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:
The growing public interest in genetic risk scores for various health conditions can be harnessed to inspire preventive health action. However, current commercially available genetic risk scores can be deceiving as they do not consider other, easily attainable risk factors, such as sex, BMI, age, smoking habits, parental disease status and physical activity. Recent scientific literature shows that adding these factors can improve PGS based predictions significantly. However, implementation of existing PGS based models that also consider these factors requires reference data based on a specific genotyping chip, which is not always available. In this paper, we offer a method naïve to the genotyping chip used. We train these models using the UK Biobank data and test these externally in the Lifelines cohort. We show improved performance at identifying the 10% most at-risk individuals for type 2 diabetes (T2D) and coronary artery disease (CAD) by including common risk factors. Incidence in the highest risk group increases from 3.0- and 4.0-fold to 5.8 for T2D, when comparing the genetics-based model, common risk factor-based model and combined model, respectively. Similarly, we observe an increase from 2.4- and 3.0-fold to 4.7-fold risk for CAD. As such, we conclude that it is paramount that these additional variables are considered when reporting risk, unlike current practice with current available genetic tests.
In een recent onderzoek worden de resultaten gepresenteerd van de insuline afgifte na een test maaltijd bij mensen met langer bestaande type 1 diabetes.
Het abstract is als volgt:
Aims: This study aims to evaluate the stability of C-peptide over time and to compare fasting C-peptide and C-peptide response after Mixed-Meal Tolerance Test (MMTT) at T90 or T120 with C-peptide area under the curve (AUC) in long-standing type 1 diabetes.
Methods: We included 607 type 1 diabetes individuals with diabetes duration >5 years. C-peptide concentrations (ultrasensitive assay) were collected in the fasting state, and in a subpopulation after MMTT (T0, just prior to, T30-T60-T90-T120, 30-120 minutes after ingestion of Mixed-meal) (n=168). Fasting C-peptide concentrations (in n=535) at Year 0 and Year 1 were compared. The clinical determinants associated with residual C-peptide secretion and the correspondence of C-peptide at MMTT T90 / T120 and total AUC were assessed.
Results: 153 participants (25%) had detectable fasting serum C-peptide (i.e ≥ 3.8 pmol/L). Fasting C-peptide was significantly lower at Year 1 (P <0.001, effect size = -0.16). Participants with higher fasting C-peptide had a higher age at diagnosis, shorter disease duration and were less frequently insulin pump users. Overall, 109 of 168 (65%) participants had both non-detectable fasting and post-meal serum C-peptide concentrations. The T90 and T120 C-peptide values at MMTT were concordant with total AUC. In 17 (10%) individuals, C-peptide was only detectable at MMTT and not in the fasting state.
Conclusions: Stimulated C-peptide was detectable in an additional 10% of individuals compared with fasting in individuals with >5 years diabetes duration. T90 and T120 MMTT measurements showed good concordance with the MMTT total AUC. Overall there was a decrease of C-peptide at 1-year follow-up.
Een arts in Dammam, dr Ahmed Badar (zie foto: ‘in 1991, I opted for teaching (and research) as my career and stopped direct interaction with patients”) bemerkte klachten van pijn in beide armen en borstkas, en psychische klachten. Een cardioloog vond geen bijzonderheden w.b. hartfunctie of -klachten. De neuroloog deed een uitgebreid onderzoek, stelde o.a. een bilateraal (mild) carpaal tunnel syndroom vast, en kwam tot een bijzondere conclusie:
“Dr. Ahmed you have very low levels of vitamin B12 (<148 pg/mL). All the other tests are normal and there is no evidence of megaloblastic anemia. Please go to the pharmacy, I have prescribed injection vitamin B12 for you. Start today, one daily for six days, followed by once weekly for four weeks and then once monthly for the rest of your life. May Allah give you a long life.”
De schrijver gaat verder: “All the symptoms including pain, numbness, and anxiety improved by the fourth injection. They completely disappeared in two weeks. They have not recurred in the last 25 months. I regularly inject myself with 1,000 µg intramuscularly monthly in the quadriceps. A few times when I delayed my monthly injection my fingers started feeling a little “different.”
Zijn conclusie als arts met een aandoening als deze is: “Vitamine B12 tekort is een frequent genegeerde oorzaak van neuropathie en psychiatrische aandoeningen”. Zelf ken ik meerdere medici met vitamine B12 tekort, bij wie de diagnose pas later gesteld werd, of die een tijdje -bij een vastgestelde B12 malabsorptie- zonder succes met orale B12 suppletie zijn behandeld.
Dat is overigens niet het enige interessante in dit verhaal. Dr. Badar verwijst ook naar een Frans onderzoek, waarin negen patiënten worden beschreven met een zgn. vitamine B12 responsieve neuropathie; mensen met neuropathie bij wie de klachten goed reageerden op behandeling met vitamine B12 . “Serum B12 level was low in only four. Four patients had sensorimotor (predominantly sensory) axonal polyneuropathy while five had only sensory neuronopathy. Six improved in less than 1 month after B12 supplementation”.
In clinical practice, the finding of an elevated serum B12 concentration is often the consequence of supplementation with B12 in either oral form or injections. Also, elevated serum B12 may be associated with underlying disorders, like liver diseases or a (haematologic) malignancy. Only a few studies have shown that it may also be the consequence of complex formation of B12-vitamin binding proteins with immunoglobulins, the so-called macro-B12. We describe a young woman who previously was diagnosed with B12 deficiency, and in whom, after cessation of B12 injection treatment, neurologic symptoms re-appeared, and despite this, repeatedly elevated serum B12 concentrations above the upper limit of the assay were found. We demonstrated that this was caused by the presence of macro-B12, which not only resulted in erroneous and longstanding elevated serum B12, but also masked her underlying B12 deficiency. After restarting the B12 injections, symptoms gradually resolved over a period of 2–3 months, and injection frequency was gradually decreased to 1000 mcg intramuscularly every month.