Diabetes After Transplant. By Ruth Diaz de Leon, MS, RN, BC-ADM, APNP August 4, 2015

Transcription

1 Diabetes After Transplant By Ruth Diaz de Leon, MS, RN, BC-ADM, APNP August 4, 2015

2 Objectives 1. Define diabetes mellitus 2. Differentiate between Type 1 and Type 2 diabetes and post-transplant diabetes mellitus (PTDM) 3. How is diabetes diagnosed? 4. How prevalent is diabetes? 5. What are the risk factors for the development of diabetes? 6. What is the clinical impact of diabetes with organ transplantation? 7. How is diabetes managed after transplant?

3 What is diabetes mellitus? The word diabetes has both Greek and Latin roots. Diabetes comes from the Greek word that means to siphon. The most obvious sign of diabetes is excessive urination. Water passes through the body of a person with diabetes as if it were being siphoned from the mouth through the urinary system and out of the body. Mellitus comes from a Latin word that means sweet like honey. The urine of a person with diabetes contains extra sugar (glucose). In 1679, the physician, Thomas Willis, tasted the urine of a person with diabetes and described it as wonderfully sweet like honey.

4 What is diabetes mellitus? The American Diabetes Association (ADA): a condition characterized by hyperglycemia (high glucose in the bloodstream) resulting from the body s inability to use blood glucose for energy. Webster s Dictionary: a disease characterized by the presence of excessive amounts of sugar in the urine and manifested by various metabolic disorders that is caused by an insulin deficiency or by faulty utilization of insulin. It is occasionally hereditary.

5 What is diabetes mellitus? Stedman s Medical Dictionary: A metabolic disease in which carbohydrate utilization is reduced and that of lipid and protein is enhanced. It is caused by deficiency of insulin and is characterized, in more severe cases, by glycosuria, water and electrolyte loss, ketoacidosis, and coma. Chronic complications include neuropathy, retinopathy, nephropathy, and generalized degenerative changes in large and small blood vessels.

6 Classifications of Diabetes Diabetes can be classified into four different categories: Type 1 Diabetes Accounts for ~5-10% of those with diabetes Results from cellular-mediated autoimmune destruction of the Beta-cells of the pancreas (i.e., The body destroys its own insulin making cells.) Usually leading to absolute insulin deficiency = no insulin Type 2 Diabetes Accounts for ~90-95% of those with diabetes Results from insulin resistance in the setting of relative insulin deficiency = not enough insulin

7 Classifications of Diabetes Other specific types of diabetes due to various causes such as genetic defects in the cells of the pancreas that make insulin (Beta-cells), genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drugor chemical-induced (such as in the treatment of HIV/AIDS or after organ transplantation.) Diabetes after transplantation is also known as post-transplant diabetes mellitus or the acronym: PTDM.

8 Classifications of Diabetes Gestational Diabetes Mellitus (GDM) Diabetes diagnosed during pregnancy that is not clearly overt diabetes ~7% of all pregnancies (ranging from 1-14%, depending on the population studied and the diagnostic tests employed) are complicated by GDM, resulting in more than 200,000 cases annually

9 How is diabetes diagnosed? A1C > or = 6.5% = average glucose of 140mg/dL or Fasting plasma glucose > or = 126 mg/dl. Fasting is defined as no caloric intake for at least 8 hours. or Two hour plasma glucose > or = 200mg/dL during an oral glucose tolerance test. Test should be performed after ingesting a glucose load of 75 grams of anhydrous glucose dissolved in water. or Random plasma glucose > or = 200mg/dL with classic symptoms of high glucose: frequent urination, excessive thirst, and/or unexplained weight loss.

10 How is diabetes diagnosed? In the absence of unequivocal high glucoses, result should be confirmed by repeat testing (American Diabetes Association: Standards of Medical Care in Diabetes 2015, Diabetes Care, Volume 38 Supplement 1, January, 2015.)

11 How is pre-diabetes diagnosed? A1C 5.7 to 6.4% = average glucose of 117 to 137 mg/dl or Impaired fasting glucose of 100 to 125 mg/dl or Impaired glucose tolerance test of mg/dl two hours after a 75 gram oral glucose tolerance test

12 Scope of the Problem In 2012, 29.1 million Americans, 9.3% of the population, had diabetes 21 million Americans have diagnosed diabetes 8.1 million Americans have undiagnosed diabetes (That is, 27.8% of diabetes is undiagnosed.) 1.7 million Americans aged 20 years or older are newly diagnosed with diabetes each year (4,660/day, one every 19 seconds) Age 20 years or older: 12.3% of all people in this age group have diabetes Age 65 years or older: 11.2 million, or 25.9% of all people in this age group, have diabetes

13 Scope of the Problem About 208,000 people younger than 20 years have diabetes (Type 1 or Type 2). This represents 0.25% of all people in this age group, or about 1 in ,436 youth are newly diagnosed with Type 1 diabetes annually 5,089 youth are newly diagnosed with Type 2 diabetes annually

14 Scope of the Problem 37% of U.S. adults aged 20 years or older have prediabetes 86 million Americans aged 20 years or older have prediabetes. Only 11.1% of Americans with prediabetes have been told that they have it.

15 Scope of the Problem The prevalence of diagnosed diabetes in the U.S. increased 128% from 1988 to 2008 As many as 1 in 3 American adults will have diabetes in 2050 if present trends continue Diabetes kills more Americans every year than AIDS and breast cancer combined A person with diagnosed diabetes at age 50 dies, on average, 6 years earlier than a counterpart without diabetes (

16 Risk Factors for Type 2 Diabetes Being overweight or obese body mass index > or = 25 (Calculate BMI at diabetes.org/bmi) Sedentary lifestyle Family history of diabetes in a first degree relative (parent or sibling) History of gestational diabetes or giving birth to a baby >9 lb Age > or = 45 Ethnic/racial background: African American, Hispanic/Latino, Native American, Asian American, Pacific Islanders

17 Risk Factors for Type 2 Diabetes Hypertension Heart disease Abnormal lipid metabolism Prediabetes Polycystic Ovarian Syndrome (PCOS) and other conditions associated with insulin resistance Treatment with atypical antipsychotics, glucocorticoids, calcineurin inhibitors, protease inhibitors, and other medications associated with high glucoses

18 Clinical Impact: Why is diabetes a concern with organ transplantation? First, how many organ transplants are we talking about? Total solid organ transplants performed in the U.S.-UNOS data (2010) Lung 20,209 Liver 102,286 Kidney 288,073 Kidney/pancreas 16,906 Intestine 1,924 Heart 48,010 Heart/lung 1,032 Pancreas 6,621 TOTAL: 485,061

19 Clinical Impact: Why is diabetes a concern with organ transplantation? Second, how common is diabetes after transplantation? Answer: Depends upon the type of organ transplanted, but overall it varies from 2% to 53% of all solid organ transplants. Hearts: 20% to 30% at 5 years Lungs: 32% overall, 6% to 43% at 1 year and 21% to 60% at 3-5 years Livers: 2.5% to 25%, 40% to 60% with Hepatitis C-infected liver recipients Kidneys: 15% to 30%

20 Clinical Impact: Why is diabetes a concern with organ transplantation? Thirdly, what are the risk factors for developing diabetes after transplant (PTDM)? Answer: Risk factors are similar to the risk factors for the development of Type 2 DM as discussed earlier and include: Age > 40 years Family history of diabetes (parent or sibling) Obesity, BMI > or = 30 African American or Hispanic ethnicity Cadaver kidney Glucose intolerance Immunosuppressive therapy corticosteroids and calcineurin inhibitors: tacrolimus and to a lesser extent cyclosporine Hepatitis C virus infection Cytomegalovirus (CMV) infection Metabolic syndrome: high triglycerides, low HDL, high blood pressure, high uric acid in the blood

21 Clinical Impact: Why is diabetes a concern with organ transplantation? Fourthly, developing PTDM is associated with the following adverse events: 1. Increased risk of fatal and nonfatal cardiovascular events (e.g., heart attacks and strokes) 2. Decreased patient survival 3. Increased risk of graft rejection (graft = the transplanted organ) 4. Increased risk of graft loss 5. Increased incidence of infectious complications (Pham, Phuong-Thu, et al, New Onset Diabetes Mellitus After Solid Organ Transplantation, Endocrinology and Metabolism Clinics of North America, 36 (2007) )

22 Detection: Pre-transplant Complete medical and family history, including documentation of glucose history Fasting plasma glucose (FPG) at regular intervals If FPG is normal, add a 2 hour oral glucose tolerance test (OGTT) If either test if abnormal, start lifestyle modifications: Weight control, diet, and exercise If overweight, losing even just 7% of initial body weight can have a significant influence on glucose control and blood pressure Consider pre-transplant treatment of hepatitis C infection

23 Management of Diabetes after Transplant Note: if you have diabetes before your transplant, you will have it after your transplant. If you were on insulin before your transplant, you will be on insulin after your transplant. If you were on oral medications to control your diabetes before transplant, you may need to be on insulin after your transplant. If your diabetes was controlled with diet and exercise before transplant, you may need to start medication(s) to control your glucoses after transplant.

24 Management of Diabetes after Transplant If you didn t have diabetes before your transplant, depending upon the type of transplant that you received and the amount and type of medications you will need to take to prevent rejection (immunosuppressive agents), you have anywhere from a 2% to 53 % possibility of developing diabetes after your transplant.

25 Management of Diabetes after Transplant So, if I don t have diabetes, how can I prevent myself from getting it? Keep your weight controlled Eat a healthy diet Exercise on a regular basis: 30 minutes daily of moderate activity Stop smoking Minimize use of rejection medications after your transplant, especially corticosteroids and tacrolimus. * Note: this is managed by your transplant team and the risk for rejection of the transplanted organ must be weighed against the benefit for better glucose control.

26 Management of Diabetes after Transplant OK, so I have diabetes now, what s next? STEP # ONE: Don t Panic!!!! Step # Two: Continue efforts at weight control, diet, and exercise. These 3 factors are the foundation of any plan of care in controlling glucoses, no matter what the cause of your diabetes.

27 Management of Diabetes after Transplant Often, the first step in taking care of your glucoses after being diagnosed with diabetes, is to start checking your glucoses at home with a meter. How often will I need to check? Varies: higher glucoses --> more checks Type of treatment Glucose meters Numerous and varied Alternate site testing Lancet devices

28 Management of Diabetes after Transplant Which medication that is chosen will depend upon how high your glucoses are elevated. If your glucoses are only moderately elevated, you may be able to start on an oral medication. Glucose checks are also less often when on orals, often once to twice daily. Sometimes more than one oral medication is needed to control glucoses. Oral medications can also be combined with insulin as needed.

29 Oral Diabetes Medications Biguanides metformin (Glucophage ) Sulfonylureas glimepiride (Amaryl ) glipizide (Glucotrol ) glyburide (Diabeta ) Meglitinides replaglinide (Prandin ) nateglinide (Starlix ) Thiazolidinedio nes pioglitazone (Actos ) rosiglitazone (Avandia ) Alphaglucosidase inhibitors acarbose (Precose ) miglitol (Glyset ) Dipeptidyl peptidase-4 inhibitors alogiptin (Nesina ) linagliptin (Tradjenta ) saxagliptin (Onglyza ) sitagliptin (Januvia ) Sodium-glucose co-transporter 2 inhibitors canagliflozin (Invokana ) dapagliflozin (Farxiga ) empagliflozin (Jardiance )

30 Oral Diabetes Medications Biguanides metformin (Glucophage ) Prevents the liver from making glucose Helps the muscles use glucose insulin sensitizer Slows down how quickly the body absorbs glucose from food May cause nausea, diarrhea, and bloating. Taking it with food may decrease side effects. Weight neutral or may promote some weight loss Inexpensive

31 Oral Diabetes Medications Sulfonylureas glimepiride (Amaryl ), glipizide (Glucotrol ), glyburide (Diabeta ) Helps the pancreas make more insulin Can cause low blood sugars Usually cause some weight gain Inexpensive

32 Oral Diabetes Medications Meglitinides replaglinide (Prandin ), nateglinide (Starlix ) Helps the pancreas make more insulin Works quickly after meals to lower blood sugar in the first hour after a meal May cause low blood sugars Can cause weight gain

33 Oral Diabetes Medications Thiazolidinediones pioglitazone (Actos ), rosiglitazone (Avandia ) Helps muscle and fat use glucose Well-tolerated with few side effects No low blood sugars Once daily dosing May cause swelling and/or weight gain Increased fracture risk in post-menopausal women

34 Oral Diabetes Medications Alpha-glucosidase inhibitors Acarbose (Precose ), miglitol (Glyset ) Delays glucose absorption from the intestine GI side effects with flatulence, diarrhea, soft stools in 20-75% of pts Excellent safety profile

35 Oral Diabetes Medications Dipeptidyl peptidase-4 inhibitors Alogiptin (Nesina ), linagliptin (Tradjenta ), saxagliptin (Onglyza ), sitagliptin (Januvia ) Helps the pancreas make more insulin in relation to current blood sugar level with eating Cuts down on glucose production by the liver Weight neutral Once daily dosing Negligible side effects

36 Oral Diabetes Medications Sodium-glucose co-transporter 2 (SGLT-2) inhibitors Canagliflozin (Invokana ), dapagliflozin (Farxiga ), empagliflozin (Jardiance ) Helps remove glucose from the body through the urine May assist with weight loss Can decrease systolic blood pressure May increase risk of genital fungal infections and urinary tract infections Can increase LDL cholesterol

37 Management of Diabetes after Transplant On the other hand with high glucoses, in order to control your sugars, you will need to start on insulin. Most people need 2 types of insulin: A long acting insulin known as a basal insulin to control your glucoses when you are not eating. This is often injected once daily, either in the am or at bedtime A short or rapid-acting insulin known as bolus insulin to control glucoses at meal times This is injected with each meal Most people on an insulin regimen such as this will need to check glucoses 4 times per day, before each meal and at bedtime This regimen requires multiple injections of insulin per day, often 4 times per day

38 Insulins Insulin type Onset of action Peak effect Duration of Action Lispro, aspart, glulisine 5 to 15 minutes 45 to 75 minutes Two to four hours Regular About 30 minutes Two to four hours Five to eight hours NPH About two hours 4 to 12 hours 18 to 28 hours Insulin glargine About two hours No peak 20 to >24 hours Insulin detemir About two hours Three to nine hours 6 to 24 hours U-500 regular About 30 minutes Two to four hours Up to 24 hours Insulin degludec About two hours No peak >40 hours (

39 Management of Diabetes after Transplant There are some insulins known as pre-mixed insulins that contain both long and short acting insulins in one injection. These insulins are injected twice per day at meal times, usually with breakfast and the evening meal.

40 Pre-Mixed Insulins Insulin Type Onset of Action Peak Effect Duration of Action Novolog Mix 70/30 <15 minutes 2.4 hours 24 hours Humalog Mix 75/25 <15 minutes minutes 24 hours Humalog Mix 50/50 <15 minutes 1 hour 16 hours Humulin 70/30 30 minutes 2-12 hours 24 hours Novolin 70/30 30 minutes 2-12 hours 24 hours

41 Non-insulin Injectables Another group of medications used to treat diabetes are called non-insulin injectables They include: Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists): albiglutide (Tanzeum )-dosed weekly dulaglutide (Trulicity )-dosed weekly exenatide (Byetta )-dosed twice per day, exenatide extended-release (Bydureon )-dosed weekly liraglutide (Victoza )-dosed daily Amylin Analogues: pramlinitide (Symlin )-dosed 1-3 times per day with meals

42 Non-insulin Injectables Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists): albiglutide (Tanzeum ), dulaglutide (Trulicity ), exenatide (Byetta ), exenatide extended-release (Bydureon ), liraglutide (Victoza ) Helps the pancreas make more insulin in relation to current blood sugar level with eating Cuts down on glucose production by the liver Can assist with weight loss Increased satiety Low risk of low blood sugars Expensive Injection site reactions GI side effects nausea and vomiting, especially with initiation of therapy

43 Non-insulin Injectables Amylin Analogues pramlinitide (Symlin ) Helps control blood sugars after eating Cuts down on glucose production by the liver Slows how fast the stomach empties May suppress hunger Must be used right before meals Can cause low blood sugars Can be use with Type 1 and Type 2 diabetes

44 Management of Diabetes after Transplant Remember: Keeping your glucoses in good control is worth the effort To keep your transplanted organ working properly To prevent complications from diabetes

45 Resources: American Diabetes Association: Website: Phone: Diabetes ( ) National Diabetes Education Program Website: ndep.nih.gov National Diabetes Information Clearinghouse Website: diabetes.niddk.nih.gov Wisconsin Department of Health Services Website: dhs.wisconsin.gov/diabetes Centers for Disease Control and Prevention (CDC) Website:

46 Questions?

47 Save the Date Saturday, January 23, 2016 Milwaukee A Dancing with the Stars-style event where your favorite transplant doctors compete for your vote on the dance floor! Attend in person Live-stream at home Donate a silent auction item Visit spotlightonlife.org or call (262)