Clinical Dilemmas in Diabetes

1 Cover

2 Title Page

3 Copyright Page

4 List of Contributors

5 Preface

6 PART I: Prediabetes and the Diagnosis of Diabetes 1 “Is Prediabetes a Risk Factor or Is It a Disease?” What is prediabetes? Rationale for the diagnostic criteria for diabetes mellitus and prediabetes Epidemiology of prediabetes Pathogenesis of impaired fasting glucose and impaired glucose tolerance Screening recommendations for prediabetes Risk of progression from prediabetes to diabetes mellitus Microvascular complications associated with prediabetes Macrovascular complications and mortality associated with prediabetes Management of prediabetes Conclusion References 2 Early Diagnosis of Type 1 Diabetes – Useful or a Pyrrhic Victory? Introduction Pathogenesis of T1D: An Update in View of Defining Preventive Tools Prediction of T1D as the Basis for Disease Prevention Prevention of T1D: Current Status Conclusions Acknowledgments References 3 Reclassifying or Declassifying Diabetes? Can Clinical Characteristics Guide Classification and Treatment? The pathophysiology of hyperglycemia – type 1 vs type 2 diabetes Genetic and environmental influences on disease presentation Measuring insulin secretion Autoantibodies “Atypical” diabetes, glucose toxicity and the honeymoon period Cystic fibrosis‐related diabetes Novel approaches to reclassifying diabetes Conclusions Bibliography 4 How Should Secondary Causes of Diabetes Be Excluded? Introduction Hereditary haemochromatosis Cystic fibrosis‐related diabetes Pancreatic‐cancer‐associated diabetes Diabetes due to hormone excess Post‐transplantation diabetes mellitus (PTDM) Diabetes associated with atypical antipsychotic drug use Diabetes associated with HIV infection and its treatment Diabetes secondary to immunotherapy Monogenic forms of diabetes References 5 How to Screen Appropriately for Monogenic Diabetes Maturity onset diabetes of the young (MODY) Differentiating monogenic diabetes from type 1 diabetes Differentiating monogenic diabetes from type 2 diabetes When to screen for monogenic diabetes? Common forms of monogenic diabetes Conclusions References

7 PART II: Initial Evaluation and Management of Diabetes 6 Managing Gestational Diabetes During and After Pregnancy Introduction GDM diagnosis GDM management Conclusion References 7 What Is the Role of Self‐Monitoring in Diabetes? Is There a Role for Postprandial Glucose Monitoring? How Does Continuous Glucose Monitoring Integrate into Clinical Practice? Self‐monitoring of blood glucose SMGB in type 1 DM and insulin‐requiring T2DM patients SMBG in non‐insulin‐requiring T2DM Postprandial SMBG Continuous glucose monitoring systems Flash glucose monitoring systems References 8 Does HbA1c Remain the Most Important Therapeutic Target in Outpatient Management of Diabetes? The glucose hypothesis and vascular risk Measuring glycemic control in the clinical management of diabetes Additional therapeutic targets to consider for hyperglycemia in the outpatient management of diabetes Summary References 9 Technology Issues: Continuous Glucose Monitoring, Insulin Pumps, and Closed Loop Control for Patients with Diabetes Introduction Continuous Glucose Monitoring (CGM) for Diabetes Care Currently Approved CLC for T1DM Post‐marketing Studies Ongoing Pivotal Studies/Anticipated Closed Loop System Closed Loop Control Initiation at Onset of T1D CLC is Being Tested in Specific Subgroups with Type 1 Diabetes at Present Cost of Diabetes Technologies Insulin Pump Use for People With T2DM Conclusion References 10 Optimizing Diet in Patients with Diabetes Summary References 11 Are Insulin Sensitizers Useful Additions to Insulin Therapy? Insulin sensitizers Biguanides Thiazolidinediones Discussion References 12 Incretin‐Based Therapy for the Management of Type 2 Diabetes Introduction The incretin effect Early development of GLP‐1 RA therapy Clinical benefits and side effects of GLP‐1 RAs The evidence for GLP‐1 ras in management of type 2 diabetes The role of DPP‐4 inhibitors in type 2 diabetes management Cardiovascular outcomes with incretin‐based therapies for type 2 diabetes Incorporating incretin‐based therapy into clinical practice Conclusions Key points References

8 PART III: Diagnosis and Management of Cardiovascular Risk Factors and Cardiovascular Disease 13 Screening Patients with Prediabetes and Diabetes for Cardiovascular Disease Introduction Guidelines Hyperglycemia and risks of CVD Traditional risk factors Diabetes‐specific clinical risk predictors of CVD Nontraditional risk factors Screening tools Risk calculators Summary References 14 Choosing Medications for Type 2 Diabetes – What Weighting Should Be Given to Cardiovascular Risk Reduction? Diabetes and cardiovascular risk: how does it affect therapeutic goals? Metformin Sulfonylureas Thiazolidinediones Acarbose Colesevelam Pramlintide Bromocriptine Glucagon‐like peptide‐1‐based therapy SGLT‐2i Conclusions References 15 Choosing Medications for Weight Loss in Type 2 Diabetes Mellitus Introduction: Prevalence and relationship of obesity and type 2 diabetes Therapeutic classes for the treatment of type 2 Diabetes and their effects on weight Use of diabetic medications for weight loss in patients without diabetes A Practical Guide to Choosing medication for type 2 diabetes with weight loss in mind References 16 Are Statins the Optimal Therapy for Cardiovascular Risk in Patients with Diabetes? What Newer Agents Are There for the Treatment for Dyslipidemia in Diabetes? Are Triglycerides an Important Risk Factor for Diabetes? Introduction Dyslipidemia in type 2 diabetes mellitus Treatment of dyslipidemia in type 2 diabetes mellitus Evidence that PSCK 9 is associated with increased CVD risk Evidence linking hypertriglyceridemia to CVD risk in diabetes mellitus Evidence that treating hypertriglyceridemia will decrease CVD risk in DM Discussion References 17 New Agents for Treatment of Dyslipidemia Introduction PCSK9 and regulation of LDL‐Cholesterol levels PCSK9 inhibitors: Efficacy and safety PCSK9 inhibitors: Cardiovascular outcome trails PCSK9 inhibitor use in patients with diabetes PCSK9 inhibitors: Clinical use and future perspectives Other novel lipid‐lowering therapies Conclusions References 18 The Role of Bariatric Surgery in Obese Patients with Diabetes: Primary or Rescue Therapy? Introduction Possible Mechanisms by Which Bariatric Surgery Improves T2DM Role of Bariatric Surgery in T2DM: First‐line Therapy or Rescue Therapy When Medical Options Fail? Role of Weight Loss Surgery in the Treatment of Patients with T2DM and BMI < 35 kg/m 2 New Techniques that can be an Option in the Future References 19 Treatment Strategies in Patients with Diabetes Mellitus and Ischemic Heart Disease Introduction Role of medical therapy and glucose control Coronary revascularization Conclusions References

9 PART IV: Management of Disease Complications 20 Diabetes Management in Patients with Critical and Non‐Critical Illness Introduction Mechanisms Mediating Adverse Effects of Hyperglycemia During Critical Illness Large Intervention Studies General Findings (Tables 20.1 and 20.2) Role of Hypoglycemia in Interpretation of Study Results (Table 20.3) Methodology for Glucose Testing The Role of Nutritional Support in Results of Trials Conclusions Acknowledgments References 21 Diagnosis and Management of Ophthalmic Complications of Diabetes Introduction Risk Factors for Diabetic Retinopathy Screening Prevention Ocular Complications Treatment of Diabetic Retinopathy Retinal Vein Occlusion Neovascular Glaucoma Diabetic Macular Edema Treatment of DME Cornea Cataract Orbital Disease References 22 Upper Gastrointestinal Manifestations of Diabetes Introduction Epidemiology Mechanisms and pathophysiology underpinning upper gastrointestinal symptoms in diabetes mellitus Upper gastrointestinal manifestations associated with diabetes Management of gastroparesis and dyspepsia Conclusion References