Describe the etiology of DM I Non-autoimmune (idiopathic) - unknown cause, less
common than autoimmune diabetes
strong genetic component
occurs mostly in people of asian or african descent
Describe the etiology of DM I autoimmune - Genetic factors:
First degree relatives with DM 1
Strongest association with MHC
Environmental factors:
viral infection
H. Pylori
exposure to cow milk proteins
relative lack of Vitamin D
Gradual process of autoimmune destruction of B cells in genetically susceptible
individuals
Natural history of DM I - Long pre-clinical period with B cell destruction, leading to
insulin deficiencies and hyperglycemia
Protein and fat breakdown:
weight loss
high levels of circulating Ketons (Think DKA!)
Pathogenesis of DM I Non autoimmune/Idiopathic - no evidence of B cell autoimmunity,
varying degrees of insulin deficiency
pathogenesis of DM I Autoimmune - Slowly progressive disease that destroys all B cells
of pancreas
How many of the B cells are destroyed with DM I autoimmune? - 80-90% of insulin
secreting B cells int eh slate of lagerhands are destroyed and insulin synthesis declines
What does insulin normally suppress? - Glucagon
What is there a decreased secretion of in DM I? and the result? - amylin - which
increases glucagon production
What is glucagon? - A hormone produced by the a cells of the islets, acts in the liver,
increases blood glucose by stimulating glycogenesis and contributes to hyperglycemia
in DM I.
, What contributes to hyperglycemia in DM I? - lack of insulin and excess glucagon
DM II Etiology - genetic susceptibility (polygenic)
environmental defects in b cell function combined with insulin resistance
associated with long-duration obesity
DM II natural history - compensatory hyperinsulinemia prevents the clinical appearance
of diabetes for many years
decrease in B cell mass and reduction in normal B cell function develops and leads to a
relative deficiency of insulin activity
Pathogenesis of DM II - Defects in uncreative insulin secretion and insulin effects on
target tissues (insulin resistance) = persistent state of hyperglycemia, inducing
metabolic alteration, cell death, and inflammation
What causes insulin resistance? - abnormality of insulin molecule
high amounts of insulin antagonists
down-regulation of insulin receptor
alteration of glucose transporter (GLUT) proteins
What is the most important contributor to insulin resistance and how? - Obesity
adipose tissue releases/produces:
fatty acids
glycerol
hormones
pro-inflammatory cytokines (adipokines)
What are other contributors to insulin resistance? - elevated glucagon
decreased amylin
decreased ghrelin
decreased responsiveness of B cells
Kidney pathophysiology
What are the classic symptoms of DM I? - polydipsia
polyuria
polyphagia
weight loss
fatigue
recurrent infections
prolonged wound healing
general pruritis
visual changes
paresthesias
CV symptoms
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