Week 2 - Diabetes Flashcards
what is glycogen
- major form of stored glucose
where is glycogen primarily found
- liver & muscle cells
what is glycogenolysis
- the breakdown of glycogen to glucose
what is gluconeogenesis
- process of producing glucose from non-carbohydrate sources
ex. proteins & fats
what is euglycemia? what is the range?
- normal blood glucose
- 4-7 mmol/L
what is glycolysis
- the breakdown of glucose into pyruvate
what is the role of insulin in regulating BG
- released when BG is elevated
- brings BG back down to normal
what are the counterregulatory hormones? what do they do & list them (4)
- hormones that oppose insulin –> they elevate BG
1. glucagon
2. epi
3. cortisol
4. GH
what is diabetes mellitus? what does it involve?
- disorder of the endocrine pancreas
- involves a deficiency in insulin function
what are 2 types of insulin dysfunction that occurs with DM
- decreased secretion
- tissue insensitivity (where they do not respond to insulin)
- or both
DM is characterized by the presence of ______
- hyperglycemia
in addition to hyperglycemia, diabetes can result in…. (3 things)
- increased catabolism of proteins & lipids
- acute emergencies
- chronic complications
what are the endocrine pancreas cells called?
islets of langerhans
what are the 2 types of islets of langerhans
- alpha & beta cells
what is the function of alpha cells
- secrete glucagon
what is the function of beta cells
- secrete insulin
what type of hormone is insulin? how does that impact the pharmacologic administration of it?
- it is a protein hormone
= cannot be given orally
insulin is manufactured exclusively by the _____
- islet beta cells
what happens to insulin once it is synthesized?
- stored in vesicles & is secreted by exocytosis when needed
insulin is a ____(anabolic or catabolic) hormone?
- anabolic
what is the primary stimukus for insulin secretion
- high blood glucose
describe how high BG stimulates insulin secretion
- glucose enters B cells & is converted into ATP thru glycolysis
- increased cellular ATP closes ATP sensitive K+ channels (remember, K+ flows out) = membrane potential becomes more positive
- this opens voltage-gated Ca++ channels which triggers release of insulin
what else is insulin secretion stimulated by?
- amino acids
- acetylcholine (PSNS)
what is insulin secretion inhibited by?
- alpha-adrenergic stimulation (SNS)
- beta blockade
insulin secretion is matched to _____ & ______
- dietary intake & metabolic rate
describe the effects of glucagon: what stimulates the release? what happens in the body?
- low blood sugar = promotes glucagon release
- glucagon acts on the liver to promote glycogen breakdown into glucose
= raised blood sugar
describe the effects of insulin: what stimulates the release? what happens in the body?
- high BG = insulin release
- this stimulates (1) glucose uptake from the blood into cells and (2) glycogen formation to be stored for later
= decreased BG
insulin also promotes the uptake of… (3)
- amino acids for protein synthesis
- fatty acids for storage of triglycerides
- uptake of K+ ions
how many types of diabetes are ther?
4
what is type 1 diabetes? what causes it?
- autoimmune disease
- caused by a T-cell & antibody mediated immune assult on beta cells
how long does the attack on beta cells last during type 1 diabetes? what effect does this have on insulin?
- typically does not stop until all beta cella are irreversibly lost
= insulin secretion virtually nonexistent
when do we start to see symptoms acutely in type 1 diabetes
- when more than 70% of beta cell are eliminated
describe treatment for patients with type 1 diabetes
- life-long exogenous insulin
what is the typical age of onset for type 1 DM
- usually under age of 30
what are 2 other names for type 1 diabetes?
- insulin-dependent diabetics
- juvenille diabetes
(but these arent rlly used anymore)
describe what patients with type 1 diabetes typically look like?
- nonobese
- with muscle wasting –> thin
what is the most common type of diabetes
- type 2
what is the cause of type 2 diabetes? why is this thought to be the cause?
- unknown
- thought to be a combo of genetic & lifestyle factors
- 80% of patients are obese (particular abdominal obesity) and 80% have family history
what are the 4 things that occur in the body with type 2 DM
- periphal insulin resistance which leads to decreased insulin-stimulated glucose uptake at the tissues
- hepatic glucose output is increased
- pancreas icreases its insulin secretion (to compensate for insulin resistance)
- altered carb absorption in the gut
describe the effect of type 2 DM on the liver
- hepatic glucose output is increased = liver is constantly exporting glucose without any response to insulin
describe the changes seen in the pancreas during type 2 DM to compensate for insulin resistance; what does this cause?
- increases its secretion of insulin
- causes hyperinsulinemia in early stages
- over time, it becomes exhausted which causes defective insulin secretion & diabetes
what is the age of onset for type 2 DM
- typically adult
- becoming common in adolescence
- bc of the gradual onset, many cases go undiagnosed
describe treatment for patients with type 2 DM
- many do not require insulin treatment bc some residual insulin function remains
- main is diet & exercise changes
what is type 3 diabetes
- miscellaneous category which represents many causes of primary or secondary diabetes
(note: i did not list all the examples bc there is way too many, so see notes for that)
what is type 4 diabetes?
- gestational diabetes
- occurs during the 3 trimester but resolves after parturition
describe the risk of type 4 diabetes and how it changes with pregnancies
- occurs in 5-10% of pregnant women
- risk increases with subsequent pregnancies
what is the cause of type 4 diabetes
- attributed to increased levels of hormones with counterregulatory hormone effects
describe the risk of type 2 diabetes for a pt with type 4
- type 4s have an increased risk of developing type 2 in future, especially obese women
list 2 consequences of type 4 diabetes
- increased birth weight
- adverse maternal & fetal outcomes
what is a key feature of diabetes
- fasting & postprandial hyperglycemia
what is the difference between fasting & postprandial BG levels
- fasting = measures BG after a 8 h or more fast
- postprandial = measures BG after eating
the degree of hyperglycemia & other metabolic abnormalities depend on….
- the degree of insulin deficit
in addition to insulin deficiency, type 1 and type 2 diabetics also have….
- elevated glucagon levels
what is the glucose tolerance test?
- helpful clinical tool to evaluate fasting & postprandial hyperglycemia
describe how the glucose tolerance test works
- the pt fasts overnight & then we take their fasting BG
- the pt then consumes a 75g glucose load
- blood is then tested every 1/2 hour for 2-3 hours
what values indicate a positive glucose tolerance test
- when the fasting BG is greater then 7 mmol OR
- if the postprandial BG exceeds 11.1 during the 2 hr followup
what does pre-diabetes mean
- term used when BG is elevated but still under the criteria
ex. 10.9
describe the relation between glucose & proteins when BG is elevated
- when BG is elevated, glucose non-enzymatically binds to proteins = glycosylation
what is glycosylated hemoglobin
- HbA1C
- hemoglobin that is binded to glucose
why do we measure the amount of glycosylated hgb?
- way to determine if BG has been elevated any tme over the previous 90-120 days
what value indicates normal vs diabetes in a glycosylated hgb test?
- <5.5% = normal
- >6.5% = diabetes
what effect does insulin deficiency have on VLDL and LDLs
- elevated blood triglycerides & lipoproteins (VLDL & LDL)
what are the 4 main manifestations of type 1 diabetes
- glucosuria
- polyuria
- polydipsia
- polyphagia
what is glucosuria
- glucose in the urine
what is polyuria
- enhanced production of urine
what is polydipsia
- excessive thirst
what is polyphagia
- excessive hunger
can glucose pass thru the glomerular cap?
- yes, it is small enough to pass thru the glomerular capillaries & enter into the tubule filtrate
describe the reabsorption of glucose under normal conditions
- normally, all of the filtered glucose is reabsorbed back into the blood by the sodium-dependent glucose transporter (SGLT) = none in the urine
how does the reabsorption of glucose effect the reabsorption of water under normal conditions
- as osmotically active molecules (Na and glucose) are removed from the filtrate, water is passively reabsorbed via osmosis
explain why we get glucosuria with diabetes
- with hyperglycemia, the amount of filtered glucose is greater than the tubules capacity to reabsorb (not enough SGLT)
= some glucose remains in the filtrate & is excreted in the urine
explain why we get polyuria with diabetes
- due to glycosuria, there is a higher conc of glucose than normal in the filtrate
- glucose is an osmotic molecule –> it attracts water to itself
= impairs the osmosis of water where water less water is reabsorbed & causes osmotic diuresis
explain why we get polydipsia with diabetes
- due to polyuria, we are losing more water in the urine = dehydration = stimulated thirst response in the hypothalamuc
explain why we get polyphagia with diabetes
- significant calories are lost in the urine & appetite center in the hypothalamuc is activated
what is DKA
- acute diabetic emergency
- diabetic ketoacidosis
what occurs in DKA
- absence of insulin –> uncontrolled lipolysis & ketogenesis
- this results in the formation of keto acids which enter the blood, accumulate, and causes metabolic acidosis
who does DKA commonly occur in? what else might cause it?
- common in type 1 diabetes
- or can occur with missed insulin dosage
why is DKA more rare in type 2 diabetes
- bc there is still some residual insulin function which inhibits profound lipolysis & ketogensis
what is ketogenesis
- the production of keto acids
what might cause DKA in type 2s (3)
- infection, trauma, and stress which can increase the body’s insulin demand
what can happen if DKA is left untreated
- coma & death
what are the 3 major manifestations of DKA
- severe hyperglycemia
- metabolic acidosis
- rapid respirations & fruity breath
what does severe hyperglycemia during DKA cause? (2)
- profound diuresis (excessive amt of urine)
- loss of electrolytes (K+) in the urine
what is metabolic acidosis
- low pH due to low bicarb
how does DKA cause metabolic acidosis?
- uncontrolled ketogensis results in the production of keto acids
- the keto acids react with bicarb to result in decreased bicarb
- the keto acids also accumulate which contributes to low pH
what does dehydration from polyuria & vomiting cause during metabolic acidosis due to DKA? (2)
- hypovolemia
- lactic acidosis
what causes rapid respirations during DKA
- to compensate for the metabolic acidosis, the patient will have rapid, deep repirations to try & decrease CO2
what are the rapid, deep respirations during DKA called?
- Kussmaul
what causes the fruity breath during DKA
- ketones are spontaneously converted to acetone in the blood
- the acetone vaporizes in the alveoli & gives the breath a fruity odor
describe treatment for DKA
- IV insulin therapy (since cause is absent insulin)
- fluid management (bc often dehydrated)
- K+ supplement
why is a K+ supplement also required for treatment of DKA
- insulin treatment will increase the cellular uptake
- K+ is lost in the urine & vomit
- is diluted with the fluid treatment
hypoglycemia is a complication of… (2)
- insulin therapy
- sulfonylureas
list 4 causes of hypoglycemia
- when the drug is over-administered
- with exercise
- with fasting or a missed meal
- with excessive alcohol consumption
hypoglycemia is sometimes referred to as…
- insulin shock
not used much nowadays
manifestations of hypoglycemia are caused by…
- increased SNS stimulation (early signs)
- decreased CNS function (late signs)
why does SNS stimulation occur during hypoglycemia
- to try and raise the BG –> epi and norepi are released & are counter regulatory hormones for insulin
what SNS effects are seen during hypoglycemia (7)
- sweating
- tachycardia
- tremor
- anxiety
- hunger
- palpitations
- nausea
at what BG level do we see SNS stimulation symptoms
- below 3.5
what causes CNS depression in hypoglycemia
- bc the brain needs a constant supply og glucose
what CNS effects are seen during hypoglycemia
- confusion
- irritability
- headaches
- loss of coordination
- convulsion
- coma
at what BG level do we see CNS depression in hypoglycemia
- below 2.5 mmol/L
describe treatment for hypoglycemia
- oral or IV glucose
- IV glucagon
what can cause a reduced SNS response in hypoglycemia (2)? what are the consequences of this?
- repeated bouts of hypoglycemia or beta-blocker can reduce the SNS response
= become desensitized & get no warning signs
what are the 3acute diabetic emergencies
- diabetic ketoacidosis
- hypoglycemia
- hyperosmolar coma
what causes a hyperosmolar coma
- as BG increases, we lose glucose & water in the urine and we become profoundly dehydrated
- this dehydration & hyperglycemia causes hyperosmolarity (more solute than water)
- this dehydration sucks water out of cells thru osmosis which is typically fine, except for in the brain
- the dehydration causes cellular dehydration of CNS neurons which will impair cognitive function
why is HHNC so dangerous?
- since there is no ketoacidosis, there is no warning signs
= can creep up on them
describe hyperosmolar coma in type 1 vs 2 diabetics
- hyperosmolar comas occur type 1 diabetics due to DKA
- in type 2s severe coma can occur in the absence of ketosis
what is a hyperosmolar hyperglycemic state (HHS)? what can it progress to?
- a hyperosmolar hyperglycemic state is when someone has super high BG & is very dehydrated, causing hyperosmolarity and beginning to lose consciousness
- can progress to a hyperosmolar hyperglycemic nonketotic coma (HHNC)
who does a HNNC occur more commonly in
- the elderly type 2 patient
why dont type 2 diabetics get DKA
- residual insulin function prevent ketoacidosis
what is HHNC often precipitated by/contributing factors? (4)
- inadequate fluid intake during another illness
- infection
- HF
- MI
why do the contributing factors often precipiate HHNC?
- these increase CRH release & can compromise bp
- the low bp can cause decreased GFR which means less glucose is lost in the urine, resulting in an even higher osmolarity
what does the absence of ketoacidosis with HHNC result in?
- patients are asymptomatic much longer = delayed care
how high can BG be with HHNC
- as high as 45-100 mmol
describe the treatment for HHNC
- same as DKA
describe the mortality rate of HHNC compared to DKA
- is 10x higher bc patients are often older & have srious complicating illnesses
list 4 chronic complications of diabetes
- microvascular disease (microangiopathy)
- macrovascular disease (macroangiopathy)
- neuropathy
- infections & foot ulcers
what are 2 kinds of microangiopathy
- retinopathy
2. nephropathy
what are 3 kinds of macroangiopathy
- CAD
- cerebral artery disease
- peripheral artery disease
what are 2 types of neuropathy
- peripheral neuropathy
2. autonomic neuropathy
what is believed to reduce the incidence of chronic complications of diabetes?
- proper glycemic control
- especially for retinopathy, nephropathy, and neuropathy
what is microangiopathy
- disease of small vessels
ex. capillaries
what causes microangiopathy
- believed to be directly related to hyperglycemia
describe what occurs during microangiopathy
- basement membranes of the capillaries thicken
- also causes increased collagen (makes it stiff) and decrease proteoglycan (makes it spongy)
what is AGE? how are they formed
Advanced Glycosylation End-products
- with prolonged hyperglycemia, glucose irreversibly binds to proteins to create them
describe how AGEs contribute to microangiopathy (4)
cause:
- accumulation of basement membrane proteins
- capture LDL
- release inflammatory cytokines
- can predispose to microaneuryms
what is the leading cause of adult-onset blindness?
- diabetes
diabetic retinopathy ocurrs in __ stages; what are they
- nonproliferative
2. proliferative
describe what occurs during the nonproliferative stage of retinopathy
- microaneurysms occur in the retinal blood vessels due to microangiopathy & loss of pericytes
- aneurysms become permeable or rupture = retinal exudate formation & hemorrhage = cells beyond the rupture do not get any blood
what are the consequences of the nonproliferative stage of retinopathy
- retinal ischemia & infarction due to lack of blood flow
- visual impairment such as blind spots due to healing with scar tissue & leakage of fluid
describe what occurs during the proliferative stage of retinopathy
- retinal ischemia stimulates angiogenesis within the retina
- infarction of the retina causes fibrous scar tissue to replace necrotic neural tissue
- as fibrous tissue accumulates, it pulls back the retina & creates tension
what does proliferative retinopathy result in
- the tension on the retina can cause retinal detachment
2. blindness
which type of diabetes dooes proliferative retinopathy occur more frequently in?
type 1 diabetes
diabetes is the leading cause of end-stage chronic ____ ____ requiring dialysis & transplant
- renal failure
diabetic nephropathy involves…
- the glomerular capillaries
what occurs in the early stages of nephropathy
- loss of negatively charged proteoglycan in the basement membrane allows small amount of albumin to filter into the tubules & enter the urine
what is an early sign of nephropathy
- microalbuminuria
what occurs later in nephropathy
- glomerulosclerosis
- the process continues, the glomerulus is destroyed & the nephron is lost
what is glomerulosclerosis
- fibrosis & thickening of the glomelular capillary basement membrane
what does the loss of nephrons cause ?
- the loss becomes so great that renal failure occurs
describe treatment of nephropathy
- ACE inhibitors
- ARBs
- SGLT2 inhibitors
why do we give ACE inhibitors and ARBs for nephropathy
- they provide renal protection
- they decrease glomerular filtration pressure which decreases sclerosis
what is macroangiopathy? what does this lead to in diabetes
- disease of large blood vessels
- in diabetes this leads to accelerated atherosclerosis
explain why macroangiopathy occurs with diabetes
- remember, with prolonger hyperglycemia, glucose binds to proteins to create advanced glycosylation end-products
- AGEs within blood vessels capture LDL, activate macrophages & inflammatory cytokines, and promote prolieration of vascular cells
- all of which accelerate athersclerosis
what conditions does macroangiopathy cause?
- prevalence of coronary heart disease is increased 2-4 times higher
- up to 80% of diabetics will die from athersclerosis related illness
- increased risk of stroke (CVA) and peripheral vascular disease
list 3 ways diabetes can increase the risk of atherosclerosis
- high levels of BG create AGEs which can damage the endothelium directly & recruit inflammatory cells (macrophages & cytokines)
- deficiency in insulin increases blood VLDL & decreases clearance of VLDL. also increases LDL
- incidence of hypertension is higher in diabetes
describe treatment for macroangiopathy
- statins (to control LDL and VLDL)
- bp meds (ACE inhibitors & ARBs)
what is neuropathy
- group of diseases resulting from damaged or malfunctioning of nerves
what is the cause of diabetic neuropathy?
- largely unknown
- believed to be combined consequences of microangiopathy & accumulation of sorbitol within neurons via the polyol pathway
how could microangiopathy cause neuropathy
- impairs nutrient delivery to neurons
= demylination & loss of nerve fibers
what is sorbitol
- type of sugar
what is the polyol pathway
- this is a 2 step process that converts glucose into fructose
glucose –> sorbitol –> fructose
what are 2 types of neuropathy
- symmetric distal polyneuropathy
2. autonomic neuropathy
what causes symmetric distal neuropathy
- demyelination of distal peripheral nerves
describe manifestations of symmetric distal neuropathy
- symmetric sensory loss in the lower extremities
- numbness & tingling often precede parathesia
- symptoms then move proximally & eventually effect the hands
what is stocking distribution
- description of the progression of neuropathy symptoms in the feet which resembles how you could put a on a sock
- starts at the toes and works its way up
what is glove distribution
- description of the progression of neuropathy symptoms in the hands which resembles how you would put on a glove
- starts at the fingers & works its way up
what is autonomic neuropathy
- neuropathy which effects autonomic (SNS or PSNS) innervation of many different systems
what are signs of cardiovascular involvement for autonomic neuropathy
- fixed, resting tachycardia
- orthostatic hypotension
what are signs of genitourinary involvement for autonomic neuropathy
- incomplete emptying of the bladder which causes overflow incontinence
- predisposition to a UTI
- 50% of diabetic men suffer from impotence
- female sexual dysfunction –> failure to meet orgasm
what is incomplete emptying of the bladder due to autonomic neuropathy called
- neurogenic bladder
describe glucogan & epi during autonomic neuropathy
- decreased glucagon & epi response to hypoglycemia
what is another manifestation of autonomic neuropathy
- exertional hypoglycemia
