Type 1 Diabetes Mellitus


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Type 1 Diabetes Mellitus

  1. 1. Type 1 Diabetes Mellitus Jason Cavolina BS, MS, PharmD Candidate Arnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University Ambulatory II Clerkship
  2. 2. Introduction <ul><li>Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia and abnormalities in carbohydrate, fat and protein metabolism </li></ul><ul><li>Type I Diabetes: </li></ul><ul><ul><li>Absolute deficiency in insulin </li></ul></ul><ul><ul><li>β -cell destruction </li></ul></ul>
  3. 3. Introduction <ul><li>DM eventually -> microvascular and macrovascular complications </li></ul><ul><ul><li>Microvascular : retinopathy, nephropathy, and peripheral neuropathy </li></ul></ul><ul><ul><li>Macrovascular : coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD) </li></ul></ul>
  4. 4. Epidemiology <ul><li>DM affects more than 170 million people worldwide </li></ul><ul><li>By 2010 this number will ↑ by as much as 50% </li></ul><ul><li>~10% of patients with diabetes have type 1 DM </li></ul><ul><li>Cardiovascular morbidity in DM patients is 2-4 times greater than in non-diabetic patients </li></ul>
  5. 5. Epidemiology <ul><li>Average onset is in childhood or early adulthood (usually before 30 years of age) </li></ul><ul><li>Characterized by autoimmune destruction of pancreatic β -cells -> absolute insulin deficiency </li></ul><ul><li>Patients dependent on exogenous insulin </li></ul>
  6. 6. Pathophysiology <ul><li>Immune-mediated destruction of pancreatic β -cells </li></ul><ul><li>Certain antibodies detected in blood </li></ul><ul><ul><li>Islet cell antibody (ICA) </li></ul></ul><ul><ul><li>Glutamic acid decarboxylase (GAD65) antibody </li></ul></ul><ul><ul><li>Insulin autoantibody (IAA) </li></ul></ul><ul><li>HLA-DR3 and HLA-DR4 as well as DQA and DQB genes are strongly associated with type 1 DM </li></ul><ul><li>Strong familial genetic link </li></ul>
  7. 7. Pathophysiology <ul><li>Environmental triggers </li></ul><ul><ul><li>Viral infections (mumps, influenza) </li></ul></ul><ul><ul><li>Early exposure to cow’s milk (bovine serum albumin) </li></ul></ul><ul><ul><li>Environmental toxins </li></ul></ul><ul><ul><li>Puberty </li></ul></ul><ul><li>“ Honeymoon” phase -> transient remission </li></ul><ul><li>Hyperglycemia occurs when 80%-90% of β -cells are destroyed </li></ul>
  8. 8. Clinical Presentation <ul><li>Moderate to severe symptoms </li></ul><ul><li>Symptoms progress rapidly </li></ul><ul><li>Onset usually childhood or adolescent </li></ul><ul><li>But, can occur at any age </li></ul><ul><li>Signs and Symptoms: </li></ul><ul><li>Polyuria </li></ul><ul><li>Polydipsea </li></ul><ul><li>Polyphagia </li></ul><ul><li>Diabetic Ketoacidosis (DKA) </li></ul><ul><li>Unexplained weight loss </li></ul>
  9. 9. Criteria for Screening <ul><li>Screening is not recommended </li></ul><ul><li>Routine testing for immune markers is not recommended: </li></ul><ul><ul><li>Cut off values for immune markers assays have not been established. </li></ul></ul><ul><ul><li>No consensus as to what action should be taken when a positive autoab test result is obtained. </li></ul></ul>
  10. 10. Diagnostic Elements <ul><li>DKA </li></ul><ul><li>Symptoms of diabetes and a casual plasma glucose ≥ 200 mg/dl </li></ul><ul><li>Fasting Plasma Glucose (FPG) ≥ 126 mg/dl </li></ul><ul><ul><li>Impaired Fasting Glucose (IFG) </li></ul></ul><ul><li>2-h plasma glucose ≥ 200 mg/dl after an OGTT </li></ul><ul><li>These criteria should be confirmed by repeat testing on a different day </li></ul>
  11. 11. Pharmacotherapeutic Goals Glycemic Control <180 mg/dL Peak postprandial capillary plasma glucose 90-130 mg/dL Pre-prandial capillary plasma glucose <7.0 – 6.5 % Hemoglobin A 1C
  12. 12. Desired Outcomes <ul><li>Reduce risk for microvascular and macrovascular complications </li></ul><ul><li>Reduce mortality </li></ul><ul><li>Achieve glycemic control </li></ul><ul><li>Improved quality of life </li></ul>
  13. 13. Overview of DM Management <ul><li>Treatment regimens should be individualized </li></ul><ul><li>Type 1 DM </li></ul><ul><ul><li>Lifetime insulin therapy </li></ul></ul><ul><ul><li>Lifestyle modification </li></ul></ul><ul><ul><ul><li>Diet </li></ul></ul></ul><ul><ul><ul><li>Exercise </li></ul></ul></ul>
  14. 14. Medical Nutrition Therapy Adjust based on age, weight and height. Total calories < 300 mg/d (< 200 mg/d in dyslipidemia) Cholesterol Up to 20% of total cal. Monounsaturated fat ~10% of total cal. Polyunsaturated fat < 10% of total cal (< 7% in dyslipidemia) Saturated fat 25-35% of total cal. Total fat 15-20% of total cal. Protein ~50-60% of total calories Carbohydrate Recommended Intake Nutrient
  15. 15. Exercise Recommendation <ul><li>ADA: 30-60 min. of aerobic activity 3-4 times a week </li></ul><ul><li>Surgeon General Report: Accumulate 30 min. of moderate physical activity on most days of the week </li></ul><ul><li>Exercise regimens should be individualized </li></ul>
  16. 16. Pharmacotherapy in Type 1 DM <ul><li>The primary therapy for type 1 DM is insulin therapy </li></ul><ul><li>Four basic forms of insulin: </li></ul><ul><ul><li>Rapid-acting </li></ul></ul><ul><ul><li>Short-acting </li></ul></ul><ul><ul><li>Intermediate-acting </li></ul></ul><ul><ul><li>Long-acting </li></ul></ul>
  17. 17. Insulin <ul><li>Which one should be used? </li></ul><ul><ul><li>Individuals lifestyle </li></ul></ul><ul><ul><li>Physicians/Pt preference </li></ul></ul><ul><ul><li>Patients blood sugar level </li></ul></ul>
  18. 18. Which one should be used? <ul><li>Source of insulin? </li></ul><ul><ul><li>By January 2006, pork/beef insulin for human use will no longer be manufactured or marketed in the U.S. </li></ul></ul><ul><li>How soon it starts working -> onset </li></ul><ul><li>When does it reach the highest -> peak </li></ul><ul><li>How long it lasts in body -> duration </li></ul>
  19. 19. Rapid-acting Insulin <ul><li>Type Onset (h) Peak (h) Duration (h) Appearance </li></ul><ul><li>insulin lispro 15-30 min 1-2 3-5 Clear </li></ul><ul><li>HUMALOG® </li></ul><ul><li>insulin aspart 15-30 min 1-2 3-5 Clear </li></ul><ul><li>NOVOLOG® </li></ul><ul><li>insulin glulisine 15-30 min 1-2 3-5 Clear </li></ul><ul><li>APIDRA® </li></ul>
  20. 20. Rapid-acting Insulin <ul><li>Dosage forms: </li></ul><ul><ul><li>HUMALOG & NOVOLOG </li></ul></ul><ul><ul><li>Pen, U-100 vial, or 1.5 ml or 3 ml pen cartridge </li></ul></ul><ul><ul><li>APIDRA </li></ul></ul><ul><ul><ul><li>U-100 Vial </li></ul></ul></ul>
  21. 21. Rapid-acting Insulin <ul><li>Inject within 10-15 minutes of meal </li></ul><ul><li>Better efficacy in ↓ post prandial blood glucose </li></ul><ul><li>Minimizes delayed postmeal hypoglycemia </li></ul><ul><li>Normally used in regimens with intermediate or long-acting insulin </li></ul><ul><li>Rapid-acting insulin can be mixed with NPH and lente -> the mixture should be injected within 15 minutes prior to a meal </li></ul>
  22. 22. Short-acting Insulin <ul><li>Type Onset (h) Peak (h) Duration (h) Appearance </li></ul><ul><li>Regular 0.5-1.0 2-3 3-6 Clear </li></ul><ul><li>HUMULIN R ® </li></ul><ul><li>NOVOLIN R ® </li></ul>
  23. 23. Short-acting Insulin <ul><li>Dosage forms: </li></ul><ul><li>HUMULIN R </li></ul><ul><ul><li>U-100 vial, 10 ml vial or U-500, 20 ml vial </li></ul></ul><ul><li>NOVOLIN R </li></ul><ul><ul><li>Insulin pen, U-100 vial, or 3 ml pen cartridge, and Innolet </li></ul></ul>
  24. 24. Short-acting Insulin <ul><li>Relatively slow onset of action when given SQ </li></ul><ul><li>Inject SQ 30 minutes prior to meal to achieve optimal post prandial glucose control and to prevent delayed postmeal hypoglycemia. </li></ul><ul><li>Eating within a few minutes after or before injecting is discouraged because it substantially ↓ the ability of that insulin to prevent a rapid rise in blood glucose and may ↑ the risk of delayed hypoglycemia. </li></ul>
  25. 25. Intermediate-acting Insulin <ul><li>Type Onset (h) Peak (h) Duration (h) Appearance </li></ul><ul><li>NPH 2-4 4-6 8-12 Cloudy </li></ul><ul><li>HUMULIN N® </li></ul><ul><li>NOVOLIN N® </li></ul><ul><li>Lente 3-4 6-12 12-18 Cloudy </li></ul><ul><li>HUMULIN L® </li></ul>
  26. 26. Intermediate-acting Insulin <ul><li>Dosage forms: </li></ul><ul><li>HUMULIN N </li></ul><ul><ul><li>U-100 vial, prefilled pen </li></ul></ul><ul><li>NOVOLIN N </li></ul><ul><ul><li>U-100 vial, prefilled pen, and Innolet </li></ul></ul><ul><li>HUMULIN L </li></ul><ul><ul><li>U-100 vial </li></ul></ul>
  27. 27. Long-acting Insulin <ul><li>Type Onset (h) Peak (h) Duration (h) Appearance </li></ul><ul><li>Glargine 4-5 Peakless 22-24 Clear </li></ul><ul><li>LANTUS® </li></ul><ul><li>Available as U-100 vial and Pens </li></ul>
  28. 28. Long-acting Insulin <ul><li>LANTUS </li></ul><ul><ul><li>‘ peakless’’ analog -> less nocturnal hypoglycemia than NPH when given at bedtime </li></ul></ul><ul><ul><li>Usually given once a day only </li></ul></ul><ul><li>Horizon </li></ul><ul><ul><li>Insulin Detemir (Levemir ®) </li></ul></ul><ul><ul><li>~ peakless, ~ 24 h duration, Clear </li></ul></ul>
  29. 29. Premixed Insulin <ul><li>Fixed ratio insulins are dosed according to patient needs </li></ul><ul><li>15 minutes before meals </li></ul><ul><li>Premixed insulin analogs </li></ul><ul><ul><li>HUMALOG Mix 75/25 (75% neutral protamine lispro, 25% lispro) </li></ul></ul><ul><ul><ul><li>U-100 vial, prefilled pen </li></ul></ul></ul><ul><ul><li>NOVOLOG Mix 70/30 (70% aspart protamine suspension, 30% aspart) </li></ul></ul><ul><ul><ul><li>U-100 vial, prefilled pen, 3 ml pen cartridge </li></ul></ul></ul>
  30. 30. Premixed Insulin <ul><li>NPH-regular combinations </li></ul><ul><ul><li>HUMULIN 70/30 </li></ul></ul><ul><ul><ul><li>Vial, prefilled pen </li></ul></ul></ul><ul><ul><li>NOVOLIN 70/30 </li></ul></ul><ul><ul><ul><li>Vial, pen cartridge, Innolet </li></ul></ul></ul><ul><ul><li>HUMULIN 50/50 </li></ul></ul><ul><ul><ul><li>Vial </li></ul></ul></ul>
  31. 31. Insulin Regimens
  32. 32. Insulin Regimens
  33. 33. Symlin® (Pramlintide acetate) <ul><li>Antihyperglycemic agent </li></ul><ul><li>Synthetic analog of human Amylin </li></ul><ul><li>Amylin: Naturally secreted from β -cell </li></ul><ul><ul><li>Suppresses glucagon secretion </li></ul></ul><ul><ul><li>slows gastric emptying time </li></ul></ul><ul><ul><li>Causes satiety -> potentially to weight loss </li></ul></ul>
  34. 34. Insulin Adverse Reactions <ul><li>Lipoatrophy : loss of fat at injection site due to antibody formation leading to breakdown of fat in the area of injection ( need to rotate sites!) </li></ul><ul><li>Hypertrophy : increase in fat mass at the site, the area is anesthetized , however leads to erratic insulin absorption </li></ul><ul><li>Resistance : require large amounts of insulin to get desired effect, due to antibody formation </li></ul>
  35. 35. Insulin Adverse Reactions <ul><li>Hypoglycemia: </li></ul><ul><li>Blood glucose < 50mg/dl </li></ul><ul><li>Hypoglycemia S&S </li></ul><ul><ul><li>Mild to moderate </li></ul></ul><ul><li>Sweating </li></ul><ul><li>Drowsiness </li></ul><ul><li>Dizziness </li></ul><ul><li>Sleep disturbances </li></ul><ul><li>Palpitation </li></ul><ul><li>Anxiety </li></ul><ul><li>Tremor </li></ul><ul><li>Blurred vision </li></ul><ul><li>Hunger </li></ul><ul><li>Slurred speech </li></ul><ul><li>Restlessness </li></ul><ul><li>Depressed mood </li></ul><ul><li>Tingling in hands, feet, lips, or tongue </li></ul><ul><li>Irritabilty </li></ul><ul><li>Lightheadednes </li></ul><ul><li>Abnormal behavior </li></ul><ul><li>Inability to concentrate </li></ul><ul><li>Unsteady movement </li></ul><ul><li>Headache </li></ul><ul><li>Personality change </li></ul>
  36. 36. Insulin Adverse Reactions <ul><li>Hypoglycemia S&S: Severe </li></ul><ul><li>Disorientation </li></ul><ul><li>Unconsciousness </li></ul><ul><li>Seizures </li></ul><ul><li>Death </li></ul>
  37. 37. Hypoglycemia <ul><li>Treatment: </li></ul><ul><li>Rule of 15 -> 15g of carbohydrates every 15 minutes until BG is greater than 70mg/dl, then follow with a simple meal </li></ul>
  38. 38. Insulin Adverse Reactions <ul><li>Foods that will provide 10g of carbs </li></ul><ul><ul><li>½ cup of orange juice or soda </li></ul></ul><ul><ul><li>Sugar: 2 teaspoons or 2 cubes </li></ul></ul><ul><ul><li>Glucose tablets: 2-4 tablets </li></ul></ul><ul><ul><li>Apple juice: 1/3 cup </li></ul></ul><ul><li>Foods to avoid </li></ul><ul><ul><li>Ice cream, candy bars, cookies, cakes </li></ul></ul><ul><ul><li>Complex carbs slowly absorbed </li></ul></ul><ul><li>If unconscious : Glucagon 1mg SQ, IM, or IV and Dextrose 50% 50ml infusion </li></ul>
  39. 39. Diabetic Adverse Event <ul><li>DKA </li></ul><ul><ul><li>Precipitated by a stressful event </li></ul></ul><ul><ul><ul><li>trauma, infection, surgery or myocardial infarction </li></ul></ul></ul><ul><ul><ul><li>increased release of cortisol, glucagon, and catecholamines ( ↑ production of glucose and ketoacids) </li></ul></ul></ul>
  40. 40. Diabetic Adverse Event <ul><li>Signs and Symptoms </li></ul><ul><ul><li>Hyperglycemia (glucose: 250-800mg/dl) </li></ul></ul><ul><ul><li>Volume depletion </li></ul></ul><ul><ul><li>High anion gap metabolic acidosis </li></ul></ul><ul><ul><li>Hypokalemia </li></ul></ul><ul><ul><li>Glucosuria </li></ul></ul><ul><ul><li>Urine ketosis </li></ul></ul><ul><ul><li>Hyperosmolality </li></ul></ul><ul><ul><li>Patients present with tachycardia, polydipsia, abdominal pain, nausea, vomiting and coma </li></ul></ul>
  41. 41. Monitoring Diabetes <ul><li>Assess nutrition and physical activity regularly </li></ul><ul><li>Blood pressure each visit </li></ul><ul><li>Alcohol and smoke cessation </li></ul><ul><li>Self-Monitoring Blood Glucose </li></ul><ul><li>Foot care </li></ul><ul><li>Assess for peripheral neuropathy </li></ul><ul><li>Monitor HgA1c every 3-6 months </li></ul><ul><li>Lipid profile yearly </li></ul><ul><li>Annual dilated eye examination </li></ul><ul><li>Thorough annual physical exam Renal assessment for microalbuminuria </li></ul><ul><li>Cardiovascular complications </li></ul><ul><li>Influenza vaccine yearly </li></ul><ul><li>Pneumococcal vaccine every 5 years </li></ul><ul><li>Assess for PVD </li></ul><ul><li>Retinopathy </li></ul>
  42. 42. Counseling Points <ul><li>Mixing Insulin: </li></ul><ul><ul><li>Pt’s well controlled on mixed insulin regimen -> maintain their standard procedure. </li></ul></ul><ul><ul><li>No other medication or diluents should be mixed with insulin. </li></ul></ul><ul><ul><li>Glargine (LANTUS) should not be mixed with any insulin. </li></ul></ul><ul><ul><li>Use of commercially available premixed insulins may be used if insulin ratio is appropriate to Pt insulin requirement. </li></ul></ul><ul><ul><li>NPH and short-acting insulin when mixed can be used immediately or stored for future use </li></ul></ul>
  43. 43. Counseling Points <ul><li>Clear insulin drawn into syringe first </li></ul><ul><li>Rapid-acting insulin can be mixed with NPH and lente </li></ul><ul><li>When rapid acting insulin is mixed with either an intermediate or long-acting insulin -> mixture should be injected within 15 min before meal. </li></ul><ul><li>Mixing of short-acting and lente insulin is not recommended except for Pt already adequately controlled on such mixture. </li></ul><ul><li>Phosphate-buffered insulins (NPH) should not be mixed lente insulin </li></ul>
  44. 44. Counseling Points <ul><li>Storage : </li></ul><ul><li>Unopened vials, cartridges and pens. </li></ul><ul><ul><li>If refrigerated use until expiration date </li></ul></ul><ul><ul><li>If room temperature, use within 28 days </li></ul></ul><ul><li>Opened </li></ul><ul><ul><li>Vials within 28 days at room temperature or refrigerated </li></ul></ul><ul><ul><li>Pen and pen cartridges within 28 days at room temperature ( do not refrigerate ) </li></ul></ul><ul><li>Do not use if insulin has been frozen or exposed to high temperatures (<2 º C or > 30 º C). </li></ul><ul><li>Excess agitation should be avoided </li></ul>
  45. 45. Insulin Administration <ul><li>Check vial before use to inspect for changes -> loss of potency </li></ul><ul><li>Vial and pens should be rolled in palms of hands before drawing with needle -> except with rapid and short acting insulin </li></ul>
  46. 46. Insulin Delivery Devices <ul><li>Insulin pens </li></ul><ul><ul><li>Pens with cartridges -> users turn a dial to select the desired dose of insulin -> press a plunger on the end to deliver insulin </li></ul></ul><ul><ul><li>Needle should be embedded within skin for 5 seconds after complete depression of plunger </li></ul></ul><ul><ul><li>Air bubbles in pen reduces rate of insulin flow </li></ul></ul><ul><ul><li>Avoid leaving needle on pen between injections and prime needle with 2 units of insulin </li></ul></ul>
  47. 47. Counseling Points <ul><li>Injection Site: </li></ul><ul><li>Subcutaneous tissue of upper arm. </li></ul><ul><li>Anterior and lateral aspects of the thigh, buttocks, and abdomen </li></ul><ul><li>IM not recommended </li></ul><ul><li>Rotation of injection site recommended </li></ul><ul><ul><li>Prevent lipohypertrophy and lipoatrophy </li></ul></ul><ul><ul><li>Rotating within one area is recommended </li></ul></ul>
  48. 48. Injection Site <ul><li>Variable absorption between sites </li></ul><ul><ul><li>Abdomen > arms >thighs > buttocks </li></ul></ul><ul><li>Exercise ↑ rate of absorption </li></ul><ul><li>Areas of lipohypertrophy have slower absorption. </li></ul><ul><li>IM > SC absorption </li></ul>
  49. 49. Preventing Painful Injections <ul><li>Inject insulin at room temp </li></ul><ul><li>Make sure no air bubbles remain in syringe before injection </li></ul><ul><li>Wait for topical alcohol to evaporate before injection </li></ul><ul><li>Relax muscle at injection site at time of injection </li></ul><ul><li>Penetrating skin quickly </li></ul><ul><li>Not changing direction of needle during insertion or withdrawal </li></ul>
  50. 50. Conclusion <ul><li>Diabetes complex disease state </li></ul><ul><li>Requires diligent daily monitoring </li></ul><ul><li>Requires coordination of care </li></ul><ul><li>Requires strong patient knowledge base </li></ul><ul><li>Requires enthusiastic pharmasist intervention </li></ul>
  51. 51. Questions
  52. 52. References <ul><li>http://guidelines.gov/summary/summary.aspx?doc_id=7212&nbr=004306&string=diabetes , accessed 03/06 </li></ul><ul><li>Treatment Guidelines from The Medical Letter. Volume 3, Issue 36. August 2005 </li></ul><ul><li>Symlin, [Package insert] Amylin Pharmaceuticals, Inc. San Diego CA </li></ul><ul><li>http://products.sanofi-aventis.us/apidra/apidra.html , accessed 03/06 </li></ul>
  53. 53. References <ul><li>Harrison's Principles of Internal Medicine - 16th Ed. (2005) </li></ul><ul><li>American Diabetes Association: Evidence based nutrition principles and recommendations for the treatment and prevention of diabetes and realted complications (Position statement). Diabetes Care. 2002;25: S50-60. </li></ul><ul><li>http://www.diabetes.org/home.jsp , accessed 03/06 </li></ul>