diabetes in the transplant patient
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DIABETES IN THE TRANSPLANT PATIENT
Susan Alexander, DNP, CNS, CRNP, BC-ADM
College of NursingUniversity of Alabama in Huntsville
Clinical Affiliation:Outpatient Diabetes Self-Management
EducationCrestwood 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 months16% at 12 months24% 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.
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 andAdipose Tissue)
Glucose
InsulinResistance
IncreasedGlucose
Production
Impaired InsulinSecretion
Hyperglycemia in Type 2 Diabetes
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-actingAnalogCorrection 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
Normal Goal
HbA1c 4-6% <7% *
Pre-prandialBlood Sugar
70-100 mg/dl 90-130 mg/dl(70-120)
Post-prandialBlood 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
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
The Plate Method
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
HepaticGlucose Output
PeripheralGlucose Uptake
Glucose Influx
InsulinSecretionHyperglycemia
Biguanides,TZD, DPP4,
Insulin TZDBiguanides
Insulin
SulfonylureasMeglitinidesInsulin, DPP4
AGI
25
Oral Diabetes Meds
Drug Class Action Names
InsulinSecretagogues
Increaseinsulin 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®)
Effects of Incretin Hormones
Ingestion of food
Pancreas2,3
β-cellsα-cells
Release of gut hormones — Incretins1,2
insulin from beta cells
(GLP-1 and GIP)
Glucose-dependentGlucose 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
ActiveGLP-1 & GIP
Inactive GLP-1and GIP
DPP-4 Enzym
e
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.
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 Emptying Gastric 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
Normal Endogenous Insulin Secretion
0
20
40
60
80
100
7:00
9:00
11:0
013
:00
15:0
017
:00
19:0
021
:00
23:0
03:
007:
009:
0011
:00
15:0
019
:00
23:0
03:
007:
00
mSe
rum
insu
lin c
once
ntra
tion
(U/m
L)
BreakfastLunch
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.
INSULIN TYPES AND ACTIONS
Type Generic/ Brand Name
Onset Peak Duration
RAPIDACTING
Glulisine/Apidra
Lispro/Humalog
Aspart/Novolog
5-15 Min.
5-15 Min.
5-15 Min.
1-2 Hours
1-2 Hours
1-2 Hours
3-4 Hours
4 Hours
4-6 Hours
Short Acting Regular/Humulin R, Novolin R
½-1 hour 2-3 hours 4-8 hours
Insulin Types and ActionType Generic/ Brand
NameOnset Peak Duration
IntermediateActing
NPH/ Humulin N
Novolin N
Reli-on N
1-1.5 Hours 4-12 Hours
18-25 Hours
Long Acting Glargine/Lantus
Detemir/Levemir
4-6 Hours
1-2 Hours
4-12 Hours1-7 Hours
24+ Hours
6-23 Hours
Idealized Insulin Action Times
The Basal/Bolus Insulin Concept Basal Insulin – NPH, Levemir,
Lantus 50% of daily needs Suppresses glucose production between
meals and overnightBolus 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
Pre-mixed InsulinProtamine + 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% AspartOnset: 0.5-2.5 hoursTime to Peak: 4-8 hoursDuration: 17-25 hoursClinical 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
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