UNDERSTANDING DIABETES -- CONTENTS -- PREFACE -- 1 DIABETES MELLITUS: A PANDEMIC IN THE MAKING -- Diabetes Prevalence and Cost in the United States -- A Dire Prediction Based on Alarming Data -- The Increase of Diabetes in Youths -- The Cost -- Diabetes Prevalence and Cost Worldwide -- A Worldwide Epidemic -- Numbers of Cases of Diabetes -- Cost -- Obesity and Overweight -- Another Epidemic in the United States -- A Parallel Pandemic -- Definitions of Overweight and Obesity -- Overweight and Obesity among Adults in the United States -- Obesity and Overweight among Children and Adolescents in the United States -- Overweight and Obesity Worldwide -- Overweight and Obesity Globally in Adults -- Overweight and Obesity in Children -- The Relationship Between Obesity and Diabetes -- Projects and Questions -- Glossary -- References -- 2 AN EARLY HISTORY OF DIABETES MELLITUS -- Translation -- More simply stated -- The Ebers Papyrus -- Neandertals -- Hippocrates, Aretaeus, and Demetrius -- Galen -- Sushruta -- Ibn Sina (Avicenna) -- The Yellow Emperor -- Japanese Medicine -- Paracelsus (Philippus Aureolus Theophrastus Bombastus von Hohenheim) -- Thomas Willis -- Johann Conrad Brunner -- Matthew Dobson -- John Rollo and William Cruickshane -- Thomas Cawley -- Michel Eugene Chevreul -- Claude Bernard -- Paul Langerhans (Edouard Laguesse and Eugene L. Opie) -- Oscar Minkowski and Josef von Mering -- Advances in Sugar (Glucose) Determinations -- Earliest Approaches-Taste and Fermentation -- Evaporation of Urine to Yield Sugar Crystals -- Moore's Test -- Trommer's Test -- Barreswil and Fehling's Solutions -- Frederick Pavy -- Benedict's Solution -- Folin-Wu Determination of Blood Glucose -- Banting, Best, and MacLeod -- Leonard Thompson -- John Jacob Abel -- Frederick Sanger -- Pedro Cuatrecasas -- Questions and Crossword Puzzle -- References.

3 A PRIMER: GLUCOSE METABOLISM -- Prolog -- The Carbohydrates and their Function -- Digestion and Absorption of Carbohydrates -- Salivary and Pancreatic Amylase -- Disaccharidases -- Absorption -- Overview of Glucose Metabolism -- Adenosine 5'-Triphosphate (ATP) -- Glucose Metabolism -- Glucose Transport into Cells -- Phosphorylation of Glucose -- Introduction to Glycogen Synthesis and Hydrolysis -- Beautiful Concepts -- Glycogen Synthesis -- Uridine Bisphosphate Glucose (UBP-Glucose) -- Glycogen Synthase -- Branching Enzyme -- Glycogenolysis -- Debranching Enzyme -- Glycogen Phosphorylase -- Phosphoglucomutase -- Glucose 6-Phosphatase -- a(1 r 4)-Glucosidase -- Synchronization of Glycogenesis and Glycogenolysis (A Beautiful Pathway) -- Dephosphorylation -- Effectors -- Glycolysis (Glycolytic Pathway) -- Phosphoglucose Isomerase -- Phosphofructokinase -- Aldolase -- Triose Phosphate Isomerase -- Glyceraldehyde 3-Phosphate Dehydrogenase -- Erythrocyte Bisphosphoglyceromutase and Bisphosphoglycerate Phosphatase -- 3-Phosphoglycerate Kinase -- Phosphoglyceromutase -- Enolase -- Pyruvate Kinase -- Lactate Dehydrogenase -- Tricarboxylic Acid Cycle -- The Coenzymes: Nicotinamide Adenine Dinucleotide (NAD+) and Flavin Adenine Dinucleotide (FADH) -- Steps in the Tricarboxylic Acid Cycle -- Pyruvate Dehydrogenase -- Acetyl CoA -- Pyruvate Decarboxylase -- Dihydrolipoyl Transacetylase -- Dihydrolipoyl Dehydrogenase -- Citrate Synthase -- Aconitase -- Isocitrate Dehydrogenase -- a-Ketoglutarate Dehydrogenase -- Succinate Dehydrogenase -- Fumarase -- l-Malate Dehydrogenase -- Pyruvate Carboxylase -- Glycolysis -- Tricarboxylic Acid Cycle -- Sum Total of Glycolysis and Tricarboxylic Acid Cycle -- Summary -- The Electron Transport System and Oxidative Phosphorylation -- Steps in the Electron Transport System -- Oxidative Phosphorylation (ATP Synthase) -- Shuttles.

Glycerol 3-Phosphate Shuttle -- Malate-Aspartate Shuttle -- Moles ATP Produced by Oxidative Phosphorylation from 1 mol of Glucose -- The Phosphogluconate Oxidative Cycle -- Steps in The Phosphogluconate Oxidative Cycle -- Glucose 6-Phosphate Dehydrogenase -- Lactonase -- Transaldolase -- Transketolase -- The Fate of Glyceraldehyde 3-phosphate -- Uronic Acid Pathway -- Hexosamine Biosynthesis Pathway -- The Steps of Gluconeogenesis -- Conclusions -- Questions -- Glossary -- 4 REGULATION OF GLUCOSE METABOLISM -- Insulin -- Structure -- Transport and Secretion of Insulin -- Insulin Signaling Pathways -- Akt Pathway -- GLUT4 Translocation -- Insulin-Stimulated Glycogenesis -- Insulin-Stimulated Inhibition of Gluconeogenesis -- Insulin-Stimulated Protein Synthesis -- Insulin-Stimulated Lipogenesis (Fatty Acid Synthesis) -- Insulin-Inhibited Lipolysis (Fatty Acid Hydrolysis) -- Scaffold Proteins -- The Incretin Hormones (Incretins) -- Amylin -- Other Hormones -- Glucagon -- Epinephrine -- Somatotropin (Growth Hormone) -- Somatostatin (SST) -- Cortisol -- Adrenocorticotropin -- Thyroid Hormones -- Insulin-Like Growth Factor (IGF) -- Fibroblast Growth Factor 19 -- Adenosine 5'-Monophosphate-Activated Protein Kinase -- Glossary -- References -- 5 GLUCOSE METABOLISM GONE WRONG -- Pancreatic b-Cell Mass -- Glucose Transport and Hexokinase -- Glycogen Synthesis and Breakdown -- Glycogen Cycling -- Gluconeogenesis and Glycogenolysis -- Glycolysis, Glucose Oxidation, and Pyruvate Dehydrogenase -- Mitochondrial Defects -- Tricarboxylic Acid Pathway and Oxidative Phosphorylation -- Hexosamine Biosynthesis Pathway -- Techniques Used in the Investigations -- Hyperinsulinemic-Euglycemic Clamp -- Vastus Lateralis Muscle Biopsy -- Glossary -- References -- 6 CLASSIFICATION SYSTEM FOR DIABETES MELLITUS -- T1D -- Latent Autoimmune Diabetes (LADA) or Type 1.5 -- T2D.

Hybrid -- Idiopathic Diabetes (T1b) -- Secondary -- Genetic Defects of b-islet Function -- Mody -- Other Genetic Defects of the b-cell -- Genetic Defects in Insulin Action -- Diseases of the Exocrine Pancreas -- Endocrinopathies -- Drug or Chemically Caused Diabetes -- Infections -- Uncommon Forms of Immune-Mediated Diseases -- Other Genetic Syndromes Sometimes Associated With Diabetes -- Prediabetes -- Gestational Diabetes Mellitus (GDM) -- Statistical Risk Classes -- Metabolic Syndrome -- Glossary -- References -- 7 DIAGNOSIS OF DIABETES MELLITUS -- PART 1: Establishing a Normal Range -- The Concept of Normal and Abnormal Populations -- The Probability Factor in Diagnosing Disease -- Probability of Disease and Prevalence -- The Normal Range -- Assay Sensitivity and Specificity -- Relationships Among Sensitivity, Specificity, Prevalence, Predictability, and Normal Range -- Exercise -- How Does One Choose a Normal Range? -- Truthfulness (Efficiency) -- Non-gaussian Distribution -- The Effect of Reproducibility on Sensitivity and Specificity -- Severity of Disease and Assay Results -- Parallel and Series Multiparameter Testing -- Exercise -- Example -- Example -- References -- PART 2: Modern Techniques for the Quantitation of Glucose -- Methods of Historical Interest -- Modern-day Methods of Measuring Glucose -- Glucose Oxidase/Peroxidase/Chromogen -- Hexokinase/NADP -- Exercise -- Glycated Hemoglobin -- Specimen Collection -- Exercise -- The Gold Standard -- Instrumentation -- References -- PART 3: Symptoms and Tools for the Diagnosis of Diabetes Mellitus -- The Symptoms of Diabetes Mellitus -- Individuals Who Should be Tested for Diabetes -- Tools for the Diagnosis of Diabetes -- Urinary Glucose -- Fasting Blood Glucose -- Oral Glucose Tolerance Test -- HbA1c -- Cut Points for the Diagnosis of Diabetes.

Diagnosis of Diabetes Using FBG, 2-h PG, or HbA1c -- Diagnosis of Gestational Diabetes Mellitus -- Autoimmune Antibodies as Predictors for T1D And LADA -- Glossary -- References -- 8 COMPLICATIONS OF DIABETES MELLITUS AND THEIR PATHOPHYSIOLOGY -- The Complications of Diabetes Mellitus -- Retinopathy and Other Eye Complications -- Neuropathy and Related Conditions -- Nephropathy, Diabetic Kidney Disease (DKD), and End-Stage Renal Disease -- Cardiovascular Disease (CVD), Hypertension, Coronary Heart Disease or Coronary Artery Disease (CHD), Cerebrovascular Accident (CVA), Pathophysiology of CVD: Endothelial Dysfunction -- The Pathophysiology of CVD: Endothelium Dysfunction -- Diabetic Ketoacidosis (DKA) -- Hyperglycemic Hyperosmolar Non-Ketotic Syndrome -- Hypoglycemia -- Infections -- Alzheimer's Disease or Alzheimer Disease (AD) -- Diabetes and Cancer -- Pathophysiology of Diabetic Complications -- Glycation -- Sorbitol Accumulation -- Reactive Oxygen Species (ROS) in Diabetes -- Glossary -- References -- 9 HEREDITARY TRANSMISSION OF DIABETES MELLITUS -- Inheritance of T1D in Monozygotic and Dizygotic Twins -- Pairwise and Probandwise Concordance in T1D -- Pairwise and Probandwise Concordance in T2D -- Diabetes in Offspring of One or Two Diabetic Conjugal (Biological) Parents -- Diabetes in Siblings of Diabetics -- Summary -- The Genetic Component of Diabetes Mellitus -- The Major Histocompatibility Complex Proteins or Human Lymphocyte Antigens and Disease -- Online Mendelian Inheritance in Man -- HLA Nomenclature -- HLas and Diabetes Mellitus -- T1D and Class II Genes -- T1D and Class I Genes -- Non-HLA T1D Promoting Alleles -- Genetics of T2D -- T1D and Environment -- Enteroviruses (Coxsackie B Virus) -- Rubella Virus (German Measles) -- Mumps Virus -- Cytomegalovirus -- Retrovirus -- Reovirus and Rotavirus -- Epstein-Barr Virus.

Viruses that Need More Evidence for the Assumption that They Promote T1D in Humans.