Insulin and Diabetes

Question 1

Insulin not orally bioavailable. What is the physiological problem with insulin injections?

Answer 1

Pancreatic insulin brought directly to liver to inhibit glucose production. Much higher concentration than is achieved via injection

Question 2

Physiologic basal insulin release

Answer 2

~50 pM

Question 3

Physiologic prandial insulin release

Answer 3

~500 pM

Question 4

PHSL fasting glucose level

Answer 4

70-100 mg/dL

Question 5

PHSL fasting glucagon

Answer 5

High glucagon –>glycogenolysis and gluconeogenesis

Question 6

PHSL post-prandial glucose level

Answer 6

130 mg/dL

• promotes insulin secretion
• Glc uptake in liver, skeletal muscle, and adipose

Question 7

Insulin secretion stimulated by____(5x)

Answer 7

1. Glucose
2. Glucagon-like peptide (GLP-1)
3. Glucose-dependent insulinotropic polypeptide (GIP)
4. Cholinergic nerves
5. Medications

Question 8

How does insulin promote Glc uptake

Answer 8

stimulates phosphorylation to Glc-6-p

–>glycogen storage, etc

Question 9

Rapid acting AA substitutions

Answer 9

Aspart
GluLisine
LisPro

Question 10

Short acting substitution

Answer 10

N/a

Question 11

Intermediate -acting formulation

Answer 11

NPH (Neutral protamine hagedorn)

Question 12

Long acting substitutions

Answer 12

Detemir

Glargine

Question 13

Regular insulin

Answer 13

(Humulin R, Novolin R)

Question 14

Humulin-R/Novolin-R
Effect
Peak
Duration

Answer 14

30 min
2-3 h
5-8 h

Question 15

How are humulin-R and novolin-R release slowed?

Answer 15

high concentration w/ Zn center –> aggregation

Question 16

Humulin-R and novolin-R administration time?

Answer 16

30-45 min pre-meal

Question 17

Primary differences between Regular and NPH

Answer 17

NPH - Lower peak but longer duration.

Still lower incidence of hypoglycemia (near basal)

Question 18

Rapid acting administration time

LisPro, Aspart, GluLisine

Answer 18

15 min or less pre meal

Question 19

Lispro (humalog) structural difference and effect

Answer 19

pro/lys 28/29 swapped.

Does not self associate –> dissociates into monomers and absorbed faster and to completeness faster

Question 20

which insulin formulation is best for continuous SC infusion pumps?

Answer 20

Rapid acting

Question 21

Rapid acting duration

Answer 21

Max ~5 h

Question 22

Intermediate Acting Insulins

Answer 22

Humulin-N
Novolin-N
Neutral protamine hagedorn (NPH)

Question 23

NPH formulation

Answer 23

Suspension of native insulin complexed w/ zinc and protamine

Question 24

How is NPH insulin delayed

Answer 24

complexed with (+) charged protamine, proteolytic tissue enzyme must degrade protamine

Question 25

NPH onset Duration

Answer 25

2-5 h | 4-12 h

Question 26

NPH dose and activity profile

Answer 26

small doses have earlier peaks and shorter duration

Question 27

NPH and variability

Answer 27

HIGH up to 50%

Question 28

Rapid acting variability

Answer 28

LOW ~5%

Question 29

Long-acting Insulin

Answer 29

Glargine (Lantus) | Detemir (Levemir)

Question 30

Glargine (Lantus) | Formulation

Answer 30

pH4 stabilizes hexamer | neutral pH on injection -->aggregation

Question 31

Glargine(Lantus) | PK PD

Answer 31

Prolonged, peakless, predictable absorption Better Q24h coverage lower risk of hypoglycemia Absorption not changed by site or exercise

Question 32

Detemir (Levemir) | Formulation

Answer 32

Removed threonine added myristic acid | Myristoylation increases self-aggregation and albumim binding

Question 33

Detemir (Levemir) PK/PD

Answer 33

slow absorption and reduced hypoglycemia compared to NPH Duration (high dose) ~23h Duration (Low dose)

Question 34

Detemir's friends

Answer 34

Cannot mix Detemir (Levemir) with other insulins

Question 35

HumuLIN 70/30

Answer 35

70% NPH | 30% Humulin-R

Question 36

General Insulin Absorption

Answer 36

More rapid if IM than SC SC variable w/ temp/exercise Site variation: faster in arm

Question 37

Average insulin dose in T1DM

Answer 37

0.7 u/kg/d

Question 38

T1DM Initial dose | *w/ketosis, during illness

Answer 38

0. 3-0.5 u/kg/d | * 1-1.5 u/kg

Question 39

T2DM with insulin resistance

Answer 39

0.7-1.5 u/kg

Question 40

Most common adverse effect with insulin therapy

Answer 40

Hypoglycemia - Inappropriately large dose - temporal mismatch, tpeak and food intake - increased sensitivity: adrenal or pituitary insufficiency - Increased insulin-independent glucose uptake (exercise)

Question 41

Mild Hypoglycemia symptoms | 60-80 mg/dL

Answer 41

60-80 mg/dL: - SNS; sweating, palpations, tremor, anxiety - PNS; Nausea, hunger

Question 42

Severe Hypoglycemia

Answer 42

Neuroglypenic; difficulty concentrating, confusion, weakness, drowsiness, dizziness, blurred vision, loss of conciousness -If untreated: Convulsions, coma, death

Question 43

Hypoglycemia Treatment

Answer 43

-Glc Admin Mild: Dex tabs, Glc gel, Sugary bev/food Severe: 20-50 no IV, 1 mg glucagon SC or IM restores conciousness w/in 15 min

Question 44

Insulin treatment of DKA

Answer 44

Insulin IV - prevents lipolysis and AA catabolism - IV fluid and electrolyte replacement, - careful monitoring

Question 45

Insulin Treatment Hyperglycemic Hyperosmolar State >600 mg/dL Osmotic diuresis Hemo-conentration

Answer 45

- Insulin admin IV (regular w/ rapid acting) - IV fluid and electrolyte replacement - Careful monitoring of clinical status