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Aims: We aimed to determine the association between serum interleukin-6 (IL-6) concentrations and new-onset heart failure (HF) in persons with type 2 diabetes (T2D)., Methods and Results: We performed a case-control study nested in the Diabetes Care System Cohort, a prospective cohort of persons with T2D in primary care. We included 724 participants, of whom 141 developed HF during 5 years of follow-up and 583 were age- and sex-matched controls. IL-6 was measured at baseline and categorized into four groups: Group 1 was composed of participants with IL-6 below the detection limit of 1.5 pg/mL, and the remainder were divided into tertiles. We performed logistic regression analyses with categorized IL-6 or continuous IL-6 as the determinant and new-onset HF as the outcome adjusted for follow-up time, age, sex, glycated haemoglobin, estimated glomerular filtration rate, albumin/creatinine ratio, and cardiovascular disease at baseline. Effect modification by sex was tested. Participants were 70.7 ± 9.0 years, and 38% were women. In comparison with Group 1, all tertiles were associated with an increased risk of HF with odds ratios of 2.1 [95% confidence interval (CI): 1.2-2.9], 2.8 (95% CI: 2.0-3.7), and 2.1 (95% CI: 1.3-3.0), respectively, for Tertiles 1-3. Continuous IL-6 was associated with the development of HF with an odds ratio of 1.2 (95% CI: 1.0-1.5). No effect modification by sex was observed., Conclusions: Higher IL-6 levels are associated with the development of HF in persons with T2D. Further research should determine whether IL-6-lowering interventions could prevent the development of HF., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

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 (-1.58 mmol/mol [95% CI: -2.54 to -0.62]), glucose (-0.19 mmoL/L [95% CI:-0.36 to -0.01]), and blood pressure (-3.70 mm Hg [95% CI: -5.36 to -2.04]), 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., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Study Objectives: We investigated the prevalence of self-reported insomnia symptoms in people with type 2 diabetes and assessed the association with metabolic outcomes and the mediating role of lifestyle factors., Methods: In a prospective cohort of 1,272 participants with type 2 diabetes (63.4% male, age 68.7 ± 9 years) we measured insomnia symptoms using the Insomnia Severity Index and metabolic outcomes as hemoglobin A1c, glucose, lipids, and body mass index at baseline and at 1 year follow-up. Linear regression analyses assessed the association between insomnia symptoms and metabolic outcomes, corrected for demographic factors, comorbidities, and body mass index. Mediation analyses were conducted for lifestyle factors., Results: The prevalence of mild and severe insomnia symptoms was 23.0% and 10.7%, respectively. When adjusted for demographic factors and comorbidities, cross-sectionally severe insomnia symptoms were associated with higher body mass index (β = 0.97 kg/m 2 ; 95% confidence interval 0.04: 1.89) compared to no insomnia symptoms. Cross-sectionally, no associations were observed for the other metabolic outcomes. Additionally, no prospective associations were observed with any of the outcomes. Finally, physical activity mediated the association between severe insomnia symptoms and body mass index by 29.3%., Conclusions: About a third of people with type 2 diabetes experience self-reported insomnia symptoms, but insomnia symptoms were not associated with metabolic outcomes in people with type 2 diabetes., Citation: Groeneveld L, den Braver NR, Beulens JWJ, et al. The prevalence of self-reported insomnia symptoms and association with metabolic outcomes in people with type 2 diabetes: the Hoorn Diabetes Care System cohort. J Clin Sleep Med . 2023;19(3):539-548., (© 2023 American Academy of Sleep Medicine.)

Background: Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease., Aims: To identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations., Methods: A systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models., Results: Of the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33-2.12; I 2 =69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08-1.50; I 2 =38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26-3.39; I 2 =78%); stroke (HR 1.59, 95% CI 1.29-1.96; I 2 =45%); sudden cardiac death (HR 1.60, 95% CI 1.14-2.25; I 2 =68%); and atrial fibrillation (HR 1.55, 95% CI 1.31-1.83; I 2 =0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population., Conclusion: QTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: This study aimed to investigate the association of burnout and vital exhaustion with measures of glycemic control and type 2 diabetes (T2D) in a systematic review and meta-analysis., Methods: PubMed, Embase, and PsycINFO were searched from inception to April 2, 2020. Data extraction and quality assessment were performed using the Effective Public Health Practice Project tool. When possible, results were meta-analyzed using random-effects models and rated using the Grading of Recommendations, Assessment, Development and Evaluation., Results: A total of 5317 titles/abstracts were screened, 140 articles were read full text, of which 29 studies were included. Eighteen studies were cross-sectional, three prospective and eight were case-control studies. Burnout and vital exhaustion were significantly associated with T2D, with a pooled odds ratio of 1.8 (95% confidence interval [CI] = 1.4 to 2.4, I2 = 79%; 9 studies). Glycated hemoglobin A1c levels were not significantly higher in people with burnout and vital exhaustion, compared to those without, with a pooled standardized mean difference of 0.35 (95% CI = -0.62 to 1.33, I2 = 98%; 7 studies). In addition, no differences in glucose levels were observed (standardized mean difference = 0.02, 95% CI = -0.26 to 0.30, I2 = 90%; 9 studies). Sensitivity analyses showed no decrease in heterogeneity when excluding studies with low quality (I2glucose = 89%) or studies with a study n < 40 population (I2T2D = 77%). The level of Grading of Recommendations, Assessment, Development and Evaluation evidence was moderate to low quality because of 18 studies having a cross-sectional design., Conclusions: Burnout and vital exhaustion might be associated with a higher risk of T2D, but not with glycemic control. Methodological shortcomings and high heterogeneity of the studies included complicate the interpretation of our results., (Copyright © 2021 by the American Psychosomatic Society.)

Background and Aims: This study aims to investigate the relationship of serum and dietary advanced glycation endproducts (AGEs) with cardiac function and structure after eight years of follow-up., Methods and Results: We included 370 Hoorn Study participants (aged 66.4 ± 6.1, 47% women). Serum protein-bound AGEs [N ε -(carboxymethyl)lysine, N ε -(carboxyethyl)lysine, and pentosidine], as well as echocardiography to assess left atrium volume index (LAVI), left ventricle ejection fraction (LVEF), and left ventricle mass index (LVMI), were measured at baseline and after 8 years of follow-up. Dietary AGEs [N ε -(carboxymethyl)lysine and N ε -(carboxyethyl)lysine] were estimated at baseline with a validated food-frequency questionnaire and an AGEs database. Increased pentosidine [-1.4% (-2.6;-0.2)] and overall serum AGEs Z-scores over time [-2.1% (-3.8;-0.5)] were associated with decreased LVEF at follow-up, adjusted for confounders. Glucose metabolism status was an effect modifier (P-for-interaction = 0.04). In participants with impaired glucose metabolism, but not type 2 diabetes, increased pentosidine was associated with decreased LVEF [-4.2 (-8.0;-0.3)%]. Higher dietary N ε -(carboxyethyl)lysine [1.9 (0.1; 3.7)%] and overall dietary AGEs Z-scores [2.1 (0.1; 4.2)%] were associated with higher LVEF at follow-up. However, prior cardiovascular disease (CVD) was an effect modifier (P = 0.02). We found a stronger, non-significant, association of higher dietary (carboxyethyl)lysine with higher LVEF at follow-up in participants without CVD [2.3 (-0.1; 4.7)%] compared to participants with CVD [0.6 (-2.1; 3.4)%]., Conclusion: Overall serum AGEs were longitudinally associated with impaired systolic function. Future research should focus on including changes in dietary AGEs intake over time and the relation of dietary AGEs with cardiac measures needs to be established in intervention studies using low AGEs diets., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

This study investigated the causal relation between circulating phylloquinone (vitamin K 1 ) concentrations and type 2 diabetes by using a Mendelian randomization (MR) approach. We used data from three studies: the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, Diabetes Genetics Replication and Meta-analysis (DIAGRAM), and the UK Biobank, resulting in 69,647 subjects with type 2 diabetes. We calculated a weighted genetic risk score including four genetic variants previously found to be associated with circulating phylloquinone concentrations. Inverse-variance weighted analysis was used to obtain a risk ratio (RR) for the causal relation between circulating phylloquinone concentrations and risk of type 2 diabetes. Presence of pleiotropy and the robustness of the results were assessed using MR-Egger and weighted-median analyses. Genetically predicted concentrations of circulating phylloquinone were associated with lower risk of type 2 diabetes with an RR of 0.93 (95% CI 0.89; 0.97) per every natural logarithm (Ln)-nmol/L-unit increase in circulating phylloquinone. The MR-Egger and weighted median analyses showed RRs of 0.94 (0.86; 1.02) and 0.93 (0.88; 0.98), respectively, indicating no pleiotropy. In conclusion, our study supports that higher circulating phylloquinone may be causally related with lower risk of type 2 diabetes, highlighting the importance of sufficient phylloquinone in the human diet., (© 2018 by the American Diabetes Association.)