Diabetes

• Insulin


  Hormone that promotes uptake and storage of glucose

  • proinsulin -> insulin and c peptide (c peptide more accurately reflects insulin production ability)
• Mechanism of action of insulin

  1. Promote uptake of glucose by skeletal muscle and adipose tissue

  2. Reduce glucose output by liver
• Type 1 diabetes mellitus


  All require insulin
• Type 2 diabetes mellitus


  Some require insulin
• Long/intermediate acting insulin


  • Mimic continuous insulin secretion by pancreas
• Bolus (rapid/short acting) insulin


  • Mimic increased insulin secretion by pancreas in response to meal
• Types of insulin

  • Rapid (glulisine, aspart, lispro, inhaled insulin)
  • Short acting (regular)
  • Intermediate acting (NPH)
  • Long acting (detemir, glargine, degludec)
• Rapid insulin


  • Take 15min/right after meal
• Short acting insulin (regular)

  • Take 30 min prior to meal
• Intermediate acting insulin (NPH)


  • Longest onset of action
  • Admin 2-3x daily
• Long acting insulin

  • Onset of action 1-2 hr
  • Detemir -1-2x daily
  • Glargine -1x daily
  • Degludec - 1x daily
• Inhaled insulin


  • Admin at beginning of meal
• Pre-mixed insulins


  Decreased number of injections but may not meet all glycemic reduction needs
• Pre-mixed insulin administration

  ⅔ given at breakfast, ⅓ at night (2-3x time daily)
• Insulin U-500 (Humulin R)

  • 5x more concentrated than regular Insulin-U (500 units insulin per mL)
  • Useful for insulin resistant pt who require daily doses > 200
  • Caution bc high risk of hypoglycemia
• Basal coverage


  Decrease fasting glucose
• Insulin regimens

  1. Treat basal coverage first and get it right before moving onto bolus

  2. Basal coverage is 40-50% of daily insulin needs

  3. Bolus coverage is rapid/short acting insulin for each meal, 10-20% of total insulin
• Bolus coverage


  Decrease postprandial glucose
• Basal and bolus coverage

  Decrease both fasting and postprandial glucose
• Pre-mixed insulin


  Combination of basal and bolus insulin
• Insulin adverse reactions

  • Hypoglycemia
  • Weight gain
  • Lipodystrophy (abnormal fat distribution through body- can avoid if rotating injection sites)
  • Local injection site reactions
  • Allergic reaction/hypersensitivity
• Insulin administration routes

  • Subcutaneous (most common)
  • Intravenous (used for hyperglycemic emergencies, rapid/short acting only)
  • insulin pump (rapid/short acting only)
  • Inhaled
• Insulin can't be oral because the GI tract would degrade it
• Regular insulin is the most commonly used insulin
• Insulin storage

  • Dependent on type of insulin, pen vs vial, open vs unopened
• Insulin dosing for T2DM

  1. Target fasting blood glucose first (basal insulin) and adjust

  2. Target postprandial blood glucose second -> bolus insulin OR add GLP-1 RA, DPP4-I, or SGLT-2
• Insulin dosing for T1DM

  1. Multiple insulin injections, including basal/bolus OR

  2. Continuous subcutaneous insulin infusion
• T2DM Regimen

  1. Consider overall med regimen
  2. Provide pt education (SMBG, admin, technique) (R/o inappropriate candidates (hypoglycemia unawareness, unable to admin properly, not willing to monitor/self-inject))
  3. Target FBG first
  4. adjust dose to reach FBG goal w/out hypoglycemia (add single bedtime basal insuline dose (intmd/long))

  • ADA -> starting dose 10 unit per day or 0.1/0.2 unit/kg
  • AACE

  1. A1C < 8% ( 0.1/0.2 unit/kg)
  2. A1C > 8% (0.2/0.3 unit/kg)
  3. If not at goal, target prandial BGL (consider addition of GLP-1 RA, SGLT-2, DPP04, mealtime insulin, premixed insulin )
• T1DM regimen


  Insulin pump therapy or multiple daily insulin injection therapy
• T1DM Calculating total daily dose (TDD) of insulin

  Based on .5 units/kg per day
• T1DM Giving insulin ratio

  1. 50% TDD as basal dose

  2. 50% bolus (split in 3 for meals)
• adjust insulin for high BGL and for meals

  • correction factor (sensitivity factor)
  • insulin to carb ratio (I:C)
• Correction factor (sensitivity factor)

  1. used to estimate serum glucose lowering effect of 1 unit of rapid/short acting insulin
  2. self monitor BGL
  3. can be used for any pt using rapid/short acting insulin

  Rule of 1800 (rapid acting) - 1800/current insulin daily dose - approx mg/dL change in glucose level per 1 unit insulin

  
  

  Rule of 1500 (short acting) - 1500/current insulin daily dose - approx mg/dL change in glucose level per 1 unit insulin
• insulin to carb ratio (I:C) 


  • used to estimate the early use of rapid acting insulin at mealtime to prospectively cover what is to be ingested
  • educate pt on carb counting 
  • most accurate in pt unable to make insulin and pt who receive 50/60% TDD as basal dose 

  
  

  Rule of 500: 500/TDD = I:C ratio
• Pump candidates


  1. pt with T1DM or intensively managed T2DM
  2. pt currently on 4+ insulin injections and 4+ SMBGL
• Hypoglycemia therapies

  1. Oral glucose
  2. glucagon
  3. IV Dextrose
• Oral glucose


  1. clinical use -> tx of hypoglycemia (BG<70)
  2. preferred tx for pt who are conscious and able to take oral replacement 
  3. dose: 15-20g, if BGL still <70 after 15 min, ingest 15-20g more
  4. once BGL returns to normal, eat meal/snack
  5. if glucose unavailable, use high sugar source (orange juice, hard candy, regular soda) 
• Glucagon


  1. clinical use: tx of severe hypoglycemia
  2. dose 1 mg IM, IV, subq; may repeat 1 mg
  3. once BLG returns to normal, eat meal/snack
• IV dextrose


  1. clinical use: emergency tx of hypoglycemia who have failed tx with glucagon
• Insulin secretagogues 


  Sulfonylureas (2nd gen)

  Meglitinides