Transcript Diabetes in the Transplant Patient - Vanderbilt University Medical

Susan Alexander, DNP, CNS, CRNP, BCADM
College of Nursing
University of Alabama in Huntsville
Clinical Affiliation:
Outpatient Diabetes Self-Management Education
Crestwood Medical Center
Huntsville, AL
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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.
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Diabetes Mellitus:
Heterogeneous Condition With Hyperglycemia
and Common Complications
Insulin Deficiency:
Relative or Absolute
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.
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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
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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 and
Adipose Tissue)
Pancreas
Impaired Insulin
Secretion
Glucose
Liver
Increased
Glucose
Production
Insulin
Resistance
Fat
Adapted from Kruszynska YT, et al. J Invest Med. 1996;44:413-428.
Henry RR. Ann Intern Med. 1996;124:97-103.
Type 1:
-Steroids increase insulin requirement
and dose
-Insulin dose will increase from ESRD
to having a working kidney
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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
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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
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Hyperglycemia
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Severe hyperglycemia (BG>250)
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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.
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Medications
Food intake
Tests and procedures
Prior history
Nutritional status
Inzucchi, S. N Engl J Med 2006;355:1903-11
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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
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
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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
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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
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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
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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.
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Insulin NPH QD or BID
0.2-0.3 u/kg/day or 50% of IV insulin dose
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Insulin Detemir QD or BID
0.2-0.3 u/kg/day or 50% of IV insulin dose
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Insulin Glargine Q day
0.2u/kg/day or 50% of IV insulin dose
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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 premeal BG is in target
Normal
Goal
HbA1c
4-6%
<7% *
Pre-prandial
Blood Sugar
70-100 mg/dl
90-130 mg/dl
(70-120)
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:S4S42, 2006
Post-prandial
Blood sugar
<140 mg/dl
<180 mg/dl
(<160)
Diabetes Care 29:S4-S42, 2006 *As close to 6.0% as possible
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
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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
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Chair exercises
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Strength training
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Water exercise
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2896 adults with DM interviewed from 1990-1991
Outcomes: All cause and CVD mortality over 8years
RESULTS:
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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.
Glucose Influx
AGI
Hepatic
Hyperglycemia
Glucose
Output Biguanides,
TZD, DPP4,
Insulin
Sulfonylureas
Meglitinides
Insulin, DPP4
Insulin
Secretion
TZD
Biguanides
Insulin
Peripheral
Glucose Uptake
25
Drug Class
Insulin
Secretagogues
Biguanides
Action
Increase
insulin secretion
hepatic glucose
output
insulin sensitivity
Names
Sulfonylureas: Glipizide,
Glyburide, Glimepiride
(Amaryl®)
Meglitinides: Nateglinide
(Starlix®) Repaglinide
(Prandin®)
Metformin
(Glucophage®)
Alphaglucosidase
Inhibitors (AGIs)
Inhibit absorption of
glucose from gut
Acarbose (Precose®),
Miglitol (Glyset®)
Thiazoladindiones
(TZDs)
DPP4 Inhibitors
Increase insulin
sensitivity
Rosiglitazone (Actos®)
Pioglitazone (Avandia®)
insulin secretion
glucagon secretion.
Sitagliptin (Januvia®)
Saxagliptin (Onglyza®)
GI tract
Ingestion
of food
Pancreas2,3
Release of gut
hormones —
Incretins1,2
Glucose-dependent
insulin from beta cells
(GLP-1 and GIP)
Active
GLP-1 & GIP
DPP-4
Enzyme
Inactive GLP-1
and GIP
2,4
Glucose
uptake
by muscles
β-cells
α-cells
Blood
glucose
Glucagon
from alpha cells
(GLP-1)
Glucose
production
by liver
Glucose dependent
•Active incretins physiologically regulate glucose by modulating insulin secretion in a glucosedependent 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
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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).
 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
 Symlin=synthetic
Amylin. Amylin is co-secreted with insulin by
pancreatic beta cells in response to food intake.
 Reduces
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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***
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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
100
Dinner
80
60
Fasting
40
20
7:00
3:00
23:00
19:00
15:00
11:00
9:00
7:00
3:00
23:00
21:00
19:00
17:00
15:00
13:00
11:00
7:00
0
9:00
Serum insulin concentration m(U/mL)
Breakfast
Lunch
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.
Type
Generic/ Brand
Name
Onset
Peak
RAPID
ACTING
Glulisine/Apidra
5-15 Min.
1-2 Hours 3-4 Hours
Lispro/Humalog
5-15 Min.
1-2 Hours 4 Hours
Aspart/Novolog
5-15 Min.
1-2 Hours 4-6 Hours
Short Acting
Regular/Humulin R, ½-1 hour
Novolin R
2-3 hours
Duration
4-8 hours
Type
Generic/ Brand
Name
Onset
Peak
Duration
Intermediate
Acting
NPH/ Humulin N
1-1.5 Hours
4-12
Hours
18-25
Hours
Glargine/Lantus
4-6 Hours
Detemir/Levemir
1-2 Hours
4-12
24+ Hours
Hours
1-7 Hours 6-23 Hours
Novolin N
Reli-on N
Long Acting
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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
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10% to 20% of total daily insulin requirement at
each meal
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
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Humalog/Novolog
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$112.00
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$225.00
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$107.99
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$47-64.00 Walmart
10ml
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Humalog/Novolog
cartridges 15ml
Lantus 10ml vial
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Hum/Novo R,N,
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$20.00
10ml vial
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Hum/Novo, R, N
Pen, cartridges 15ml
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$130-150.00
* 1 vial = 30-day supply if using <33u per day
** 5 pens of 3ml each = 15ml, 1500 units
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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
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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, automatic
monitoring of glucose in the
subcutaneous tissue
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Target blood glucose 70-120 mg/dl
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Below 70: Rule of 15
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Causes
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Severe Hypoglycemia - rare
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Hypoglycemia Unawareness