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Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark
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Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
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Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Objective
The aim was to examine the association between hospital-diagnosed overweight/obesity and incident CVD according to the time period of the overweight/obesity diagnosis.
Design
This is a cohort study.
Methods
From Danish national health registries, we identified all residents with a first-time hospital-based overweight/obesity diagnosis code, 1977–2018 (n = 195,221), and an age and sex-matched general population comparison cohort (n = 1,952,210). We computed adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox regression. We adjusted for comorbidities and educational level and applied 10 years of follow-up.
Results
The overall incidence rate was 10.1 (95% CI 10.0–10.1) per 1000 person-years for the comparison cohort and 25.1 (95% CI 24.8–25.4) per 1000 person-years for the overweight/obesity cohort, corresponding to an aHR of 2.5 (95% CI 2.4–2.5). The aHR was elevated for all subtypes of CVD: heart failure: 3.9 (95% CI 3.7–4.1), bradyarrhythmia: 2.9 (95% CI 2.7–3.1), angina pectoris: 2.7 (95% CI 2.7–2.8), atrial fibrillation or flutter: 2.6 (95% CI 2.5–2.6), acute myocardial infarction: 2.4 (95% CI 2.3–2.4), revascularization procedure: 2.4 (95% CI 2.2–2.5), valvular heart disease: 1.7 (95% CI 1.6–1.8), ischemic stroke: 1.6 (95% CI 1.4–1.7), transient ischemic attack: 1.6 (95% CI 1.5–1.7), and cardiovascular death: 1.6 (95% CI 1.5–1.6). The 1–10-year aHR of any CVD associated with an overweight/obesity diagnosis decreased from 2.8 (95% CI 2.7–2.9) in 1977–1987 to 1.8 (95% CI 1.8–1.9) in 2008–2018.
Conclusion
Patients with hospital-diagnosed overweight/obesity had high rates of ischemic heart disease, heart failure, structural heart disease, arrhythmia, stroke, and death, although the strength of the association decreased in recent years.
Significance statement
Obesity is linked to metabolic abnormalities that predispose individuals to an increased risk of subtypes of CVD. In this population-based nationwide 40-year cohort study, we found that of 195,221 patients with an overweight/obesity diagnosis, more than 31,000 (15.9%) were admitted to hospital within 10 years because of CVD; corresponding to a 2.5-fold greater relative risk of any CVD associated with overweight/obesity than in the general population. We observed an increased risk for most CVD subtypes, including ischemic heart disease, heart failure, structural heart disease, arrhythmia, stroke, and cardiovascular death, although the strength of the association decreased in recent years. Our study emphasizes the importance of improved clinical handling of obesity and underscores the need to prevent associated complications to alleviate the burden of obesity.
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Objective
Real-world-based population data about the optimal low-density lipoprotein cholesterol (LDL-C) level for preventing cardiovascular disease in very high-risk populations is scarce.
Methods
From 2009 to 2012, 26,922 people aged ≥ 40 years with type 2 diabetes mellitus (T2DM) who had a history of percutaneous coronary intervention (PCI) were analyzed. Data from the Korean National Health Insurance System were used. They were followed up to the date of a cardiovascular event or the time to death, or until December 31, 2018. Endpoints were recurrent PCI, newly stroke or heart failure, cardiovascular death, and all-cause death. Participants were divided into the following categories according to LDL-C level: <55 mg/dL, 55–69 mg/dL, 70–99 mg/dL, 100–129 mg/dL, 130–159 mg/dL, and ≥ 160 mg/dL.
Results
Compared to LDL-C < 55 mg/dL, the hazard ratios (HR) for re-PCI and stroke increased linearly with increasing LDL-C level in the population < 65 years. However, in ≥ 65 years old, HRs for re-PCI and stroke in LDL-C = 55–69 mg/dL were 0.97 (95% CI: 0.85–1.11) and 0.96 (95% CI: 0.79–2.23), respectively. The optimal range with the lowest HR for heart failure and all-cause mortality were LDL-C = 70–99 mg/dL and LDL-C = 55–69 mg/dL, respectively, in all age groups (HR: 0.99, 95% CI: 0.91–1.08 and HR: 0.91, 95% CI: 0.81–1.01).
Conclusion
LDL-C level below 55 mg/dL appears to be optimal in T2DM patients with established cardiovascular disease aged < 65 years, while an LDL-C level of 55–69 mg/dL may be optimal for preventing recurrent PCI and stroke in patients over 65 years old.
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Faculty of Medicine, University of Latvia, Riga, Latvia
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The increasing prevalence of ‘diabesity’, a combination of type 2 diabetes and obesity, poses a significant global health challenge. Unhealthy lifestyle factors, including poor diet, sedentary behaviour, and high stress levels, combined with genetic and epigenetic factors, contribute to the diabesity epidemic. Diabesity leads to various significant complications such as cardiovascular diseases, stroke, and certain cancers. Incretin-based therapies, such as GLP-1 receptor agonists and dual hormone therapies, have shown promising results in improving glycaemic control and inducing weight loss. However, these therapies also come with certain disadvantages, including potential withdrawal effects. This review aims to provide insights into the cross-interactions of insulin, glucagon, and GLP-1, revealing the complex hormonal dynamics during fasting and postprandial states, impacting glucose homeostasis, energy expenditure, and other metabolic functions. Understanding these hormonal interactions may offer novel hypotheses in the development of ‘anti-diabesity’ treatment strategies. The article also explores the question of the antagonism of insulin and glucagon, providing insights into the potential synergy and hormonal overlaps between these hormones.
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Objective
Uridine might be a common link between pathological pathways in diabetes and cardiovascular diseases. This study aimed to investigate the predictive value of plasma uridine for type 2 diabetes (T2D) and T2D with atherosclerosis.
Methods
Individuals with T2D and healthy controls (n = 218) were randomly enrolled in a cross-sectional study. Patients with T2D were divided into two groups based on carotid ultrasound: patients with carotid atherosclerosis (CA) (group DCA) and patients without CA (group D). Plasma uridine was determined using HPLC-MS/MS. Correlation and logistic regression analyses were used to analyze the results.
Results
Fasting and postprandial uridine were significantly increased in patients with T2D compared with healthy individuals. Logistic regression suggested that fasting and postprandial uridine were independent risk factors for T2D. The receiver operating characteristic (ROC) curve showed that fasting uridine had a predictive value on T2D (95% CI, 0.686–0.863, sensitivity 74.3%, specificity 71.8%). Fasting uridine was positively correlated with LDL-c, FBG, and PBG and negatively correlated with fasting C-peptide (CP-0h) and HOMA-IS. The change in postprandial uridine from fasting baseline (Δuridine) was smaller in T2D patients with CA compared with those without (0.80 (0.04–2.46) vs 2.01 (0.49–3.15), P = 0.010). Δuridine was also associated with T2D with CA and negatively correlated with BMI, CP-0h, and HOMA-IR.
Conclusion
Fasting uridine has potential as a predictor of diabetes. Δuridine is closely associated with carotid atherosclerosis in patients with T2D.
Comprehensive Heart Failure Center, University & University Hospital Würzburg, Würzburg, Germany
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Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital, University of Würzburg, Würzburg, Germany
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Division of Cardiology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
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Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany
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Division of Cardiology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
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Division of Cardiology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
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Comprehensive Heart Failure Center, University & University Hospital Würzburg, Würzburg, Germany
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Obesity is a rapidly emerging health problem and an established risk factor for cardiovascular diseases. Bariatric surgery profoundly reduces body weight and mitigates sequelae of obesity. The open, randomized controlled Würzburg Adipositas Studie (WAS) trial compares the effects of Roux-en-Y gastric bypass (RYGB) vs psychotherapy-supported lifestyle modification in morbidly obese patients. The co-primary endpoint addresses 1-year changes in cardiovascular function (peak VO2 during cardiopulmonary exercise testing) and the quality of life (QoL) (Short-Form-36 physical functioning scale). Prior to randomization, all included patients underwent a multimodal anti-obesity treatment for 6–12 months. Thereafter, the patients were randomized and followed through month 12 to collect the primary endpoints. Afterwards, patients in the lifestyle group could opt for surgery, and final visit was scheduled for all patients 24 months after randomization. Sample size calculation suggested to enroll 90 patients in order to arrive at minimally 22 patients per group evaluable for the primary endpoint. Secondary objectives were to quantify changes in body weight, left ventricular hypertrophy, systolic and diastolic function (by echocardiography and cardiac MRI), functional brain MRI, psychometric scales, and endothelial and metabolic function. WAS enrolled 93 patients (72 women, median age 38 years, BMI 47.5 kg/m2) exhibiting a relevantly compromised exercise capacity (median peakVO2 18.3 mL/min/kg) and the QoL (median physical functioning scale 50). WAS is the first randomized controlled trial focusing on the effects of RYGB on cardiovascular function beyond hypertension. In addition, it will provide a wealth of high-quality data on the cerebral, psychiatric, hepatic, and metabolic function in obese patients after RYGB.
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Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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Department of Renal Medicine, St George Hospital, Sydney, NSW, Australia
Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
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Sodium‐glucose co-transporter 2 (SGLT2) inhibitors have recently emerged as an effective means to protect kidney function in people with type 2 diabetes and chronic kidney disease (CKD). In this review, we explore the role of SGLT2 inhibition in these individuals. SGLT2 inhibitors specifically act to inhibit sodium and glucose reabsorption in the early proximal tubule of the renal nephron. Although originally developed as glucose-lowering agents through their ability to induce glycosuria, it became apparent in cardiovascular outcome trials that the trajectory of kidney function decline was significantly slowed and the incidence of serious falls in kidney function was reduced in participants receiving an SGLT2 inhibitor. These observations have recently led to specific outcome trials in participants with CKD, including DAPA-CKD, CREDENCE and EMPA-KIDNEY, and real-world studies, like CVD-REAL-3, that have confirmed the observation of kidney benefits in this setting. In response, recent KDIGO Guidelines have recommended the use of SGLT2 inhibitors as first-line therapy in patients with CKD, alongside statins, renin–angiotensin–aldosterone system inhibitors and multifactorial risk factor management as indicated. However, SGLT2 inhibitors remain significantly underutilized in the setting of CKD. Indeed, an inertia paradox exists, with patients with more severe disease less likely to receive an SGLT2 inhibitor. Concerns regarding safety appear unfounded, as acute kidney injury, hyperkalaemia, major acute cardiovascular events and cardiac death in patients with CKD appear to be lower following SGLT2 inhibition. The first-in-class indication of dapagliflozin for CKD may begin a new approach to managing kidney disease in type 2 diabetes.
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Background
The aim of the study was to explore whether plasma stromal cell-derived factor 1 (SDF-1) levels are associated with the EZSCAN score and its derived indicators in patients with type 2 diabetes (T2D).
Methods
From July 2020 to December 2020, a total of 253 patients with T2D were consecutively recruited. Serum SDF-1 levels were measured by sandwich ELISA. EZSCAN test was applied to evaluate the sudomotor function of each patient, and based on the results, EZSCAN score, cardiac autonomic neuropathy risk score (CANRS) and cardiovascular risk score (CVDRS) were calculated by particular algorithms. In addition, other relevant clinical data were also collected.
Results
With increasing tertiles of serum SDF-1 levels, the CANRS and CVDRS significantly increased (both Pfor trend <0.001), while the EZSCAN score significantly decreased (Pfor trend <0.001). Moreover, serum SDF-1 levels were significantly and positively correlated with the CANRS and CVDRS (r = 0.496 and 0.510, respectively, both P < 0.001), and negatively correlated with the EZSCAN score (r = −0.391, P < 0.001). Furthermore, multivariate linear regression analyses were constructed, and after adjusting for other clinical covariates, serum SDF-1 levels were independently responsible for EZSCAN score (β = −0.273, t = −3.679, P < 0.001), CANRS (β = 0.334, t = 5.110, P < 0.001) and CVDRS (β = 0.191, t = 4.983, P = 0.003).
Conclusions
SDF-1 levels in serum were independently associated with the EZSCAN score and its derived indicators, such as CANRS and CVDRS in patients with T2D.
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Objective
To examine the dose-dependent influence of oral alpha-lipoic acid (ALA) supplementation on cardiometabolic risk factors in patients with type 2 diabetes (T2D).
Design
We followed the instructions outlined in the Cochrane Handbook for Systematic Reviews of Interventions and the Grading of Recommendations, Assessment, Development, and Evaluation Handbook to conduct our systematic review. The protocol of the study was registered in PROSPERO (CRD42021260587).
Method
We searched PubMed, Scopus, and Web of Science to May 2021 for trials of oral ALA supplementation in adults with T2D. The primary outcomes were HbA1c, weight loss, and LDL cholesterol (LDL-C). Secondary outcomes included fasting plasma glucose (FPG), triglyceride (TG), C-reactive protein (CRP), and blood pressure. We conducted a random-effects dose–response meta-analysis to calculate the mean difference (MD) and 95% CI for each 500 mg/day oral ALA supplementation. We performed a nonlinear dose–response meta-analysis using a restricted cubic spline.
Results
We included 16 trials with 1035 patients. Each 500 mg/day increase in oral ALA supplementation significantly reduced HbA1c, body weight, CRP, FPG, and TG. Dose–response meta-analyses indicated a linear decrement in body weight at ALA supplementation of more than 600 mg/day (MD600 mg/day: −0.30 kg, 95% CI: −0.04, −0.57). A relatively J-shaped effect was seen for HbA1c (MD: −0.32%, 95% CI: −0.45, −0.18). Levels of FPG and LDL-C decreased up to 600 mg/day ALA intake. The point estimates were below minimal clinically important difference thresholds for all outcomes.
Conclusion
Despite significant improvements, the effects of oral ALA supplementation on cardiometabolic risk factors in patients with T2D were not clinically important.
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Global Health Research Institute, School of Human Development and Health, University of Southampton, Southampton, UK
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Gluteofemoral fat correlates negatively with a number of cardiometabolic disease risk factors, but the mechanisms involved in these relationships are unknown. The aim of this study was to test the hypothesis that gluteofemoral fat attenuates the risk of cardiometabolic disease by increasing blood adiponectin levels. This was a cross-sectional study in which arm, leg, gluteofemoral, abdominal s.c. and visceral fat levels were measured by dual-energy X-ray absorptiometry in 648 African females. Fasting serum adiponectin, lipid, insulin and plasma glucose levels and blood pressure were measured. Relationships between variables were analysed using multivariable linear regression and structural equation modelling. Adiponectin correlated positively (β = 0.45, P < 0.0001) with gluteofemoral fat in a multivariable regression model that included age, height, and arm, s.c. and visceral fat levels. In further regression models, there was a negative correlation of gluteofemoral fat with fasting glucose (β = −0.28; P < 0.0001) and triglyceride levels (β = −0.29; P < 0.0001) and insulin resistance (HOMA; β = −0.26; P < 0.0001). Structural equation modelling demonstrated that adiponectin mediated 20.7% (P < 0.01) of the association of gluteofemoral fat with insulin resistance and 16.1% (P < 0.01) of the association with triglyceride levels but only 6.67% (P = 0.31) of the association with glucose levels. These results demonstrate that gluteofemoral and leg fat are positively associated with adiponectin levels and that the negative association of lower body fat with insulin resistance and triglyceride levels may partially be mediated by this adipokine. Further studies are required to determine other factors that mediate the effect of lower body fat on cardiometabolic disease risk factors.
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Previous studies have shown that the elevated levels of circulating branched-chain amino acids (BCAAs) are associated with the development of insulin resistance and its complications, including obesity, type 2 diabetes, cardiovascular disease and some cancers. However, animal models that can mimic the metabolic state of chronically elevated BCAAs in humans are rare. Therefore, the aim of this study was to establish the above animal model and analyse the metabolic changes associated with high BCAA levels. Sixteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into two groups and given either a high fructose diet or a normal diet. BCAA levels as well as blood glucose and lipid levels were measured at different time points of feeding. The mRNA expression levels of two key enzymes of BCAA catabolism, ACAD (acyl-CoA dehydrogenase) and BCKDH (branched-chain α-keto acid dehydrogenase), were measured by qPCR, and the protein expression levels of these two enzymes were analysed by immunohistochemistry. Finally, the metabolite expression differences between the two groups were analysed by Q300 metabolomics technology. Our study confirms that defects in the catabolic pathways of BCAAs lead to increased levels of circulating BCAAs, resulting in disorders of glucose and lipid metabolism characterized by insulin resistance by affecting metabolic pathways associated with amino acids and bile acids.
