L42 -Insulin and anti-diabetic agents Flashcards
(52 cards)
List some complications of hyperglycemia and hypoglycemia?
Hyper = nephropathy, neuropathy, retinopathy, stroke, gangrene, heart attack
Hypo = fatigue, nausea, dizziness, coma, confusion
Define the spectrum of type I DM?
- Type 1 IDDM
- Type 1.5 latent autoimmune diabetes of adulthood (LADA)
- Type 1B – idiopathic diabetes
- Maturity onset diabetes of young: single gene mutation (MODY)
Briefly define the cause of IDDM and NIDDM?
IDDM = Autoimmune disease that causes pancreatic islet cell destruction = lack of insulin production
NIDDM = combined defect of insulin secretion and insulin resistance
Treatment strageties for Type 1, 2 DM and GDM?
Type 1 = Diet, exercise, Insulin-dependent
Type 2 = Diet, exercise, Anti-diabetic drug, Insulin (1/3)
GDM = Diet, Insulin, Anti-diabetic drugs
Which insulin precursors are used to evaluate insulin function?
Preproinsulin = signal sequence + C peptide = determine ability to secrete insulin
Proinsulin and C peptide = determine dynamic range of B cell function
Describe the 24-h physiological insulin secretion trend?
almost identical to 24-hour glucose profile
|»_space; admin of exogenous insulin should mimic the pattern of endogenous insulin secretion
Compare basal and bolus insulin admin.?
1) Basal insulin: Mimics normal pancreatic basal insulin secretion
- Long lasting
- Smooth, peakless to avoid hypoglycaemia
2) Bolus insulin: Give before meals
- Short duration
- Avoid
hypoglycaemia
Both predictable and reproducible
List 4 principal types of insulin prearation based on acting time?
– Short acting : Regular human insulin (Humulin®, Novolin®)
– Rapid onset and ultrashort-acting: Insulin Lispro and Insulin Aspart
– Intermediate acting: protamine (NPH) and lente
– Long acting : Insulin Glargine, Insulin Detemir
Explain how regular human insulin/ Humulin®/ Novolin® extends it’s onset and duration of action?
1) self-aggregate in antiparallel fashion to form active dimers
2) stabilize around Zn2+ = inactive hexamers = cannot bind to insulin
Indications for regular human insulin injection? Define the onset and acting time?
Short onset: 30min, peak 1-2h
Short acting: 5-8h
Bolus injection for diabetic ketoacidosis, Changing insulin requirements (e.g. infection, post-op)
Give 4 limitations of regular human insulin?
- Inconvenient admin. before meal
- Risk of hypoglycaemia if delayed meal
- Mismatch with postprandial hyperglycaemia peak
- Late postprandial hypoglycaemia
Describe the structure of insulin Lispro?
Anti-aggregation: Reverse the 2 amino acids (Proline 28, Lysine 29) at C-terminal of B-chhain
> > prevents hexameric formation
Define the onset and acting time of Insulin Lispro. Give one advantage?
- Rapid onset = 10-15 min (taken just before meal)
- Ultrashort acting = 2-4h
- Peak effect 30-60 min
Mimics endogenous insulin secretion = improves postprandial glucose control without risk of hypoglycemia between meals
Describe the structure of Insulin Aspart?
Substitute the B-chain proline 28 with aspartic acid
|»_space; rapidly breaks into biologically active monomer after subcutaneous injectio
Define the onset and acting time of Insulin Aspart?
Rapid onset (10-20 min)
Ultrashort acting: 2-4 hours
Peak effect: 1 hour
Name 2 intermediate acting insulin.
Protamine (NPH) insulin
Lente insulin
Describe the structure of Protamine (NPH) insulin and Lente insulin
Neutral protamine Hagedorn (NPH) insulin = mixture of insulin + protamine
Lente insulin = mixture of 30% semilente + 70% ultralente insulin (very insoluble, delayed onset and prolonged duration of action)
Define the onset and acting time of NPH insulin?
Insulin bound to protamine slowly dissolves
Intermediate onset: peak 4-10h
Intermediate acting: 10-18h
Define the onset and acting time of Lente insulin?
Zinc-bound insulin slowly dissolves:
Intermediate onset: peak 4-10h
Intermediate acting: 10-18h
Name 2 long-acting insulin?
Insulin Glargine (Lantus)
Detemir Insulin (Levemir)
Describe the structure and MoA of Insulin Glargine?
- Attach 2 arginines to the B chain c-terminal
- Substitute asparagine with glycine at A21 (A chain)
Isoelectric point shifted to pH 7.0 (close to body pH)
> > precipitates in the subcutaneous milieu»_space; stabilizes insulin hexamers
slow, consistent absorption into systemic circulation
Describe the structure and MoA of Detemir Insulin?
- Add myristic acid (FA) to lysine at position B29
- Omit threonine in position B30
fatty acid causes it to bind to albumin
» slow release, extended circulating life
Define the acting time of Insulin Glargine and Detemir insulin?
Insulin Glargine = Ultra-long-acting (maximum activity maintained for >=24 hours)
Detemir insulin = Long acting, 23 hours
List some complications of insulin therapy?
- Hypoglycemia: confusion, weakness, coma…
- Insulin allergy, immune resistance
- Lipodystrophy at injection sites (use multi-site injection)
- Abuse: Development of type 2 diabetes + lifetime dependency
