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57 Cards in this Set

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differentiate hypoglycemia with low and elevated C-peptide levels
low C-peptide - exogenous insulin administration
high C-peptide - insulin secreting tumor
What does hypokalemia do to insulin release by B-cells
B-cells are hyperpolarized due to efflux of potassium leading to decreased ability to depolariza them and release insulin
mechanism of insulin secretion by B-cells
glucose is metabolized to yeild ATP, ATP closes Katp channel in the B-cells leading to depolarization via Ca influx. Depolarzaition activates exocytosis
what is the rate-limiting step in insulin secretion
Ca influx via L-type Ca channels
syndrome associated with reduced glucokinase activity
Maturity onset diabetes of youth
what is the mechanism of MODY
reduced glucokinase deficiency leading to an inability to phosphorylate glucose and sense the amount of glucose in the blood; insulin secretion decreases
differentiate a2, B2 adrenergic and M3 cholinergic stimulation on B islet cells
a2 stimulation inhibits insulin release by decreasing cAMP
B2 stimulation increases insulin release by raising cAMP
M3 stimulation increases insulin release by raising IP3
describe the effect on B islet cells with B-blocker administration
this would block the B2 release of insulin; however it also decreases hepatic gluconeogenesis and have the potential to enhance the effect of hypoglycemia drugs
mechanism of glucotoxicity in type 2 DM
chronic hyperglycemia causes progressive impairment of insulin secretion by desensitizing Katp channel
mechanism of lipotoxicity in type 2 DM
fatty acids released from visceral adipose tissue causes insulin resistance by inhibiting IRS-1 activation of PI3K and GLUT-4
complete insulin deficiency secondary to autoimmune destruction of B islet cells
Type 1 DM
Lab tests that would distinguish between type 1 and 2 DM
type 1 - pancreatic islet antibodies (GAD65) and low C-peptide levels
type 2 - hyperinsulinemia with high C-peptide levels
peripheral resistance to insulin secondary to obesity and eventual B islet cell exhaustion
type 2 DM
mechanism of insulin resistance in type 2 DM
decreased PI3K activity due to lipotoxicity
describe post-receptor signaling cascade of insulin receptor on target tissue
1. insulin-stimulated phosphorylation of insulin receptor substrate (IRS-1)
2. IRS-1 activates phosphoinositol 3-kinase (PI3K)
3. PI3K activates GLUT-4 transporter activity
in a patient with type 2 DM (insulin resistance) what is increased in their target tissues by hyperinsulinemia
increased mitogen activated protein kinase (MAPK) leading to vascular smooth muscle proliferation, cell adhesion, increased coagulation, and activation of inflammation
what do somatostaninoma and glucogonoma cause
secondary diabetes
classic triad of somatostatinoma
hyperglycemia
steatorrhea
cholithiasis
*decreased gastric secretion
this form of secondary diabetes has both reduced glucagon and insulin secretion
somatostatinoma
*both fasting hypoglycemia and postprandial hyperglycemia
this tumor is associated with hyperglycemia and necrolytic migratory erythema
glucagonoma
3 mechanisms of glucocorticoid-induced secondary DM
1. insulin resistance in liver and skeletal muscle
2. decrease insulin secretion
3. stimulate hepatic glucose synthesis
mechanism of polyuria and polydipsia in uncontrolled hyperglycemia
polyuria - glycosuria trigger osmotic diuresis
polydipsia - volume depletion secondary to osmotic diuresis causes vasopressin release stimulating thirst
volume and salt status of patient with uncontrolled hyperglycemia
hypovolemia hypertonic hyponatremia
*hypernatremia may develop is H20 is not replaced due to polyuria
mechanism of reversible visual loss in hyperglycemia
glucose freely diffuses into the lens of the eye, it is converted to sorbitol by aldose reductase. Sorbitol accumulates and osmotically attracts water and an acute myopic shift
describe how hyperglycemia results in development of accelerated atherosclerosis
1. excess glucose overwhelms the mitochondrial ETC and result in generation of ROS
2. ROS lead to inactivation of GA3PDH, inactivation of this shunts glucose into sorbitol pathway depleting NADPH. Nitric oxide synthesis requires adequate supply of NADPH
3. increases platelet aggregation and activation by reducing NO synthesis in platelets
4. impair fibrolysis by increasing synthesis of plasminogen-activator inhibitor (PAI-1)
what does NO synthesis from arginine need an adequate supply of
NADPH
what does activation of PKC lead to
formation of AGEs that activate surface receptors (RAGE) to increase inflammation via NF-kB signaling
inactivation of what enzyme via ROS leading to the depletion of NADPH
glyceraldehyde-3-phosphate dehydrogenase
deficiency in what leads to increased platelet aggregation and vascular smooth muscle proliferation and contraction
NO
characteristics of diabetic nephropathy
proteinuria
GBM thickening
mesangial proliferation
nodular glomerulosclerosis
initiating event of diabetic nephropathy
increased GFR due to dilation of glomerular afferent arterioles leading to hyperfiltration
describe the mechanism that decreases GFR in diabetic kidney disease
initially there is hyperfiltration leading to microalbuminuria, eventually more and more albumin is excreted leading to dependent pitting edema and a declining GFR
mechanism of GBM thickening and mesangial expansion causing nodular glomeruloslerosis in diabetic nephropathy
increased ATN II and AGE by the mesangial cells, these bind to receptors generating ROS and activate PKC as well as MAPK transcription of NF-kB to promote the expression of growth factors
lesions associated with nonproliferative diabetic retinopathy
microaneuysms
hemorrhages
hard exudates
what pathologic changes in diabetic retinopathy indicate progression to the proliferative stage
venous beading
soft exudates
characteristic lesion of proliferative diabetic retinopathy
neovascularizations
what is the initiating even that leads to proliferative retinopathy
retinal ischemia due to microthrombi (hypercoagulability from increased PAI-1) stimulates production of angiogenic substances
4 neuropathies of DM
1. stocking-glove distribution of parasthesias and pain
2. distal symmetric polyneuropathy
3. autonomic polyneuropathy
4. proximal motor neuropathy
what is used to diagnose small-fiber polyneuropathy
reduced sensitivity to a 5.07 monofilament
neuropathy associated with severe pain in the thigh, hips, buttocks, with proximal leg muscle weakness
proximal motor neuropathy
patients with DM presents with hyporeflexia, loss of vibration and proprioception, paresthesias, and superficial burning pain on both lower extremities
distal symmetric polyneuropathy
mechanisms resulting for decreased nerve conduction in peripheral polyneuropathy (3)
1. sorbitol accumulation leads to inhibition of myoinositol transport (important for secondary messangers)
2. AGEs alter structure and function of neuronal cell membrane
3. C-peptide stimulates Na/K ATPase, decreased C-peptide leads to decreased conduction
two exam findings in diabetic dermopathy
1. shin spots (brown atrophic lesions)
2. necrosis lipoidca (red-brown elevated plaques covered by yellow skin)
mechanisms of diabetic foot ulcers
1. decreased cutaneous sensation interferes with normal protective mechanism
2. motor polyneuropathy causes abnormal foot mechanics
3. autonomic polyneuropathy impairs cutaneous blood flow
best exam to differentiate diabetic foot ulcer from an arterial foot ulcer
inability to detect 5.07 monofilament is associated with diabetic foot ulcers
mechanism of diabetic ostoeoarthropathy
combination of vascular and mechanical abnormalities that result from peripheral and autonomic neuropathy
mechanism of erectile dysfunction in DM
1. decreased blood flow due to atherosclerosis and autonomic neuropathy
2. neurologic dysfunction due to neuropathies
3. decreased NO synthesis due to NADPH depletion
single most important mechanism for erectile dysfunction in DM
impaired NO release - due to destruction of parasympathetic nerve endings and decreased synthesis
how do insulin and glucagon regulate ketoacid synthesis
low insulin and high plasma glucagon levels regulate ketoacid synthesis
what inhibits the formation of Malonyl-CoA from Acetyl-CoA
decreased insulin and increased glucagon
why can type 1 DM develop ketoacidosis
this disorder is characterized by no insulin and increased plasma glucagon levels. increased glucagon and catecholamines causes increased triglyceride breakdown and decreased fatty acid synthesis. Excess acetyl-CoA formed from triglyceride breakdown forms ketoacids. this system goes unchecked due to lack of malonyl-CoA (formed during fatty acid synthesis)
*insulin normally stimulates fatty acid synthesis
lack of insulin leads to an inability to form what product during fatty acid synthesis to keep ketogenesis in check
Malonyl-CoA
in what patient population does hyperosmolar coma occur
elderly patients with type 2 DM - associated with lower catecholamine levels and some insulin in portal tract to prevent full activation of carnitine palmitoyltransferase shuttle
precipitating events associated with both ketoacidosis and hyperosmolar coma
MI, infection, trauma, pregnancy, ethanol intoxication, medication non-compliance
why are B-blockers contraindicated in management of HTN in patient with DM
can enhance the effects of hypoglycemia drugs by inhibiting hepatic gluconeogenesis
why are K+ sparing diuretics contraindicated in management of HTN in patient with DM
in patients with DM these drugs can lead to severe cardiac arrhythmias and acidosis
fluid and electrolyte changes in diabetic ketoacidosis
1. anion-gap metabolic acidosis
2. hypovolemic hypertonicity
3. low total content of Na and K even though plasma concentration is hypertonic