Week 2 - Diabetes Flashcards
(163 cards)
1
Q
what is glycogen
A
- major form of stored glucose
2
Q
where is glycogen primarily found
A
- liver & muscle cells
3
Q
what is glycogenolysis
A
- the breakdown of glycogen to glucose
4
Q
what is gluconeogenesis
A
- process of producing glucose from non-carbohydrate sources
ex. proteins & fats
5
Q
what is euglycemia? what is the range?
A
- normal blood glucose
- 4-7 mmol/L
6
Q
what is glycolysis
A
- the breakdown of glucose into pyruvate
7
Q
what is the role of insulin in regulating BG
A
- released when BG is elevated
- brings BG back down to normal
8
Q
what are the counterregulatory hormones? what do they do & list them (4)
A
- hormones that oppose insulin –> they elevate BG
1. glucagon
2. epi
3. cortisol
4. GH
9
Q
what is diabetes mellitus? what does it involve?
A
- disorder of the endocrine pancreas
- involves a deficiency in insulin function
10
Q
what are 2 types of insulin dysfunction that occurs with DM
A
- decreased secretion
- tissue insensitivity (where they do not respond to insulin)
- or both
11
Q
DM is characterized by the presence of ______
A
- hyperglycemia
12
Q
in addition to hyperglycemia, diabetes can result in…. (3 things)
A
- increased catabolism of proteins & lipids
- acute emergencies
- chronic complications
13
Q
what are the endocrine pancreas cells called?
A
islets of langerhans
14
Q
what are the 2 types of islets of langerhans
A
- alpha & beta cells
15
Q
what is the function of alpha cells
A
- secrete glucagon
16
Q
what is the function of beta cells
A
- secrete insulin
17
Q
what type of hormone is insulin? how does that impact the pharmacologic administration of it?
A
- it is a protein hormone
= cannot be given orally
18
Q
insulin is manufactured exclusively by the _____
A
- islet beta cells
19
Q
what happens to insulin once it is synthesized?
A
- stored in vesicles & is secreted by exocytosis when needed
20
Q
insulin is a ____(anabolic or catabolic) hormone?
A
- anabolic
21
Q
what is the primary stimukus for insulin secretion
A
- high blood glucose
22
Q
describe how high BG stimulates insulin secretion
A
- 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
23
Q
what else is insulin secretion stimulated by?
A
- amino acids
- acetylcholine (PSNS)
24
Q
what is insulin secretion inhibited by?
A
- alpha-adrenergic stimulation (SNS)
- beta blockade
25
insulin secretion is matched to _____ & ______
- dietary intake & metabolic rate
26
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
27
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
28
insulin also promotes the uptake of... (3)
1. amino acids for protein synthesis
2. fatty acids for storage of triglycerides
3. uptake of K+ ions
29
how many types of diabetes are ther?
4
30
what is type 1 diabetes? what causes it?
- autoimmune disease
| - caused by a T-cell & antibody mediated immune assult on beta cells
31
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
32
when do we start to see symptoms acutely in type 1 diabetes
- when more than 70% of beta cell are eliminated
33
describe treatment for patients with type 1 diabetes
- life-long exogenous insulin
34
what is the typical age of onset for type 1 DM
- usually under age of 30
35
what are 2 other names for type 1 diabetes?
- insulin-dependent diabetics
- juvenille diabetes
(but these arent rlly used anymore)
36
describe what patients with type 1 diabetes typically look like?
- nonobese
| - with muscle wasting --> thin
37
what is the most common type of diabetes
- type 2
38
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
39
what are the 4 things that occur in the body with type 2 DM
1. periphal insulin resistance which leads to decreased insulin-stimulated glucose uptake at the tissues
2. hepatic glucose output is increased
3. pancreas icreases its insulin secretion (to compensate for insulin resistance)
4. altered carb absorption in the gut
40
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
41
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
42
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
43
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
44
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)
45
what is type 4 diabetes?
- gestational diabetes
| - occurs during the 3 trimester but resolves after parturition
46
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
47
what is the cause of type 4 diabetes
- attributed to increased levels of hormones with counterregulatory hormone effects
48
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
49
list 2 consequences of type 4 diabetes
- increased birth weight
| - adverse maternal & fetal outcomes
50
what is a key feature of diabetes
- fasting & postprandial hyperglycemia
51
what is the difference between fasting & postprandial BG levels
- fasting = measures BG after a 8 h or more fast
| - postprandial = measures BG after eating
52
the degree of hyperglycemia & other metabolic abnormalities depend on....
- the degree of insulin deficit
53
in addition to insulin deficiency, type 1 and type 2 diabetics also have....
- elevated glucagon levels
54
what is the glucose tolerance test?
- helpful clinical tool to evaluate fasting & postprandial hyperglycemia
55
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
56
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
57
what does pre-diabetes mean
- term used when BG is elevated but still under the criteria
ex. 10.9
58
describe the relation between glucose & proteins when BG is elevated
- when BG is elevated, glucose non-enzymatically binds to proteins = glycosylation
59
what is glycosylated hemoglobin
- HbA1C
| - hemoglobin that is binded to glucose
60
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
61
what value indicates normal vs diabetes in a glycosylated hgb test?
- <5.5% = normal
| - >6.5% = diabetes
62
what effect does insulin deficiency have on VLDL and LDLs
- elevated blood triglycerides & lipoproteins (VLDL & LDL)
63
what are the 4 main manifestations of type 1 diabetes
1. glucosuria
2. polyuria
3. polydipsia
4. polyphagia
64
what is glucosuria
- glucose in the urine
65
what is polyuria
- enhanced production of urine
66
what is polydipsia
- excessive thirst
67
what is polyphagia
- excessive hunger
68
can glucose pass thru the glomerular cap?
- yes, it is small enough to pass thru the glomerular capillaries & enter into the tubule filtrate
69
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
70
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
71
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
72
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
73
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
74
explain why we get polyphagia with diabetes
- significant calories are lost in the urine & appetite center in the hypothalamuc is activated
75
what is DKA
- acute diabetic emergency
| - diabetic ketoacidosis
76
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
77
who does DKA commonly occur in? what else might cause it?
- common in type 1 diabetes
| - or can occur with missed insulin dosage
78
why is DKA more rare in type 2 diabetes
- bc there is still some residual insulin function which inhibits profound lipolysis & ketogensis
79
what is ketogenesis
- the production of keto acids
80
what might cause DKA in type 2s (3)
- infection, trauma, and stress which can increase the body's insulin demand
81
what can happen if DKA is left untreated
- coma & death
82
what are the 3 major manifestations of DKA
1. severe hyperglycemia
2. metabolic acidosis
3. rapid respirations & fruity breath
83
what does severe hyperglycemia during DKA cause? (2)
- profound diuresis (excessive amt of urine)
| - loss of electrolytes (K+) in the urine
84
what is metabolic acidosis
- low pH due to low bicarb
85
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
86
what does dehydration from polyuria & vomiting cause during metabolic acidosis due to DKA? (2)
- hypovolemia
| - lactic acidosis
87
what causes rapid respirations during DKA
- to compensate for the metabolic acidosis, the patient will have rapid, deep repirations to try & decrease CO2
88
what are the rapid, deep respirations during DKA called?
- Kussmaul
89
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
90
describe treatment for DKA
- IV insulin therapy (since cause is absent insulin)
- fluid management (bc often dehydrated)
- K+ supplement
91
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
92
hypoglycemia is a complication of... (2)
- insulin therapy
| - sulfonylureas
93
list 4 causes of hypoglycemia
- when the drug is over-administered
- with exercise
- with fasting or a missed meal
- with excessive alcohol consumption
94
hypoglycemia is sometimes referred to as...
- insulin shock
| not used much nowadays
95
manifestations of hypoglycemia are caused by...
- increased SNS stimulation (early signs)
| - decreased CNS function (late signs)
96
why does SNS stimulation occur during hypoglycemia
- to try and raise the BG --> epi and norepi are released & are counter regulatory hormones for insulin
97
what SNS effects are seen during hypoglycemia (7)
- sweating
- tachycardia
- tremor
- anxiety
- hunger
- palpitations
- nausea
98
at what BG level do we see SNS stimulation symptoms
- below 3.5
99
what causes CNS depression in hypoglycemia
- bc the brain needs a constant supply og glucose
100
what CNS effects are seen during hypoglycemia
- confusion
- irritability
- headaches
- loss of coordination
- convulsion
- coma
101
at what BG level do we see CNS depression in hypoglycemia
- below 2.5 mmol/L
102
describe treatment for hypoglycemia
- oral or IV glucose
| - IV glucagon
103
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
104
what are the 3acute diabetic emergencies
1. diabetic ketoacidosis
2. hypoglycemia
3. hyperosmolar coma
105
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
106
why is HHNC so dangerous?
- since there is no ketoacidosis, there is no warning signs
| = can creep up on them
107
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
108
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)
109
who does a HNNC occur more commonly in
- the elderly type 2 patient
110
why dont type 2 diabetics get DKA
- residual insulin function prevent ketoacidosis
111
what is HHNC often precipitated by/contributing factors? (4)
- inadequate fluid intake during another illness
- infection
- HF
- MI
112
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
113
what does the absence of ketoacidosis with HHNC result in?
- patients are asymptomatic much longer = delayed care
114
how high can BG be with HHNC
- as high as 45-100 mmol
115
describe the treatment for HHNC
- same as DKA
116
describe the mortality rate of HHNC compared to DKA
- is 10x higher bc patients are often older & have srious complicating illnesses
117
list 4 chronic complications of diabetes
1. microvascular disease (microangiopathy)
2. macrovascular disease (macroangiopathy)
3. neuropathy
4. infections & foot ulcers
118
what are 2 kinds of microangiopathy
1. retinopathy
| 2. nephropathy
119
what are 3 kinds of macroangiopathy
1. CAD
2. cerebral artery disease
3. peripheral artery disease
120
what are 2 types of neuropathy
1. peripheral neuropathy
| 2. autonomic neuropathy
121
what is believed to reduce the incidence of chronic complications of diabetes?
- proper glycemic control
| - especially for retinopathy, nephropathy, and neuropathy
122
what is microangiopathy
- disease of small vessels
| ex. capillaries
123
what causes microangiopathy
- believed to be directly related to hyperglycemia
124
describe what occurs during microangiopathy
- basement membranes of the capillaries thicken
| - also causes increased collagen (makes it stiff) and decrease proteoglycan (makes it spongy)
125
what is AGE? how are they formed
Advanced Glycosylation End-products
| - with prolonged hyperglycemia, glucose irreversibly binds to proteins to create them
126
describe how AGEs contribute to microangiopathy (4)
cause:
- accumulation of basement membrane proteins
- capture LDL
- release inflammatory cytokines
- can predispose to microaneuryms
127
what is the leading cause of adult-onset blindness?
- diabetes
128
diabetic retinopathy ocurrs in __ stages; what are they
1. nonproliferative
| 2. proliferative
129
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
130
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
131
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
132
what does proliferative retinopathy result in
1. the tension on the retina can cause retinal detachment
| 2. blindness
133
which type of diabetes dooes proliferative retinopathy occur more frequently in?
type 1 diabetes
134
diabetes is the leading cause of end-stage chronic ____ ____ requiring dialysis & transplant
- renal failure
135
diabetic nephropathy involves...
- the glomerular capillaries
136
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
137
what is an early sign of nephropathy
- microalbuminuria
138
what occurs later in nephropathy
- glomerulosclerosis
| - the process continues, the glomerulus is destroyed & the nephron is lost
139
what is glomerulosclerosis
- fibrosis & thickening of the glomelular capillary basement membrane
140
what does the loss of nephrons cause ?
- the loss becomes so great that renal failure occurs
141
describe treatment of nephropathy
- ACE inhibitors
- ARBs
- SGLT2 inhibitors
142
why do we give ACE inhibitors and ARBs for nephropathy
- they provide renal protection
| - they decrease glomerular filtration pressure which decreases sclerosis
143
what is macroangiopathy? what does this lead to in diabetes
- disease of large blood vessels
| - in diabetes this leads to accelerated atherosclerosis
144
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
145
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
146
list 3 ways diabetes can increase the risk of atherosclerosis
1. high levels of BG create AGEs which can damage the endothelium directly & recruit inflammatory cells (macrophages & cytokines)
2. deficiency in insulin increases blood VLDL & decreases clearance of VLDL. also increases LDL
3. incidence of hypertension is higher in diabetes
147
describe treatment for macroangiopathy
- statins (to control LDL and VLDL)
| - bp meds (ACE inhibitors & ARBs)
148
what is neuropathy
- group of diseases resulting from damaged or malfunctioning of nerves
149
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
150
how could microangiopathy cause neuropathy
- impairs nutrient delivery to neurons
| = demylination & loss of nerve fibers
151
what is sorbitol
- type of sugar
152
what is the polyol pathway
- this is a 2 step process that converts glucose into fructose
glucose --> sorbitol --> fructose
153
what are 2 types of neuropathy
1. symmetric distal polyneuropathy
| 2. autonomic neuropathy
154
what causes symmetric distal neuropathy
- demyelination of distal peripheral nerves
155
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
156
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
157
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
158
what is autonomic neuropathy
- neuropathy which effects autonomic (SNS or PSNS) innervation of many different systems
159
what are signs of cardiovascular involvement for autonomic neuropathy
- fixed, resting tachycardia
| - orthostatic hypotension
160
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
161
what is incomplete emptying of the bladder due to autonomic neuropathy called
- neurogenic bladder
162
describe glucogan & epi during autonomic neuropathy
- decreased glucagon & epi response to hypoglycemia
163
what is another manifestation of autonomic neuropathy
- exertional hypoglycemia
