Part 2 DM

Question 1

Type 1 DM

Induced By autoimmune response to?

Tepluzumab?

Answer 1

Response to B-cells

Reduced the loss of C-peptide 2 years after the first treatment in the subsets of patients with ne onset T1D

Question 2

Insulin therapy?

Goal?

Limitation?

Answer 2

• Emulate the physiological actions of natural insulin release in response to the size and nature of each meal
• Limited in restoring postprandail glucose homeostasis is due to compartmentation mismatch which makes it hard to fully mimic insulin
• Sc insulin leads to high insulin in the peripheral tissue

Question 3

Insulin therapy ADA guidelines

Preprandial glucose?

Preak postprandial

Answer 3

5-7.2

<10

Can use various combinations of different insulin formulations to accommodate the short term postprandial insulin burst necessary following ingestion of a meal with requirements for lower but prolonged basal insulin levels between meals and overnight to avoid episodes.

Question 4

Endogenous insulin circulates in the plasma as a _____ and this form is required for interaction with the insulin receptor and proper insulin action

Insulin readilty undergoes _____ and forms a hexameric crystals in most pharmaceutical preparations of insulin containing Zn2+ ions and typical excipients

Rate of dissociation is directly related to?

Answer 4

Monomer

Self aggregation

time required for peak plasma monomer concentrations and duration of action

Question 5

Humalog (insulin lispro)

Answer 5

• Rapid acting
• Recombinant human insulin-AA 28 (proline) lysine (29) in the B-chain are reversed, decreases the tendency of insulin to form hexamers, when injected s.c. rapidly dissociates into the protein monomer and is rapidly absorbed
• Aspart=Lispro=Glulisine>regular>NPH>lente>ultralente>glargine=determir=degludec

Question 6

Human Novolog

(insulin aspart)

Answer 6

• Rapid acting
• Recombinant human insulin, proline residue at the B28 is replaced by asspartic acid, this increases the rate of absorption by increasing rate of destabilization

Aspart=Lispro=Glulisine>regular>NPH>lente>ultralente>glargine=determir=degludec

Question 7

Apidra (insulin glulisine)

DOA of all Insulins?

Answer 7

• Rapid acting
• Recombinant humna insulin - asparagine residue at the B 3 position is replaced with lysine and lysine at the 29 position is replaced by glutamic acid, increases the rate of absorption by increasing hexamer destabilization

Aspart=Lispro=Glulisine>regular>NPH>lente>ultralente>glargine=determir=degludec

Question 8

Regular short acting (Onset- .5-2 hours)

Humulin R

Answer 8

First recombinant human insulin, soluble zinc crystalline insulin

Question 9

Intermediate acting insulin (2-4)

HUmulin N and Novolin N

NPH

Answer 9

Produced microcrystalline suspension buffered at neutral pH called hagedorn NPH 12:1

Question 10

Lantus, Tujeo, Basaglar

glargine

Answer 10

Recombinant insulin that has 2 arginine residues added at the C-terminus of the B-chain and contains the substitution of glycine for asparagine A21

Aspart=Lispro=Glulisine>regular>NPH>lente>ultralente>glargine=determir=degludec

Question 11

Lantus and Tujeo

Glargine

Answer 11

• Addition of the arginine increase the isoelectic point and renders the insulin less soluble and induces its precipitation at the site of injection, replacement of asparagine by glycine results in a more dense crystal and slower dissolution
• Acidic pH associated with the site of injecction pain and can be problematic for mixing with other insulins

Question 12

Levemir

determir

Answer 12

• Deletion of threonine 30 from B chain with addition of a C-14 fatty acid on terminal lysine [LysB29(Nε-tetradecanoyl) des(B30 human insulin]
• neutral pH, long chain fat binds to albumin, 98% associated with albumin which decreases free detemir, slow dissociation contributes to prolonged activity, subcutaneous injection only

Question 13

Tresiba (degludec)

Answer 13

• B29 lysine conjugated to hexadecanedioic acid via gammaglutamyl spacer [B29N(epsilon)-omega-carboxypentadecanoyl-gamma-L-glutamyl desB30 human ins
• neutral pH, long chain fat binds to albumin, very slow dissociation from subcutaneous depot, 30-90 minutes for onset of action and has a duration of action of 40 hrs
• Approved Sept 25, 2015- has shown lower incidence of nocturnal hypoglycemia versus glargine and detemir

Question 14

Ryzodeg

Insulin degludec + insulin aspart

Answer 14

• Approved Sept. 25, 2015
• effective in controlling blood glucose levels in patients with type- 1 and type-2 diabetes.
• generally safe and its side effects are comparable to those of other insulin analogues with no unexpected side effects reported
• reduces the risk of hypoglycemia during the night in patients with type-1 and type-2 diabetes

Question 15

Inhaled human insulin

Answer 15

• Afrezza (MannKind)- insulin with particle diameters between 1 - 5 mm with stabilization of the insulin molecule to make it bioavailable in the dry powder form
• • a rapid-acting inhaled insulin to be administered prior to meals or within 20 minutes of starting a meal.
• • not a substitute for long-acting insulin, must be used in combination with long-acting insulin in patients T1D.
• • not recommended for the treatment of diabetic ketoacidosis or in patients who smoke or who have chronic lung disease.
• • common adverse reactions were hypoglycemia, cough, and throat pain or irritation.
• • will have a boxed warning advising that acute bronchospasm has been observed in patients with asthma and chronic obstructive pulmonary disease.