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