5.2 CV system & diabetes Flashcards
- prevalence of diabetes in Canada: increase with (2)
- increases with age and with increasing richness ish (rich ppl disease)
*but actually increasing in all ages now
what happens/is when blood glucose is
- 5mM (90 mg/dL)
- 6.1 mM (110 mg/dL)
- 7.8mM (140 mg/dL)
- 11.1mM (200 mg/dL)
- 16.6mM (300 mg/dL)
- 22.2mM (400 mg/dL)
- 33.3mM (600 mg/dL)
- 5mM (90 mg/dL): nothing
- 6.1 mM (110 mg/dL): normal
- 7.8mM (140 mg/dL): prediabetes
- 11.1mM (200 mg/dL): diabetes
- 16.6mM (300 mg/dL): b cell destruction begins
- 22.2mM (400 mg/dL): b cell destruction + ketoacidosis –> T2D becomes insulin dependant
- 33.3mM (600 mg/dL): diabetic coma
what happens/is when glycated hemoglobin (HbA1C) is:
- <5.7%:
- 5.7-6.4%:
- > 6.4%:
- <5.7%: normal
- 5.7-6.4%: prediabetes
- > 6.4%: diabetes
give blood glucose values for:
- normal
- prediabetes
- diabetes
- b-cell destruction begins
- b-cell destruction + ketoacidosis
- diabetic coma
- 5mM (90 mg/dL): nothing
- 6.1 mM (110 mg/dL): normal
- 7.8mM (140 mg/dL): prediabetes
- 11.1mM (200 mg/dL): diabetes
- 16.6mM (300 mg/dL): b cell destruction begins
- 22.2mM (400 mg/dL): b cell destruction + ketoacidosis –> T2D becomes insulin dependant
- 33.3mM (600 mg/dL): diabetic coma
what does it mean to be prediabetic?
- blood glucose and glycated hemoglobin are a bit high –> still normal glucose metabolism but higher risk of diabetes
what are the 2 forms of diabetes mellitus?
- cause?
- usually develops when?
Type 1:
- insufficient production of insulin –> usually due to autoimmune destruction of b-cells
- usually develops early in life (but possible in older adults as well
- used to be called insulin-dependant or juvenile diabetes, but not anymore
TYPE 2:
- insulin resistance! –> cells don’t respond appropriately to insulin
- usually develops in late adulthood –> associated with obesity (but not all obese are diabetic)
insulin resistance:
- is it metabolic actions or endocrine actions that are altered? give examples
METABOLIC!!
- how glucose metabolism is regulated
- glucose uptake in muscle/adipocytes, glycolysis, glycogenolysis, lipolysis, gluconeogenesis
VS ENDOCRINE:
- growth factor: cell proliferation and differentiation
*prolonged diabetes can lead to abnormal endocrine functions as well
etiology of Type 1 diabetes:
- ___-____% of cases
- autoantibodies against (3)
- OR _____________
- 5-10% of cases
1. INSULIN: b cells function normally but antibodies for insulin in body = insulin function doesn’t take place –> glucose metabolism is disrupted –> can lead to overproduction of insulin/overactivation of b-cells –> eventually get destroyed bc of increased function
2. GLUTAMATE DECARBOXYLASE (GAD): - converts glutamate to GABA (neurotransmitter)
- GAD promotes insulin release in b-cells (not synthesis)
- multiple types of GAD antibodies = issue in insulin release = more insulin is produced…
3. ISLET ANTIGEN-2 - isoform of tyrosine phosphatase-like protein in b-cells –> function unknown but antibodies against it leads to abnormal release of insulin, leading to T1D
OR idiopathic! (causes remain unknown)
*antibodies of GAD and islet antigen-2 were discovered in clinical samples of people who have T1D
etiology of diabetes type 2:
- __-__% of cases
- main (general) cause: insulin ________ or insulin _______ ________
- 3 possible causes
- 80-95% of cases
- insulin resistance or insulin secretory defect (or insulin resistance leading to insulin secretory defect)
1. genetic defects of b-cell function: mutations
2. disease of exocrine pancreas
3. endocrinopathies: abnormal functioning of another hormonal system
describe the genetic defects of b-cell functions (mutations) that can cause T2D (1 with lots of info + 3)
- glucokinase (GCK) (hexokinase 4)
- present in liver and pancreas (b-cells)
- hexokinase IV = smallest of the hexokinases
- sense glucose in b-cells
- mutation = 30x more sensitive –> can lead to increase insulin or insulin release defects –> leads to abnormal glucose homeostasis/insulin resistance = T2D - HNF (a transcription factor)
- PDX1 (transcription factor)
- mitochondrial DNA 3242
which diseases of the exocrine pancreas can lead to T2D? (4)
- pancreatitis
- trauma
- surgery (pancreatectomy)
- tumor
*all would lead to abnormal b-cell function = T2D
which endocrinopathies can lead to T2D? (6)
- CUSHING’S SYNDROME
- high cortisol –> inhibits insulin and promotes gluconeogenesis
- cortisol = opposite of insulin action –> glu stays in blood = tells b-cells to make more insulin –> b-cells work too hard - ACROMEGALY:
- high GH –> opposite of insulin actioss of glucose uptake and lipogenesis –> same as cortisol - PHEOCROMOCYTOMA
- tumor of adrenal medulla –> high catecholamine –> need more glu in circulation –> leads to overfunction of b-cells = IR = T2D - GLUCAGONOMA
- tumors of a-cells –> produce glucagon
- too much glucagon = increase insulin = IR or destruction of b-cells - HYPERTHYROIDISM
- T3/T4 stimulate lipolysis, muscle catabolism and carbohydrate absorption VS insulin promotes reduction of all 3
- increase T3/T4 leads to overprod of insulin = IR and T2D - SOMATOSTATINOMA
- somatostatin produced in multiple locations –> inhibits insulin secretion in islets of lagerhans + hypothalamus + GI –> leads to defective insulin function
why does an increase in a hormone opposite of insulin can lead to T2D?
- bc hormone will make more glucose stay in bloodstream –> GCK senses it –> produces more insulin to decrease blood glucose –> overprod of insulin –> leads to overfunction of b-cells OR insulin resistance (abnormal response to insulin from muscle, adipose and liver)
explainpre-receptor (2) vs receptor (4) insulin resistance
- which one is more common?
PRE-RECEPTOR:
- antibodies against insulin
- mutant insulin: A-C and B-C insulin (vs A-B)
*both lead to abnormal signaling
RECEPTOR: (after ligand binds)
- reduced INSR expression
- reduced affinity for insulin: need more insulin to elicit same response
- impaired tyrosine-kinase activity (intrinsic) –> leads to abnormal signaling
- INSR antibodies
*or any abnormality in any stage of INSR signaling (ie negative feedback regulators…) –> leads to IR
- receptor is more common! pre-receptor is less common
insulin action: normal vs diabetes SCHÉMA!
- insulin from pancreas acts on (3) –> what happens?
NORMAL glucose homeostasis
- insulin reaches brain –> decrease sympathetic outflow to adipose tissue = decrease lipolysis
- insulin reaches brain –> unknown neuronal signal to liver to increase TG secretion
- insulin reaches fat to decrease lipolysis –> signals to fat to decrease TG synthesis
- insulin reaches liver to decrease gluconeogenesis and decrease TG secretion
DIABETES: = decrease insulin!
- less insulin reaches brain –> INCREASE sympathetic outflow to adipose tissue = INCREASE lipolysis
- less insulin reaches brain –> unknown neuronal signal to liver to DECREASE TG secretion + more glucose from liver to brain!
- less insulin reaches fat –> INCREASE lipolysis –> INCREASE NEFA signals liver to increase TG synthesis
- LESS insulin reaches liver: INCREASE gluconeogenesis and decrease TG secretion
*overall increase in TG synthesis and decrease TG secretion = fatty liver –> abnormal energy met (glu and fat)
