College aantekeningen diabetes en cardiovascular ageing (week 1-4) voor de Minor Clinical Research in Internal Medicine , met per college de leerdoelen uitgeschreven
INCL OEFENVRAGEN en op het einde de belangrijkste onderwerpen samengevat in het Engels
Groen = belangrijk
Underline = leerdoel
Week 1-4 colleges
Epidemiology and pathogenesis of type 1 diabetes.............................................................................................3
How the microbiota may modulate metabolic disease in humans......................................................................5
How perivascular adipose tissue and vascular insulin resistance modulates cardiovascular risk and glucose
uptake..................................................................................................................................................................5
Ma 12/09/2022.............................................................................................................................................. 7
New treatment modalities and treatment goals in type 1 diabetes....................................................................7
Complications in diabetes – diabetic foot............................................................................................................8
Di 13/09/2022............................................................................................................................................... 9
Complications in diabetes - nephropathology.....................................................................................................9
The role of central reward and satiety centers in the etiology of obesity and diabetes....................................10
Experimental research of cardiovascular disease in diabetes...........................................................................11
Vr 16/09/2022............................................................................................................................................. 12
Type 2 Diabetes and cardiovascular disease......................................................................................................12
Complications in diabetes – heart failure..........................................................................................................12
Ma 19-09-2022............................................................................................................................................. 13
Incretin biology and pleiotropic effects of incretin-based therapies..................................................................13
Complication in diabetes – hypoglycemia..........................................................................................................14
Bariatric surgery.................................................................................................................................................16
Vr 23/09/2022............................................................................................................................................. 17
Islet transplantation to combat type 1 diabetes................................................................................................17
Complications in diabetes – ketoacidosis and hyperosmolar hyperglycemic state...........................................19
Ma 26/09/2022............................................................................................................................................ 19
(Un)thrustworthy science/scientists...................................................................................................................19
Lifestyle: a risk factor amenable to therapy?.....................................................................................................20
Di 27/09/2022............................................................................................................................................. 21
Psychological aspects of diabetes......................................................................................................................21
Complications in diabetes – NAFLD....................................................................................................................22
Onderwerpen.............................................................................................................................................. 30
Pathofysiology of type 1 diabetes......................................................................................................................30
Hypo unawareness.............................................................................................................................................31
Pathofysiology of type 2 diabetes......................................................................................................................31
Hypoglycemia.....................................................................................................................................................32
SGLT2 (RAAS + tubuloglomerular feedback)......................................................................................................33
1
,Ma 05/09/2022
Classification of diabetes
Diagnostic tests for diabetes
- Vingerpriktest niet, want hoge variabiliteitscoëfficiënt
- Oral glucose tolerance test (OGTT) = tijdens de zwangerschap
o Hoge variabiliteit dus is geen standaard
o Andere methodes niet veilig
- HbA1c = graadmeter hoeveelheid suiker in afgelopen 3 maanden
o Kan worden beïnvloed door verhoogde turnover van rode bloedcellen vals
lager
Tijdens zwangerschap, groot trauma of hemolyse door ijzergebreksanemie
o Tussen 6-6,5% is zeer verhoogde prevalentie van retinopathie
- Glucose fasting/non-fasting
4 general categories of diabetes (athena p.28)
1. Type 1 diabetes
2. Type 2 diabetes
3. Specific types like MODY
4. Pregnancy diabetes (GDM)
a. Diagnosed in 2nd or 3rd trimester
Monogenic defects that cause β-cell dysfunction
Een T-cel gemedieerde auto-immuun reactie zorgt voor lymfocytaire infiltratie en destructie
van B-cellen.
Inflammatoire stress ontstaat door migratie van T-cellen naar eilandjes B-cellen
apoptose
Er ontstaat stress van het endoplasmatisch reticulum
Excessieve vraag naar insuline ontstaat
Histologische beelden: chronische inflammatie, verhoogde CD8+ infiltratie en neutrofiele
infiltratie
Pas bij nog maar 10-15% van de B-cellen aanwezig ontstaan er symptomen
- Tepilizumab grijpt aan op de CD8+ T-lymfocyten
Hoeveelheid betacellen hangt af van
- BMI en/of leeftijd
- Milieu in de eerste 20 levensjaren
- In utero ontwikkelingen van de foetus
- Genetica
- Onbekende omgevingsfactoren
2
,Rol van genetica
HLA-DQ alfa en HLA-DQ bèta en HLA-DR spelen rol
- Vormen het MHC-II complex, wat rol speelt van presenteren van auto-antilichamen
buiten de cel
HLA-DR3 en HLA-DR4 is bij 45% van patiënten met DM1
HLA-DR2 beschermt tegen DM1
Categories of Increased Risk for Diabetes
Risk factors
- Dyslipidemia
- Hyperglycaemia
- Obesity
- Hypertension
- Metabolic syndrome (3 or more) type 2
o HDL low
o High triglycerides in blood
o Hypertension
o Obesitas
o Hyperglycemia
Epidemiology and pathogenesis of type 1 diabetes
The role of autoantigens within the pancreatic beta cells that may play important roles
in the initiation or progression of autoimmune islet injury
A number of autoantigens within the pancreatic beta cells may play important roles in the
initiation or progression of autoimmune islet injury
Autolichamen:
- ICA (Islet cell cytoplasmic autoantibody): eilandjes
- IAA (Insulin autoantibodies): insuline
- GAD (Glutamic Acid Decarboxylase): antilichaam tegen glutamic acid decarboxylase
- Antilichamen tegen tyrosine phosphatase; IA-2 (insulinoma-associated protein 2) of
ICA-512
- ZnT8: antilichaam tegen zink transporter
Environmental factors that may affect risk of diabetes including pregnancy-related and
perinatal influences, viruses, and ingestion of cow’s milk and cereals
Rol van omgeving
- Virus
- Koeienmelk
- Nitraten
- Vitamin D en omega-3 vetzuren
- Hygiëne hypothese
- Chemicaliën
Zwangerschap gerelateerde factoren
- Moeder < 25 jaar
- Pre-eclampsie = hoge bloeddruk en albuminuria
3
, - Neonatal respiratory disease
- Jicht
- Laag geboortegewicht en kleine geboortelengte beschermen tegen DM1
New treatment approaches to modulate the auto-immune process
Tepilizumab grijpt aan op de CD8+ T-lymfocyten. Omdat de T-cel de auto-immuun reactie
medieert
Di 06/09/2022
The epidemiology and pathogenesis of type 2 diabetes
Genetic susceptibility
Als 1 van de tweeling DM2 heeft, dan heeft de andere 80-90% kans
Als 1 van de tweeling DM1 heeft, dan heeft de andere 30-40% kans
Bekende type 2 genen zijn verantwoordelijk voor 10% van genetische predispositie, want het
is een multifactoriële ziekte. Maar dus meer genetische invloed voor obesitas
Polymorphisms of genes known to influence the risk of type 2 diabetes
Genes linked to type 2 diabetes are mainly Beta-cell function related, those genes give a 1.2x
increased risk.
Environmental factors that may affect risk of diabetes
In ontwikkelingslanden waar BMI omhooggaat, stijgt ook de prevalentie van DM2
The classical triumvirate of organs involved in the pathogenesis of type 2 diabetes
1. Pancreas
Beta-cel dysfunctie Minder insuline secretie
2. Liver
Wordt insuline resistent meer hepatische glucose productie
3. Muscle
Wordt insuline resistent minder glucose opname
Insulin resistance
Causes hyperglycemia
Hepatic and muscle insulin resistance combined with impaired insulin production is part of
the pathogenesis of type 2 diabetes
Beta-cell dysfunction
Causes hyperglycemia
Pathogenic mechanisms as therapeutic targets in type 2 diabetes
Hepatic and muscle insulin resistance combined with impaired insulin production is part of
the pathogenesis of type 2 diabetes
Restoration of these defects are attractive treatment targets
A defect incretin (GIP EN GLP 1) system is part of the pathogenesis of type 2 diabetes
(incretin resistance)
4
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