1. 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.  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.  Diabetes Mellitus: Heterogeneous Condition With Hyperglycemia and Common Complications  Insulin Deficiency: Relative or Absolute

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

7.  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.  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.  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.  Medications  Food intake  Tests and procedures  Prior history  Nutritional status Inzucchi, S. N Engl J Med 2006;355:1903-11

11.  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. 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.  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.  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.  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.  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.  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.  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. NormalGoal HbA1c4-6%<7% * Pre-prandial Blood Sugar 70-100 mg/dl90-130 mg/dl (70-120) Post-prandial Blood sugar <140 mg/dl<180 mg/dl (<160) Diabetes Care 29:S4-S42, 2006 * As close to 6.0% as possible 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

20.  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

22.  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.  Chair exercises  Strength training  Water exercise

24.  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.  Hepatic Glucose Output  Peripheral Glucose Uptake Glucose Influx  Insulin Secretion Hyperglycemia Biguanides, TZD, DPP4, Insulin TZD Biguanides Insulin Sulfonylureas Meglitinides Insulin, DPP4 AGI 25

26. Drug Class ActionNames Insulin Secretagogues Increase insulin secretion Sulfonylureas: Glipizide, Glyburide, Glimepiride (Amaryl ® ) Meglitinides: Nateglinide (Starlix ®) Repaglinide (Prandin ®) Biguanides hepatic glucose output insulin sensitivity Metformin (Glucophage®) Alphaglucosidase Inhibitors (AGIs) Inhibit absorption of glucose from gut Acarbose (Precose®), Miglitol (Glyset®) Thiazoladindiones (TZDs) Increase insulin sensitivity Rosiglitazone (Actos®) Pioglitazone (Avandia®) DPP4 Inhibitors insulin secretion Sitagliptin (Januvia®) glucagon secretion. Saxagliptin (Onglyza ® )

27. Ingestion of food Pancreas 2,3 β -cells α -cells Release of gut hormones — Incretins 1,2 insulin from beta cells (GLP-1 and GIP) Glucose-dependent Glucose uptake by muscles Glucose production by liver Blood glucose Glucagon from alpha cells (GLP-1) Glucose dependent 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. GI tract Active GLP-1 & GIP Inactive GLP-1 and GIP DPP-4 Enzyme 2,4 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.  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.  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.  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 and Not Corrected by Exogenous Insulin in Diabetes  Slows Gastric Emptying Gastric Emptying Is Accelerated in Diabetes  Reduces Caloric Intake by promoting satiety *** Slowed gastric emptying will effect immunosuppressive drug levels ***

31.  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. 0 20 40 60 80 100 7:009:00 11:0013:0015:0017:0019:0021:0023:00 3:007:00 9:00 11:0015:0019:00 23:00 3:00 7:00  Serum insulin concentration ( U/mL) Breakfast Lunch Dinner Fasting 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. TypeGeneric/ Brand Name OnsetPeakDuration RAPID ACTING Glulisine/Apidra Lispro/Humalog Aspart/Novolog 5-15 Min. 1-2 Hours 3-4 Hours 4 Hours 4-6 Hours Short ActingRegular/Humulin R, Novolin R ½-1 hour2-3 hours4-8 hours

34. TypeGeneric/ Brand Name OnsetPeakDuration Intermediate Acting NPH/ Humulin N Novolin N Reli-on N 1-1.5 Hours4-12 Hours 18-25 Hours Long ActingGlargine/Lantus Detemir/Levemir 4-6 Hours 1-2 Hours 4-12 Hours 1-7 Hours 24+ Hours 6-23 Hours

36.  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 insulin requirement at each meal

37. 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.  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.  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.  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, automatic monitoring of glucose in the subcutaneous tissue

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