Diabetes: from Research to Clinical Practice: Volume 4

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Contents
Diabetes: From Research to Clinical Practice
	References
Glucose Lowering Treatment Modalities of Type 2 Diabetes Mellitus
	1 Introduction
	2 Pharmacotherapy for Type 2 Diabetes
		2.1 Biguanides
			2.1.1 Metformin
		2.2 Incretin Mimetics
			2.2.1 DPP4 Inhibitors
				GLP-1RA
			2.2.2 Exenatide
			2.2.3 Liraglutide
			2.2.4 Albiglutide
			2.2.5 Dulaglutide
			2.2.6 Lixisenatide
		2.3 Sodium Glucose Co-Transporter Inhibitors
		2.4 Insulin Secretagogues
			2.4.1 Sulfonylureas
			2.4.2 Meglitinide Analogs
		2.5 Peroxisome Proliferator-Activated Receptor (PPARγ) Agonists
		2.6 Alpha-Glucosidase Inhibitors
		2.7 Colesevelam
		2.8 Bromocriptine
			2.8.1 Dual or Triple Therapy Strategies
	3 The Role of Co-Morbidity and Special Conditions in the Selection of Antidiabetic Pharmacotherapy in Type-2 Diabetes
		3.1 Chronic Kidney Disease
		3.2 Chronic Liver Disease or Liver Dysfunction
		3.3 Cardiovascular Disease and Chronic Heart Failure
		3.4 Cerebrovascular Disease
		3.5 Gestational Diabetes Mellitus
		3.6 Recommendations According to the Recent Society Guidelines
			3.6.1 Shared Decision Making with Patient Preference
	4 Conclusion
	References
Latent Autoimmune Diabetes in Adults: A Review of Clinically Relevant Issues
	1 Latent Autoimmune Diabetes in Adults: A Review of Clinically Relevant Issues
	2 Clinical Problem #1. What Is LADA?
	3 Clinical Problem #2. What Is the Best Method to Diagnose LADA?
	4 Clinical Problem #3. How Prevalent Is LADA?
	5 Clinical Problem #4. What Is the Clinical Phenotype of a Subject with LADA?
	6 Clinical Problem #5. Chronic Diabetes Complications in Patients with LADA
	7 Clinical Problem #6. What Is the Best Strategy to Treat LADA?
	8 Clinical Problem #7. Patient-Reported Outcomes in LADA
	9 Clinical Problem #8. Who Should Be Screened for LADA?
	References
Hypoglycaemia
	1 Introduction
	2 Definition and Classification: Diabetic Hypoglycaemia
	3 Epidemiology
	4 Pathophysiology
		4.1 Physiological Defence in Hypoglycaemia
		4.2 Hypoglycaemia Counterregulation in T1D
		4.3 Hypoglycaemia Counterregulation in T2D
		4.4 Impaired Awareness of Hypoglycaemia
		4.5 Nocturnal Hypoglycaemia
	5 Hypoglycaemia in Special Groups
		5.1 Hypoglycaemia in Pregnancy
		5.2 Exercise and Hypoglycaemia
		5.3 Hypoglycaemia in Children
		5.4 Hypoglycaemia in Elderly
		5.5 Hypoglycaemia and Driving
	6 Hypoglycaemia and Cariovascular Morbidity and Mortality
	7 Causes of Hypoglycaemia
	8 Risk Factors
	9 Clinical Presentation
	10 Diagnosis and Work-Up
	11 Management
		11.1 Management in Adult
		11.2 Management in Children
		11.3 Management: Recurrent Hypoglycaemia
	12 Prevention
	13 Conclusion
	References
Hypoglycemia, Malnutrition and Body Composition
	1 Introduction
	2 Classification of Hypoglycemia and Association with Prognosis
	3 Spontaneous Hypoglycemia
	4 Hypoglycemia and Malnutrition
	5 Kidney Function
	6 Hypoglycemia, Body Composition and Muscle Metabolism
	7 Hypoglycemia and Endocrine Disorders
	8 Treatment and Prevention of Hypoglycemia
	9 Conclusions and Recommendations
	Bibliography
Acute Metabolic Emergencies in Diabetes: DKA, HHS and EDKA
	1 Introduction
	2 Classification and Diagnostic Criteria
	3 Epidemiology
	4 Pathophysiology
		4.1 DKA
		4.2 HHS
		4.3 EDKA
	5 Precipitating Factors
	6 Clinical Presentation
	7 Laboratory Investigations
	8 Differential Diagnosis
	9 Management: General
		9.1 Management: From Admission to 24-48 Hours
		9.2 Management: Acute Hyperglycaemic Crisis Due to COVID-19
		9.3 Management: Some Controversial Issues
		9.4 Management: DKA and EDKA IN Pregnancy
		9.5 Management: Key Calculations
	10 Complications
	11 Prevention
	12 Conclusion
	References
The Role of the Mediterranean Dietary Pattern on Metabolic Control of Patients with Diabetes Mellitus: A Narrative Review
	1 Introduction
	2 MedDiet: General Aspects
	3 MedDiet and its Effects on DM
		3.1 Effects of the MedDiet on Postprandial Glycemia and HbA1c
		3.2 MedDiet, Inflammation and Oxidative Stress
		3.3 MedDiet Benefits in the Management of DM-Related Complications
		3.4 MedDiet and CVD Risk in T2DM
		3.5 MedDiet and Obesity Control
	4 MedDiet and DM: Current Evidence
	5 Other Foods Patterns and Their Effects on T2DM
	6 Conclusion
	References
Glycaemic Control and Vascular Complications in Diabetes Mellitus Type 2
	1 Introduction
	2 Pathophysiology and Molecular Mechanism at the Basis of Vascular Insult in Diabetes
	3 Classification of Vascular Complications
		3.1 Diabetic Retinopathy
		3.2 Diabetic Nephropathy
		3.3 Diabetic Neuropathy
		3.4 Coronary Artery Disease
		3.5 Cerebrovascular Disease
		3.6 Peripheral Artery Disease
	4 Efficacy of Glycaemic Control on Coronary Artery Disease
		4.1 Relationship Between Hyperglycaemia and Cardiovascular Outcome
		4.2 Hypoglycemia and the Possible Explanation of the U-Shaped Mortality Curve
		4.3 Intensive Versus Conventional Glucose-Lowering Strategies
		4.4 Previous Evidences from Early Trials Concerning Specific Drug Classes
		4.5 The Cardiovascular Outcome Trials (CVOTs) in the Era of Novel Glucose-Lowering Drugs
			4.5.1 History and Concepts Behind CVOTs in Diabetes
			4.5.2 Dipeptidyl-Peptidase-4 Inhibitors (DPP-4i)
			4.5.3 Sodium-Glucose Linked Transporter-2 Inhibitors (SGLT-2i)
			4.5.4 Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA)
			4.5.5 Insulin
			4.5.6 Effects on CV Risk Beyond Simple Glycaemic Control
	5 Efficacy of Glycaemic Control on Other Vascular Complications
	6 Conclusions and Guidelines Recommendations
	Bibliography
Diabetes Mellitus and Acute Myocardial Infarction: Impact on Short and Long-Term Mortality
	1 Introduction
	2 Prevalence of DM Among AMI Patients
	3 In-Hospital Mortality of AMI Patients with DM
	4 In-Hospital Clinical Relevance of Admission Glycemia in AMI
	5 Long-Term Mortality of AMI Patients with DM
	6 Current and Emerging Therapeutic Strategies
	7 Conclusions
	References
Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity
	1 Introduction
	2 Synthesis, Actions, and Degradation of Glucagon-Like Peptide 1
	3 Structures and Formulations of GLP-1 Agonists and Analogs
	4 Effects of GLP-1 on Gastric Functions in Health
	5 Methodological Assessment of Gastric Emptying
	6 Mechanism of Impairment of GI Motor Function by GLP-1 Agonists
	7 Effect of GLP-1 Receptor Agonism in Disease State: Diabetes Mellitus
	8 Effects on Gastric Emptying with GLP-1 Receptor Agonists in Obesity
	9 Short- vs. Long-Acting GLP-1 Receptor Agonists and Gastric Emptying and Tachyphylaxis
	10 Effects of GLP-1 Agonist on Pharmacokinetics and Pharmacodynamics of Other Medications
	11 Variations in GLP-1 Receptor and Responses to GLP-1 Agonists
	12 Oral Semaglutide
	13 Effects of Combined GLP-1 and Other Hormone Agonism on Gastric Motor Functions
	14 Conclusion
	References
GLP-1 Receptor Agonists and SGLT2 Inhibitors for the Treatment of Type 2 Diabetes: New Insights and Opportunities for Cardiova...
	1 Cardiovascular Risk in Type 2 Diabetes
	2 SGLT2 Inhibitors
		2.1 Mechanisms of Action of SGLT-2 Inhibitors
		2.2 Cardiovascular Outcome Trials
		2.3 Cardiovascular Protection Mechanisms of SGLT2 Inhibitors
			2.3.1 Metabolic Effects of SGLT2i
			2.3.2 Cardio-Hemodynamic Effects of SGLT2i
	3 GLP-1 Receptor Agonists (GLP-1RA)
		3.1 Mechanisms of Action of GLP-1RA
		3.2 Cardiovascular Outcome Trials
		3.3 Cardiovascular Protection Mechanisms of GLP1-RA
	4 Conclusions
	Glossary
	References
Glucose Lowering Efficacy and Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitors
	1 Introduction
	2 Historical Perspective
	3 Renal Handling of Glucose and SGLT2 Inhibition
	4 Glucose Lowering Efficacy of SGLT2 Inhibitors
	5 Pleiotropic Effects of SGLT2 Inhibitors
		5.1 Cardiovascular Protection
		5.2 Renal Protection
		5.3 Weight Reducing Effect
		5.4 Blood Pressure Lowering Effect
		5.5 Uricosuric Effect
		5.6 Changes in Lipid Metabolism
		5.7 Improvement in Nonalcoholic Fatty Liver Disease
	6 Adverse Effects of SGLT2 Inhibitors
		6.1 Genital Mycotic Infections
		6.2 Orthostatic Hypotension
		6.3 Diabetic Ketoacidosis
		6.4 Bone Fractures
		6.5 Risk of Lower Limb Amputation
	7 Conclusions
	References
Gestational Diabetes Mellitus Screening and Diagnosis
	1 Introduction
	2 History of GDM
	3 Definition
	4 GDM Screening
		4.1 Indications for Screening
			4.1.1 Risk Factor-Based Screening or Universal Screening?
		4.2 When to the Screen?
			4.2.1 Pre-conceptual Prediction of GDM
			4.2.2 First-Trimester Screening
			4.2.3 24-28 Weeks Screening
			4.2.4 Screening and Diagnostic Criteria
			4.2.5 Universal Testing During the First Trimester
			4.2.6 100-g OGTT and Two-Step Screening
			4.2.7 75-g OGTT and One Step Screening
			4.2.8 Advantages and Disadvantages of One-Step and Two-Step Methods
			4.2.9 Role of FPG and Postprandial Plasma Glucose (PPG) for Screening GDM
			4.2.10 Role of HbA1c for Screening GDM
	5 Conclusion and Recommendations
		5.1 Overt Diabetes
		5.2 One-Step Versus Two-Step Testing
	References
Management of Gestational Diabetes Mellitus
	1 Nutritional Therapy
		1.1 Ideal Diet
		1.2 Ideal Weight Gain According to Pre-pregnancy BMI (Institute of Medicine Recommendations) (Rasmussen and Yaktine 2009; Nati...
		1.3 Recommended Calories
	2 Exercise
	3 Monitorization of Laboratory Parameters
		3.1 Glucose Monitoring
		3.2 Glucose Target
		3.3 Glycated Hemoglobin (HbA1c)
		3.4 Ketonuria
	4 Medical Therapy
		4.1 Insulin
		4.2 Oral Antihyperglycemic Agents
			4.2.1 Metformin
			4.2.2 Glyburide
		4.3 Management of Hypoglycemia
	5 Follow-Up for Pregnancy
		5.1 Antepartum Fetal Assessment
	6 Delivery
		6.1 Birth Method
	7 Postpartum Management
	8 Recommendations of Major Societies and Latest Guidelines
	References
From Entero-Endocrine Cell Biology to Surgical Interventional Therapies for Type 2 Diabetes
	1 Anatomy and Physiology of the Enteroendocrine System
	2 Experimental Data Supporting Enteroendocrine System Modulation through Interventional Therapies for Type 2 Diabetes
		2.1 Ghrelin
		2.2 Cholecystokinin
		2.3 Incretins
		2.4 Peptide YY and Oxyntomodulin
		2.5 Anti-incretin Factors
		2.6 Bile Acids and Gut Microbiota
	3 Clinical Evidence on the Use of Gastro-Intestinal Interventions to Treat Type 2 Diabetes
		3.1 Surgical Interventions
		3.2 Endoscopic Interventions
	4 Current Clinical Recommendations and Guidelines
	5 Concluding Remarks
	References
Laparoscopic Vertical Sleeve Gastrectomy as a Treatment Option for Adults with Diabetes Mellitus
	1 Introduction
	2 Medical Management of Type 2 Diabetes Related to Obesity
	3 The Role of Bariatric Surgery in Diabetes Mellitus
		3.1 Prevention of Diabetes Mellitus in Obese Individuals
		3.2 Bariatric Procedures for Treatment of Obesity and Diabetes Mellitus
		3.3 Mechanisms of Weight Loss After Vertical Sleeve Gastrectomy
		3.4 Nutritional Requirements After Vertical Sleeve Gastrectomy
		3.5 Short Term Complications After Vertical Sleeve Gastrectomy
		3.6 Long Term Complications After Vertical Sleeve Gastrectomy
		3.7 Preoperative Micronutrients
		3.8 Potential Mechanisms of Micronutrient Deficiencies After Vertical Sleeve Gastrectomy
		3.9 Postoperative Screening for Micronutrient Deficiencies
		3.10 Micronutrients Deficiencies After Vertical Sleeve Gastrectomy
		3.11 Repletion of Micronutrient Deficiencies
			3.11.1 Fat Soluble Vitamins
			3.11.2 Water Soluble Vitamins
			3.11.3 Minerals
			3.11.4 Trace Elements
	4 Outcomes After Vertical Sleeve Gastrectomy in Morbidly Obese Individuals
		4.1 Long Term Mortality in Morbidly Obese Individuals After Vertical Sleeve Gastrectomy
		4.2 Long Term Weight Loss in Morbidly Obese Individuals After Vertical Sleeve Gastrectomy
		4.3 Long Term Control of Diabetes Mellitus After Vertical Sleeve Gastrectomy
	5 Conclusions
	References
Surgical Treatment of Type 2 Diabetes Mellitus in Youth
	1 Introduction
	2 Current Management of T2D in Youth
	3 Metabolic and Bariatric Surgery
	4 Different Types of Bariatric Surgery
	5 Effect of Bariatric Surgery on GI Physiology and Metabolism
	6 The Impact of Bariatric Surgery on Obesity and Type 2 Diabetes
	7 Criteria for Use of Bariatric Surgery in Youth
	8 Potential Complications of Bariatric Surgery
		8.1 Need for Repeat Surgery
		8.2 Vitamin and Mineral Deficiencies
		8.3 Bone Disease
		8.4 Psychological Function
	9 Conclusion
	References
Insulin Recommender Systems for T1DM: A Review
	1 Introduction
	2 Insulin Recommender System Basics
	3 Methodology
		3.1 Selection of the Works Surveyed
		3.2 Comparison Criteria
			3.2.1 Technology
			3.2.2 Control Procedures
			3.2.3 Complementary Processes
			3.2.4 Hardware
			3.2.5 Testing and Assessment
			3.2.6 System Estimated Price
			3.2.7 Results
	4 Discussion
		4.1 Technology
		4.2 Control Measures
		4.3 Complementary Procedures
		4.4 Hardware
		4.5 Testing
		4.6 Pricing
		4.7 Results
	5 Conclusions
	Bibliography
Algorithms for Diagnosis of Diabetic Retinopathy and Diabetic Macula Edema- A Review
	1 Introduction
	2 Fundus Photography
	3 Retinal Image Analysis System
	4 Retinal Manifestation of Eye Diseases
		4.1 Diabetic Retinopathy
			4.1.1 Signs and Symptoms of DR
			4.1.2 Classification of DR
		4.2 Diabetic Macula Edema
			4.2.1 Types of DME
			4.2.2 Signs and Symptoms of DME
			4.2.3 Diagnosis of DME
			4.2.4 Management of DME
	5 Retinal Image Database
	6 Detection of Diabetic Retinopathy
		6.1 Segmentation of Blood Vessel
			6.1.1 Supervised Methods
			6.1.2 Matched Filters
			6.1.3 Thresholding-Based Approach
			6.1.4 Other Methods
	7 Detection of Diabetic Macula Edema
	8 Conclusion
	References
Diabetic Macular Edema: State of Art and Intraocular Pharmacological Approaches
	1 Introduction
	2 Epidemiology and Risk Factors of Diabetic Retinopathy and Diabetic Macular Edema
	3 Pathogenesis of DME
	4 Classification
	5 Multimodal Imaging in DME
	6 Pharmacologic Intravitreal Therapy
	7 Anti-angiogenic Agents
	8 Steroids
	9 Conclusion
	References
New Concepts in the Management of Charcot Neuroarthropathy in Diabetes
	1 Introduction
	2 Pathophysiology
	3 Classifications
	4 Clinical Presentation
	5 Diagnosis
		5.1 Imaging
		5.2 Nerve Conduction
		5.3 Nerve Biopsy and Histopathological Studies
	6 Management
		6.1 Bisphosphonates
		6.2 Calcitonin
		6.3 RANKL Antibody
		6.4 Surgical Options
	7 Summarizing the Clinical Approach to CN
	8 Conclusion
	References
Non-alcoholic Fatty Liver Disease and Diabetes Mellitus
	1 Introduction
	2 Risk Factors for NAFLD
	3 Epidemiology and Burden of NAFLD on Healthcare Systems
	4 NAFLD Awareness in the Primary Care Setting
	5 Guidelines on Screening for NAFLD in High-Risk Groups
	6 Diagnostic Approach to NAFLD in Diabetes
	7 NAFLD Interaction with Metabolic Syndrome and Diabetes
	8 NAFLD in Type 1 Diabetes Mellitus
	9 Pathophysiology of NAFLD in T2DM
	10 Management of NAFLD
		10.1 Weight Loss Through Lifestyle Intervention
		10.2 Effects of Different Diets on NAFLD
		10.3 Effects of Physical Activity on NAFLD
		10.4 Bariatric Surgery
		10.5 Pharmacologic Therapy for NAFLD
			10.5.1 Vitamin E
		10.6 Insulin Sensitizers
			10.6.1 Metformin
		10.7 Thiazolidinediones
		10.8 Glucagon-Like Peptide Agonists
		10.9 Liraglutide
		10.10 Exenatide
		10.11 Semaglutide
		10.12 Sitagliptin and Vildagliptin
		10.13 Sodium-Glucose Cotransporter-2 Inhibitors
		10.14 Farsenoid X Receptors Agonists
	11 Conclusions
	References
Global Experience of Diabetes Registries: A Systematic Review
	1 Introduction
	2 Methods
		2.1 Design
		2.2 Input and Output Criteria
		2.3 Search Strategy
		2.4 Data Extraction and Synthesis
	3 Results
		3.1 Bibliographic Research Results
		3.2 Results of Each Question
			3.2.1 Q1: What Are the Goals of the Diabetes Registry Systems?
			3.2.2 Q2: What Are the Capabilities and Data Sources of the Diabetes Registry Systems?
			3.2.3 Q3: What Are the Data Elements of the Diabetes Registry Systems?
			3.2.4 Q4: What Are the Reports of the Diabetes Registry Systems?
	4 Discussion
	5 Conclusions
	6 Research Limitation
	7 Strengths of Research
	References
Diabetes and Genetics: A Relationship Between Genetic Risk Alleles, Clinical Phenotypes and Therapeutic Approaches
	1 Introduction
	2 Type 1 Diabetes and Genetics
	3 Type 2 Diabetes and Genetics
	4 Diabetes, Genetic Variation and Precision Medicine
	5 Use of Personalized Medicine to Treat Monogenic Diabetes
	6 Variation in Genetics and their Role in Precision Medicine for Patients with Diabetes
	7 Genetic Variants and Their Influence on Anti-diabetic Drugs
	8 Conclusion and Future Directions
	References
Dietary SCFAs Immunotherapy: Reshaping the Gut Microbiota in Diabetes
	1 Factors Influencing the Gut Microbiota and Type 1 Diabetes
	2 Dietary Short-Chain Fatty Acids and Type 1 Diabetes
	3 Diet/Gut Microbiota-Interventions in Type 1 Diabetes: Clinical Trials
	4 Type 2 Diabetes: A ``Gut Origin´´ Disease
	5 Dietary Short-Chain Fatty Acids: Modulators of Meta-Inflammation in Type 2 Diabetes
	6 Harnessing the Potential of the Microbiota for Diabetes Therapy
	7 Diet/Gut Microbiota-Interventions in Type 2 Diabetes
	8 Conclusions and Future Perspectives
	References
Animal Models and Renal Biomarkers of Diabetic Nephropathy
	1 Introduction
	2 Brief Review of Kidney Anatomy and Physiology
	3 Pathophysiology of Diabetic Nephropathy
		3.1 Hemodynamic Factors
		3.2 Metabolic and Inflammatory Factors
		3.3 Histologic Changes
	4 Animal Models
		4.1 Rodents
			4.1.1 Mouse Models
			4.1.2 Rat Models
		4.2 Companion Animals
			4.2.1 Cats
			4.2.2 Dogs
		4.3 Production Animals
	5 Assessment of Renal Function
		5.1 Routine Evaluation of DN and Gold Standard Methods
		5.2 Indirect Markers of Glomerular Filtration Rate
			5.2.1 Serum Creatinine
			5.2.2 Symmetric Dimethylarginine
		5.3 Markers of Glomerular Damage
			5.3.1 Urine Albumin
			5.3.2 Urine Immunoglobulin G
		5.4 Markers of Tubular Damage
			5.4.1 Serum and Urine Cystatin C
			5.4.2 Retinol-Binding Protein 4 (RBP4)
			5.4.3 Uromodulin (Tamm-Horsfall Protein)
			5.4.4 Neutrophil Gelatinase-Associated Lipocalin (NGAL)
			5.4.5 Kidney Injury Molecule -1 (KIM-1)
		5.5 Markers of Fibrosis and Inflammation
			5.5.1 Transforming Growth Factor-β1 (TGFβ1)
			5.5.2 Vascular Endothelial Growth Factor (VEGF)
			5.5.3 Soluble Urokinase Type Plasminogen Activator Receptor (suPAR)
		5.6 Panels of Candidate Biomarkers, Proteomic and Metabolomic Approaches
	6 Conclusions
	References
In Vivo and In Vitro Models of Diabetes: A Focus on Pregnancy
	1 Animal Models of Diabetes
		1.1 Animal Models of Gestational and Pregestational Diabetes
			1.1.1 Surgically Induced Models (SIM)
			1.1.2 Chemically, Toxic or Drug Induced Models (CIM)
			1.1.3 Diet Induced Models (DIM)
			1.1.4 Genetic Models
		1.2 Animal Studies on Gestational and Pregestational Diabetes
			1.2.1 Fertility
			1.2.2 Placentation
			1.2.3 Perinatal Outcomes
			1.2.4 Intrauterine Programming
	2 In Vitro Models
		2.1 In Vitro Models of Diabetes
			2.1.1 Cell Models of Diabetes
			2.1.2 Pancreatic Islets
			2.1.3 Human Stem Cells
			2.1.4 Organoid Cultures
		2.2 In Vitro Models of Diabetes in Pregnancy
			2.2.1 Primary Cell Lines
			2.2.2 Choriocarcinoma Cells
			2.2.3 Immortalized Cells
			2.2.4 Human Trophoblast Stem Cells
			2.2.5 Placental Organoids
			2.2.6 Embryo Cultures
		2.3 Recreation of the Diabetic Milieu
	3 Potential Translation, Research Gaps and Future Perspectives
	4 Summary and Recommendations
	5 Funding
	References
Correction to: Hypoglycemia, Malnutrition and Body Composition
	Correction to: Adv Exp Med Biol - Advances in Internal Medicine https://doi.org/10.1007/5584_2020_526
Index