1. Type I Diabetes: Adult Case Study Presented by: Sarah Devries, Jamie Hillman, Mary Ann Hudson, and Heather Usher The Ohio State College of Nursing August 2, 2010

2. Client Chief Complaint and Past Medical History 45-year-old caucasian female with chief complaints of fatigue, weight-loss of 20 pounds in one month, extreme thirst, and frequent urination. Patient has changed eyeglass prescription twice in six months. Patient has abandoned near-daily aerobic exercise due to fatigue, denies anorexia, dysuria, abnormal stress, recreational drug use, ETOH abuse, smoking, prior hospitalizations, allergies,or chronic disease.

3. Client Social and Family History Client lives with husband of 21 years and two children aged 16 and 17. Husband is employed as high school teacher, client is 22 year employee of a company as an accountant. Client states family life is busy and enjoyable. Client denies abnormal social or familial stressors. Client’s mother is alive with not significant medical history. Father is alive and diagnosed with hypertension managed well with ACEi. Grandparents deceased. Only grandparent history is that paternal grandfather died of MI at 62.

4. Client Physical Exam Ht: 5’7” Wt: 130 lbs VS: 128/78, 72, 20 All physical findings in head to toe exam, including cranial nerve exam, are within normal limits.

5. Client Diagnostic Laboratory Results and Diagnosis Fasting Blood Glucose: 250 HbA1c: 9 Ketones: Negative Diagnosis is Type I Diabetes Mellitus

6. Diagnosis Criteria for Type I Diabetes Mellitus Diagnostic Criteria Symptoms of diabetes (polyuria, polydipsia, unexplained weight loss) Plus casual plasma glucose concentration ≥200 mg/dL or Fasting plasma glucose concentration ≥126 mg/dL or 2-hour postchallenge glucose concentration ≥200 mg/dL during a 75-g oral glucose tolerance test One of the 3 criteria listed is sufficient to establish the diagnosis of diabetes mellitus. These assessments should be confirmed by repeated testing on a subsequent day in the absence of unequivocal hyperglycemia. 1

7. Brief Pathophysiological Review of Type I Diabetes Mellitus Type 1 Diabetes Mellitus Accounts for only 5% to 10% of all diabetes mellitus cases. Caused by an absolute deficiency of insulin secretion due to a cellular-mediated autoimmune destruction of the pancreatic β-cells. Viruses associated with initiation of β-cell destruction include congenital rubella, coxsackievirus B, cytomegalovirus, adenovirus, and mumps. Rate of β-cell destruction varies. Infants and children often experience rapid β-cell destruction; rate of destruction is usually slower in adults. Individuals at increased risk can often be identified by serological evidence of an autoimmune pathologic process occurring in the pancreatic islet cells and by genetic markers. 2

8. Treatment and Therapeutic Objectives Guidelines Established by American Academy of Clinical Endocrinologists Academy partners with American Diabetes Association for Patient Information and Education

9. Therapeutic Objectives of Client Treatment Plan Encourage patients to achieve glycemic levels as near normal as possible without inducing clinically significant hypoglycemia (grade A AACE Guideline); glycemic targets include: HbA1c ≤6.5% Fasting plasma glucose concentration <110 mg/dL 2-hour postprandial glucose concentration <140 mg/dL 3

10. Therapeutic Objectives of Client Treatment Plan Refer patient for comprehensive, ongoing education in diabetes self-management skills and nutrition therapy (grade A AACE Guideline); education should: Be provided by a qualified health care professional Focus on all aspects of diabetes self- management relevant to each patient treatment plan Promote behavioral changes to support effective and consistent application of the prescribed diabetes treatment plan and an overall healthy lifestyle Be continued as an ongoing intervention to accommodate changes in the treatment plan and patient status Initiate self-monitoring of blood glucose levels 4

11. Specific Therapeutic Objectives for Treatment of DM I Patient 1.Obtain baseline glycemic profile including HbA1c, fasting BG, pre/postprandial BG for 7 days 2.After initiation of Rx therapy, monitor and titrate patient for 2-3 months until ideal glycemic profile is achieved 3. If glycemic goals are NOT achieved, intiate more intense therapy and monitor and titrate patient for another 2-3 months until ideal glycemic profile is achieved.

12. Specific Therapeutic Objectives for Treatment of DM I Patient 4.Instruct patient to always check BG before injection of insulin or before insulin pump adjustment 5.Instruct patient if meeting BG target check BG 4x/day. If NOT meeting BG target, check BG pre/postprandial, 2 hours postprandial, and 2 or 3 a.m. spot checks 6.Instruct patient to check BG with suspected hypoglycemia, when at risk for hypoglycemia, or before driving 7.Instruct patient to check BG more frequently during illness or intense exercise 8.Instruct patient to check ketones after a BG reading of 250 mg/dL or above. 9. Instruct patient to recognize the signs and symptoms of hypoglycemia and how to treat it 5

13. DCCT Trial--Clinical Guidelines Diabetes control and Complications Trial Study with 29 medical centers and 1400 patients with Type 1 between the ages of 13 and 39 with diabetes for at least one year. Study ran from 1983-1993 Objectives: to compare the effect of standard diabetes therapy to intensive diabetes therapy and to determine if type of insulin therapy had an effect on preventing complications from diabetes. Findings:Patients in the intensive insulin therapy group had 76% reduced risk of retinopathy, 50% reduced risk of nephropathy, 60% reduced risk of neuropathy, 57% reduction in nonfatal heart attacks, strokes, and heart disease, 35% reduction in LDL, and an average HgbA1C of 7.2% Findings were so significant, the study ended 2 years early Recommendations:Check BG 4 times daily. Administer at least 4 injections of rapid- acting insulin daily or bolus at least 4 times with pump therapy. Adjust insulin doses for food and exercise. Keep scheduled appointments with health care team.

14. Team Approach for Therapeutic Objectives for Treatment of DM I Managing diabetes mellitus requires a team approach to patient care. However, because diabetes is primarily a self-managed disease, education in self-management skills is essential in implementing interventions. Initial and ongoing self- management education must be made available to all patients with diabetes mellitus. Self-management education improves HbA1c levels, and increased contact time with educators enhances the positive effect. 6

15. Drug Classes Used to Treat Type I Diabetes

16. Pancreatics--Rapid Acting

19. Pancreatics--Short Acting

20. Pancreatics--Intermediate Acting

21. Pancreatics--Long Acting

23. Pancreatics--Mixtures

26. Hormones

27. Type I DM P-Drug Tables

32. Rationale for Selecting P-drug (Rapid- Acting Insulin)

33. Rationale for Selecting P-drug (Long- Acting Insulin)

34. Selected p-drug combination: insuline glargine (Lantus) + insulin aspart (Novolog) Rationale for choosing combined therapy of insulin glargine (Lantus) + insulin aspart (Novolog) Recommended therapy according to American Diabetes Association Clinical Guideline 2010: Recommended therapy for type 1 diabetes consists of the following components: 1) use of multiple dose insulin injections (3 to 4 injections per day of basal and prandial insulin) or continuous subcutaneous insulin infusion (CSII) therapy; 2) matching of prandial insulin to carbohydrate intake, premeal blood glucose, and anticipated activity; and 3) for many patients (especially if hypoglycemia is a problem), use of insulin analogs. Less expensive than CSII therapy, despite no difference in glycemic control (Bolli et al, 2009)

35. Rationale for choosing insulin glargine Can be given just 1 time daily (usually at night before bed) – better compliance Proven to provide better glycemic control when used with rapid-acting insulin (like insulin aspart or lispro) than compared to NPH and regular insulin therapy (Sharplin et al, 2009)

36. Rationale for choosing insulin aspart Shown to be as effective in stabilizing blood glucose rapidly as insulin lispro (Homko et al, 2003) More cost effective than insulin lispro

37. Insulin Main Action: Lower blood glucose by stimulating glucose uptake in skeletal muscle and fat Also inhibit lipolysis and proteolysis, enhances protein synthesis Indication: Control of hyperglycemia in patients with Type I or Type II Diabetes Mellitus

38. Pharmacokinetics & Pharmacodynamics

39. Drug Cautions Contraindications: Hypoglycemia Allergy or hypersensitivity to insulin glargine Caution: Stress, infection – decrease insulin requirements Renal or hepatic impairment – may decrease insulin requirements Pediatrics – safety not established in pts < 6yrs old Pregnancy – may temporarily increase insulin requirements Adverse Reactions/Side Effects: Endo: Hypoglycemia Local: lipodystrophy, pruritus, erythema, swelling Misc: allergic reactions (anaphylaxis)

40. Drug Interactions Interactions Drug-drug: Beta-blockers, clonidine, reserpine – may mask signs/sx of hypoglycemia Corticosteroids, thyroid supplements, estrogens, isoniazid, niacin, phenothiazines, rifampin – may increase insulin requirements Alcohol, ACE inhibitors, MAO inhibitors, salicylates – may decrease insulin requirements Drug-herbal: Glucosamine – may worsen blood glucose control Fenugreek, chromium, conenzyme q10 – may give additive hypoglycemic effects

41. Patient Education & Teaching

42. Determining Insulin regimen To determine total daily dose of insulin in units = (Multiply by 0.3 to 0.6) x (weight in kg) Example of Beth: (0.3) x (58.967) = 17.7 ~ 17 units May need to increase insulin requirements later depending on glucose control 40-50% of daily insulin requirements will be given in long-acting insulin (insulin glargine) Example of Beth: 17 units / 2 = 8.5 units Rest of insulin requirements to be given throughout the day with meals and snacks as rapid-acting insulin (insulin aspart)

43. Carbohydrate Coverage Example: if your insulin to carbohydrate ratio is 1:10  and you eat 20 g of carbs for lunch  20 g/10 = 2 units of insulin to cover your meal Correction factor for high glucose: [(Actual blood sugar) – (Target blood sugar)] / [Correction Factor] Total Meal Dose = (units for CHO) + (units for high glucose correction) Example: if Beth’s pre-lunch glucose is 220 mg/dL and her target is 120 mg/dL with a correction factor of 50, and she plans to eat 20 g of carbs (with a insulin to carb ratio of 10) High sugar correction = (220 – 120)/(50) = 2 units CHO = 20/10 = 2 units Total meal insulin = 2 units + 2 units = 4 units

44. Storage/Preparation Do not mix insulin glargine with any other insulin or solution; do not use same syringe May mix insulin aspart with other types of insulin First draw insulin aspart into syringe Store unopened vials and cartridges in refrigerator; do not freeze

45. Administration Give insulin glargine at approximately the same time every day, usually before bedtime Give insulin aspart right before or right after meals Importance of selection & rotation of injection sites (abdominal wall, thigh, or upper arm) Importance of compliance with regimen

46. Monitoring Instruction in proper testing of serum glucose 3 or more times per day (ADA Clinical Guidelines, 2010) Before all meals Instruction in testing of ketones Especially important during times of stress or illness Instruction in signs/sx of hypoglycemia Nervousness, sweating, hunger, trembling, weakness, palpitations Carry around source of glucose at all times (candy, glucose gel) Monitoring Hemoglobin A1C (goal < 7%) 2-3 times per year in patients with good glycemic control 4 times per year in patients whose glucose needs have changed or who show poor glycemic control

47. Follow/Up Schedule a visit to office in 2-3 days to go over blood glucose readings, correction factors, and carbohydrate ratios in order to optimize insulin requirements Schedule appointment for 3 month follow up visits to monitor Hgb A1c and fasting blood glucose until treatment is stable Encourage pt to maintain physical activity routine and encourage healthy eating Encourage yearly appointments with primary care provider to monitor cardiovascular health, esp d/t family history

48. Are they both in the Ohio Board of Nursing Formulary? Yes, under Section 3 – Endocrine & Metabolic Agents – INSULIN Note: If giving insulin aspart as IV, must do so with institution approved protocol May APNs prescribe? Yes, with CTP

49. Example of Written Prescription: Gus Hudson-Vadnais, CFNP 123 Somewhere Road, Columbus, OH 43210 614-123-4567 (office) Date of Prescription: Aug 2, 2010 Patient Name: Beth Smith Patient Weight:130 lbs (58.967 kg) Patient Address: 123 Somewhere Road, Columbus, OH 43210 Rx: Insulin glargine, 5 x 3mL cartridges for use with OptiPen One Insulin Delivery Device –o Give 8.5 units one time a day at bedtime –o Administer to back of arm, thigh, or abdomen Insulin aspart, 5 x 3mL cartridges (100 units/mL) –o Pt taking up to 10 units per day. Dose subject to change as ratios change –Take blood glucose reading prior to each meal –o Administer insulin aspart based on appropriate carbohydrate ratio and high blood sugar correction factor Please schedule a follow-up visit to my office in 2-3 days. Prescriber Signature: Gus Hudson-Vadnais Date: 8-2-2010

50. Clinical Studies

51. Homko, C., Deluzio, A., Jimenez, C., Kolaczynski, J. W., & Boden, G. (2003). Comparison of insulin aspart and lispro: pharmacokinetic and metabolic effects. Diabetes Care, 26(7), 2027-31. Objectives: To compare insulin levels and actions in patients with type 1 diabetes after subcutaneous injection of the rapid-acting insulin analogs aspart and lispro. Population: 7 patients with type I diabetes (2 male, 5 female) 5 used insulin pumps (CSII) 2 used MDI regimen Method: Participants were studied at the General Clinical Research Center at Temple University Hospital two times, 1 month apart Plasma glucose was normalized overnight by intravenous infusion of insulin next morning, they received SQ injections of either aspart or lispro in random order Over the next 4–5 h, their plasma glucose was clamped at ~5.5 mmol/l with a variable infusion of 20% glucose. Study ended after 8 h Results: Actions of both insulin lispro and aspart are the same in terms of effect on carbohydrate and lipid metabolism Found them to be equally effective in treating diabetic patients

52. Bolli, G. B., Kerr, D., Thomas, R., Torlone, E., Sola-Gazagnes, A., Vitacolonna, E., Selam, J. L., & Home, P. D. (2009). Comparison of a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) in type 1 diabetes: a randomized open parallel multicenter study. Diabetes Care, 32(10), 1170-76.Comparison of a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) in type 1 diabetes: a randomized open parallel multicenter study. Objectives: to assess the difference in glycemic control when people with type 1 diabetes using NPH insulin-based MDIs Population: 58 participants ages 18–70 years from 3 European countries – oBMI ≤ 27.0 kg/m2 – odiabetes for > 1 year – oHbg A1c between 6.5–9.0% – ocurrently using an MDI regimen with NPH insulin Excluded participants with hepatic or renal impairments Method: People with type 1 diabetes on NPH-based insulin therapy were randomized to CSII or glargine-based MDI (both otherwise using lispro) Participants asked to perform 3-4 daily insulin checks (before meals and bedtime) Results: Both regimens showed similar results in terms of insulin dose, blood glucose control, hypoglycemic events, treatment satisfaction Cost was lower for MDI regimen

53. Sharplin, P., Gordon, J., Peters, J. R., Tetlow, A. P., Longman, A. J., & McEwan, P. (2009). Improved glycaemic control by switching from insulin NPH to insulin glargine: a retrospective observational study. Cardiovascular Diabetology, 8(3), 1- 8. Objectives: To assess the impact on hemoglobin A1C, weight, and insulin use of switching from NPH (Neutral Protamine Hagedorn) to insulin glargine Population: 701 total patients from a United Kingdom primary care network 304 (43%) with type 1 diabetes 397 (57%) with type 2 diabetes Method: 24 month, nonrandomized, retrospective observational study Data extracted from a UK primary care database (The Health Improvement Network) between 2002-2005 Patients were required to have at least 12 months of data before and after switching from NPH to glargine Primary analysis: the change in HbA1c after 12 months treatment with insulin glargine Secondary analyses: change in weight and total daily insulin dose Results: in diabetes patients treated with NPH and with evidence of suboptimal efficacy and/or poor tolerability, switching to insulin glargine offers opportunity for improved glycaemic control

54. References--Materials American Diabetes Association (2010). Standards of medical care in diabetes. V. Diabetes care. Diabetes Care, Suppl 1: S16-29. Blong, Lawrence, et. al. (2007). American association of clincal endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus.Endocrine Practice, Vol. 13 (Suppl 1: footnotes in powerpoint 1-6. Bolli, G. B., Kerr, D., Thomas, R., Torlone, E., Sola-Gazagnes, A., Vitacolonna, E., Selam, J. L., & Home, P. D. (2009). Comparison of a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) in type 1 diabetes: a randomized open parallel multicenter study. Diabetes Care, 32(10), 1170-76. Comparison of a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) in type 1 diabetes: a randomized open parallel multicenter study. Davis’s Drug Guide (2000-2010). Unbound Medicine [PDA software]. Diabetes Education Online (2010). Diabetes Teaching Center at the University of San Francisco. Retrieved July 23, 2010 from http://www.deo.ucsf.edu/type1/diabetes-treatment/medications-and-therapies/type-1-insulin-rx/calculating- insuliin-dose.html.http://www.deo.ucsf.edu/type1/diabetes-treatment/medications-and-therapies/type-1-insulin-rx/calculating- insuliin-dose.html Homko, C., Deluzio, A., Jimenez, C., Kolaczynski, J. W., & Boden, G. (2003). Comparison of insulin aspart and lispro: pharmacokinetic and metabolic effects. Diabetes Care, 26(7), 2027-31. Katzung, B. G, Masters, S.B., & Trevor, A. J. (2009) Basic & Clinical Pharmacology (11 th ed). New York: The McGraw- Hill. ISBN: 978-0-07-160405-5. Sharplin, P., Gordon, J., Peters, J. R., Tetlow, A. P., Longman, A. J., & McEwan, P. (2009). Improved glycaemic control by switching from insulin NPH to insulin glargine: a retrospective observational study. Cardiovascular Diabetology, 8(3), 1-8.

55. References--Tables Katzung, B.G., Masters, S.B., & Trevor, A.J. (2009) Basic and Clinical Pharmacology (11th ed). New York: The McGraw-Hill. Lehne, R.A., (1998). Pharmacology for nursing care (3rd ed.). Philadelphia: W.B. Saunders Company. Deglin, J.H. & Vallerand, A.H. (1999) Davis's Drug Guide (6th ed). Philadelphia: F.A. Davis Company. Epocrates Rx (2010). [database for PDA, Version 8.10]. San Mateo, CA: Epocrates, Inc. available from: http://www.epocrates.com.http://www.epocrates.com