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Flashcards in Part 2 DM Deck (16):

Type 1 DM 

Induced By autoimmune response to?



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


Insulin therapy? 




  • 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



Insulin therapy ADA guidelines 

Preprandial glucose?

Preak postprandial 



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. 


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? 



Self aggregation

time required for peak plasma monomer concentrations and duration of action 


Humalog (insulin lispro) 


  • 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



Human Novolog

(insulin aspart) 


  • 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 



Apidra (insulin glulisine)

DOA of all Insulins?


  • 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 




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

Humulin R 


First recombinant human insulin, soluble zinc crystalline insulin 


Intermediate acting insulin (2-4) 

HUmulin N and Novolin N 



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



Lantus, Tujeo, Basaglar 



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



Lantus and Tujeo



  • 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 




  • 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


Tresiba (degludec)

  • 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



Insulin degludec + insulin aspart


  • 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


Inhaled human insulin 


  • 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.