De blaaskatheter
Mijn meest recente column in het HYPOnieuws van Februari 2024.
Auto-immune gastritis
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 disruptors project
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:
- To investigate whether exposures to EDC as measured in urine increase the risk of T2D and how this risk is modified by lifestyle and genetic predisposition
- To examine the effects of EDC on metabolism and to establish EDC-related alterations in gene function (i.e. DNA methylation and gene expression)
Click on ‘meer’ to read further..
Questionnaire-based prediction for type 2 diabetes
Background
Type 2 diabetes disproportionately affects individuals of non-White ethnicity through a complex interaction of multiple factors. Therefore, early disease detection and prediction are essential and require tools that can be deployed on a large scale. We aimed to tackle this problem by developing questionnaire-based prediction models for type 2 diabetes prevalence and incidence for multiple ethnicities.
Methods
In this proof of principle analysis, logistic regression models to predict type 2 diabetes prevalence and incidence, using questionnaire-only variables reflecting health state and lifestyle, were trained on the White population of the UK Biobank (n = 472,696 total, aged 37–73 years, data collected 2006–2010) and validated in five other ethnicities (n = 29,811 total) and externally in Lifelines (n = 168,205 total, aged 0–93 years, collected between 2006 and 2013). In total, 631,748 individuals were included for prevalence prediction and 67,083 individuals for the eight-year incidence prediction. Type 2 diabetes prevalence in the UK Biobank ranged between 6% in the White population to 23.3% in the South Asian population, while in Lifelines, the prevalence was 1.9%. Predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC), and a detailed sensitivity analysis was conducted to assess potential clinical utility. We compared the questionnaire-only models to models containing physical measurements and biomarkers as well as to clinical non-laboratory type 2 diabetes risk tools and conducted a reclassification analysis.
Findings
Our algorithms accurately predicted type 2 diabetes prevalence (AUC = 0.901) and eight-year incidence (AUC = 0.873) in the White UK Biobank population. Both models replicated well in the Lifelines external validation, with AUCs of 0.917 and 0.817 for prevalence and incidence, respectively. Both models performed consistently well across different ethnicities, with AUCs of 0.855–0.894 for prevalence and 0.819–0.883 for incidence. These models generally outperformed two clinically validated non-laboratory tools and correctly reclassified >3,000 additional cases. Model performance improved with the addition of blood biomarkers but not with the addition of physical measurements.
Interpretation
Our findings suggest that easy-to-implement, questionnaire-based models could be used to predict prevalent and incident type 2 diabetes with high accuracy across several ethnicities, providing a highly scalable solution for population-wide risk stratification. Future work should determine the effectiveness of these models in identifying undiagnosed type 2 diabetes, validated in cohorts of different populations and ethnic representation.
You can download the full article HERE.
Metformin during pregnancy
During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.
You may find the full (Open Access) article HERE.
Therapeutics: B12
Het volledige artikel vindt U HIER.
Samen beslissen
Mijn laatste column in het HYPOnieuws van November 2023.
Schildklier en kwaliteit van leven
Hypothyroidism is associated with a decreased health-related quality of life (HRQoL). Wehypothesized that individuals with hypothyroidism (defined as use of thyroid hormone (TH)) and especially those having an impaired HRQoL are characterized by a high prevalence of comorbid disorders, and that the impact of hypothyroidism and comorbidity on HRQoL is synergistic. Presence of comorbidity was based on data obtained using structured questionnaires, physical examination, biochemical measurements and verified medication use. Single morbidities were clustered into 14 different disease domains. HRQoL was measured using the RAND-36. Logistic regression analyses were used to determine the effect of TH-use on the odds of having an affected disease domain and a lower score than an age-and sex-specific reference value for HRQoL. TH was used by 4537/147201 participants of the population-based Lifelines cohort with a mean(±SD) age of 51.0±12.8 years (88% females). 85% of the TH-users had ≥1 affected disease domain, in contrast to 71% of non-users. TH-use was associated with a higher odds of 13/14 affected disease domains, independent of age and sex. In a multivariable model, TH-use was associated with a decreased HRQoL across 6/8 dimensions. No significant interactions between TH-use and affected disease domains were observed. TH-users with an impaired HRQoL had significantly more comorbidity than those not having an impaired HRQoL. In this large, population-based study, we demonstrated that TH-users had more comorbidity than individuals not using TH. The co-existence of other chronic medical conditions in subjects with TH-use led to further lowering of HRQoL in an additive manner.
Find the current accepted version of this article at: https://ec.bioscientifica.com/view/journals/ec/aop/ec-23-0266/ec-23-0266.xml
Objectives: Cardiovascular disease (CVD) is a precarious complication of type 1 diabetes (T1D). Alongside glycaemic control, lipid and blood pressure (BP) management are essential for the prevention of CVD. However, age-specific differences in lipid and BP between individuals with T1D and the general population are relatively unknown.
Design: Cross-sectional study.
Setting: Six diabetes outpatient clinics and individuals from the Lifelines cohort, a multigenerational cohort from the Northern Netherlands.
Participants: 2178 adults with T1D and 146 22 individuals without diabetes from the general population.
Primary and secondary outcome measures: Total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), systolic BP (SBP) and diastolic BP (DBP), stratified by age group, glycated haemoglobin category, medication use and sex.
Results: In total, 2178 individuals with T1D and 146 822 without diabetes were included in this study. Total cholesterol and LDL-cholesterol were lower and SBP and DBP were higher in individuals with T1D in comparison to the background population. When stratified by age and medication use, total cholesterol and LDL-cholesterol were lower and SBP and DBP were higher in the T1D population. Men with T1D achieved lower LDL-cholesterol levels both with and without medication in older age groups in comparison to women. Women with T1D had up to 8 mm Hg higher SBP compared with the background population, this difference was not present in men.
Conclusions: Lipid and BP measurements are not comparable between individuals with T1D and the general population and are particularly unfavourable for BP in the T1D group. There are potential sex differences in the management of LDL-cholesterol and BP.
Read the full article at: https://bmjopen.bmj.com/content/13/10/e073690.long
Subtyperen van type 2 diabetes
Al jaren wordt getracht om de heterogeniteit van type 2 diabetes beter in kaart te brengen. Recentelijk zijn verschillende manieren van subtypering van type 2 diabetes gepubliceerd. De meeste aandacht gaat naar een onderverdeling in 5 subtypen, vlak na het stellen van de diagnose. Twee van deze subtypen worden gekenmerkt door insulinedeficiëntie; circa de helft van deze patiënten moet relatief vroeg beginnen met insuline. Eén subtype wordt gekenmerkt door ernstige insulineresistentie en een verhoogd risico op nierschade en niet-alcoholische leverziekte.
Subtypering kan leiden tot beter inzicht in de pathofysiologische achtergronden bij een specifiek individu, tot een beter onderbouwde aanpassing van de leefstijl, een betere inschatting van het risico op late complicaties en persoonsgerichte medicamenteuze behandeling. Er is ook meer aandacht voor specifieke factoren die de individuele respons op medicatie beïnvloeden, zoals geslacht, leeftijd en relatief lichaamsgewicht.
Het is te hopen dat deze ontwikkelingen in de nabije toekomst leiden tot een beter op het individu gerichte begeleiding en behandeling van type 2 diabetes.
Het volledige artikel vindt u HIER. (mogelijk moet u eerst inloggen)
Genezen en toch klachten
Mijn recente column in het magazine Hypo Nieuws. Het mooie wetenschappelijke artikel van de collegae uit Leiden, waar ik in de column naar verwijs, heet: Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing’s disease: a case–control study. De eerste auteur is Cornelie Andela. U vindt het HIER.
De link in de column verwijst naar een wikipedia pagina over DNA methylering.
Wanneer u als wetenschapper geïnteresseerd bent in de rol van DNA methylering bij endocriene of metabole aandoeningen, kijk dan ook eens naar de volgende publicaties:
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