How to Manage Steroid Diabetes in the Patient with Cancer David S

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How to Manage Steroid Diabetes in the Patient with Cancer David S HOW WE DO IT How to Manage Steroid Diabetes in the Patient With Cancer David S. Oyer, MD, FACE, Ajul Shah, BS, and Susan Bettenhausen, APRN, CDE lucocorticosteroids (steroids) have profound perglycemic nonketotic hyperosmolar coma may effects on glucose metabolism, particularly even ensue. Increased steroid levels are not the G on postprandial hyperglycemia. Patients with only factor promoting diabetes in cancer patients; Dr. Oyer is Assistant cancer often receive steroids as a component of infection, inactivity, emotional stress, intravenous Professor of Clinical Medicine, Division their chemotherapy, as a measure to treat or pre- glucose, and high carbohydrate diets also increase of Endocrinology, vent nausea, or as adjuvant therapy following neu- the tendency toward hyperglycemia. Feinberg School of rosurgical procedures. The oncology caregiver may Multiple reviews have emphasized the impor- Medicine, Northwestern not notice steroid-induced hyperglycemia, either tance of intensive insulin therapy in hospitalized University, Chicago, Illinois. Mr. Shah is a 2–5 because it is not considered or because steroids af- patients, and several studies reinforce the im- medical student, the fect post-meal glucose much more so than morning portance of tight glucose control in this patient University of Texas fasting sugars. A recent study suggests that even a population. Furnary et al1,6,7 showed that aggres- Southwestern Medical School, Dallas. Ms. few days of hyperglycemia have deleterious effects sive control of postoperative blood glucose levels Bettenhausen is a 1 on the immune system. The current trend for in diabetic patients who had undergone a coronary Clinical Nurse Specialist maintaining near-euglycemia in hospitalized pa- artery bypass graft reduced sternal wound infec- and Certified Diabetes tients is the use of intensive insulin therapy in hy- tions and also improved morbidity and mortality. Educator, Associates in Internal Medicine, perglycemic patients with or without diabetes. This The Diabetes Mellitus, Insulin-Glucose Infusion Ltd., Chicago, Illinois. article will discuss steroid effects on glucose metab- in Acute Myocardial Infarction (DIGAMI) study8 olism, recommend levels at which therapy should showed that, compared with conventional therapy, be considered, and discuss the options available for 48 hours of tight glucose control in patients with treating hyperglycemia caused by steroids. At this acute myocardial infarction reduced mortality. time, there are no official guidelines for the cancer The Van den Berghe study9 may be relevant to patient with steroid diabetes, but the guidelines for steroid-induced hyperglycemic patients, since the diabetes care in general will be reviewed. study population consisted largely of patients in the intensive care unit (ICU) not known to be dia- Pathophysiology betic who developed hyperglycemia in the hospital. Steroids induce a state of relative insulin re- This response may have been related to the infused sistance. Steroid effects on glucose metabolism glucose and the stress-induced endogenous steroid include down-regulation of glucose transporter 4 production. Patients who had a glucose reading (GLUT-4) in the muscle so that more insulin is above 110 mg/dL were randomized to receive in- needed for the uptake of glucose into cells. Ste- tensive insulin therapy or conventional therapy. roids may also promote glucose production in the Patients in the intensive insulin group received in- liver, reduce binding of insulin to the insulin recep- sulin infusions set to reduce their glucose level to tor on cells, and decrease insulin secretion from 80–110 mg/dL, whereas those in the conventional the islet cell. In patients known to have diabetes, therapy group received insulin treatment only if the steroids will worsen the hyperglycemia, whereas glucose level went above 215 mg/dL and mainte- non-diabetic patients, depending on the state of nance of glucose at a level between 180 and 200 their islet cell reserve, may experience hyperglyce- mg/dL. The final glucose averages of the intensive mia or even overt diabetes. In rare instances, hy- and conventional groups were 103 mg/dL and 153 mg/dL, respectively. The benefits of tight glucose control in the intensive insulin group included a re- Correspondence to: David S. Oyer, MD, 211 E. Chicago Av- enue, Suite 1050, Chicago, IL 60611; telephone: (312) 944- duction in overall mortality, particularly in patients 6677; fax: (312) 944-3346; e-mail: [email protected] who remained in the ICU > 5 days, and a reduced J Support Oncol 2006;4:479–483 © 2006 Elsevier Inc. All rights reserved. risk of sepsis, transfusions, renal failure, and ICU VOLUME 4, NUMBER 9 ■ OCTOBER 2006 www.SupportiveOncology.net 479 Steroid Diabetes in the Patient With Cancer glucose levels; the most sensitive time to test for hypergly- Table 1 cemia is 2 hours after lunch. The normal range for fasting Preparations of Glucocorticosteroids glucose is below 100 mg/dL, and the normal level for the GLUCOCORTICOID MINERALOCORTICOID 2-hour postprandial reading is below 140 mg/dL. Diabetic PREPARATION POTENCY EFFECT HALF-LIFE levels are 127 mg/dL or more for fasting glucose and 200 mg/ Cortisone 1.0 ++ 4–6 h dL or more for the 2-hour postprandial level. Glucose values Prednisone 4.0 + 6–12 h between 100 and 126 mg/dL represent impaired fasting glu- Methylprednisolone 4.8 +/– 6–12 h cose, and postprandial glucose levels of 141–199 mg/dL rep- Dexamethasone 20.0 0 1–2 d resent impaired glucose tolerance. There is no way to predict whether glucose values will return to normal after cessation of steroids, since steroids may have unmasked a pre-exist- neuropathy. ing tendency toward diabetes. Current glucose monitors for In a more recent study, Van den Berghe et al10 achieved home use are accurate to within ± 10%, and there are few reduced morbidity, but not reduced mortality, using an in- drugs that interfere with the current monitoring strips. Se- tensive insulin therapy protocol in a medical ICU (MICU). vere anemia may cause false meter readings. A1C testing is Mortality was reduced only in those in the MICU for longer not indicated to monitor short-term hyperglycemia, since it than 3 days. Hyperglycemic patients not known to be diabetic represents a 90-day summation of all the glucose variations suffered greater morbidity from hyperglycemia than known but should be done at least once whenever hyperglycemia diabetics with the same degree of hyperglycemia. A 2005 is noted. A high A1C would indicate undetected previous study11 showed less morbidity postoperatively if the glucose diabetes. It should be noted that the A1C test is only valid was controlled during surgery to a level < 140 mg/dL by in- if the life of the red cell is normal; in transfused or anemic sulin infusions compared with a control group that averaged patients, false low A1C readings may be seen. 180 mg/dL during surgery. In all of these studies, insulin was used for glycemic control, so it is unknown if the benefits re- When to Treat sult from the lower glucose or possibly from direct effects of For outpatients with only a few days of mild steroid hy- the insulin itself.12,13 In vitro studies have shown that insulin perglycemia, therapy may not be needed. Treatment would can reduce many of the factors elicited in stress and infection, require patients to learn to test their glucose, take pills, or such as nuclear-factor kappa B,14 and these factors may be as give insulin, all with no proven benefit. In the hospital, how- important in the cancer patient as they are in the ICU patient, ever, this type of management is possible and should be con- which is one reason to prefer insulin therapy over oral therapy. sidered for even brief episodes of hyperglycemia. If the patient The aforementioned studies were all performed on inpatients, has only a few days of steroid therapy, and hyperglycemia is so we can only assume that outpatients might benefit as well. not causing symptoms, no therapy is indicated. However, pa- There is no proof that the benefits of intensive glucose control tients in the hospital for 3 days or more with a fasting glucose will extrapolate to hyperglycemic cancer patients on steroids, level over 110 mg/dL or a postprandial glucose level over 140 and prospective studies targeting this group are needed. mg/dL would be candidates for therapy. Preparations of Glucocorticosteroids Options for Therapy Steroid diabetes is related to the dose of steroids used but The first steps in the management of steroid diabetes are diet not the type. Insulin resistance causes primarily postprandial and exercise. The appropriate diet is low in carbohydrates to hyperglycemia. This causal relationship is particularly evident minimize postprandial hyperglycemia, but if the cancer patient with morning doses of prednisone and could be partially related has anorexia or cachexia, limiting the choices of food is not de- to the steroid effect wearing off overnight, but the improvement sirable. In these cases, nutritional consultation is recommended. in glucose overnight is also seen with the longer-acting dexa- Avoidance of other medications that may promote hyperglyce- methasone. A typical patient will have elevated glucose values mia, such as hydrochlorothiazide (> 12.5 mg/d), niacin, and after breakfast, lunch, dinner, and at bedtime but will have a some selective serotonin reuptake inhibitors, might be helpful. significant drop toward normal glucose overnight. Therefore, hyperglycemia is greatest 1–2 hours after a meal, with persis- ORAL AGENTS tent elevation until the following meal, followed by a return to The role of oral agents in the oncology patient with steroid normal between 4:00 am and 7:00 am. Table 1 shows different diabetes is limited because of potential side effects, slow onset preparations of glucocorticosteroids; it is not clear that the hy- of action, and lack of flexibility. Oral secretagogues (Table 2) perglycemic effects will differ despite the different half-lives.
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