Iedere twee jaar wordt ter ere van Ernst Laqueur, die wordt beschouwd als een van de grondleggers van de moderne endocrinologie, een lezing gehouden door een onderzoek(st)er die in de afgelopen decennia veel voor de (neuro)endocrinologie heeft betekent. Het bestuur van de NVE selecteert de Laqueur lecturer.
Er zijn verschillende manieren om het risico op het ontstaan van hart- en vaatziekten beter in te schatten. Eén ervan is het meten van de huid autofluorescentie (skin autofluorescence, SAF) met behulp van de zgn. AGE-reader, een andere is het doen van een CT-scan van de kransvaten van het hart en het meten van de verkalkingen hierin, de ‘coronary artery calcium score’ (CACS). In een unieke samenwerking met de collega’s van de afdelingen Radiologie, Epidemiologie en Cardiologie hebben wij beide methoden met elkaar vergeleken bij mensen die deelnamen aan de Lifelines Cohort studie.
Background & aims: Noninvasive tools (NITs) are currently used to stratify the risk of having or developing hepatic steatosis or fibrosis. Their performance and a proteomic-enabled improvement in forecasting long-term cardio-renal-metabolic morbidity, malignancies, as well as cause-specific and all-cause mortality, are lacking. Therefore, the performance of established NITs needs to be investigated in identifying cardio-renal-metabolic morbidity, malignancies, cause-specific and overall mortality and improve their performance with novel, proteomic-enabled NITs, including growth differentiation factor 15 (GDF-15), allowing multipurpose utilization.
Methods: 502,359 UK Biobank participants free of the study outcomes at baseline with a 14-year median follow-up were grouped into three categories: a) general population, b) potentially metabolic dysfunction-associated steatotic liver disease (MASLD) population, c) individuals with type 2 diabetes mellitus. The investigated NITs include Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis 4 Index (FIB-4), Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), Lipid Accumulation Product (LAP), and metabolic dysfunction-associated fibrosis (MAF-5) score.
Results: Adding GDF-15 to the existing NITs led to significantly increased prognostic performance compared to the traditional NITs in almost all instances, reaching substantially high C-indices, ranging between 0.601 and 0.808, with an overall >0.2 improvement in C-index. Overall, with the GDF-15 enhanced NITs, up to more than seven times fewer individuals need to be screened to identify more incident cases of adverse outcomes compared to the traditional NITs. The cumulative incidence of all outcomes, based on the continuous value percentiles of NITs, is increasing exponentially in the upper quintile of the GDF-15 enhanced NITs.
Conclusions: The herein-developed GDF-15 enhanced indices demonstrate higher screening effectiveness and significantly improved prognostic abilities, which are reduced to practice through an easy-to-use web-based calculator tool (https://clinicalpredictor.shinyapps.io/multimorbidity-mortality-risk/).
Het resultaat van een mooie samenwerking tussen UMCG (Klinische Farmacie & Farmacologie, en Endocrinologie), Ancora Health, en Harvard Medical School.
Download het volledige artikel hier: https://www.metabolismjournal.com/article/S0026-0495(24)00275-0/fulltext
Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts—both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG.
You can download the article HERE.
Endocrine-Disrupting Chemicals and type 2 diabetes: what is their relationship?
Summary of all research performed in the Department of Endocrinology of the UMCG, on endocrine disruptors, obesity and type 2 diabetes through a personal researcher grant awarded by DiabetesFonds Nederland to dr Jana van Vliet-Ostaptchouk.
Endocrine disrupting chemicals (EDCs) are exogenous compounds with the potential to disturb hormonal regulation and the endocrine system, consequently affecting health and reproduction in animals and humans (1). EDCs can interfere with the production, release, metabolism, and elimination of or can mimic the occurrence of natural hormones. Parabens, bisphenols and phthalates are EDCs which have in common that even though having lipophilic properties, they are quickly metabolized into more water-soluble chemicals. These chemicals in turn are easily excreted via the kidneys from the body. Due to their short half-lives of less than 24 hour, these chemicals are considered to be non-persistent (2-4). In contrast, persistent EDCs are often more resilient to metabolic degradation, making it harder to excrete these chemicals. For example, polychlorinated biphenyls (PCBs) contain chlorine atoms, which make hydroxylation by the liver much harder and leads to half-live times of months to decades. As a result, PCBs are still widely detected in blood regardless of the fact that they have been banned at least in part in Europe in 1985. Even though non-persistent EDCs are easily metabolized and excreted, their use in a wide variety of daily used consumer products has led to an ubiquitous exposure around the world.
For example, bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl)propane, is a synthetic compound that is widely used as a monomer in polycarbonate plastics and epoxy resins, being one of the world’s highest production volumechemicals (Source: paper #13, Environ Int 2015). This means that humans are widely exposed to chlorinated derivatives and structural analogs of bisphenol A.
Exposure to EDCs may play an important role in the global escalating incidence of type 2 diabetes observed in the last few decades (5). Based on the observations that EDCs interfere with the body’s endocrine system, a connection between EDC and altered glucose metabolism and increased risk for T2D is proposed. This project aimed to investigate how EDC determine the risk of T2D and to pinpoint the underlying pathophysiological mechanisms. Our hypothesis was that chronic daily exposure to EDC increases the risk of developing T2D through a cascade of adverse metabolic changes. We performed systematic analysis of EDC-related changes (single and multiple EDC effects) in metabolic functioning, epigenetics and gene expression patterns, combined with an analysis of individual genetic profiles and lifestyle. This strategy aimed to uncover mechanisms underlying EDC-induced metabolic dysregulation. Our main objectives were:
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Zo’n 20 jaar geleden was de start van het grote onderzoek Lifelines:
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