type 1 and type 2 diabetes Flashcards
(51 cards)
pathogenesis of type 1 diabetes and what are the main infiltrators
- pancreatic beta cell destroyed by an autoimmune process
- T cell mediated autoimmune and also get B cells
- T lymphocytes destroy beta cells directly eg cytotoxic eg CD
- B cells secrete antibodies
- loss of beta cells and loss of function leading to reduced insulin
- also get increased resistance to insulin
autoantibodies assoc to type 1 dm 4
- anti GAD glutamic acid decarboxylase
- antibodies to insulin
- antibodies to islet cell surface IA2 antibodies
- protein tyrosine phosphatase antibodies
what % do symptoms occur of beta cells lost
80-90%
which one has a more genetic implication type 1 or type 2
type 2 dm
prevalence of dm 1
0.5% of population
what genes is type 1 dm assoc too
HLA
-Dr3 and Dr4 in caucasians
risk of diabetes in father, mother, non hla identical sibling, hla identical sibling, non identical twin and identical
9% 3 3 16 20 35
other than genetics what other factors trigger dm1
- environment: exposure to cow milk, viruses
- geographic variation
- seasonal variation: peaks in winter
- inverse assoc. to BMI and age of onset
children who are younger at dx are more likely to over weight
childhood obesity increase risk
what is the accelerator hypothesis of type 1 dm
obesity causes insulin resistance and hence greater insulin secretion leading to increased exposure of immune system to insulin and the pancreas so increase auto-immune response
what other autoimmune diseases is diabetes assoc. too
coeliac disease addison hypothyroidism grave's rheumatoid arthritis
symptoms of type 1 dm
- fatigue
- polyuria: as glucose pulls water with it and more glucose in renal then can be absorbed
- kussmaul breathing
- nocturia
- thirst
- polydipsia
- tachycardia
- hypotension
- weight loss as unrestrained lipolysis
- ketoacidosis: elevated H+ drives out K+
what does LADA stand for
latent autoimmune diabetes of adulthood
ie as usually presents 5-7 years old 1dm
-defined as the presence of islet autoantibodies in high titre, without rapid progression to insulin therapy
what is kussmaul respiration
increased rate of breathing- greater total expiration of CO2 to blow off co2 and raise Ph of blood due to ketoacidosis
acute presentation of DM1
- usually <40
- failure to grow
- short hx of florid osmotic symptoms and rapid weight loss
what is uncontrolled in diabetes
ie get uncontrolled glucagon
-uncontrolled gluconeogenesis as unsuppressed glucagon release
-uncontrolled lipolysis
-uncontrolled ketone generation
-uncontrolled glycogenolysis
-decreased protein synthesis and lipogenesis
so overall get weight loss as insulin
glucagon or insulin which is anabolic and which is catabolic
insulin is anabolic ie it builds
glucagon is catabolic ie it breaks down
what happens in renal failure with ketoacidosis
if there is severe dehydration then polyuria goes to oligouria
ketones accumulate so get ketoacidosis
how are ketones made
- uncontrolled lipolysis-> FFA accumulation
- uncontrolled hepatic beta oxidation means accumulation of acetyl coA
- acetyl coA build up is shunted to the ketone pathway
If we see lots of lymphocytes destroying the beta cells in the pancreatic islets, what name would we give to this inflammatory process affecting the islets?
-Insulitis: infiltration of the islets by mononuclear cells containing activated macrophages,helper cytotoxic and suppressor T lymphocytes
do the b or t cells destroy the beta cells
the T cells
what is also found alongisde autoantibodies in diabetes patients and what are the 3 main ones
- Firstly some patients have antibodies in the blood not only to beta cells but also certain viruses that have been implicated in leading to beta cell damage and dm
o Coxsackie B
o Mumps
o Cytomegalovirus
what affects insulin requirenment
meals carbs stress alcohol illness prolonged exercise some drugs
how does alcohol affect insulin requirenment
need less as suppress hepatic gluconeogenensis
how does illness affect insulin requirenment
induces insulin resistance
and increases glucose so need more insulin
