Medical Management of Type 2 Diabetes

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The suggestions and information contained in this publication are generally consistent with the Clinical Practice Recommendations 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: 10.2337/9781580404570

Library of Congress Cataloging-in-Publication Data

Medical management of type 2 diabetes / Charles F. Burant, editor.—7th ed.

p. cm.

Includes bibliographical references and index.

ISBN 978-1-58040-457-0 (pbk.)

1. Non-insulin-dependent diabetes. I. Burant, Charles F. II. American Diabetes Association. III. Title: Medical management of type two diabetes.

RC662.18.M43 2012

616.4'624--dc23

2012004880

eISBN: 978-1-58040-491-4

Contents

A Word About This Guide

Contributors to the Seventh Edition

Acknowledgments

Diagnosis and Classification

Highlights

Definition of Diabetes

Diagnosis of Diabetes

Classification of Diabetes

Type 1 diabetes

Type 2 diabetes

Other specific types of diabetes

Stage of disease

Screening for Diabetes

Categories of Increased Risk for Diabetes

Gestational Diabetes Mellitus

Metabolic Syndrome

Evaluation and Classification of Patients Before Treatment

Pathogenesis

Highlights

Genetic and Environmental Factors

Insulin Resistance

Sites of insulin resistance

Mechanisms of insulin resistance

The Fat Cell as an Endocrine Organ

Defects in Insulin Secretion

Factors modulating insulin secretion

Physiological consequences of defective insulin secretion

Conclusion

Management

Highlights

Therapeutic Objectives and Plan

MNT Effectiveness, Process, and Goals

Energy balance and weight loss

Carbohydrate

Protein

Fat

Sodium

Alcohol

Vitamins and minerals

Exercise

Potential benefits of exercise

Precautions and considerations

The exercise prescription

Pharmacologic Intervention

Available agents

Insulins

Long-term combinations of oral agents with insulin

Adjusting insulin dosage in long-term type 2 diabetes

Assessment of Treatment Efficacy

Office methods

Self-monitoring

Special Therapeutic Situations

Highlights

Diabetes in Pregnancy

Diabetes in Youth

Differentiation of type 1 and type 2 diabetes in youth

Screening for type 2 diabetes in youth

Treating type 2 diabetes in youth

Diabetes in Hospitalized and Critically Ill Patients

Major Acute Complications

Hyperosmolar hyperglycemic state

Hypoglycemia

Infection

Detection and Treatment of Chronic Complications

Highlights

Rationale for Optimizing Glycemic Control in Type 2 Diabetes

Accelerated Macrovascular Disease

Diabetes as a cardiovascular risk factor

Screening for cardiovascular disease

Importance of modifying vascular risk factors

Treatment of cardiovascular disease

Diabetic Retinopathy

Stages of diabetic retinopathy

Prevention of vision loss from retinopathy

Treatment of retinopathy

Diabetic Renal Disease

Clinical presentation of nephropathy

Conditions that influence renal function

Prevention and treatment of diabetic renal disease

Diabetic Foot Problems

Causes of diabetic foot problems

Prevention of foot problems

Treatment of foot problems

Diabetic Neuropathies

Diagnosis and treatment of neuropathy

Autonomic neuropathy

Other varieties of diabetic neuropathy

Behavior Change Strategies

Highlights

Influences on Behavior Change

Strategies for Behavior Change

Diabetes Self-Management Support

Redesigning Practice to Support Behavior Change

Summary

A Word About This Guide

Type 2 diabetes is now a worldwide epidemic. The increasing prevalence of obesity and sedentary lifestyles is a driving force in the dramatic increase of type 2 diabetes in our society. If these trends continue, one in three American children born in 2000 faces the probability of developing type 2 diabetes with the attendant risks of morbidity and early mortality. The care of individuals with diabetes will take an increasing portion of expenditures for health care, making this disease a problem for society as well as the individual. Reversing these trends will take a concerted effort in public education directed toward developing better lifestyle habits. The results of several studies have already shown that relatively small lifestyle changes to decrease caloric intake and increase exercise can slow or prevent the transition from impaired glucose tolerance to type 2 diabetes.

Although prevention of type 2 diabetes is a necessary key to addressing the epidemic, for the foreseeable future the practitioner will be caring for an increasing number of patients with diabetes. Since the last edition of this guide, there has been a significant increase in our knowledge of the pathogenesis of type 2 diabetes, its complications, and the options for treatment. Numerous studies have shown that lifestyle changes and pharmacological interventions make a significant impact on the well-being of the patient. Several cardiovascular intervention trials have demonstrated the importance, or even preeminence, of aggressive intervention with medications to control blood pressure and lipids, in addition to glucose, to prevent cardiovascular events in people with type 2 diabetes. It is also becoming clear that when diabetes needs to be treated with medications, multiple drugs can and should be used in combination to control hyperglycemia. The rapid introduction of additional medications when the first therapeutic options fail is of critical importance to control glucose in the short term and to prevent long-term complications. The recent introduction of medications that have unique mechanisms of action has made treatment of type 2 diabetes with oral agents easier and more effective. New insulin analogs and improved delivery devices that make insulin therapy safer and easier to use have increased patient acceptance and compliance. Using all available behavioral and therapeutic tools to improve the care of individuals with type 2 diabetes will likely save lives and decrease microvascular and macrovascular complications. Ultimately, this will improve the lives of those who have or are at risk for diabetes and decrease the cost to society.

This edition of Medical Management of Type 2 Diabetes has been updated to provide state-of-the-art information on these issues by a select group of experts. It also reflects the most recent Clinical Practice Recommendations from the American Diabetes Association, including the diagnostic and classification criteria adopted by the Association in 2004. This book, along with other American Diabetes Association publications, including Medical Management of Type 1 Diabetes, Therapy for Diabetes Mellitus and Related Disorders, Intensive Diabetes Management, and Medical Management of Pregnancy Complicated by Diabetes, were designed to provide health care professionals with the comprehensive information needed to give the best possible medical care to patients with diabetes mellitus.

The American Diabetes Association believes that you will find this book as useful as its predecessors. We hope that it will encourage you to add other American Diabetes Association publications to your library, which can help you manage patients with diabetes more effectively.

CHARLES F. BURANT, MD, PhD

Editor

Contributors to the Seventh Edition

EDITORS

Charles F. Burant, MD, PhD

University of Michigan

Ann Arbor, Michigan

Laura A. Young, MD, PhD

University of North Carolina

Chapel Hill , North Carolina

CONTRIBUTORS

Robert M. Anderson, EdD

University of Michigan

Ann Arbor, Michigan

Komel Benjamin Craig, MPH, RD, LDN

University of North Carolina

Chapel Hill, North Carolina

John B. Buse, MD, PhD

University of North Carolina

Chapel Hill, North Carolina

Martha M. Funnell, MS, RN, CDE

University of Michigan

Ann Arbor, Michigan

Roma Gianchandani, MD

University of Michigan

Ann Arbor, Michigan

William Herman, MD, MPH

University of Michigan

Ann Arbor, Michigan

Robin B. Nwankwo, MPH, RD, CDE

University of Michigan

Ann Arbor, Michigan

Rodica Pop-Busui, MD, PhD

University of Michigan

Ann Arbor, Michigan

Martin Stevens, MD

University of Birmingham

Birmingham, England

Jennifer Wyckoff, MD

University of Michigan

Ann Arbor, Michigan

Acknowledgments

The American Diabetes Association gratefully acknowledges the contributions of the following health care professionals and members of the Association’s Professional Section to previous editions of this work:

Christine A. Beebe, MS, RD, CDE; Nathaniel G. Clark, MD, MS, RD; Mayer B. Davidson, MD; Harold E. Lebovitz, MD; David Nathan, MD; Philip Raskin, MD; Matthew C. Riddle, MD; Harold Rifkin, MD; Robert A. Rizza, MD; F. John Service, MD, PhD; Robert Sherwin, MD; and Bruce R. Zimmerman, MD.

The Association gratefully acknowledges the review by M. Sue Kirkman, MD.

Diagnosis and Classification

Highlights

Definition of Diabetes

Diagnosis of Diabetes

Classification of Diabetes

Type 1 diabetes

Type 2 diabetes

Other specific types of diabetes

Stage of disease

Screening for Diabetes

Categories of Increased Risk for Diabetes

Gestational Diabetes Mellitus

Metabolic Syndrome

Evaluation and Classification of Patients Before Treatment

Highlights

Diagnosis and Classification

• Diabetes is diagnosed by one of the following, confirmed by repeat testing in the absence of unequivocal hyperglycemia :

— Hemoglobin A1c (A1c) ≥6.5%. The test should be performed in a laboratory using a method that is National Glycohemoglobin Standardization Program certified and standardized to the Diabetes Control and Complications Trial assay. Point-of-care A1c assays are not sufficiently accurate to use for diagnostic purposes.

— Fasting Plasma Glucose (FPG) ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.

— 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) during an oral glucose tolerance test (OGTT). The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.

— In a patient with classic symptoms of hyperglycemia (polydipsia, polyuria, unintentional weight loss) or hyperglycemic crisis, a random plasma glucose ≥200 mg/dl (11.1 mmol/l)

• There are two main types of diabetes: type 1 diabetes, which has absolute insulin deficiency and propensity to develop ketoacidosis; and type 2 diabetes, which has relative insulin deficiency combined with defects in insulin action. Type 2 diabetes is the most common form of diabetes, accounting for 90–95% of the incidence of the disease in Western societies. It is most often found in obese individuals.

• Categories of increased risk for diabetes (prediabetes) describe an intermediate group of individuals with plasma glucose levels higher than normal but lower than those diagnostic of diabetes mellitus. Such individuals are at higher risk for both diabetes and cardiovascular disease. For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at the higher end of the range. They may be identified according to the following criteria:

• A1c 5.7–6.4%

— FPG 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9 mmol/l), also known as impaired fasting glucose (IFG)

— 2-h PG during the 75-g OGTT 140 mg/dl (7.8 mmol/l) to 199 mg/dl (11.0 mmol/l), also known as impaired glucose tolerance (IGT)

• Gestational diabetes mellitus (GDM), glucose intolerance developing during pregnanc. It affects approximately 7% of all pregnancies in the U.S. As many as 50% of women with GDM later develop type 2 diabetes. Screening for GDM is recommended for all women who are not known to have diabetes between the 24th and 28th week of pregnancy. A 75-g OGTT is recommended in the morning after an overnight fast of at least 8 h with plasma glucose measurement fasting and at 1 and 2. High-risk women found to have diabetes at their initial prenatal visit, using standard criteria for diabetes, should receive a diagnosis of overt, not gestational diabetes. The diagnosis of GDM is made when one or more of the following plasma glucose values are exceeded:

— Fasting: ≥92 mg/dl (5.1 mmol/l)

— 1 h: ≥180 mg/dl (10.0 mmol/l)

— 2 h: ≥153 mg/dl (8.5 mmol/)

     High-risk women found to have diabetes at their initial prenatal visit, using standard criteria for diabetes, should receive a diagnosis of overt, not gestational diabetes.

DEFINITION OF DIABETES

Diabetes mellitus is a chronic disorder characterized by abnormalities in the metabolism of carbohydrate, protein, and fat. Chronic, sustained exposure to these abnormalities is accompanied by microvascular complications (e.g., retinopathy, nephropathy, and neuropathy), as well as macrovascular complications (e.g., stroke, myocardial infarction, and peripheral arterial disease). It is now recognized that diabetes mellitus encompasses a group of genetically and clinically heterogeneous disorders in which glucose intolerance is the common denominator. Thus, although diabetes mellitus affects the metabolism of all body fuels, its diagnosis depends on identification of specific abnormalities of glycemia.

Because the syndrome of diabetes mellitus encompasses many disorders that differ in pathogenesis, natural history, and responses to treatment, it is important that clinicians and researchers use commonly accepted terminology as well as standardized classification and diagnostic criteria when categorizing patients with glucose intolerance. In January 2010, the American Diabetes Association published diagnostic and classification criteria, replacing its 2003 and 1997 criteria and the criteria of the National Diabetes Data Group published in 1979.

Following the findings of the Diabetes Prevention Program, recognition of degrees of carbohydrate intolerance short of diabetes led to the description of categories of increased risk for diabetes as well as cardiovascular disease (prediabetes). The designation encompasses states described previously as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and individuals with A1c of 5.7 to 6.4%. Identification of such individuals should facilitate efforts to intervene to reduce the incidence of diabetes and cardiovascular disease.

Following the findings of the Hyperglycemia and Adverse Pregnancy Outcomes Study (HAPO), a large, multinational epidemiologic study that demonstrated that the risk of adverse maternal, fetal, and neonatal outcomes of pregnancy increase as a function of maternal glycemia at 24–28 weeks gestation even within ranges previously considered normal for pregnancy, the ADA developed revised recommendations for the diagnosis of gestational diabetes. These new criteria will significantly increase the prevalence of GDM, but with appropriate treatment, should optimize gestational outcomes for women and their babies.

DIAGNOSIS OF DIABETES

According to current ADA criteria, there are four ways to diagnose diabetes (Table 1.1). Each must be confirmed on a subsequent day by any one of the four methods. When a subject is symptomatic and the random glucose is unequivocally elevated, the diagnosis of diabetes presents no difficulty. In general, if diabetes is initially diagnosed on the basis of symptoms and a random glucose ≥200 mg/dl, it is confirmed with an A1c ≥6.5% or, on a subsequent day, a fasting glucose ≥126 mg/dl. When a subject is without clinical symptoms, the diagnosis of diabetes is more difficult. If the initial diagnosis is suggested on the basis of an A1c ≥6.5% or a fasting glucose ≥126 mg/dl, it is confirmed on a subsequent day with a repeat A1c or fasting glucose.

Table 1.1 Criteria for the Diagnosis of Diabetes

1. A1c ≥6.5%. The test should be performed in a laboratory using a method that is National Glycohemoglobin Standardization Program certified and standardized to the Diabetes Control and Complications Trial assay. Point-of-care A1c assays are not sufficiently accurate to use for diagnostic purposes.

OR

2. Fasting plasma glucose (FPG) ≥126 mg/dl (≥7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.

OR

3. 2-h plasma glucose ≥200 mg/dl (≥11.1 mmol/l) during an oral glucose tolerance test (OGTT). The test should be performed as described by the World Health Organization (WHO), using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.

OR

4. In a patient with classic symptoms of hyperglycemia (polydipsia, polyuria, unintentional weight loss) or hyperglycemic crisis, a random plasma glucose ≥200 mg/dl (11.1 mmol/l).

A clear advantage of the A1c test for the diagnosis of diabetes is its greater convenience—the patient does not need to fast. In addition, there is less day-to-day variation in A1c and greater preanalytic stability. Relative disadvantages include its greater cost as compared to glucose and its limited availability in some regions of the developing world. In addition, although highly specific for the diagnosis of diabetes, A1c is less sensitive than fasting glucose or 2-h PG. In addition, A1c may be an inaccurate measure of average glycemia in patients with hemoglobinopathies, thalassemia syndromes, states of increased red cell turnover, including those related to hemolysis, erythropoietin therapy, or transfusion, and in patients with iron deficiency. Uremia and hyperbilirubinemia may also interfere with some assays. In such patients, the diagnosis of diabetes must employ glucose criteria.

The oral glucose tolerance test (OGTT) is performed only in patients with elevated but nondiagnostic A1c or fasting glucose levels in whom there is a high index of suspicion for diabetes. Such patients might, for example, have an A1c of 6.3% or a fasting glucose of 115 mg/dl and evidence of cardiovascular disease or diffuse symmetric peripheral polyneuropathy. In such patients, the OGTT may be informative. The OGTT is essentially never indicated in patients with symptoms and random glucose levels ≥200 mg/dl or in patients with A1c ≥6.5% or fasting glucose level ≥126 mg/dl.

CLASSIFICATION OF DIABETES

Having established a diagnosis of diabetes, the next task is to classify the type. The purpose of classification is to differentiate and identify the various forms of the disease. The first generally accepted classification system was developed by the National Diabetes Data Group (NDDG) and published in 1979. The World