Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: Associations with inflammatory and cardiometabolic markers in 4391 subjects

AimThis study aimed to compare concentrations of serum 25-hydroxy vitamin D and inflammatory markers in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and to determine whether the relationship between vitamin D levels and both cardiometabolic and inflammatory markers differs between MHO and MUO.MethodsThis cross-sectional study comprised 4391 obese subjects aged > 18 years. A panel of cardiometabolic and inflammatory markers, including anthropometric variables, glycaemic indices, lipid profiles, liver enzymes, homocysteine, C-reactive protein (CRP), fibrinogen and serum 25-hydroxy vitamin D levels, was investigated. All cardiometabolic and inflammatory markers in MHO and MUO as well as in vitamin D deficiency were compared.ResultsPrevalence of MHO was 41.9% in our obese subjects using International Diabetes Federation criteria. Considering insulin resistance and inflammation, the prevalence of MHO was 38.4%. Individuals with MHO had significantly higher vitamin D concentrations compared with MUO, and this difference in vitamin D status persisted after accounting for BMI and waist circumference. Subjects with MHO had significantly better metabolic status, lower liver enzymes, lower inflammatory markers and higher serum 25-hydroxy vitamin D than those with MUO. Associations between vitamin D levels and inflammatory and cardiometabolic markers differed according to MHO/MUO status. Among MUO subjects, vitamin D deficiency was associated with higher liver marker and homocysteine levels. Serum vitamin D was negatively associated with fasting plasma glucose and HbA_1c in MHO only.ConclusionSerum 25-hydroxy vitamin D levels were lower in MUO vs MHO, and reduced vitamin D concentrations were more strongly associated with cardiometabolic and inflammatory markers in MUO than in MHO subjects. These findings suggest that a deficiency in vitamin D could be a key component of MUO.     

Aging dilates atrium and pulmonary veins: implications for the genesis of atrial fibrillation

BACKGROUNDS: Aging plays a critical role in the pathophysiology of atrial fibrillation (AF). The left atrium (LA) and pulmonary veins (PVs) are essential components for the genesis and maintenance of AF. The purpose of this study was to investigate the effects of aging on the AF substrate and the initiator (PVs). METHODS: A total of 180 patients undergoing multidetector CT were enrolled and classified into six groups according to the decade of their age. LA, LA appendage (LAA), and orifice of the four PVs were measured. RESULTS: The LA anterior-posterior diameter and wall thickness became increased with aging after the age of 50 years (p < 0.001). Similarly, the LAA and four PV trunks also became dilated after the patients were > 50 years old (p < 0.001). The anterior wall was consistently thicker than the posterior wall in each group. Aging also increased both anterior and posterior wall thickness after the patients became > 50 years old. However, LA diameter, PV diameter, and LA wall thickness in the patients aged 70 to 79 years and > 80 years did not significantly differ. Age correlated well with the four PVs, LA diameter, and wall thickness with linear regression. CONCLUSIONS: Age significantly determines LA and PV structures. These findings show the important contributing effects involved in aging-induced AF in the general population.     

Basal insulin treatment intensification in patients with type 2 diabetes mellitus: A comprehensive systematic review of current options

AimAs type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium–glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin.MethodsMEDLINE, EMBASE and EBSCOhost were searched for English-language articles, and all those captured were original articles (case studies and narrative reviews were omitted). Data on study design, population demographics, interventions and outcomes were tabulated. The extracted outcome data included changes in glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), as well as body weight and safety data.ResultsA total of 88 publications were deemed relevant. All treatments reduced HbA_1c and FPG. The most pronounced reductions in PPG, an unmet need in patients not controlled by basal insulin, were seen following administration of RAIs and short-acting GLP-1 RAs, although data for this outcome are generally lacking. Body weight benefits were observed with GLP-1 RAs and SGLT-2 inhibitors. However, as only articles in English were included, the result was a possible publication bias, while the diversity of study designs and drug combinations limited comparisons between studies.ConclusionThe evidence supports effectiveness of the available add-on treatments to basal insulin. However, other factors, such as potential body-weight increases, convenience/compliance and adverse events, particularly hypoglycaemia, should be considered on a patient-by-patient basis to optimalize treatment outcomes.     

T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population

AimAdiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population.MethodsTwo polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n = 5212) and people with T2D in the DIABHYCAR study (n = 3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n = 230), and in controls who remained normoglycaemic (n = 226) throughout.ResultsIn a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04–1.18; P = 0.001) and 0.92 (95% CI: 0.87–0.98; P = 0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P = 0.03) and HbA_1c (P = 0.006), and lower plasma adiponectin levels (P = 0.03) in the D.E.S.I.R. participants. Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P = 0.03), HbA_1c (P = 0.02) and Fatty Liver Index (FLI; P ≤ 0.01), and higher plasma adiponectin levels (P = 0.002). Associations with HbA_1c, FLI and adiponectin levels persisted after adjusting for BMI.ConclusionCDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.     

Left atrial appendage dysfunction in acute embolic stroke young patients with sinus rhythm: Correlation with Tissue Doppler mitral annular systolic velocity

BackgroundTrans-esophageal echocardiogram (TEE) is a gold standard test for diagnosis of left atrial (LA) appendage function.AimTo evaluate left atrial appendage (LAA) dysfunction using mitral annular systolic velocity measured by tissue Doppler imaging “Sm” in acute embolic stroke young patients with sinus rhythm.MethodsTransthoracic (TTE) and transesophageal echocardiography (TEE) were performed in 70 consecutive patients with sinus rhythm without obvious left ventricular dysfunction within 2 weeks after embolic stroke. Two groups were identified: LAA dysfunction [LAA emptying peak flow velocity (LAA-eV) <0.55 m/s, n = 28, age 52 ± 11 years] and without LAA dysfunction (LAA-eV ≥ 0.55 m/s, n = 42, age 54 ± 10 years) on TEE. Tissue Doppler mitral annular systolic velocity “Sm” was obtained in apical four chambers view on TTE and D-dimer level estimated for all patients.ResultsSm was significantly lower in patients with than in those without LAA dysfunction (P < 0.0001). There was a significant correlation between Sm, LAVI, LAEF%, E/A ratio and LAA-eV in all selected patients groups. The optimum cut-off value of Sm for predicting LAA dysfunction was below or equal 8 cm/s (sensitivity 89.6% and specificity 94.2%).ConclusionTissue Doppler mitral annular systolic velocity is an independent non-invasive easy predictor of LAA dysfunction and significantly correlated with LAA-eV (p < 0.0001) in acute embolic stroke young patients with sinus rhythm.     

Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a metaanalysis

BACKGROUND: Venous thromboembolism (VTE) remains a major cause of morbidity following stroke. The optimal form of pharmacologic prophylaxis following stroke is unknown. METHODS: We identified randomized trials comparing unfractionated heparin (UFH) to low-molecular-weight heparin (LMWH) for VTE prevention in ischemic stroke patients. We focused on the risk for VTE, pulmonary embolism (PE), bleeding, and mortality as a function of the type of agent used for prophylaxis. Findings were pooled with a random-effects model. RESULTS: We identified three trials including 2,028 patients. Two of the studies were blinded, two studies relied on enoxaparin, while one study utilized certoparin. In two studies, UFH was administered three times a day, while it was administered twice daily in the remaining study. The use of LMWH was associated with a significant risk reduction for any VTE (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41 to 0.70; p < 0.001). Limiting the analysis to proximal VTEs also indicated that LMWHs were superior (OR with LMWH vs UFH, 0.53; 95% CI, 0.37 to 0.75; p < 0.001). LMWH use led to fewer PEs as well (OR, 0.26; 95% CI, 0.07 to 0.95; p = 0.042). There were no differences in rates of overall bleeding, intracranial hemorrhage, or mortality based on the type of agent employed. Restricting the analysis to the reports employing enoxaparin did not alter our findings. CONCLUSIONS: The prophylactic use of LMWH compared to UFH following ischemic stroke is associated with a reduction in both VTE and PE. This benefit is not associated with an increased incidence of bleeding. Broader use of LMWH for VTE prevention after ischemic stroke is warranted.     

The impact of new-onset atrial fibrillation on in-hospital mortality following cardiac surgery

BACKGROUND: The impact of new-onset postoperative atrial fibrillation (NAF) on in-hospital mortality (IHM) following cardiac surgery is unknown. METHODS: All patients without preoperative atrial fibrillation undergoing isolated coronary artery bypass graft surgery (CABG) and concomitant CABG and valve surgery were identified (n = 7,347). The association between NAF and IHM was determined using logistic regression modeling. Also, propensity score analysis was used to create two matched subgroups of patients with and without NAF (n = 2,015 in each group). The secondary outcomes examined were stroke, myocardial infarction (MI), intra-aortic balloon pump use, GI complications, deep sternal wound infection (DSWI), septicemia, renal failure, and length of stay. RESULTS: NAF developed in 2,047 patients (27.9%). NAF was not an independent predictor of IHM (odds ratio, 0.8; 95% confidence interval, 0.6 to 1.2; p = 0.3). In multivariate analysis, NAF was associated with age >/= 60 years, combined procedures, preoperative MI within 7 days of surgery, COPD, cerebrovascular disease, and male gender. Propensity-adjusted results revealed no difference in IHM between NAF vs no-NAF patients (2.9% vs 3.5%, respectively; Bonferroni-corrected p = 0.99). However, GI complications (4.2% vs 2.1%), DSWI (1.3% vs 0.4%), septicemia (4.0% vs 1.1%), renal failure (7.6% vs 4.3%), and length of stay (8 days vs 6 days) were significantly increased in patients with NAF. CONCLUSION: NAF following cardiac surgery is not associated with increased IHM.