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Diabetes in the Transplant Patient

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  1. Diabetes in the Transplant Patient Susan Alexander, DNP, CNS, CRNP, BC-ADM College of Nursing University of Alabama in Huntsville Clinical Affiliation: Outpatient Diabetes Self-Management Education Crestwood Medical Center Huntsville, AL

  2. Diabetes in the Transplant Patient • Describe factors associated with worsening of DM control in the patient with pre-TXP DM. • Describe risk factors associated with development of DM in the post-TXP patient • Discuss management strategies for optimization of DM control in the post-TXP patient.

  3. Definition of Diabetes • Diabetes Mellitus: Heterogeneous Condition With Hyperglycemia and Common Complications • Insulin Deficiency: Relative or Absolute

  4. Risk Factors for Post Transplant Diabetes Diabetes occurs post transplant at rate of: 9% at 3 months 16% at 12 months 24% at 36 months Risk factors: Age >40-45, Obesity, AA and Hispanic Race, Family History, Hepatitis C and CMV, Polycystic kidneys Post-transplant Diabetes Mellitus in Renal Transplant Recipiants. Tobin, G et al, UpToDate, May 31, 2008.

  5. Diabetogenic Factors and Screening for Diabetes • Calcineurin Inhibitors Reversible islet cell toxicity, (tacrolimus) • Glucocorticoids are insulin antagonists that insulin resistance, hepatic glucose production and inhibit glucose transport into cells • Screening for Diabetes: -Monitor blood sugar prior to transplant -Monitor blood sugar post transplant with FBS weekly X4, recheck in 3 months, 6 months and annually thereafter Post-transplant Diabetes Mellitus in Renal Transplant Recipients. Tobin, G et al, UpToDate, May 31, 2008.


  6. Hyperglycemia in Type 2 Diabetes Peripheral Tissues (Skeletal Muscle andAdipose Tissue) Pancreas Impaired Insulin Secretion Glucose Increased Glucose Production Insulin Resistance Liver Fat Adapted from Kruszynska YT, et al. J Invest Med. 1996;44:413-428. Henry RR. Ann Intern Med. 1996;124:97-103.

  7. Pre-existing Diabetes • Type 1: -Steroids increase insulin requirement and dose -Insulin dose will increase from ESRD to having a working kidney • Type 2 -Cannot use all oral agents -Usually require insulin -Insulin and/or oral agent dose will increase from ESRD to having a working kidney

  8. Chronic Effects of Diabetes • Large blood vessel disease MI, stroke, peripheral artery disease and LE amputation • Small vessel disease retinopathy/vision loss and blindness, kidney damage/renal failure • Neuropathy with pain, loss of protective sensation

  9. Managing Diabetes In Hospitalized Patients • Hyperglycemia • Severe hyperglycemia (BG>250) • Does improving glycemic control relate to improved outcomes for patients? • Medical ICU, CV surgery and general surgery patients have higher risk of death if hyperglycemia is present.

  10. Factors Effecting Treatment Strategies in Hospitalized Patients • Medications • Food intake • Tests and procedures • Prior history • Nutritional status Inzucchi, S. N Engl J Med 2006;355:1903-11

  11. Insulin Treatment of Patients in ICU • IV insulin infusion • Hourly BG monitoring • Transition to subcutaneous • Overlap IV and subcutaneous Insulin • Type 2 DM with <2u/h Inzucchi, S. N Engl J Med 2006;355:1903-11

  12. Insulin Use in Non-ICU Setting Before meals: • Regular insulin (R) - Rapid-actingAnalog Correction Dose: insulin sensitive/resistant Adjust dose based on BG before lunch, supper or HS Inzucchi, S. N Engl J Med 2006;355:1903-11

  13. Guidelines for Glycemic Targets in Hospitalized Patients • ADA: ICU target = As close to 110 as possible and <180. General med. target = 90-130 and <180 after meals. • ACE: ICU target = <110. General med. Target = <110 with max of 180. • Guidelines are controversial, not based on clinical data from non-ICU patients. Inzucchi, S. N Engl J Med 2006;355:1903-11

  14. Insulin Dosing in Hospital: Impact of Nutrition Status • No Food Intake: Give IV infusion or basal insulin qd or bid + regular or rapid acting analog q 6h based on blood glucose. • Continuous Enteral Feeding: Basal insulin + correction dose q 6h. If feeding interrupted, give IV glucose to prevent hypoglycemia. • Total Parenteral Nutrition: Add regular insulin to IV bag and titrate dose in increments of 5-10u/liter. • Reassess insulin requirement with any change in nutritional status. Inzucchi, S. N Engl J Med 2006;355:1903-11

  15. Proposed Moderate Glycemic Targets and Insulin Dosing in Hospitalized Patients • Medical and surgical ICU targets: Suggest <140 and consider <110 • IV insulin allows more rapid titration and absorption in critically ill • Non critically ill target: 90-150 pre meals • Adjust dose q 1-2 days to optimize glycemic control ASAP Inzucchi, S. N Engl J Med 2006;355:1903-11

  16. Proposed Moderate Glycemic Targets and Insulin Dosing in Hospitalized Patients (Cont’d) • Before making insulin adjustment, consider factors that can cause hyperglycemia: -Missed insulin doses -Snacking -Infection -BG testing and/or insulin administration after versus before meals • Frequent monitoring and dose adjustment is essential. Adjust dose based on fingerstick BG before each meal and HS. • Transition to out patient regimen requires education of patient and a manageable regimen.

  17. Transition to Subcutaneous Insulin: Basal Insulin Dose • Insulin NPH QD or BID 0.2-0.3 u/kg/day or 50% of IV insulin dose • Insulin Detemir QD or BID 0.2-0.3 u/kg/day or 50% of IV insulin dose • Insulin Glargine Q day 0.2u/kg/day or 50% of IV insulin dose

  18. Transition To Subcutaneous Insulin: Meal Dose Insulin • Regular, Lispro, Aspart, Glulisine • 0.20 units/kg/meal or 50% of IV insulin dose type 2 Diabetes • 0.30 units/kg/meal or 50% of IV insulin dose High Steroid Dose • Consistent carb intake across meals (45-60 grams/meal) to avoid hypo- and hyperglycemia • Adjust each dose by 10-20 % q 1-2 days until pre-meal BG is in target

  19. Outpatient Management of Diabetes: ADA Glycemic Targets ADA Recommendation: Check A1c at least 2 x/yr if in target and stable; q 3 months if therapy has changed or not meeting goals. Diabetes Care 29:S4-S42, 2006 Diabetes Care 29:S4-S42, 2006 *As close to 6.0% as possible

  20. Self Blood Glucose Monitoring • Provides vital data for clinical decision making • Provides patient with accountability and feedback about his/her behavior • Advise patient about: -Appropriate meter -When to test -How to record results -How to interpret and respond to results -Insurance/financial issues, prescription required for reimbursement

  21. The Plate Method

  22. DM Management Strategies: Increase Physical Activity • Set small, reasonable goals: Something is better than nothing • Long term goal: Aerobic activity 30 minutes per day, 5 days per week, 1-3 sessions per day; resistance/strength training 3x/week

  23. Exercise for Patients with Limited Mobility • Chair exercises • Strength training • Water exercise

  24. Walking Leads to Reductions in Mortality in People with Diabetes • 2896 adults with DM interviewed from 1990-1991 • Outcomes: All cause and CVD mortality over 8-years RESULTS: • Walking 17-minutes/day 39% in all cause mortality; 34% in CVD • Walking 30 minutes/day 46% all cause mortality; 47% in CVD Arch Intern Med. 2003 Jun 23;163(12):1440-7.

  25. Matching Pharmacology to Pathophysiology Glucose Influx Sulfonylureas MeglitinidesInsulin, DPP4 AGI Hepatic Glucose Output InsulinSecretion Hyperglycemia Biguanides, TZD, DPP4, Insulin TZDBiguanides Insulin PeripheralGlucose Uptake 25

  26. Oral Diabetes Meds DPP4Inhibitorsinsulin secretion Sitagliptin (Januvia®) glucagon secretion. Saxagliptin (Onglyza®)

  27. GI tract Glucose-dependent insulin from beta cells (GLP-1 and GIP) Glucose uptake by muscles Blood glucose Glucose production by liver Glucagon from alpha cells (GLP-1) Glucose dependent Effects of Incretin Hormones Pancreas2,3 2,4 Release of gut hormones — Incretins1,2 Ingestion of food β-cells α-cells Active GLP-1 & GIP DPP-4 Enzyme Inactive GLP-1 and GIP • Active incretins physiologically regulate glucose by modulating insulin secretion in a glucose-dependent manner. • GLP-1 also modulates glucagon secretion in a glucose-dependent manner. 1. Kieffer TJ, Habener JF. Endocr Rev. 1999;20:876–913. 3.Drucker DJ. Diabetes Care. 2003;26:2929–2940. 2. Ahrén B. Curr Diab Rep. 2003;2:365–372. 4. Holst JJ. Diabetes Metab Res Rev. 2002;18:430–441 .

  28. Incretin Mimetics: Exenatide (Byetta®) and Liraglutide (Victoza®): Clinical Use • Treatment of type 2 diabetes in patients on metformin or sulfonylurea and not taking insulin • Byetta 5 mcg bid x 1 month, the 10 mcg bid within 1 hour of meal • Liraglutide 0.6 mg per day for one week, then 1.2 mg daily with max. dose ofto 1.8 mg (2).

  29. Incretin Mimetics: Exenatide (Byetta®) and Liraglutide (Victoza®): Mechanism of Action • Stimulates first phase insulin release by pancreas when glucose levels are elevated • Reduces glucagon secretion • Slows Gastric Emptying (gastric emptying is accelerated in diabetes) • Reduces caloric intake by promoting satiety

  30. AmylinomimeticsPramlintide (Symlin®) • Symlin=synthetic Amylin. Amylin is co-secreted with insulin by pancreatic beta cells in response to food intake. • Reduces Postprandial Glucagon • Postprandial Glucagon is Excessive andNot Corrected by Exogenous Insulin in Diabetes • Slows Gastric EmptyingGastric Emptying Is Accelerated in Diabetes • Reduces Caloric Intake by promoting satiety *** Slowed gastric emptying will effect immunosuppressive drug levels***

  31. Insulin As A Drug • Described by duration of action -Absorption -Clearance Maintenance Insulin (Basal) -Dose effectiveness evident in fasting blood glucose -Dose is based on body mass and insulin sensitivity Meal Insulin -Impacts post prandial blood glucose -Dose based on meal timing and size, insulin sensitivity

  32. Breakfast Dinner Lunch 100 U/mL) m 80 60 Fasting 40 Serum insulin concentration ( 20 0 9:00 7:00 9:00 3:00 7:00 3:00 7:00 23:00 11:00 13:00 15:00 17:00 19:00 21:00 23:00 11:00 15:00 19:00 Normal Endogenous Insulin Secretion Insulin is normally produced endogenously at a constant (i.e., basal) rate of 0.5 - 1.0 units/hour as well as in response to increases in blood glucose concentration after a meal.

  33. INSULIN TYPES AND ACTIONS

  34. Insulin Types and Action

  35. Idealized Insulin Action Times

  36. The Basal/Bolus Insulin Concept • Basal Insulin – NPH, Levemir, Lantus • 50% of daily needs • Suppresses glucose production between meals and overnight Bolus Insulin (Mealtime or Prandial) Novolog, Humalog, Apridra Regular • Limits hyperglycemia after meals • Immediate rise and sharp peak at 1 to 1½ hour • 10% to 20% of total daily insulinrequirementat each meal

  37. Pre-mixed Insulin Protamine + Short or Rapid-Acting Insulin -Novolin 70/30® = 70% NPH+30% Regular -Humulin 70/30®, Humulin 50/50® -Humalog 75/25® = 75% NPL+25% Lispro -Novolog 70/30® = 70% NPH + 30% Aspart Onset: 0.5-2.5 hours Time to Peak: 4-8 hours Duration: 17-25 hours Clinical Use: Elderly, cognitive or psych. impairment, multiple co-morbid illnesses

  38. Average Retail Cost Of Insulin In 2009*(10ml,1000 u in vial or 15ml,1500u in pens**) • Humalog/Novolog 10ml • Humalog/Novolog cartridges 15ml • Lantus 10ml vial • Hum/Novo R,N, 10ml vial • Hum/Novo, R, N Pen, cartridges 15ml • $112.00 • $225.00 • $107.99 • $47-64.00 Walmart $20.00 • $130-150.00 * 1 vial = 30-day supply if using <33u per day ** 5 pens of 3ml each = 15ml, 1500 units

  39. Challenges of Diabetes Management in Transplant Patients • Fluctuating prednisone dose requires frequent monitoring of blood sugar and flexibility in insulin and/or oral medication dosing • Prednisone will increase appetite • Insulin or oral medication doses will increase after kidney transplant

  40. Outpatient Follow-up • Adjust dose and number of injections based on home capillary glucose readings • Monitor in 1-2 week intervals • Steroid-induced hyperglycemia is less severe when dose is < 10mg/day • Prednisone dosed in morning elevated lunch and suppertime glucose, minimally elevated FBG

  41. Continuous Glucose Monitoring Sensor Continuous, automatic monitoring of glucose in the subcutaneous tissue

  42. Hypoglycemia • Target blood glucose 70-120 mg/dl • Below 70: Rule of 15 • Causes • Severe Hypoglycemia - rare • Hypoglycemia Unawareness