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PRACTICAL INSULIN USE or, how to think like a pancreas

PRACTICAL INSULIN USE or, how to think like a pancreas. Oliver Z. Graham, MD Department of Internal Medicine Virtual Endocrinologist. “Truly understanding issues such as when to use regular insulin, when it would be better to use insulin lispro or aspart… simply requires

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PRACTICAL INSULIN USE or, how to think like a pancreas

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  1. PRACTICAL INSULIN USEor, how to think like a pancreas Oliver Z. Graham, MD Department of Internal Medicine Virtual Endocrinologist

  2. “Truly understanding issues such as when to use regular insulin, when it would be better to use insulin lispro or aspart… simply requires a great deal of experience.” --Irl Hirsch, MD, UC San Diego, Clinical Diabetes 2001

  3. “It tends to be more difficult to manage a patient on insulin if you don’t really understand what you’re doing.” --Oliver Z. Graham, MD, reflecting on personal Experience, Pittsburgh Health Center

  4. Types of Insulin

  5. Types of Insulin

  6. Types of Insulin:Lispro and Aspart (Humalog/Novolog) • Fast acting (works within 5 min) • Better matches carbohydrate intake to insulin dose • Can take right before meals

  7. Types of Insulin:Regular • Slower onset and later peaking • Must take 30-45 min before meals • Doesn’t really match blood sugar levels, especially with high carbo meals • May lead to hyperglycemia immediately after meals with hypoglycemia several hours thereafter

  8. Types of Insulin:NPH • Long acting, with peak at 6-10 hours • May be used for AM dosing to cover midday meals, used in PM to cover overnight • Commonly used BID as 70/30

  9. Types of Insulin:Glargine (Lantus) • A true basal insulin with a 24 hour, peakless, predictable effect • Simulates basal pancreatic insulin secretion

  10. 70/30 (NPH/Regular) BID

  11. 2 Injections/day (ie 70/30)using regular/NPH • Postprandial glucose levels for breakfast/dinner covered by short acting insulins, lunch and overnight sugars covered by NPH • Advantage: 2 Injections/day • Disadvantage: • NPH given at supper does not last until breakfast, leading to high AM BS • NPH in AM does not cover lunch BS well

  12. Lispro/Glargine

  13. 4 Injections/day using Lispro/Glargine • One dose basal insulin during day and overnight, with rapid/short acting insulin covering meals • Advantage: • Allows for meal to meal adjustments of insulin in accordance to food intake, preprandial blood glucose levels, and exercise. • With lispro, probably offers the tightest control of BS given its physiologic simulation of insulin secretion (the “poor man’s insulin pump”) • Disadvantage: • Its 4 injections

  14. Case Study #1 • See your handout for details

  15. Question 1: • How would you go about improving John’s glycemic control?

  16. Question #2: • If you choose insulin, should you start a long acting/short acting or both?

  17. Relative contribution of fasting and postprandial glucose to A1C.

  18. Starting Insulin 101 • For HA1C > 9, FIX FASTING FIRST • Self monitoring on fasting glucose is easier for most patients • Fasting glucose is primarily influenced by stage of disease and meds • Diet and activity have limited influence on fasting BS • Controlling postprandial BS is difficult with poorly controlled fasting sugars

  19. Starting Insulin 101 • As you near target A1C (<7), post prandial control gets more important

  20. Question #3: • If basal insulin, how/which do you start? • Lantus (glargine)? • NPH?

  21. Lantus vs. NPH • Equally efficacious when added to orals in achieving HA1c value • Lantus associated with 41% lower risk of severe hypoglycemia (BS < 51)

  22. How to start insulin gently • Continue oral agents at same dosage • Consider d/c sulfonyurea • Add single dose at 10 U or 0.15 U/kg • NPH at bedtime • Glargine anytime

  23. How to start insulin gently, continued • Have patient adjust dose by fasting BG every 3-5 days • Increase 4 U if FBG > 140 • Increase 2 U if FBG 120-140 • No change if FBG < 120 • Decrease dose by 2 U if FBG < 72 or sx hypoglycemia • Check in by phone in 1-2 weeks

  24. Question #3: • What about Byetta (exanatide)? Would that be a reasonable alternative to insulin?

  25. Byetta (exanatide) • Naturally occurring component of Gila Monster Saliva • Stimulates insulin release from pancreas, slows gastric emptying, inhibits glucagon release

  26. Why use Byetta? • Most patients gain weight with DM tx • Insulin tx 4 lb increase for every 1% A1c reduction • With Byetta  WEIGHT LOSS • 12 pound loss at 2 years tx • A1c reduction about 1.1% • ? Animal studies suggest beta cell regeneration

  27. Why not use Byetta? • Expensive (1 year -- $2700) • Long term data not available (lessons from Avandia & Rezulin…) • Nausea very common (50-60%) • Because slows gastric emptying CONTRAINDICATED in GASTROPARESIS • 2 injections/day

  28. Who might get Byetta? • Obese patients not at A1C target who are already on metformin, sulfonyurea or both or glitazone +/- metformin • Not FDA approved for pts on 3 oral agents or on insulin

  29. How to use Byetta • Start 5 mcg BID prior to meals, titrate up to 10 mcg BID as tolerated at one month

  30. Question #4: • Should John get Byetta?

  31. Case study, continued • John has titrated up his Glargine to 40 U daily, and his A1c decreased to 7.8%. He then missed his next appointment, and comes back 6 months later.

  32. Case study, continued • Current meds: • Lantus 40 U daily • Metformin 1000 BID • Glipizide 10 mg BID • HA1c 8.5% • What do you do now? Are “lifestyle” changes still worthwhile?

  33. Exercise and DM • Studies show regular exercise • reduced A1c from 8.3  7.65%

  34. Diet and DM • Caloric restriction and weight loss (even 5-10% of body weight) can lead to: • Improved glucose control • Improved sensitivity to insulin • Improved lipid profiles and BP

  35. Case study, continued • Current meds: • Lantus 40 U daily • Metformin 1000 BID • Glipizide 10 mg BID • HA1c 8.5% • He says his knees hurt and he doesn’t want to start an exercise program. His diet is reasonable, but he is unable to lose more weight. How would you adjust his insulin at this time?

  36. How to initially dose prandial insulin • 1 unit for every 10 g carb (needs to learn carb counting) • OR • 5 units for a small meal • 8-10 units for a large meal • OR • Start with 4 units largest meal, titrate up every three days (see algorithm) • OR • Calculate insulin needs (0.1 U/kg prior to each meal) • AND • 1 unit additional correction factor for every 30-50 mg/dl above 100 mg/dl preprandial (see handout)

  37. Case Study, continued • John really doesn’t want to do more than 2 injections/day. How do you manage his insulin now?

  38. Insulin Regimens:2 Injections/ day • Postprandial glucose levels for breakfast/dinner covered by short acting insulins, lunch and overnight sugars covered by NPH • Advantage: 2 Injections/day • Disadvantage: • NPH given at supper does not last until breakfast, leading to high AM BS • NPH in AM does not cover lunch BS well

  39. Transition From One Regimen to Another

  40. Case continued • John comes in two weeks later on the following DM meds: • 70/30 20 U BID • Metformin 1000 BID • Glipizide 10 mg BID • AM BS – 100, 90, 120, 111, 110 • PM BS -- 150, 144, 179, 180, 168 • What is your next step?

  41. 70/30 (NPH/Regular) BID

  42. Dosage Titration for Once-Daily or Twice-Daily Insulin Regimens

  43. Case Study #2 • RR is a 32 year old type I diabetic who was first diagnosed at age 12. Her HgA1c have ranged between 10-12 over the past ten years, and she is now legally blind from diabetic retinopathy and has a creatinine of 2.6. Her current insulin regimen is N 22 (AM) N 18 (PM) as well as sliding scale regular prior to meals. There have been 3 episodes of hypoglycemia in the past 2 weeks. She now comes to your clinic for the first time in 6 months without a blood sugar log book and wants you to “fix her diabetes” as well as signing some paperwork for in home support services and giving her some vicodin for her neuropathy. • What do you think her target blood sugars should be?

  44. Glycemic Goals forIntensive Insulin Therapy • Preprandial: 90-130 • 1-2 Hours Postprandial: 160-180 • Target HbA1c < 6.5 - 7

  45. Intensive Insulin Therapy:Relative Contraindications • Individuals with hypoglycemia awareness • Individuals with recurrent, severe hypoglycemic episodes • Individuals with severe emotional disorders or psychosocial stressors • Individuals with alcohol or drug abuse problems • Individuals with advanced, end stage diabetic complications • Individuals with medical conditions that can be aggravated by hypoglycemia, I.e. cerebrovascular disease, angina, or cardiac arrhythmia Intensive Diabetes Management, 1998

  46. Intensive Insulin Therapy:Relative Contraindications, cont • Individuals unable or unwilling to commit to the personal effort and involvement required for intensive diabetes management • Individuals with concurrent illness and/or conditions that would functionally limit intensive management I.e. debilitating arthritis or severe visual impairment • Individuals with a relatively short life expectancy • Individuals who live alone Intensive Diabetes Management, 1998

  47. Glycemic Goals for not-so-Intensive Insulin Therapy • “Good control”: HbA1c<8 • “Fair control”: pre-meal BG<200 • “Do no harm control”: Avoid hyper/hypoglycemic symptoms only • One blood sugar target does not fit all

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