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
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.
Definition of Diabetes • Diabetes Mellitus: Heterogeneous Condition With Hyperglycemia and Common Complications • Insulin Deficiency: Relative or Absolute
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.
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.
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.
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
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
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.
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
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
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
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
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
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
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.
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
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
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
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
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
Exercise for Patients with Limited Mobility • Chair exercises • Strength training • Water exercise
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.
Matching Pharmacology to Pathophysiology Glucose Influx Sulfonylureas MeglitinidesInsulin, DPP4 AGI Hepatic Glucose Output InsulinSecretion Hyperglycemia Biguanides, TZD, DPP4, Insulin TZDBiguanides Insulin PeripheralGlucose Uptake 25
Oral Diabetes Meds DPP4Inhibitorsinsulin secretion Sitagliptin (Januvia®) glucagon secretion. Saxagliptin (Onglyza®)
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 .
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).
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
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***
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
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.
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
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
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
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
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
Continuous Glucose Monitoring Sensor Continuous, automatic monitoring of glucose in the subcutaneous tissue
Hypoglycemia • Target blood glucose 70-120 mg/dl • Below 70: Rule of 15 • Causes • Severe Hypoglycemia - rare • Hypoglycemia Unawareness