Diabetes treatments

Question 1

Types of insulin

Answer 1

Human:

• Regular, short acting
  
  • Onset: 30 minutes,
  • Peak: 1-3 hours
  • Duration 4-8 hours
• Intermediate acting
  
  • Onset 1-2 hours
  • Peak 4-6 hours
  • Duration 8-12 hours

Analogs: Have a single amino acid change, that prevents aggregation and causes them to be absorbed faster after subcutaneous injection. Has no effect on the development of lipohypertrophy, lumps.

• Rapid acting, aspart, lispro
  
  • onset: 5-15 minutes
  • peak, 1 hour
  • duration, 3-4 hours
• Long acting
  
  • onset: 2 hours
  • no peak, flat curve
  • duration 24 hours, 12-20 hours.

Question 2

Types of insulin treatment/injection and food regimens

Answer 2

see picture, injections are top arrows, meals are bottom arrows

Question 3

When is insulin therapy indicated in type 2 diabetes?

Answer 3

If fasting blood glucose is above 13.9mM

If random blood glucose is above 16.7 mM

If HbA1C is above 10%

If there is ketonuria

Question 4

T2DM drugs and their actions

Answer 4

Metformin: Decreases insulin resistance, decreases liver gluconeogenesis

unclear mechanism, proposed actions: inhibition of the mitochondrial respiratory chain (complex I), activation of AMP-activated protein kinase (AMPK), inhibition of glucagon-induced elevation of cyclic adenosine monophosphate (cAMP) with reduced activation of protein kinase A (PKA), inhibition of mitochondrial glycerophosphate dehydrogenase,

To use metformin the GFR must be above 60 ml/min, Also has a possible side effect of GI irritation and diarrhea, and also a risk of lactic acidosis.

Sulfonylurea - closes the ATP-sensitive K+ channel, causing depolarization of the cell, increasing insulin release. Side effect is weight gain and potential for hypoglycemia, as it increases insulin action. Meglitinides have the same mechanism as sulfonylureas.

SGLT2 inhibitors - inhibit sodium/glucose reuptake in the tubules. Causes weight loss, high glucose exretion in urine. High risk of genitourinary infections. expensive

Thiazolidinediones, TZDs - Pioglitazone PPAR gamma agonists, inhibit adipocyte lipolysis and lower circulating fatty acids, increasing glucose consumption/reliance.

GLP-1 receptor agonists. Mimic the incretin effect of GLP-1, increase insulin sensitivity and inhibits glucagon release. GI side effects and counterintuitively causes weight loss. expensive

DPP-4 inhibitor. Increase endogenous incretin availability, by inhibiting their degradation by DPP-4. Doesn’t affect weight.

Acarbose: inhibits gut carbohydrate absorption, by inhibiting luminal glucosidases, glycoside hydrolases.

Question 5

Progression of therapy in T2DM

Answer 5

1. Step 1
   
   1. First is behavioral, lifestyle, and diet change.
      
      • cut juices, sugary drinks, alcohol
      • coffee without sugar or milk
      • decrease carbs and sweets,
      • increase vegetables
      • whole grain bread and high fiber cereals
      • legumes
   2. Metformin treatment monotherapy.
   3. Check HbA1c every 3 months
2. Dual drug therapy
   
   • Metformin and GLP-1 agonist
   • Metformin and pioglitazone, TZD
   • Metformin and basal Insulin
   • Metformin and Sulfonylurea
3. Triple drug therapy, increased insulin