Diabetes Pharamcology

Question 1

What glucose transport protein does insulin binding up regulate?

Answer 1

GLUT4 on peripheral cells

- induces facilitated diffusion of glucose into cells

Question 2

How does polyphagia occur in diabetes mellitus?

Answer 2

Improper insulin release results in poor GLUT4 upregulation which makes the cells think they are starving and signals ghrelin release from hypothalamus as well as lipolysis

This leads to polyphagia with weight loss

Question 3

What are the 2 potential mechanisms for pathogenesis in insulin resistance

Answer 3

1) ectopic accumulation of lipids in liver and muscle

2) obesity-induced inflammation

Question 4

At what percentage of B-cell dysfunction is the usual cutoff for asymptomatic-> symptomatic Type 2 diabetes?

Answer 4

50% of normal B-cell function

- at this point symptoms start to develop

Question 5

How long does glycated hemoglobin last in the body

Answer 5

8-12 weeks
- this is why this level is monitored for losing-term blood glucose control

• *a fasting blood glucose can manipulated, this cant**
• fasting blood glucose only shows glucose levels for the past 8 hrs

Question 6

What are diagnostics test cut offs for diabetes and prediabetes

Answer 6

Pre-diabetic mellitus

• FBG = 100-125 mg/dL
• A1C = 5.7-6.4%
• OGTT post 2hrs draw = 140-199 mg/dL

Diabetes

• FBG = >126 mg/dL
• A1C = >6.5%
• OGTT post 2hrs draw = >200 mg/dL

Question 7

What is the rough conversion of mean plasma glucose: A1C?

Answer 7

A 3.5-4 mg/dL or 0.2 mmol/L increase in plasma glucose = 0.1% increase in A1C

A 36 mg/dL or 2.0 mmol/L increase in plasma glucose = 1% increase in A1C

Question 8

Different between mealtime insulin’s and basal insulin’s

Answer 8

Mealtime = rapid and short acting

Basal = intermediate and long acting
- used to counter the liver gluconeogenesis that occurs overnight in patients

Question 9

What are the three rapid acting insulin’s

Answer 9

“LAG”

1) Lispro
2) Aspart
3) Glulisine

All takes 20 minutes to onset and peaks concentration in 1hr

All have the same duration of 3-4 hrs

All are used after meals and acute hyperglycemia

can also used inhaled versions over IM injections

Question 10

Short acting insulin

Answer 10

Two types and are normal insulin

1) novolin R
2) humblin R

Onset = 30 min-1 hr

Peaks within 2-3 hrs

Duration is 3-6 hrs

Used after meals, in acute hyperglycemia or to manage ketoacidosis

Question 11

Concentrated regular insulin (insulin U-500)

Answer 11

Only used in severe insulin resistance (type-2 DM)
- patient requires >200 units of insulin daily

Onset = 30 min-1 hr

Peak = 4-8 hrs

Duration = 13-24hrs

Question 12

Intermediate acting insulin

Answer 12

Three types

1) NPH isophane
2) Novolin N
3) Humulin N

All have an onset of 2-4 hrs

All have a peak of 4-6 hrs

All have a duration of 8-12 hrs

All are used for basal insulin, overnight coverage

Question 13

Lon-acting insulin’s

Answer 13

Include the following three

1) glargine
2) Detemir
3) Degludec

All three have onset of 1-2 hrs

All have no peak and have durations greater than 24hrs

don’t mix with other insulin doses

Question 14

How is NPH formulated

Answer 14

Combination of insulin and protamine

• the protamine is degraded by proteolytic tissues permitting insulin absorption
• this one can be mixed with other insulin’s

Question 15

How is glargine formulated

Answer 15

Combined 2 arginine molecules
- are soluble in acidic only solutions but precipitates in neutral body pH after injection

The pH must be stable at 4.0 so DONT mix with other insulin’s

Question 16

How are insulin detemir and degludec formulated

Answer 16

Detemir

• replaces threonine at B30 position with myositis acid at B29 lysine position
• induces self aggregetion of insulin in high levels, so DONT mix with other insulin’s

Degludec

• replaces threonine at B30 position with hexadecnoic acid at B29
• when injected, the solution forms multihexameric chains and dissolves into insulin monomers slowly.
• Because of the multihexameric chains, DONT mix with other insulin’s

Question 17

Vial concentrations vs pen concentrations

Answer 17

Vial = less expensive but more inconvenient since you need to dose your self

Pen = more expensive but comes in select doses already so more convenient

both require you to throw it out in 30 days (they expire)

Question 18

What are the insulin’s that are often mixed together?

Answer 18

Almost always it sNPH mixed with one foot he short acting (lisopril, aspart, glulisine)

Question 19

ADRs of insulin

Answer 19

1 is hypoglycemic events

• inital stage = sweating/hunger/tremor and anxiety
• 2nd stage = confusion/weakness/drowsiness/warmth/dizziness/blurred vision

Others

• weight gain
• lipodystrophy (increased risk if you continue to inject at the same injection site)
• anti-insulin antibodies
• hypokalemia

Question 20

What is the interaction between exogenous insulin and potassium levels

Answer 20

Exogenous insulin = promotes K+/Na+ channel and K+/ATPase action in muscles and fat cells
- this presents as mild hypokalemia if not replenished

Question 21

What are additional ADRs for inhaled insulin

Answer 21

Coughing, throat pain and irritation

also has black box warning for:
- acute bronchospasms with asthma and COPD
DONT give to any patients with any chronic lung disease

Before initiating therapy, must perform spirometry and screen for lung diseases in patient

Question 22

Why can bromocriptine and other dopamine receptor agonists be used as an adjuvant therapy for type 2 diabetes

Answer 22

When dopamine is low

• hepatic glucose goes up
• insulin resistance goes up
• FFA’s go up
• triglycerides go up

so if you use agonists, it will take all of the above

Question 23

What is first line in type 2 diabetes always?

Answer 23

Lifestyle modifications and metforamin

You begin changes from this if the patient begins to be high risk of develops CKD/HF or if the A1C remains high