Diabetes Flashcards
1
Q
Islets of Langerhans
A
Group of Endocrine cells
- alpha- releases glucagon (18-20% of endocrine cells)
- beta- releases insulin (73-75% of endocrine cells)
- delta- somatostatin (4-6% of endocrine cells)
3
Q
What stimulates insulin secretion?
A
glucose
4
Q
What is the process for insulin secretion?
A
- glucose enters beta cell through GLUT2 transporter by diffusion
- glucose goes through glycolysis, turning ADP into ATP
- ATP is the ligand for the K channel. K channel closes.
- cell starts to depolarize with K channel closed
- Once cell depolarizes to threshold of voltage gated calcium channel, Ca channel opens and Ca rushes in
- Calcium causes release of insulin vesicles and the making of more insulin
5
Q
What inhibits glucagon secretion?
A
insulin
7
Q
When is glucagon released?
What is the target organ for glucagon?
A
when insulin levels are low
Target: liver
8
Q
How does insulin get glucose into the cell?
A
- insulin binds to the GPCR
- GLUT4 transporter is recruited to the plasma membrane and facilitates glucose into the cell along with amino acids, K, Mg, and Phosphate.
9
Q
What happens to:
insulin
glucagon
free fatty acids
blood glucose
liver glycogen
blood ketone bodies
As hours of starvation increases?
A
10
Q
Effects of insulin
A
- decreased appetite
- decreased glucagon
- increased glucose uptake by muscles and fat
- increased glycolysis
- increased glycogen synthesis
- increased triglyceride synthesis
- increased amino acid uptake
- increased protein synthesis
11
Q
Effects of lack of Insulin
primarily because of glucagon
A
- increased appetite
- increased glucagon
- decreased glucose uptake by muscle and fat
- increase blood glucose
- increase gluconeogenesis
- increased lipolysis
- increased protein breakdown
- increase glycogenolysis
- Increase ketone body production
- decrease protein synthesis
13
Q
Type 1 Diabetes mellitus
A
Autoimmune destruction of Beta cells
about 10% of diabetes
14
Q
Type 2 diabetes mellitus
A
Insulin resistance
about 90%
15
Q
Mature onset diabetes of youth (MODY)
A
- Genetic defect in insulin production or release
- insulin will help, but not as much as oral meds that increas K channel sensitivity
- about 2% of young diabetics
16
Q
Gestational diabetes
A
Any diabetes identified during pregnancy
*precursor to actual diabetes
17
Q
How does Type 1 diabetes happen?
A
- Pancreatic Beta cells get destroyed.
- person gets some kind of bug
- body makes antigen
- proteins coming off the beta cell matches antigens too closely
- Beta cell gets attacked by immune system
- body continues to make the beta cells, but they all get killed by the antibodies
18
Q
gluconeogenesis
A
making glucose from non carbohydrates; lactate, glycerol, amino acids
*Important to get glucose to the brain. Everything else can survive on ketones. Happens in liver.
19
Q
What is gestational diabetes?
When does it occur?
How does this affect the baby?
A
- During pregnancy, hormonal changes can cause impaired insulin sensitivity
- diagnosis cutoffs are lower than with normal DM
- Occurs btw weeks 24 and 28 of pregnancy
- If poorly controlled, glucose can cross the placenta, giving the baby hyperglycemia
- these babies have a higher risk for developing HTN and cardiovascular disease
- dangerous for mother and baby
- mother is 2-3x more likely to get gestational diabetes in future pregnancies
20
Q
What is pre-diabetes?
A
- aka impaired fasting glucose and/or impaired glucose tolerance
- IFG is blood glucose level 100-125 after an overnight fast, not high enough to be considered diabetic
- IGT is glucose level of 140-199 after 2 hour oral glucose tolerance test
- about 40% of US adults ages 40-74 have pre-diabetes
21
Q
What are the acute complications of DM?
A
- hypoglycemia
- diabic ketoacidosis
- hyperosmolar hyperglycemic nonketotic syndrome
22
Q
What are the chronic complications of DM?
A
- Hyperglycemia and non-enzymatic glycosylation
- advanced glycosylation end-products (AGEs)
- Microvascular disease
- diabetic retinopathy, nephropathy, cardiomyopathy
- Macrovascular disease
- CAD, stroke, PVD
- Increased activity of polyol/sorbitol pathway (ETOH produced by glucose)
- diabetic neuropathy
- cataracts
- gloucoma???
- infection
23
Q
What are the symptoms of mild hypoglycemia?
severe hypoglycemia?
A
- mild: <70 mg/dl
- hunger
- shakiness
- paleness
- blurry vision
- sweating
- anxiety
- severe: <20 mg/dl
- extreme tiredness
- confusion
- dazed appearance
- sz
- unconsciousness leading to coma and death
24
Q
What is DKA?
symptoms?
A
- Life threatening hyperglycemia, can cause brain damage
- Ketosis results from breakdown of fat and protein when cells can’t get glusose
- symptoms
- fruity acetone breath
- kussmaul breathing
- dehydration
- N/v abdominal pain
- altered LOC, weakness, paresthesia
- severe hyperglycemia, electrolyte imbalance, metabolic acidosis, ketones in urine
25
Q
1 mM of glucose = _____ mg/dl
If GFR = 125 ml/min, Tmax = _____
How do you calculate how much glucose is reabsorbed?
A
18
300 mg/min
Filtered load = BS * GFR
Normal GFR = 125
*if calculated value is higher than 300, that much is not reabsorbed and will be excreted in the urine
26
Q
What causes Ketogenesis?
A
- Very high rates of gluconeogenesis will deplete oxaloacetate and slow the entry of acetylCoA into the Krebs cycle
- Instead, acetyl-CoA will be converted into ketone bodies for use by:
- brain
- heart
- kidney
- liver
27
Q
What are the different types of ketone bodies?
A
- acetoacetate
- acetone
- B-hydroxybutyrate
28
What are the major differences between HHNKS and DKA?
* HHNKS is more of an osmolarity problem than an acidotic problem (pH of about 7.3)
* due to the high glucose in the blood, raising osmolarity and pulling water out of tissues like brain
* HHNKS:
* very high BS
* high osmolarity
* normalish pH
* only slightly elevated ketones and B-hydroybutyrate
* elevated C-peptide
* DKA
* elevated glucose, but not as high as HHNKS
* elevated osmolarity, but not as high as HHNKS
* much more acidotic (7.12)
* much higher B-hydroxybuterate and other ketones
* low C-peptide and elevated anion gap
29
What complications are seen with chronic diabetes?
(pic)
everything in pic plus autonomic neuropathy
30
What is Advance glycosylation End-products (AGEs)?
* When glucose binds to a protein causing crosslinking
* this is seen normally with aging, but happens at an increased rate for diabetics
* It is still reversible as a schiff base and an Amadori product, but then two proteins crosslink together, it is irreversible
* causes stiff valves, arteries, wrinkles and everything else associated with aging
31
What are the average BS goasl and A1C for diabetic patients?
BS 170
A1C under 7.0
32
What are the different phases of diabetic retinopathy?
* Background diabetic retinopathy (earliest phase)
* the arteries in the retina become weakened and leak, forming small, dot-like hemorrhages
* Proliferative diabetic retinopathy (later stage)
* circulation problems cause areas of the retina to become oxygen-deprived/ischemic.
* new, fragile vessels develop to improve oxygenation to the retina, but they hemorrhage easily
* After I typed this all up I read my note that says "dont worry about different stages" so dont spend too much time memorizing this crap
33
Why is an assessment of the retina useful?
Because if the microvasculature of the retina looks good, then most likely so does the microvasculature everywhere else, like the heart and autonomic nervous system
34
What happens with diabetic nephropathy?
* leakiness of glomerular capillaries causing microalbuminuria and proteinuria
* Glomerulosclerosis and tubulointerstitial fibrosis
* Arteriolar sclerosis
* All this leads to renal failure, HTN and cardiovascular disease
35
What causes diabetic nephropathy?
* Aggregates of proteins and collagen form nodules is the glomerulus faster than macrophages can clear keep up
* this decreases surface area and decreases GFR
* ppl with type 1 and type 2 DM are at risk
* greatest progression seen in pts with poor glucose control
* Once proteinuria is noted, main treatment is BP control under 130/80
36
What is the difference between peripheral neuropathy, autonomic neuropathy, and focal neuropathy?
* peripheal neuropathy- causes pain or loss of feeling in extremeties
* blisters and sores appear, become easily infected, pt doesnt notice the pain
* Autonomic neuropathy-- causes changes to digestion, bowel/bladder function, sexual response, perspiration, and can affect the heart and control blood pressure
* Focal neuropathy- results in sudden weakness of one nerve or a group of nerves, causing muscle weakness or pain. Can happen to any nerve in the body.
