid-Femoral Pulse Wave Velocity (cfPWV) and Augmentation Index (AIx) are increased in PE. In view of simplicity, reliability, and reproducibility, there is an interest in oscillometric AS measurements in pregnancies complicated by PE.