Diabetes Lecture Flashcards
Diabetes definition
group of metabolic diseases characterized by high BGL, resulting from defects of insulin secretion, action, or both
What are 3 major health complications that DM is the #1 cause of?
Blindness, leg amputation, and chronic renal failure
Acute complications of DM:
4 things
- ketoacidotic coma (DKA)
- hyperosmolar hyperglycemic non-ketoacidotic syndrome
- lactic acidosis
- hypoglycemia
Chronic complications of DM:
4 things
- microangiopathia (retino, nephro, neuro)
- macroangiopathia (atherosclerosis, HTN)
- neuropathia (sensory-motor, autonomous)
- increased risk of infection
Prevalence of DM in developed countries, and difference between type I and II
5-5.5% of population
90% are type II
5-10% type I
What type of type II diabetes might be confused for type I?
LADA: Latent Autoimmune Diabetes in Adults
Up to 20% of type II diagnoses may actually be this
What is MODY?
Matury Onset Diabetes of Young. Caused by genetic mutations of beta cell function that reduce insulin production. 6 types but most common if HNF1-alpha
Monogenic mutations related to MODY:
this is a bullshit list but they seem to love bullshit on the quizzes
HNF1-alpha, GCK, HNF4-alpha, IPF1, HNF1-beta, NEUROD1
What is Rabson-Mendenhall syndrome?
severe insulin resistance due to mutations in insulin receptor gene
What are some drugs that affect pancreas functioning?
Pentamidin, nicotinic acid, glucocorticoids, thiazids, beta adrenegic agonists
What are some genetic abnormalities related to DM type I? (i.e. sex chromosome linked diseases, etc)
Down syndrome, Turner syndrome, Klinefelter syndrome, Huntington’s chorea, Porphyria, Myotonic Dystrophy
What are some endocrinopathies related to DM?
Acromegaly, Cushing syndrome, hyperthyreosis, pheochromocytoma
What is the difference between the two types of DM type I?
Type 1a: classic autoimmune cause, covers vast majority of cases
Type 1b: rare, non-autoimmune, idiopathic cause. More common in Asian or African people. May not need insulin.
What are the 3 classic symptoms of DM type I?
excluding DKA from untreated diabetes
Poluria
Polydipsia
Polyphagia (yet weight loss)
What is the total mass of islet cells?
1-1.5g
What are some HLA alleles that are correlated to more or less diabetes mellitus type I risk?
HLA Class I: A, B, C all increase
HLA Class II: DRB1, DQA1, DQB1 increase
But DRB10403 and DRB10406 decrease chance
What are some non-HLA gene regions of the human genome that are associated with DM type I?
Insulin, CTLA4, PTPN22, IL2RA
These have overlap with other autoimmune diseases
How is the incidence of DM influenced by geography?
Incidence decreases from North to South direction (at least in Europe and China)
What are 3 ways that viruses could trigger autoimmune destruction of beta cells?
- viral epitopes and antigens being similar matches
- cytolytic infections might present the sequestred proteins
- moleculary mimicry (coxsackie P2-C and GAD65; enterovirus VP1 and tyrosine phosphase IA-2)
What are 4 viruses in the etiology of type 1 DM?
Mumps
Coxsackie A, B
Rubeola
Cytomegalovirus
Polymorphisms in which genes are related to response to viral infections and have a link to DM type I?
IFIH1, MDA5, OAS1
What are 3 toxins in the etiology of Type 1 DM?
Alloxan
Streptozotocin
Nitrozamin
What type of food product that kids frequently ingest shows a relation with DM type I, and why?
Cow Milk: has bovine serum albumin (BSA), where a 17 AA fragment might induce immune rxn in which antibodies cross-react with human beta cell proteins.
Could be bovine insulin in the milk too.
What is the order of pathogenesis of type I DM?
- Genetic predisposition
- Trigger (virus or toxin)
- Insulitis
- Autoimmune rxn
- Beta cell destruction (via cytotoxic T cells and specific antibodies)
- Clinical manifestations on destruction of 80-90% of beta cells
What is the difference between early and late stage insulitis?
Early stage: CD8+ T cells and macrophages attack beta cells
Late stage: mature B cells have specific antibodies against beta cells
What are 3 antibodies related to developing type I DM?
- Islet cell antibody (ICA)
- Insulin autoantibodies (IAA)
- Glutamic acid decarboxylase antibodies (GADA)
3 factors of the etiology of type 2 DM:
- genetic predisposition
- insulin resistance
- decreased insulin secretion (insufficient beta cell function)
Metabolic syndrome requires at least 3 of these 5 traits:
- abdominal obesity (>102cm in males, >88 in females)
- Raised triglycerides >1.7 mM
- Reduced HDL cholesterol (<1 mM in male, <1.3 mM in females)
- Raised BP >130/85
- Insulin Resistance
Stopping here
Incomplete deck
