L25- Endocrine Pathology V (pancreas) Flashcards
describe the maturation of insulin
1) Preproinsulin
- -> Endoplasmic Reticulum
2) cleavage of N-terminal + production of 2 disulfide bonds => Proinsulin
- -> Golgi Apparatus
3) cleavage of proinsulin => Insulin + C-peptide (both stored in granules and released together)
what is the key laboratory difference from over-injection of insulin versus an insulinoma
Injection: low glucose, high insulin, LOW C-peptide
Insulinoma: low glucose, high insulin, HIGH C-peptide
describe the effects of insulin (hint- 3 tissues affected, 3 main effects each)
Liver:
- inc glycogen synthesis
- inc lipogenesis
- dec gluconeogenesis
Muscle:
- inc glucose uptake
- inc glycogen synthesis
- inc protein synthesis
Adipose:
- inc glucose uptake
- inc lipogenesis
- dec lipolysis
describe the types of Presentations DM may have
1) asymptomatic: elevated blood glucose
2) classical symptoms: polyuria, polydipsia, elevated glucose
3) severe presentation / coma
what are the normal glucose values (fasting and random)
Fasting: 70 - 100 mg/dL (4.0-5.6 mmol/L)
Random: 79-140 mg/dL (4.4-7.8 mmol/L)
list some secondary causes of DM
-pancreatic disease (no insulin production)
- hormonal antagonists to insulin (cortisol, GH, catecholamines)
- drug / chemical induced
- Infections: CMV, mumps, coxsackie B
- Genetics: down syndrome, turner syndrome
- Gestational DM (typically resolved after delivery)
Features of DM I:
- (1)% of DM cases
- (2) age of onset
- (3) rate of onset
- (4) weight of patient
- (5) prevalence of ketosis
- (6) insulin levels
- (7) link to HLA?
- (8) auto-antibodies?
1- 10% 2- <40 y/o 3- rapid 4- lean / normal 5- prone to ketosis 6- low to absent insulin levels 7- presence of HLA link 8- commonly linked to auto-antibodies
Features of DM II:
- (1)% of DM cases
- (2) age of onset
- (3) rate of onset
- (4) weight of patient
- (5) prevalence of ketosis
- (6) insulin levels
- (7) link to HLA?
- (8) auto-antibodies?
1- 90% 2- >40 y/o 3- slow 4- obese 5- rarely in ketosis 6- high (normal or reduced) insulin 7- no HLA link 8- no auto-antibody link
list / describe the genetic factors affecting DM I
- 40% concordance between monozygotic twins
- association with HLA-: DR3, DR4, DQA1, DQB1
list the environmental factors affecting DM I
Viruses: coxsackie B, rubella, CMV, mumps
drugs and toxins
DM I Autoimmunity:
- arises from a failure of (1)
- most antibodies are considered (2)
- (3) occurs and is defined as DM I once (4) has happened
1- failure T-cell self-tolerance
2- islet cell antibodies (ICA)
3- long pre-diabetic phase (destruction of β-cells)
4- 90% of β-cells are destroyed
describe the etiological hypothesis of DM type I
1) viral / chemical attack on β-cells
2) exposure of new β-cell Ags OR molecular mimicry of viral / β-cell structures
3) Ags –> activate T-cells in pancreatic lymph nodes
4)
- CD4+ (Th) / CD8+ (Tc) cells are involved in β-cell damage
- HLA system is involved in Ag presentation
- CKs from Th1 can activate B-cells –> Ig production against β-cell Ags
what are the two key factors involved in DM type II etiopathogenesis
- insulin resistance
- β-cell exhaustion / failure
describe the genetic factors involved with DM II
- > 90% concordance between monozygotic twins
- 5-10x inc risk if 1st degree relative has it
-typically polygenic disorder –> simultaneous presence of several genes + environmental factors
(NO HLA association)
describe the environmental factors involved in etiopathogenesis of DM II
Obesity:
- 80% Pts are obese
- risk increases with BMI
- fat distribution- higher risk with central obesity (apple shaped) > peripheral obesity (pear shaped))
Lack of Exercise
-independent from obesity
