Diabetes

Question 1

Islets of Langerhans

Answer 1

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)

Question 3

What stimulates insulin secretion?

Answer 3

glucose

Question 4

What is the process for insulin secretion?

Answer 4

• 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

Question 5

What inhibits glucagon secretion?

Answer 5

insulin

Question 7

When is glucagon released?

What is the target organ for glucagon?

Answer 7

when insulin levels are low

Target: liver

Question 8

How does insulin get glucose into the cell?

Answer 8

• 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.

Question 9

What happens to:

insulin

glucagon

free fatty acids

blood glucose

liver glycogen

blood ketone bodies

As hours of starvation increases?

Answer 9

Question 10

Effects of insulin

Answer 10

• 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

Question 11

Effects of lack of Insulin

primarily because of glucagon

Answer 11

• 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

Question 13

Type 1 Diabetes mellitus

Answer 13

Autoimmune destruction of Beta cells

about 10% of diabetes

Question 14

Type 2 diabetes mellitus

Answer 14

Insulin resistance

about 90%

Question 15

Mature onset diabetes of youth (MODY)

Answer 15

• 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

Question 16

Gestational diabetes

Answer 16

Any diabetes identified during pregnancy

*precursor to actual diabetes

Question 17

How does Type 1 diabetes happen?

Answer 17

• 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

Question 18

gluconeogenesis

Answer 18

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.

Question 19

What is gestational diabetes?

When does it occur?

How does this affect the baby?

Answer 19

• 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

Question 20

What is pre-diabetes?

Answer 20

• 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

Question 21

What are the acute complications of DM?

Answer 21

• hypoglycemia
• diabic ketoacidosis
• hyperosmolar hyperglycemic nonketotic syndrome

Question 22

What are the chronic complications of DM?

Answer 22

• 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

Question 23

What are the symptoms of mild hypoglycemia?

severe hypoglycemia?

Answer 23

• 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

Question 24

What is DKA?

symptoms?

Answer 24

• 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

Question 25

1 mM of glucose = _____ mg/dl

If GFR = 125 ml/min, Tmax = _____

How do you calculate how much glucose is reabsorbed?

Answer 25

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

Question 26

What causes Ketogenesis?

Answer 26

• 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

Question 27

What are the different types of ketone bodies?

Answer 27

• acetoacetate
• acetone
• B-hydroxybutyrate

Question 28

What are the major differences between HHNKS and DKA?

Answer 28

* 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

Question 29

What complications are seen with chronic diabetes? (pic)

Answer 29

everything in pic plus autonomic neuropathy

Question 30

What is Advance glycosylation End-products (AGEs)?

Answer 30

* 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

Question 31

What are the average BS goasl and A1C for diabetic patients?

Answer 31

BS 170 A1C under 7.0

Question 32

What are the different phases of diabetic retinopathy?

Answer 32

* 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

Question 33

Why is an assessment of the retina useful?

Answer 33

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

Question 34

What happens with diabetic nephropathy?

Answer 34

* leakiness of glomerular capillaries causing microalbuminuria and proteinuria * Glomerulosclerosis and tubulointerstitial fibrosis * Arteriolar sclerosis * All this leads to renal failure, HTN and cardiovascular disease

Question 35

What causes diabetic nephropathy?

Answer 35

* 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

Question 36

What is the difference between peripheral neuropathy, autonomic neuropathy, and focal neuropathy?

Answer 36

* 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.