Atrial fibrillation (AF), the most common, progressive tachyarrhythmia is associated with serious complications, such as stroke and heart failure. Early recognition of AF, essential to prevent disease progression and therapy failure, is hampered by the lack of accurate diagnostic serum biomarkers to identify the AF stage. As we previously showed mitochondrial dysfunction to drive experimental and human AF, we evaluated whether cell-free circulating mitochondrial DNA (cfc-mtDNA) represents a potential serum marker. Therefore, the levels of two mtDNA genes, COX3 and ND1, were measured in 84 control patients (C), 59 patients undergoing cardiac surgery without a history of AF (SR), 100 paroxysmal (PAF), 116 persistent (PeAF), and 20 longstanding-persistent (LS-PeAF) AF patients undergoing either cardiac surgery or AF treatment (electrical cardioversion or pulmonary vein isolation). Cfc-mtDNA levels were significantly increased in PAF patients undergoing AF treatment, especially in males and patients with AF recurrence after AF treatment. In PeAF and LS-PeAF, cfc-mtDNA levels gradually decreased. Importantly, cfc-mtDNA in serum may originate from cardiomyocytes, as in vitro tachypaced cardiomyocytes release mtDNA in the medium. The findings suggest that cfc-mtDNA is associated with AF stage, especially in males, and with patients at risk for AF recurrence after treatment.
The causal effects of alcohol-in-moderation on cardiometabolic health are continuously debated. Mendelian randomization (MR) is an established method to address causal questions in observational studies. We performed a systematic review of the current evidence from MR studies on the association between alcohol consumption and cardiometabolic diseases, all-cause mortality and cardiovascular risk factors. We performed a systematic search of the literature, including search terms on type of design and exposure. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. We additionally looked at exploration of non-linearity. We reported the direction of the studied associations. Our search yielded 24 studies that were eligible for inclusion. A full instrumental variable analysis was performed in 17 studies (71%) and 13 out of 24 studies (54%) validated all three key assumptions. Five studies (21%) assessed potential non-linearity. In general, null associations were reported for genetically predicted alcohol consumption with the primary outcomes cardiovascular disease (67%) and diabetes (75%), while the only study on all-cause mortality reported a detrimental association. Considering the heterogeneity in methodological quality of the included MR studies, it is not yet possible to draw conclusions on the causal role of moderate alcohol consumption on cardiometabolic health. As MR is a rapidly evolving field, we expect that future MR studies, especially with recent developments regarding instrument selection and non-linearity methodology, will further substantiate this discussion.
This study aims to determine the association between social jetlag and parameters of metabolic syndrome and type 2 diabetes (T2D) in a systematic review and meta-analysis.A systematic literature search was conducted in PubMed/Embase/Scopus until May 2022. Included studies described an association between social jetlag and parameters of the metabolic syndrome and/or T2D, were available full text and written in English or Dutch. Data extraction and quality assessment were performed on pre-piloted forms independently by two reviewers. Results were meta-analysed using random-effects analysis. A total of 6,290 titles/abstracts were screened, 176 papers were read full-text, 68 studies were included. Three studies were rated as low quality, 27 were moderate, and 38 were high quality. High quality studies showed that having social jetlag compared to no social jetlag was significantly associated with higher body mass index in 20 studies (0.49 kg/m 2 , 95% confidence interval [CI] 0.21-0.77; I 2 = 100%), higher waist circumference in seven studies (1.11 cm, 95% CI 0.42-1.80; I 2 = 25%), higher systolic blood pressure in 10 studies (0.37 mmHg, 95% CI 0.00-0.74; I 2 = 94%) and higher glycated haemoglobin in 12 studies (0.42%, 95% CI 0.12-0.72; I 2 = 100%). No statistically significant associations were found for obesity, abdominal obesity, high-and low-density lipoprotein levels, cholesterol, triglycerides, diastolic blood pressure, hypertension, fasting glucose, homeostatic model assessment for insulin resistance, metabolic syndrome or T2D. Sensitivity analyses did not reduce heterogeneity. Despite substantial heterogeneity, social jetlag is associated with certain parameters of the metabolic syndrome and T2D, but not with prevalent metabolic syndrome or T2D. These findings should be interpreted with caution as the level of evidence is low and mostly based on cross-sectional data. Longitudinal studies are needed to further assess the direction of causality.
Objective: Social jet lag, i.e., the discordance among social and biological rhythms, is associated with poor metabolic control. This study aimed to assess cross-sectional and longitudinal associations among social jet lag and glycemic and metabolic control in people with type 2 diabetes.Methods: In a prospective cohort (N = 990) with type 2 diabetes, social jet lag was measured at baseline using daily diaries and was categorized (high, moderate, or low).Metabolic outcomes were assessed at baseline and at 1 and 2 years of follow-up.Associations among social jet lag and glycemic and metabolic control were analyzed using linear regression and linear mixed models adjusted for confounding factors.Analyses were stratified for work status (retired vs. working; p value for interaction = 0.007 for glycated hemoglobin [HbA1c]).Results: In working people, a cross-sectional association between high social jet lag and HbA1c (1.87 mmol/mol [95% CI: 0.75 to 2.99]) and blood pressure (5.81 mm Hg [95% CI: 4.04 to 7.59]) was observed. For retired people, high social jet lag was negatively associated with HbA1c (À1.58 mmol/mol [95% CI: À2.54 to À0.62]), glucose (À0.19 mmoL/L [95% CI:À0.36 to À0.01]), and blood pressure (À3.70 mm Hg [95% CI: À5.36 to À2.04]), and the association with BMI was positive (1.12 kg/m 2 [95% CI: 0.74 to 1.51]). Prospective associations had the same direction as cross-sectional findings but were nonsignificant for working or retired people.Conclusions: Social jet lag was cross-sectionally, but not prospectively, associated with glycemic and metabolic markers. Interaction with work status was present, and directions of the associations were generally detrimental in the working population, whereas higher social jet lag was associated with improved glycemic and metabolic control for retired people.
Objective Diabetic kidney disease is a microvascular complication of diabetes. Here, we assessed the association between skin microvascular function and renal hemodynamic function in a cohort of well‐phenotyped adults with type 2 diabetes (T2D). Methods We included 81 overweight/obese adults (age: 62 ± 8 years; BMI: 32 ± 4 kg/m2) with well‐controlled T2D and no renal impairment. Skin microvascular function was assessed by nailfold capillary density in rest and after arterial occlusion (ie, peak capillary density). Renal hemodynamic functions (ie, measured glomerular filtration rate [mGFR], effective renal blood flow [ERBF], filtration fraction [FF], and effective renal vascular resistance [ERVR]) were assessed by combined inulin and para‐aminohippurate clearances and blood pressure measurements. Results Skin capillary density was 45 ± 10 capillaries/mm2 at baseline and 57 ± 11 capillaries/mm2 during post‐occlusive peak; mGFR averaged 108 ± 20 ml/min. In multivariable regression analyses, positive associations between capillary density during post‐occlusive peak and mGFR (β = 0.224; p = 0.022) and ERBF (β = 0.203; p = 0.020) and a positive trend for hyperemia and mGFR (β = 0.391; p = 0.053) were observed, while a negative association for post‐occlusive capillary density with ERVR (β = −0.196; p = 0.027) was found. Conclusion These findings indicate that microvascular dysfunction in overweight adults with T2D is associated with lower mGFR and ERPF and higher ERVR. We hypothesize that increased renal vascular resistance may contribute to glomerular dysfunction due to impaired renal perfusion.
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