The Effect of Sargassum fusiforme and Fucus vesiculosus on Continuous Glucose Levels in Overweight Patients with Type 2 Diabetes Mellitus: A Feasibility Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Brown seaweed is promising for the treatment of type 2 diabetes mellitus (T2DM). Its bioactive constituents can positively affect plasma glucose homeostasis in healthy humans. We investigated the effect of the brown seaweeds Sargassum (S.) fusiforme and Fucus (F.) vesiculosus in their natural form on glucose regulation in patients with T2DM. METHODS: We conducted a randomized, double-blind, placebo-controlled pilot trial. Thirty-six participants with T2DM received, on a daily basis, either 5 g of dried S. fusiforme, 5 g of dried F. vesiculosus, or 0.5 g of dried Porphyra (control) for 5 weeks, alongside regular treatment. The primary outcome was the between-group difference in the change in weekly average blood glucose levels (continuous glucose monitoring). The secondary outcomes were the changes in anthropometrics, plasma lipid levels, and dietary intake. The data were analyzed using a linear mixed-effects model. RESULTS: The change in weekly average glucose levels was 8.2 ± 2.1 to 9.0 ± 0.7 mmol/L (p = 0.2) in the S. fusiforme group (n = 12) and 10.1 ± 3.3 to 9.2 ± 0.7 mmol/L (p = 0.9) in the F. vesiculosus group (n = 10). The between-group difference was non-significant. Similarly, no between-group differences were observed for the changes in the secondary outcomes. DISCUSSION: A daily intake of 5 g of fresh, dried S. fusiforme or F. vesiculosus alongside regular treatment had no differential effect on weekly average blood glucose levels in T2DM.

Metabolic dysfunction-associated steatotic liver disease and the heart.

The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing. Physicians who treat patients with MASLD may acknowledge the strong coincidence with cardiometabolic disease, including atherosclerotic cardiovascular disease (asCVD). This raises questions on co-occurrence, causality, and the need for screening and multidisciplinary care for MASLD in patients with asCVD, and vice versa. Here, we review the interrelations of MASLD and heart disease and formulate answers to these matters. Epidemiological studies scoring proxies for atherosclerosis and actual cardiovascular events indicate increased atherosclerosis in patients with MASLD, yet no increased risk of asCVD mortality. MASLD and asCVD share common drivers: obesity, insulin resistance and type 2 diabetes mellitus (T2DM), smoking, hypertension, and sleep apnea syndrome. In addition, Mendelian randomization studies support that MASLD may cause atherosclerosis through mixed hyperlipidemia, while such evidence is lacking for liver-derived procoagulant factors. In the more advanced fibrotic stages, MASLD may contribute to heart failure with preserved ejection fraction by reduced filling of the right ventricle, which may induce fatigue upon exertion, often mentioned by patients with MASLD. Some evidence points to an association between MASLD and cardiac arrhythmias. Regarding treatment and given the strong co-occurrence of MASLD and asCVD, pharmacotherapy in development for advanced stages of MASLD would ideally also reduce cardiovascular events, as has been demonstrated for T2DM treatments. Given the common drivers, potential causal factors and especially given the increased rate of cardiovascular events, comprehensive cardiometabolic risk management is warranted in patients with MASLD, preferably in a multidisciplinary approach.

A global survey of health care workers' awareness of non-alcoholic fatty liver disease: The AwareNASH survey.

BACKGROUND: The estimated global prevalence and burden of non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), is increasing. Yet, NAFLD remains largely underdiagnosed. In addition to hepatic morbidity and mortality, NAFLD is associated with increased cardiovascular complications, warranting a multidisciplinary approach. Despite its rapidly increasing prevalence, knowledge of NAFLD among healthcare workers is limited, especially with specialists outside the field of hepatology and gastroenterology. OBJECTIVES: To investigate knowledge, practice and opinions/attitudes of healthcare workers towards diagnosis and management of NAFLD/NASH. METHODS: The survey was designed in collaboration with a multidisciplinary scientific committee established especially for this study. The survey was disseminated to healthcare workers from seven different disciplines through four collaborating societies, social media and at a cardiology-themed conference from February to June 2022. Median and interquartile range were mentioned for numeric responses and proportions for categorical responses or responses on a Likert scale. Likert scale responses were treated as ordinal data and analysed with the appropriate tests. RESULTS: The full dataset included 613 respondents from 88 different countries (including 488 physicians). 64% of the surveyed physicians underestimated the prevalence of NAFLD. General practitioners and cardiologists underestimated the prevalence most often (74% and 77%, respectively). Compared to the other disciplines, cardiologists were least familiar with the symptoms and diagnostic criteria and felt least confident in diagnosing and managing NAFLD. Overall, 65% of physicians reported regularly using evidence-based guidelines for managing NAFLD, yet 72% reported challenges in providing lifestyle recommendations. A lack of awareness was the most common reported reason for the lack of screening for NAFLD (68% respectively). CONCLUSIONS: Despite the growing burden of NAFLD, there is a significant gap in awareness, knowledge, and management among physicians treating patients with cardiometabolic comorbidities, particularly cardiologists. Hepatologists and gastroenterologists could play a role in educating their fellow physicians.

Effect of bariatric surgery on NAFLD/NASH: a single-centre observational prospective cohort study.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 25% in the general population to 90% in patients with obesity scheduled for bariatric surgery. NAFLD can progress towards non-alcoholic steatohepatitis (NASH) associated with complications such as cirrhosis, hepatocellular carcinoma and cardiovascular disease. To date, losing weight and lifestyle modifications are the best known treatments for NASH. Bariatric surgery significantly improves NAFLD/NASH in the short term. However, the extent of this improvement is not yet clear and long-term data on the natural course of NAFLD/NASH after bariatric surgery are lacking. The factors involved in NAFLD/NASH regression after bariatric surgery have not been elucidated. METHODS AND ANALYSIS: This is an observational prospective cohort study including patients scheduled for bariatric surgery. Extensive metabolic and cardiovascular analyses will be carried out including measurements of carotid intima media thickness and pulse wave velocity. Genomic, proteomic, lipidomic and metabolomic studies will be done. Microbioma analyses before and 1 year after surgery will be done. Transient elastography measurements will be performed before and at 1, 3 and 5 years after surgery. For those with an elevated preoperative transient elastography measurement by Fibroscan, a laparoscopic liver biopsy will be performed during surgery. Primary outcome measures are the change of steatosis and liver fibrosis 5 years after surgery. Secondary outcome measure is the comparison of the transient elastography measurements with the NAFLD Activity Score from the biopsies. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 1 March 2022 (registration code R21.103/NL79423.100.21). The study results will be submitted for publication in peer-reviewed journals and data will be presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05499949.

Establishing a Multicenter Network for Patients With Thyroid Nodules and Cancer: Effects on Referral Patterns.

OBJECTIVE: To perform a qualitative evaluation of the Thyroid Network, with a quantitative analysis of second opinion referrals for patients in the southwestern part of the Netherlands who have thyroid nodules and cancer. METHODS: This prospective observational study registered all patients with thyroid nodules and cancer who were referred to the academic hospital from 2 years before and 4 years after the foundation of the Thyroid Network. We implemented biweekly regional multidisciplinary tumor boards using video conference and a regional patient care pathway for patients with thyroid nodules and cancer. For qualitative evaluation, interviews were conducted with a broad selection of stakeholders via maximum variation sampling. The primary outcome was the change in second opinions after the foundation of the Thyroid Network. RESULTS: Second opinions from Thyroid Network hospitals to the academic hospital decreased from 10 (30%) to 2 (7%) two years after the start of the Thyroid Network (P = .001), while patient referrals remained stable (n = 108 to 106). Qualitative evaluation indicated that the uniform care pathway and the regional multidisciplinary tumor board were valued high. DISCUSSION: Establishing a regional network, including multidisciplinary tumor boards and a care pathway for patients with thyroid nodules and cancer, resulted in a decrease in second opinions of in-network hospitals and high satisfaction of participating specialists. IMPLICATIONS FOR PRACTICE: The concept of the Thyroid Network could spread to other regions as well as to other specialties in health care. Future steps would be to assess the effect of regional collaboration on quality of care and patient satisfaction.

Improvement of non-invasive tests of liver steatosis and fibrosis as indicators for non-alcoholic fatty liver disease in type 2 diabetes mellitus patients with elevated cardiovascular risk profile using the PPAR-α/γ agonist aleglitazar.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR) agonists may have favorable outcomes on non-alcoholic fatty liver disease. This study serves as proof of concept to evaluate whether dual PPAR-α/γ agonists improve non-invasive tests of liver steatosis and fibrosis. METHODS: This is a post-hoc analysis of a randomized, double-blind, placebo-controlled, multi-center trial comprising 7226 patients with type 2 diabetes mellitus and recent coronary artery disease randomized to receive aleglitazar, a PPAR-α/γ agonists, or placebo for two years. Main outcomes were change in non-invasive tests for liver steatosis and fibrosis: Liver Fat Score (LFS), Liver Accumulation Product (LAP), Fibrosis-4 (FIB-4), and NAFLD Fibrosis Score (NFS). RESULTS: LFS, LAP and FIB-4 decreased upon treatment, whereas scores in the placebo group remained the same or increased (P<0.001). NFS responded differently but remained consistently lower than placebo. In the treatment group more participants shifted to a lower FIB-4 and NFS category, or improved in respect to the LAP cut-off values compared to the placebo group (P<0.001 for FIB-4 and LAP, P<0.004 for NFS). LFS had a low discriminative power in this study. CONCLUSION: This post-hoc analysis showed improvement of non-invasive tests of liver steatosis and fibrosis after starting dual PPAR-α/γ agonist treatment, adding to the evidence that this pathway has potential in non-alcoholic fatty liver disease treatment.

Evaluation of nonalcoholic fatty liver disease (NAFLD) in severe obesity using noninvasive tests and imaging techniques.

The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high-risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality-in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma-it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood- and imaging-based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity.

Effects of dapagliflozin on postprandial lipid metabolism in type 2 diabetes mellitus.

Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) modulate lipid metabolism and improve cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The exact cardioprotective mechanism of SGLT2i is unclear. We evaluated the effects of SGLT2i on postprandial lipids, lipoprotein concentrations, glucose and fatty acids. Design: A placebo-controlled randomized, proof-of-concept study. Methods: Fourteen male patients with T2DM on intensive insulin regimen were randomly and double-blind allocated to 12 weeks dapagliflozin (10 mg) or placebo. Postprandial effects were assessed with an 8-h standardized oral fat loading test. Results: Mean glycated A1c did not change by dapagliflozin, but the mean daily insulin dose was significantly reduced. Although dapagliflozin did not affect fasting or postprandial levels of glucose and insulin, it increased the postprandial levels of glucagon. While fasting levels of free fatty acids and beta-hydroxybutyrate (bHBA) were unchanged, dapagliflozin significantly increased the postprandial bHBA response. This was seen in the context of increased postprandial glucagon levels by dapagliflozin, without influencing postprandial insulin or glucose levels. Dapagliflozin did not affect fasting or postprandial plasma cholesterol and triglycerides nor postprandial inflammatory markers. Fasting apolipoprotein B48 was decreased without affecting the postprandial response. Markers of inflammation and vascular function did not change. Conclusion: Treatment with dapagliflozin of patients with T2DM led to a reduction of fasting chylomicron remnants and increased postprandial ketone bodies compared to placebo suggesting enhanced hepatic fatty acid oxidation. The latter may have been caused by decreasing the insulin-glucagon ratio. The beneficial clinical effects seen in the trials using dapagliflozin most likely are not due to effects on postprandial inflammation nor postprandial lipemia.

Cardiovascular Biomarker Profiles in Obesity and Relation to Normalization of Subclinical Cardiac Dysfunction after Bariatric Surgery.

AIMS: We aimed to gain insight into the underlying pathophysiology of cardiac dysfunction in obesity patients and the improvement of cardiac function after weight loss. METHODS: This is a longitudinal study in which 92 cardiovascular biomarkers were measured by multiplex immunoassays in obesity patients without known cardiovascular disease, before and one year after bariatric surgery. RESULTS: Out of 100 eligible patients, 72 patients completed the follow-up. A total of 72 (78%) biomarkers changed significantly. The biomarkers with the highest relative changes represented processes linked mainly to insulin resistance and inflammation. In the patients with persistent subclinical cardiac dysfunction, the baseline values of 10 biomarkers were different from values in patients with normalization of cardiac function. Most of these biomarkers were linked to inflammation or atherosclerosis. Finally, a model was developed to investigate the relationship between changes in the biomarkers and persistent subclinical cardiac dysfunction. Seven biomarkers were retained in this model, mainly linked to inflammation, atherosclerosis, and hypercoagulability. CONCLUSION: The majority (78%) of cardiovascular biomarkers changed, pointing mainly to modulation of insulin resistance and inflammation. The baseline levels of 10 biomarkers, as well as pre- to post-bariatric surgery changes in seven biomarkers, were related to persistent subclinical cardiac dysfunction after bariatric surgery.

Cost-Effectiveness of Lower Extremity Nerve Decompression Surgery in the Prevention of Ulcers and Amputations: A Markov Analysis.

BACKGROUND: The costs and health effects associated with lower extremity complications in diabetes mellitus are an increasing burden to society. In selected patients, lower extremity nerve decompression is able to reduce symptoms of neuropathy and the concomitant risks of diabetic foot ulcers and amputations. To estimate the health and economic effects of this type of surgery, the cost-effectiveness of this intervention compared to current nonsurgical care was studied. METHODS: To estimate the incremental cost-effectiveness of lower extremity nerve decompression over a 10-year period, a Markov model was developed to simulate the onset and progression of diabetic foot disease in patients with diabetes and neuropathy who underwent lower extremity nerve decompression surgery, compared to a group undergoing current nonsurgical care. Mean survival time, health-related quality of life, presence or risk of lower extremity complications, and in-hospital costs were the outcome measures assessed. Data from the Rotterdam Diabetic Foot Study were used as current care, complemented with information from international studies on the epidemiology of diabetic foot disease, resource use, and costs, to feed the model. RESULTS: Lower extremity nerve decompression surgery resulted in improved life expectancy (88,369.5 life-years versus 86,513.6 life-years), gain of quality-adjusted life-years (67,652.5 versus 64,082.3), and reduced incidence of foot complications compared to current care (490 versus 1087). The incremental cost-effectiveness analysis was -€59,279.6 per quality-adjusted life-year gained, which is below the Dutch critical threshold of less than €80,000 per quality-adjusted life-year. CONCLUSIONS: Decompression surgery of lower extremity nerves improves survival, reduces diabetic foot complications, and is cost saving and cost-effective compared with current care, suggesting considerable socioeconomic benefit for society.