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©2016 by the American Diabetes Association, Inc.® All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including duplication, recording, or any information storage and retrieval system, without the prior written permission of the American Diabetes Association.
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The suggestions and information contained in this publication are generally consistent with the Standards of Medical Care in Diabetes and other policies of the American Diabetes Association, but they do not represent the policy or position of the Association or any of its boards or committees. Reasonable steps have been taken to ensure the accuracy of the information presented. However, the American Diabetes Association cannot ensure the safety or efficacy of any product or service described in this publication. Individuals are advised to consult a physician or other appropriate health care professional before undertaking any diet or exercise program or taking any medication referred to in this publication. Professionals must use and apply their own professional judgment, experience, and training and should not rely solely on the information contained in this publication before prescribing any diet, exercise, or medication. The American Diabetes Association—its officers, directors, employees, volunteers, and members—assumes no responsibility or liability for personal or other injury, loss, or damage that may result from the suggestions or information in this publication.
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American Diabetes Association
1701 North Beauregard Street
Alexandria, Virginia 22311
DOI: 10.2337/9781580406192
Library of Congress Cataloging-in-Publication Data
Names: Dagogo-Jack, Sam, 1954- , author. | American Diabetes Association, issuing body.
Title: Diabetes risks from prescription and non-prescription drugs: mechanisms and approaches to risk reduction / Sam Dagogo-Jack.
Description: Alexandria : American Diabetes Association, [2016] | Includes bibliographical references and index.
Identifiers: LCCN 2015030720 | ISBN 9781580406192 (alk. paper)
Subjects: | MESH: Diabetes Mellitus--etiology. | Prediabetic State. |
Drug-Related Side Effects and Adverse Reactions. | Risk
Assessment--methods. | Risk Factors.
Classification: LCC RC660 | NLM WK 810 | DDC 616.4/62061--dc23
LC record available at http://lccn.loc.gov/2015030720
Dedication
This treatise on the expected and unexpected effects of commonly used prescription and nonprescription drugs on glucose metabolism is dedicated to the medicinal chemists, physicians, and scientists who serve society by discovering and testing medicinal products for the alleviation of human suffering and to the research volunteers and test subjects who make such knowledge possible.
Disclosures
Dr. Dagogo-Jack is a principal investigator or coinvestigator for clinical trials contracts between the University of Tennessee and AstraZeneca, Novo Nordisk, and Boehringer-Ingelheim and has served as a consultant and an advisory board member for Merck, Novo Nordisk, Boehringer-Ingelheim, Eli Lilly, GlaxoSmithKline, Sanofi, and Janssen Pharmaceuticals. He also has served as an expert for Sidley Austin, and Adam and Reese, on diabetes-related litigation.
Table of Contents
1. Overview of Diagnosis, Classification, and Pathophysiology of Diabetes Diabetes Diagnosis of Diabetes and Prediabetes Demographic Factors Insulin Resistance Conclusion
2. Medications and Diabetes Risk: General Mechanisms Risk Factor versus Causation: The Bradford Hill’s Criteria Drugs Associated with Type 1 Diabetes Drugs Associated with Type 2 Diabetes
3. Glucocorticoid, Mineralocorticoid, and Immunomodulatory Agents Glucocorticoid Steroids Mineralocorticoids: Aldosterone and Glucoregulation Immunomodulatory Agents
4. Sex Steroids and Gonadotropin-Releasing Hormone Analogs Estrogens and Progestins Androgens, Sex Hormone Binding Globulin, and Glucoregulation Androgen-Deprivation Therapy with Gonadotropin-Releasing Hormone Agonists
5. Antihypertensive Agents Diuretics β-Adrenoreceptor Blockers α-Adrenoreceptor Blockers Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Calcium-Channel Blockers Diazoxide and Other Peripheral Vasodilators Other Agents
6. Catecholamines, β-Adrenergic Agonists, and Bronchodilators β-Adrenergic Agonists Theophylline
7. Lipid-Lowering Agents Nicotinic Acid Statins Fibrates Colesevelam and Bile Acid Sequestrants Lipid-Lowering Drugs and Diabetes Complications
8. Antimicrobial Agents Antibiotics Fluoroquinolones Antiretroviral Agents
9. Atypical Antipsychotic and Antidepressant Agents Atypical Antipsychotic Agents Antidepressants
10. Recreational Drugs Alcohol Nicotine Marijuana and Cannabinoids Opioids Cocaine, Amphetamine, and Psychostimulant Drugs
11. Miscellaneous Agents Nonsteroidal Anti-Inflammatory Drugs, Glucosamine, and Acetaminophen Thyroid Hormone Phenytoin and Anticonvulsants Growth Hormone Total Parenteral Nutrition and Inpatient Hyperglycemia
12. General Approach to Risk Reduction Lifestyle Intervention for Diabetes Prevention Limitations of Lifestyle Intervention Medications for Diabetes Prevention Limitations of Medications Current Guidelines for Use of Medications for Diabetes Prevention Diabetes Pharmacoprophylaxis
More than 29 million Americans currently have diabetes and approximately 86 million have prediabetes. People with diabetes often also require medications for several comorbid conditions (including hypertension, dyslipidemia, depression, heart disease, pain syndromes). A vast literature abounds, however, on the potential adverse effects of numerous medications on glucose metabolism. There is, thus, genuine clinical concern that certain medications used for treatment of comorbid conditions and other indications (such as hormone replacement, contraception, infections) might worsen glycemic control in diabetic patients or trigger diabetes in others. These concerns influence therapeutic decisions in a manner that sometimes emphasizes avoidance of possible dysglycemia over effective control of the comorbid conditions. The same concerns may also weigh against the otherwise appropriate use of necessary medications.
The purpose of this concise book is to provide clinicians with actionable knowledge regarding the effects of various medications on glucose regulation and diabetes risk. Beginning with a brief overview of diabetes pathophysiology, the different drugs have been organized by class, and the scientific evidence for the diabetes risk and possible mechanisms have been presented for each drug. The agents discussed include widely prescribed medication classes: antibiotics, antidepressants, antihypertensives, bronchodilators, sex hormones (androgens, estrogens, and oral contraceptives), glucocorticoids, lipid-lowering agents, nonsteroidal anti-inflammatory drugs, acetaminophen, and thyroid hormone. Although less widely prescribed than the foregoing list, atypical antipsychotics, HIV antiretrovirals, immunomodulatory agents used in transplant medicine, gonadotropin-releasing hormone analogs, and human growth hormone also have been included because of the interest generated by their link to diabetes risk. In addition to medications used in ambulatory practice, this work includes a discussion of total parenteral nutrition (TPN)–induced hyperglycemia, which is associated with increased morbidity and mortality among hospitalized patients. For completeness, because of the possible intersection between these addictive agents and the global diabetes epidemic, an account of the growing link between the use of recreational drugs (alcohol, nicotine, marijuana, opioids, cocaine, amphetamine-like drugs and other psychostimulants) and glucose abnormalities has been included.
With some medications, the data presented should help debunk myths, clarify misperceptions, and provide reassurance to practicing clinicians. Wherever the evidence supports increased diabetes risk, clear suggestions are given on how to reduce the risk. Also covered in this book are diabetes management guidelines for special situations, including new-onset diabetes after transplant and TPN-induced hyperglycemia. The final chapter provides a general approach to the prevention or attenuation of diabetes risk, focusing on risk stratification, lifestyle modification, and a critical appraisal of the medications that have been demonstrated, in clinical trials, to prevent or delay diabetes. Also introduced is the emerging concept of diabetes pharmacoprophylaxis in high-risk individuals receiving treatment with potentially diabetogenic agents.
The knowledge gained from reading this book should enable clinicians to become well informed regarding the impact of a wide variety of commonly used medications on glucose homeostasis and the risks of drug-induced diabetes or exacerbation of preexisting diabetes. With such knowledge, clinicians will be better positioned to design and select therapeutic regimens that embody the best risk–benefit profile with regard to glycemia and concurrent management of the primary or comorbid conditions.
