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Preface

As the global epidemic of diabetes continues to expand, the prevalence of type 2 diabetes is predicted to double in the next 20 years. Continued population growth, increasing age, and worldwide globalization leading to changes in diet and patterns of physical inactivity have resulted in staggering numbers of individuals affected by the disease. A haphazard approach to treatment for a problem of this magnitude could easily overburden the healthcare system, particularly in areas of the world with limited resources. The development of a rational approach to therapy should be based on data derived from the strongest level of clinical evidence available, with the goal of balancing the risks, benefits, and cost of care.

In Type 2 Diabetes Mellitus: An Evidence-Based Approach to Practical Management, the authors of each chapter have synthesized the currently available evidence regarding specific issues in diabetes care. We begin with background information on the epidemiology and pathology of the disease. Following are chapters addressing specific issues in the diagnosis and treatment of type 2 diabetes. Chapters integrating the best evidence for the evaluation and treatment of comorbidities of diabetes, including hypertension, hyperlipidemia, and vascular disease collect a wealth of information in a single resource. Finally, we have highlighted related conditions, including fatty liver disease, pregnancy, and polycystic ovarian syndrome, and barriers to treatment, including stress, depression, and patient motivation. To quantify the strength of evidence supporting current practices, each chapter concludes with a series of recommendations, quantified by their level of evidence as defined in the Users' Guides to the Medical Literature, published by the American Medical Association.

The chapters in this book have been written by an interdisciplinary team of scientists and medical professionals. Such an approach emphasizes the need for collaboration in the care of any individual with diabetes and in the effort to find new therapies for the disease. We hope that this reference can provide practical guidance in a single resource for clinicians and scientist alike in our combined endeavor to provide the best care and new opportunities for the treatment of type 2 diabetes.

Mark N. Feinglos, md, cm M. Angelyn Bethel, md

Contents

Preface v

Contributors ix

Color Plates xiii

1 Epidemiology of Type 2 Diabetes

Jonathan E. Shaw and Richard Sicree 1

2 Pathogenesis of Type 2 Diabetes Mellitus

Jack L. Leahy 17

3 Metabolic Mechanisms of Muscle Insulin Resistance

Deborah M. Muoio, Timothy R. Koves, Jie An, and Christopher B. Newgard 35

4 Fat Metabolism in Insulin Resistance and Type 2 Diabetes

5 Detection and Diagnosis of Type 2 Diabetes

Adrian Vella 75

6 Therapies for Delay or Prevention of Type 2 Diabetes

Mary Angelyn Bethel 85

7 Postprandial Hyperglycemia

Vasudevan A. Raghavan and Alan J. Garber 97

8 Medical Nutrition Therapy in Type 2 Diabetes

Melinda D. Maryniuk and Mary Jean Christian 115

9 Exercise as an Effective Treatment for Type 2 Diabetes

Leslie A. Consitt, Kristen E. Boyle, and Joseph A. Houmard 135

10 Type 2 Diabetes Mellitus: An Evidence-Based Approach to Practical Management:

Noninsulin Pharmacological Therapies

Ildiko Lingvay, Chanhaeng Rhee, and Philip Raskin 151

11 The Transition from Oral Agents to Combination Insulin/Oral Therapy

Matthew C. Riddle 169

12 Intensive Insulin Therapy in T2DM

Steven V. Edelman 183

13 Hypoglycemia in Type 2 Diabetes

Philip E. Cryer 193

14 Type 2 Diabetes and Concomitant Illness: The Prepared Practice

Kathleen Dungan, Elizabeth Harris, and Susan S. Braithwaite 203

15 Adherence to Practice Guidelines for People with Diabetes Mellitus

Marideli Colon Scanlan and Lawrence Blonde 235

16 Treatment of Hypertension in Type 2 Diabetes

David C. Goff, Jr. and William C. Cushman 251

17 Lipoproteins in Diabetes: Risk and Opportunity

John R. Guyton 265

18 Management of Coronary Artery Disease in Type 2 Diabetes Mellitus

John L. Petersen and Darren K. McGuire 289

19 Peripheral Vascular Disease and Stroke in Type 2 Diabetes

Robert G. Mitchell and Brian H. Annex 321

20 Obesity and Its Treatment in Type 2 Diabetes

Frank L. Greenway and William T. Cefalu 333

21 The Liver in Type 2 Diabetes Mellitus

Anna Mae Diehl and Steve S. Choi 351

22 Developing Criteria for Defining Type 2 Diabetes in Pregnancy

Lois Jovanovic and Seanna Martin 365

23 Metabolic Complications of Polycystic Ovary Syndrome

Tracy L. Setji and Ann J. Brown 377

24 Erectile Dysfunction in Diabetes

25 Sexual Dysfunction in Women with Type 2 Diabetes

Ann J. Brown and Kathryn P. Lowry 399

26 Depression in Type 2 Diabetes

Miranda A. L. van Tilburg, Anastasia Georgiades, and Richard S. Surwit 403

27 Atypical Forms of Type 2 Diabetes

Vinaya Simha and Abhimanyu Garg 413

28 Diabetes Mellitus Type 2 and Stress: Pathophysiology and Treatment

Bryan C. Batch and Richard S. Surwit 433

29 Pharmacologic Factors Affecting Glycemic Control

Lillian F. Lien and James D. Lane 439

30 Influencing Self-Management: From Compliance to Collaboration

Martha M. Funnell and Robert M. Anderson 455

Index 467

Contributors

Jie An, phD, Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina, USA

Robert M. Anderson, edd, Department of Medical Education, University of Michigan Medical School, Ann Arbor, Michigan, USA

Brian H. Annex, md, Division of Cardiology, Department of Medicine, Duke University Medical Center and

Durham Veterans Affairs, Durham, North Carolina, USA Bryan C. Batch, md, Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke

University Medical Center, Durham, North Carolina, USA Mary Angelyn Bethel, md, Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine,

Duke University Medical Center, Durham, North Carolina, USA Lawrence Blonde, md, facp, face, Department of Endocrinology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA

Andrew J. M. Boulton, md, dsc(hon), frcp, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Manchester Royal Infirmary, Manchester, UK Kristen E. Boyle, ms, Department of Exercise and Sport Science, East Carolina University, Greenville, North Carolina, USA

Susan S. Braithwaite, md, Diabetes Care Center, University of North Carolina, Durham, North Carolina, USA Ann J. Brown, md, mhs, Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke

University Medical Center, Durham, North Carolina, USA William T. Cefalu, md, Division of Nutrition and Chronic Diseases, Pennington Biomedical Research Center,

Baton Rouge, Louisiana, USA Steve S. Choi, md, Division of Gastroenterology and Hepatology, Department of Medicine, Duke University

Medical Center, Durham, North Carolina, USA Mary Jean Christian, ma, rd, cde, Joslin Diabetes Center at University of California, Irvine, Irvine, California, USA

Leslie A. Consitt, phD, Department of Exercise and Sport Science, East Carolina University, Greenville, North Carolina, USA

Philip E. Cryer, md, Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine,

Washington University School of Medicine, St. Louis, Missouri, USA William C. Cushman, md, Division of Cardiovascular Diseases, Memphis Veterans Affairs Medical Center,

University of Tennessee College of Medicine, Memphis, Tennessee, USA Anna Mae Diehl, md, Division of Gastroenterology and Hepatology, Department of Medicine, Duke University

Medical Center, Durham, North Carolina, USA Helene Duez, phD, Department of Medicine and Physiology, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada

Kathleen Dungan, md, Department of Endocrinology, Diabetes, and Metabolism, Ohio State University College of Medicine, Columbus, Ohio, USA Steven V. Edelman, md, University of California San Diego and Division of Endocrinology and Metabolism,

Veterans Affairs Medical Center, San Diego, California, USA Martha M. Funnell, ms, rn, cde, Michigan Diabetes Research and Training Center and Department of

Medical Education, University of Michigan Medical School, Ann Arbor, Michigan, USA Alan J. Garber, md, phD, Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

Abhimanyu Garg, md, Division of Nutrition and Metabolic Diseases, Department of Internal Medicine,

University of Texas Southwestern Medical Center, Dallas, Texas, USA Anastasia Georgiades, PhD, Department of Psychiatry and Behavioral Sciences, Duke University Medical

Center, Durham, North Carolina, USA David C. Goff, Jr., md, PhD, Department of Public Health Sciences and Internal Medicine, Wake Forest

University School of Medicine, Winston-Salem, North Carolina, USA Frank L. Greenway, md, Outpatient Clinic Unit, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA

John R. Guyton, md, Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke

University Medical Center, Durham, North Carolina, USA Elizabeth Harris, md, Diabetes Care Center, Department of Medicine, University of North Carolina, Durham, North Carolina, USA

Joseph A. Houmard, PhD, Department of Exercise and Sport Science, East Carolina University, Greenville, North Carolina, USA

Lois Jovanovic, md, Sansum Diabetes Research Institute, Santa Barbara, California, USA

Timothy R. Koves, PhD, Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center,

Durham, North Carolina, USA James D. Lane, PhD, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center,

Durham, North Carolina, USA Jack L. Leahy, md, Division of Endocrinology, Diabetes, and Metabolism, University of Vermont College of

Medicine, Burlington, Vermont, USA Gary F. Lewis, md, frcpc, Division of Endocrinology, Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada

Lillian F. Lien, md, Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke

University Medical Center, Durham, North Carolina, USA Ildiko Lingvay, md, Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine,

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA Kathryn P. Lowry, bs, Harvard Medical School, Boston, Massachusetts, USA Seanna Martin, bs, Sansum Diabetes Research Institute, Santa Barbara, California, USA Melinda D. Maryniuk, MEd, rd, cde, Affiliated Programs, Joslin Diabetes Center, Boston, Massachusetts, USA Darren K. McGuire, md, mhs, The Donald W. Reynolds Cardiovascular Clinical Research Center, Division of

Cardiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA Robert G. Mitchell, md, Division of Cardiology, Department of Medicine, Duke University Medical Center,

Durham, North Carolina, USA Deborah M. Muoio, PhD, Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical

Center, Durham, North Carolina, USA Christopher B. Newgard, PhD, Department of Pharmacology and Cancer Biology, Duke University Medical

Center, Durham, North Carolina, USA Elif A. Oral, md, Division of Endocrinology and Metabolism, University of Michigan, Ann Arbor, Michigan, USA

John L. Petersen, md, Clinical Research Institute, Division of Cardiovascular Medicine, Duke University

Medical Center, Durham, North Carolina, USA Vasudevan A. Raghavan, mbbs, md, mrcp(uk), Division of Endocrinology, Diabetes, and Metabolism,

Department of Medicine, Ohio State University, Columbus, Ohio, USA Philip Raskin, md, Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine,

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA Chanhaeng Rhee, md, Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine,

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA Matthew C. Riddle, md, Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine, Oregon Health Sciences University and Hospital, Portland, Oregon, USA

Marideli Colón Scanlan, md, Department of Endocrinology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA

Tracy L. Setji, md, Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke

University Medical Center, Durham, North Carolina, USA Jonathan E. Shaw, md, mrcp(uk), fracp, International Diabetes Institute Clinical Research, Caulfield, Victoria, Australia

Richard Sicree, mbbs, mph, Department of Epidemiology, International Diabetes Institute, Caulfield, Victoria, Australia

Vinaya Simha, md, Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA Richard S. Surwit, PhD, Division of Medical Psychology and Department of Psychiatry and Behavioral Sciences,

Duke University Medical Center, Durham, North Carolina, USA Miranda A. L. van Tilburg, PhD, Division of Gastroenterology and Hepatology, University of North Carolina

School of Medicine, Chapel Hill, North Carolina, USA Adrian Vella, md, mrcp(uk), Department of Endocrinology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

Color Plates

Color plates follow p. 34.

Color Plate 1 Global projections for the diabetes epidemic: 2007-2025 (Fig. 1, Chapter 1; see complete caption and discussion on p. 2).

Color Plate 2 Glucose and FFA homeostasis (Fig. 1, Chapter 4; see complete caption and discussion on p. 50).

Color Plate 3 Control of fatty acid uptake and release by adipose tissue (Fig. 2, Chapter 4; see complete caption and discussion on p. 53).

Color Plate 4 Detrimental effects of chronic positive net energy balance (Fig. 3, Chapter 4; see complete caption on p. 59 and discussion on p. 58).

Color Plate 5 Photomicrographs of macrovesicular steatosis (Fig. 1, Chapter 21; see complete caption on p. 352 and discussion on p. 351).

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