Diabetes diagnosis and pathogenesis Flashcards
Diabetes classification breakdown
- Type 1 (ß cell destruction): A. Autoimmune. B. Idiopathic. 2. Type 2 (Spectrum: resistance or secretory defect). 3. Other. 4. Gestational (insulin resistance during pregnancy only - some can handle it, some can’t - increase risk of type 2).
Genetic contribution to Type 1 and Type 2
Type 1: 25-50%. Type 2: 90% (from twin studies), i.e. higher risk.
What are the “other types” of diabetes
genetic defects ß cell or insulin action, pancreatitis, CF, w/ other hormone issues which counteract insulin (Cushings (cortisol), acromegaly (too much GH), hyperthyroid (leads to epinephrine), infections, steroids, genetic syndrome (kleinfelter, etc)
Diagnosis of diabetes
FPG ≥7mmol/L or A1C ≥6.5% (adults) or 2hPG (oral glucose) ≥11.1mmol/L or Random PG ≥11.1 (PG = plasma glucose). Need to have symptoms too, can be faulty test.
Diagnostic threshold chart
Insert chart. High fasting but normal 2h is probably insulin deficient, vice versa is probably resistance. Blue is pre-diabetes aka at risk for diabetes, and for heart attack etc.
Diagnosis flow chart
Insert chart here
Describe HbA1C and its diagnostic cutoff
≥6.5% indicates diabetes. Repeat to confirm. Glucose sticks irreversibly (glycation) to HbA1 (type of Hb). RBC turnover indicates the A1c over the last 3 months (but mostly 1 month). Can also be affected if disease shortens RBC lifespan (anemia, thallasemia, sickle-cell). It is an average tho so you can miss extremes and it is individual. But if you have high A1c you have diabetes.
Diagnostic performance of FPG, 2hrG and A1c
FPG diagnoses many people, 2hrG diagnoses a big overlap of that and probably some extras, A1c is more specific and misses many.
A couple cons to some of the tests
blood samples are not stable (RBCs consume glucose over time), A1c is expensive and can be affected by other conditions.
Cautions with diabetic tests
NOT point of care A1c’s; NOT GDM/pregnancy; Hemoglobinopathies; Anemias; High red cell turnover; All’s fine because A1c is “Normal” - debatable
Type 1 diabetes pathogenesis overview
Timeline
Why is it important to understand that Type 1 diabetes is an autoimmune disease?
It is associated to other autoimmune diseases and associated with HLA (MHC1s). Autoantibodies are not pathogenic, but probably develop after ß cell destruction (presented to B cells after phagocytosis).
What autoantibodies are found in diabetes?
Glutamic Acid Decarboxylase (GAD) more in adults. Insulinoma-Associated 2 (IA-2). Insulin autoantibodies (IAA) after giving insulin eventually. Zinc-transporter 8 (ZnT8). The more you have the more likely you’ll get diabetes
Should we screen for T1DM risk?
NO. 90% of new cases have no Fam Hx.
How do people find out they have diabetes type 1?
Incidental, osmotic symptoms, medical emergency, and the classic symptoms (esp recurrent infection (esp yeast) and weight loss - insulin!).
Which factors are involved in Type 2 diabetes?
Genetic factors and ethnic and environmental background (non caucasian), High fat diet and obesity, Pancreatic dysfunction, Insulin resistance in liver & muscle. Everyone is different as to their combination! Ultimately it is due to insulin resistance AND insulin secretory defects/ß cell failure
Type 2 diabetes pathogenesis 1 overview
Timeline
Type 2 diabetes pathogenesis 2 overview
Timeline
Causes of ß cell failure
Age, Effect, Genes, resistance, lipotoxicity, glucose toxicity, amyloid deposition. Don’t really know the mechanism.
Metabolic syndrome
defined by 3 out of 5 risk factors : Abdominal obesity, high triglycerides, low HDL, high BP, high fasting glucose. Insulin resistance seems to be at the core
What is Central obesity?
Pear shape (ie big bum) is metabolically better than apple (huge gut)
Acanthosis nigricans
hyperkeratosis (thickening of stratum corneum) from high insulin. Looks like “dirty”, esp on neck
