Search

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. [ABSTRACT FROM AUTHOR]

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/m2 [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. [ABSTRACT FROM AUTHOR]

• QTc prolongation was associated with atrial fibrillation. • QTc prolongation was associated with stroke and sudden cardiac death. • No association was found for myocardial infarction. Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease. 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. 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. 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. QTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population. [ABSTRACT FROM AUTHOR]

Persons with diabetes mellitus may have an increased risk of severe illness or death from COVID-19 compared to persons without diabetes. Prior studies indicate that immune response and thus vaccine effectiveness might be lower in persons with diabetes. We aimed to systematically review the effectiveness of COVID-19 vaccines in adults with diabetes. Pubmed, Embase, Web of Science and Cochrane Library were searched for studies that evaluated the effectiveness of COVID-19 vaccines in adults with diabetes, published before 4 March 2022. Risk of bias in the included studies was evaluated using the ROBINS-I tool. At least two reviewers conducted the study selection, data extraction, and risk of bias assessment independently. After screening of 2196 studies, a total of 17 articles were included. Six different COVID-19 vaccines (Ad5-nCoV-S, AZD1222, BNT162b2, CoronaVac, JNJ-78436735, and mRNA-1273) were included in the synthesis. Vaccine effectiveness was reported for SARS-CoV-2 infection, symptomatic COVID-19, hospitalization, and death, and ranged from 24 to 96% in persons with diabetes, and from 33 to 97% in total study populations; effectiveness was generally lower for persons with diabetes. Odds ratios for breakthrough infection or severe COVID-19 ranged from 1.03 to 2.41 in vaccinated persons with diabetes compared to persons without diabetes. Even though the included studies were very heterogeneous, results from the synthesis indicate that effectiveness of COVID-19 vaccines might be lower in persons with diabetes. More research is needed on the comparison of vaccine effectiveness between persons with and without diabetes, and the effectiveness of repeat COVID-19 vaccinations. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with HER2-positive metastatic breast cancer develop brain metastases in up to 30% of cases. The aim of this systematic review and meta-analysis was to determine the effect of different systemic therapies in patients with HER2-positive metastatic breast cancer and brain metastases, acknowledging the heterogeneity and sometimes low quality of 51 included studies. Tucatinib (combined with trastuzumab and capecitabine) and trastuzumab-deruxtecan appear to constitute the most effective systemic therapy, while pyrotinib might be an option in Asian patients. Preferably, future research will comprise of randomized controlled trials, including patients with active and/or inactive brain metastases. Aim: Patients with HER2-positive (HER2+) metastatic breast cancer (mBC) develop brain metastases (BM) in up to 30% of cases. Treatment of patients with BM can consist of local treatment (surgery and/or radiotherapy) and/or systemic treatment. We undertook a systematic review and meta-analysis to determine the effect of different systemic therapies in patients with HER2+ mBC and BM. Methods: A systematic search was performed in the databases PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection and the Wiley/Cochrane Library. Eligible articles included prospective or retrospective studies reporting on the effect of systemic therapy on objective response rate (ORR) and/or median progression free survival (mPFS) in patients with HER2+ mBC and BM. The timeframe within the databases was from inception to 19 January 2022. Fixed-effects meta-analyses were used. Quality appraisal was performed using the ROBINS-I tool. Results: Fifty-one studies were included, involving 3118 patients. Most studies, which contained the largest patient numbers, but also often carried a moderate-serious risk of bias, investigated lapatinib and capecitabine (LC), trastuzumab-emtansine (T-DM1) or pyrotinib. The best quality data and/or highest ORR were described with tucatinib (combined with trastuzumab and capecitabine, TTC) and trastuzumab-deruxtecan (T-DXd). TTC demonstrated an ORR of 47.3% in patients with asymptomatic and/or active BM. T-DXd achieved a pooled ORR of 64% (95% CI 43–85%, I2 0%) in a heavily pretreated population with asymptomatic BM (3 studies, n = 96). Conclusions: Though our meta-analysis should be interpreted with caution due to the heterogeneity of included studies and a related serious risk of bias, this review provides a comprehensive overview of all currently available systemic treatment options. T-Dxd and TTC that appear to constitute the most effective systemic therapy in patients with HER2+ mBC and BM, while pyrotinib might be an option in Asian patients. [ABSTRACT FROM AUTHOR]

Aims The HFA-PEFF score was developed to optimize diagnosis and to aid in early recognition of heart failure (HF) with preserved ejection fraction (HFpEF) in patients who present with HF-like symptoms. Recognizing early-HFpEF phenogroups is essential to better understand progression towards overt HFpEF and pave the way for early intervention and treatment. Whether the HFA-PEFF domain scores can identify ‘early-HFpEF’ phenogroups remains unknown. The aims of this pilot study are to (i) identify distinct phenogroups by cluster analysis of HFA-PEFF domain scores in subjects that present with HF-like symptoms and (ii) study whether these phenogroups may be associated with distinct blood proteome profiles. Methods and results Subjects referred to the Cardiology Centers of the Netherlands, location Utrecht, with non-acute possibly cardiac-related symptoms (such as dyspnoea or fatigue) were prospectively enrolled in the HELPFul cohort (N = 507) and were included in the current analysis. Inclusion criteria for this study were (i) age ≥ 45 years and (ii) a left ventricular ejection fraction (LVEF) ≥ 50%, in the absence of a history of HF, coronary artery disease, congenital heart disease, or any previous cardiac interventions. Multinominal-based clustering with latent class model using the HFA-PEFF domain scores (functional, structural, and biomarker scores) as input was used to detect distinct phenotypic clusters. For each bootstrapping run, the 92 Olink proteins were analysed for their association with the identified phenogroups. Four distinct phenogroups were identified in the current analysis (validated by bootstrapping 1000×): (i) no left ventricular diastolic dysfunction (no LVDD, N = 102); (ii) LVDD with functional left ventricular (LV) abnormalities (N = 204); (iii) LVDD with functional and structural LV abnormalities (N = 204); and (iv) LVDD with functional and structural LV abnormalities and elevated BNP (N = 107). The HFA-PEFF total score risk categories significantly differed between the phenogroups (P < 0.001), with an increase of the HFA-PEFF score from Phenogroup 1 to 4 (low/intermediate/high HFA-PEFF risk score: Phenogroup 1: 88%/12%/0%; Phenogroup 2: 9%/91%/0%; Phenogroup 3: 0%/92%/8%; Phenogroup 4: 5%/83%/12%). Thirty-two out of the 92 Olink protein biomarkers significantly differed among the phenogroups. The top eight biomarkers—N-terminal prohormone brain natriuretic peptide, growth differentiation factor-15, matrix metalloproteinase-2, osteoprotegerin, tissue inhibitor of metalloproteinase-4, chitinase-3-like protein 1, insulin-like growth factor-binding protein 2, and insulin-like growth factor-binding protein 7—are mainly involved in inflammation and extracellular matrix remodelling, which are currently proposed key processes in HFpEF pathophysiology. Conclusions This study identified distinct phenogroups by using the HFA-PEFF domain scores in ambulant subjects referred for HF-like symptoms. The newly identified phenogroups accompanied by their circulating biomarkers profile might aid in a better understanding of the pathophysiological processes involved during the early stages of the HFpEF syndrome. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex. Methods: Biomarkers and echocardiographic measures were measured at both baseline and follow-up in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders. Results: Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %. Conclusion: Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers. [ABSTRACT FROM AUTHOR]

Aim: Diagnosing heart failure with preserved ejection fraction (HFpEF) in the non‐acute setting remains challenging. Natriuretic peptides have limited value for this purpose, and a multitude of studies investigating novel diagnostic circulating biomarkers have not resulted in their implementation. This review aims to provide an overview of studies investigating novel circulating biomarkers for the diagnosis of HFpEF and determine their risk of bias (ROB). Methods and results: A systematic literature search for studies investigating novel diagnostic HFpEF circulating biomarkers in humans was performed up until 21 April 2020. Those without diagnostic performance measures reported, or performed in an acute heart failure population were excluded, leading to a total of 28 studies. For each study, four reviewers determined the ROB within the QUADAS‐2 domains: patient selection, index test, reference standard, and flow and timing. At least one domain with a high ROB was present in all studies. Use of case‐control/two‐gated designs, exclusion of difficult‐to‐diagnose patients, absence of a pre‐specified cut‐off value for the index test without the performance of external validation, the use of inappropriate reference standards and unclear timing of the index test and/or reference standard were the main bias determinants. Due to the high ROB and different patient populations, no meta‐analysis was performed. Conclusion: The majority of current diagnostic HFpEF biomarker studies have a high ROB, reducing the reproducibility and the potential for clinical care. Methodological well‐designed studies with a uniform reference diagnosis are urgently needed to determine the incremental value of circulating biomarkers for the diagnosis of HFpEF. [ABSTRACT FROM AUTHOR]

This study investigated the causal relation between circulating phylloquinone (vitamin K1) 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. [ABSTRACT FROM AUTHOR]

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.)

Persons with diabetes mellitus may have an increased risk of severe illness or death from COVID-19 compared to persons without diabetes. Prior studies indicate that immune response and thus vaccine effectiveness might be lower in persons with diabetes. We aimed to systematically review the effectiveness of COVID-19 vaccines in adults with diabetes. Pubmed, Embase, Web of Science and Cochrane Library were searched for studies that evaluated the effectiveness of COVID-19 vaccines in adults with diabetes, published before 4 March 2022. Risk of bias in the included studies was evaluated using the ROBINS-I tool. At least two reviewers conducted the study selection, data extraction, and risk of bias assessment independently. After screening of 2196 studies, a total of 17 articles were included. Six different COVID-19 vaccines (Ad5-nCoV-S, AZD1222, BNT162b2, CoronaVac, JNJ-78436735, and mRNA-1273) were included in the synthesis. Vaccine effectiveness was reported for SARS-CoV-2 infection, symptomatic COVID-19, hospitalization, and death, and ranged from 24 to 96% in persons with diabetes, and from 33 to 97% in total study populations; effectiveness was generally lower for persons with diabetes. Odds ratios for breakthrough infection or severe COVID-19 ranged from 1.03 to 2.41 in vaccinated persons with diabetes compared to persons without diabetes. Even though the included studies were very heterogeneous, results from the synthesis indicate that effectiveness of COVID-19 vaccines might be lower in persons with diabetes. More research is needed on the comparison of vaccine effectiveness between persons with and without diabetes, and the effectiveness of repeat COVID-19 vaccinations.