Comprehensive Clinical Approach to Diabetes During Pregnancy

Contents
Contributors
Abbreviations
Chapter 1: Introduction
	References
Part I: Setting the Diagnosis
	Chapter 2: Epidemiology
		1 Hyperglycemia in Pregnancy
		2 Epidemiology of Preexisting Diabetes in Pregnancy
			2.1 Prevalence of Preexisting Type 1 and Type 2 Diabetes in Pregnancy
			2.2 Prevalence of Other Forms of Preexisting Diabetes in Pregnancy
		3 Epidemiology of Diabetes Arising in Pregnancy
			3.1 Gestational Diabetes Mellitus
			3.2 Screening Approaches and Diagnostic Criteria
			3.3 Timing of Screening and Diagnosis
			3.4 Rare Causes of Gestational Diabetes
			3.5 Type 1 and Type 2 Diabetes Mellitus First Detected in Pregnancy
		4 Differences in Prevalence Over Time and Reasons
			4.1 The Global Epidemic of Obesity
			4.2 Older Maternal Age
			4.3 Prevalence Estimates and Future Projections
		5 Differences in Prevalence by Country and Reasons
		6 Impact of Hyperglycemia in Pregnancy on Public Health
		7 Directions for Future Research and Challenges for Clinical Practice
		8 Conclusions
		References
	Chapter 3: Diagnosis of Gestational Diabetes Mellitus
		1 Introduction
		2 Diagnosis: International Diagnostic Thresholds
		3 Universal or Risk Factor–Based Screening
		4 One-Step or Two-Step Approach
		5 Prevalence of GDM
		6 Specific Thresholds for Fasting and 2-h Glucose Levels
		7 The Role of Obesity
		8 Testing in Early Pregnancy
			8.1 Preexisting or Early-Onset Diabetes
			8.2 Early Risk Assessment for Later GDM Development
		9 Conclusions
		References
Part II: Defining the Pathophysiology
	Chapter 4: Risk Factors for Developing Gestational Diabetes Mellitus
		1 Introduction
		2 Risk Factors for the Development of GDM
			2.1 Maternal Age
			2.2 Geography and Ethnicity
			2.3 Genetic Factors
			2.4 Family History of Diabetes
			2.5 Previous History of GDM
			2.6 Male Fetus
			2.7 Multiple Pregnancy
			2.8 Multiparous Pregnancy
			2.9 Maternal Body Weight
			2.10 Maternal Smoking
			2.11 Physical Activity
			2.12 Dietary Factors
			2.13 Polycystic Ovary Syndrome
		3 Emerging Risk Factors for the Development of GDM
			3.1 Persistent Organic Pollutants and Endocrine Disruptors
			3.2 Depression
			3.3 γ-Glutamyltransferase (GGT)
		4 Interventions for the Prevention of Gestational Diabetes
		5 Conclusions
		References
	Chapter 5: Pathophysiology
		1 General Considerations
		2 Carbohydrate Metabolism, Insulin Secretion, and Sensitivity During Pregnancy
			2.1 Early Increased Insulin Sensitivity
			2.2 Mechanisms Underlying the Insulin Resistance Later in Pregnancy
		3 The Supply of Glucose to the Fetus
		4 Lipid and Amino Acid Metabolism During Pregnancy
		5 Changes in Gestational Diabetes
		6 Macrosomia
		7 Gestational Diabetic Pregnancy as an Inflammatory State
		8 Immunological Influences in Gestational Diabetic Pregnancy
		9 Genetic Influences in Gestational Diabetes
			9.1 Genetic Variation
			9.2 Epigenetic and Other Associations
		10 The Placenta in Gestational Diabetes
		11 Pregnancy in Women with Pregestational Diabetes
			11.1 General Considerations
			11.2 Pregestational Type 1 Diabetes
			11.3 Pregestational Type 2 Diabetes
			11.4 Implications for Preexisting Diabetic Complications
		12 Timing of Delivery
		13 Shoulder Dystocia
		14 Cesarean Section
		15 Breastfeeding
		References
	Chapter 6: Fetal Origin of Adult Disease: The Case of GDM
		1 Fetal Origin of Adult Disease
		2 Embryonic Development in Pregnancy Complicated with DM/Normal and Abnormal Fetal Growth
			2.1 Diabetic Embryopathy
			2.2 Diabetic Fetopathy
		3 GDM and Long-Term Outcomes in Offspring
			3.1 Diabetes in the Offspring of Mothers with GDM
			3.2 Obesity and Growth in the Offspring of Mothers with GDM
			3.3 Cardiovascular Risk Factors in the Offspring of Mothers with GDM
			3.4 Gestational Diabetes and Pubertal Timing
		4 Can Treatment of GDM During Pregnancy Prevent Long-Term Offspring Outcomes?
		5 Mechanisms of Fetal Programming and Fuel-Mediated “Functional Teratogenesis”
		6 Nutrient (Fuel) Transport in GDM
		7 Placental Adaptation in GDM
		8 Oxidative Stress and Inflammatory Response
		9 Is It All Genetics? The Role of Epigenetic Modification in GDM and Fetal Programming
		10 Hormonal Regulation: The Role of Insulin and Leptin
		11 Neuroendocrine Control of Fetal Programming
		12 Conclusions
		References
Part III: Monitoring
	Chapter 7: Medical Monitoring of Preexisting DM and GDM
		1 Body Weight Monitoring
		2 Glucose Monitoring
			2.1 Self-Monitoring of Blood Glucose
			2.2 Continuous Glucose Monitoring
		3 Ketone Monitoring
		4 Conclusions
		References
	Chapter 8: Obstetrical Monitoring
		1 Introduction
		2 Methods of Fetal Monitoring
			2.1 Initial Evaluation
			2.2 Methods of Monitoring
		3 Fetal Screening
			3.1 First Trimester
			3.2 Second Trimester
				3.2.1 Triple and Quadruple Test
				3.2.2 Anomaly Scan
			3.3 Third Trimester
				3.3.1 Preexisting Diabetes
				3.3.2 Gestational Diabetes
		4 Fetal Surveillance
			4.1 Fetal Growth
				4.1.1 Macrosomia
				4.1.2 Fetal Growth Restriction
			4.2 Fetal Hypoxia
				4.2.1 Hypertensive Disorders
				4.2.2 Stillbirth
		5 Conclusions
		References
Part IV: Management
	Chapter 9: Targets and Rationale for Treatment
		1 Introduction
		2 Current Guidelines from International Organizations
		3 Normative Glycemic Data in Nondiabetes Pregnancy
		4 Preprandial Versus Postprandial Blood Glucose Monitoring
		5 Review of Research Studies Supporting Recommendations for Glycemic Targets in Preexisting Diabetes and Gestational Diabetes
			5.1 Preexisting Diabetes in Pregnancy
			5.2 Gestational Diabetes
		6 Use of HbA1c for Glycemic Monitoring in Pregnancy
		7 Use of Continuous Glucose Monitoring (CGM) and Time in Range (TIR) in Pregnancy
		8 Conclusions
		References
	Chapter 10: Prepregnancy Management in the Clinical Approach to Diabetes Mellitus
		1 Prepregnancy Management Of Type 1 and Type 2 Diabetes Mellitus
			1.1 Preconception Care
				1.1.1 Lifestyle Management
				1.1.2 Optimization of Glycemic Control
				1.1.3 Assessment and Management of Diabetes-Related Complications
			1.2 Conclusions
		2 Prevention of Gestational Diabetes
			2.1 Prevention Strategies
				2.1.1 Dietary Adjustments and Physical Exercise
				2.1.2 Use of Medications
			2.2 Conclusions
		References
	Chapter 11: Medical Nutrition Therapy
		1 Introduction
		2 Lifestyle Interventions: Is Dietary Advice Adequate?
			2.1 Specific Dietary Patterns and Primary Prevention of GDM
			2.2 Mediterranean Diet and Secondary Prevention of GDM
		3 Energy Equilibrium
			3.1 Energy Restriction and Weight Loss
			3.2 Energy Intake Goals for Women with GDM
		4 Optimal Macronutrient Components of the Diet
			4.1 Effect of Fiber and Glycemic Index
			4.2 Carbohydrate Restriction vs. Ketogenic Diets
			4.3 Non-nutritive Sweeteners
			4.4 Protein Intake
		5 Dietary Supplements
			5.1 Vitamin D
			5.2 Probiotics
		6 Managing Dyslipidemia in Women with GDM or Maternal Obesity
		7 Managing Pregnant Women with Preexisting Diabetes
		8 Nutritional Assessment
		9 Conclusions
		References
	Chapter 12: Physical Activity and Exercise in Diabetes During Pregnancy
		1 Exercise-Induced Benefits in Gestational Diabetes
			1.1 Benefits of Acute Exercise in Improving the Glycemic Control
			1.2 Benefits of Chronic Exercise in Improving Glycemic Control
				1.2.1 Regular Exercise Improves Insulin Sensitivity, Glucose Clearance, Mitochondrial Function, and Enhances Overall Metabolic Health
				1.2.2 Obesity and the Role of Weight Reduction Through Exercise Training in Reducing Chronic Inflammation
			1.3 The Benefits of Maternal Exercise in Health Outcomes of the Offspring
		2 Prevention of Gestational Diabetes Through Physical Activity and Exercise
			2.1 The Role of Physical Activity Before and During Early Pregnancy in Preventing Gestational Diabetes
			2.2 The Effectiveness of Physical Activity and Diet Interventions in Gestational Diabetes Prevention
			2.3 The Effectiveness of Supervised Exercise Interventions in Gestational Diabetes Prevention
			2.4 Barriers for Not Adopting a Healthy Lifestyle Reported by Pregnant Women
		3 Exercise Prescription During Pregnancy in Women with Diabetes
			3.1 Exercise During Pregnancy in Women with Gestational Diabetes and Preexisting Diabetes
				3.1.1 Exercise During Pregnancy in Women with Gestational Diabetes
				3.1.2 Exercise During Pregnancy in Women with Pregestational Diabetes
				3.1.3 Exercise and Insulin Requirements
			3.2 Metabolic and Inflammatory Dysfunctions That Can Alter the Exercise Adaptations in Gestational Diabetes
			3.3 The Exercise Prescription Based on the FITT Principle
				3.3.1 Recommendations for Prescribing an Individualized Exercise Program in a Pregnant Woman with Diabetes
					Frequency of Exercise
					Exercise Intensity
					Duration (Time) of the Exercise Session
					Type of Exercise
				3.3.2 Warning Signs or Symptoms
				3.3.3 Points to Consider When Exercising
				3.3.4 Contraindications to Exercise in Pregnancy
				3.3.5 Preventing Gestational Diabetes in Subsequent Pregnancies
		4 Conclusions
		References
	Chapter 13: Oral Anti-Hyperglycemic Agents
		1 Introduction
		2 Metformin
			2.1 Clinical Studies
			2.2 Guidelines
			2.3 Points to Consider
		3 Sulfonylureas
			3.1 Clinical Studies
			3.2 Guidelines
			3.3 Points to Consider
		4 Other Categories of Oral Hypoglycemic Agents
		References
	Chapter 14: Insulin
		1 Introduction
		2 Short-Acting Insulin and Rapid-Acting Insulin Analogs
		3 Intermediate-Acting Insulin and Long-Acting Insulin Analogs
		4 Regimens of Insulin Therapy
			4.1 Pre-existing Type 1 Diabetes Mellitus
			4.2 Pre-existing Type 2 Diabetes Mellitus
			4.3 Risks: Hypoglycemia and Diabetic Ketοacidosis
			4.4 Continuous Subcutaneous Insulin Infusion (CSII) vs. Multiple Daily Injections (MDI)
			4.5 Special Conditions
			4.6 Needs of Insulin During Labor and Postpartum
		5 Gestational Diabetes Mellitus
		References
	Chapter 15: Delivery, Intrapartum Management, and Puerperium
		1 Introduction
		2 Delivery
			2.1 Timing of Delivery
				2.1.1 GDM
				2.1.2 Pre-existing Diabetes
				2.1.3 Macrosomia
			2.2 Mode of Delivery
				2.2.1 Induction of Labor
				2.2.2 Cesarean Section: When?
		3 Preterm Labor
		4 Intrapartum Management
			4.1 Diabetic Management
			4.2 Obstetric Management
		5 Obstetrical Care During the Puerperium
			5.1 The Puerperium
			5.2 Breastfeeding
			5.3 Postnatal Depression
			5.4 Long-Term Follow-Up and Contraception
		6 Conclusions
		References
Part V: Complications and Their Management
	Chapter 16: Fetal Complications
		1 Congenital Malformations
			1.1 Overview
			1.2 Glycemic Control and Fetal Outcomes
			1.3 Susceptibility to the Deleterious Effects of Hyperglycemia
			1.4 Epigenetics
			1.5 Types of Abnormalities
				1.5.1 Cardiac Anomalies
				1.5.2 Central Nervous System
				1.5.3 Facial Malformations
				1.5.4 Gastrointestinal Malformations
				1.5.5 Urinary Tract
				1.5.6 Genital System
		2 Other Pregnancy Complications
			2.1 Fetal Macrosomia
				2.1.1 The Role of Hyperglycemia and Hyperinsulinemia
				2.1.2 The Role of Hyperlipidemia
			2.2 Polyhydramnios
			2.3 Late Fetal Death and Intrapartum Fetal Distress
		3 Management
			3.1 Pregestational Diabetes
			3.2 Gestational Diabetes
			3.3 Pharmacological Agents
				3.3.1 Insulin
				3.3.2 Oral Antihyperglycemic Agents
		4 Guidelines
			4.1 NICE Guidelines [60]
				4.1.1 Pregestational Diabetes
					Monitoring the Baby
					Planning Birth
				4.1.2 Gestational Diabetes
					Monitoring the Baby
					Planning birth
			4.2 ACOG Guidelines [35]
				4.2.1 Pregestational Diabetes
					Monitoring the Baby
					Planning Birth
				4.2.2 Gestational Diabetes
					Monitoring the Baby
					Planning Birth
		References
	Chapter 17: Diabetes During Pregnancy: Neonatal and Childhood Complications
		1 Introduction
		2 Diabetes in Pregnancy
		3 Hyperglycemic Exposure and Offspring Outcomes
		4 Neonatal Complications
			4.1 Fetal Growth, LGA, and Macrosomia
			4.2 Neonatal Hypoglycemia
		5 Infancy and Childhood Complications
			5.1 Post-natal Growth and Body Composition Development
			5.2 Metabolic Abnormalities
			5.3 Gastrointestinal Microbiota Development
			5.4 Brain Development, Cognitive Function, and Behavior
		6 Nutritional Gaps in Infancy and Childhood
		7 Conclusions
		References
	Chapter 18: Pregnancy-Associated Maternal Complications
		1 Pre-eclampsia
		2 Hypertensive Disorders
		3 Management
			3.1 Chronic Hypertension
			3.2 Gestational Hypertension
			3.3 Pre-eclampsia
		4 Metabolic and Microvascular Complications
			4.1 Diabetic Retinopathy
			4.2 Diabetic Nephropathy
			4.3 Diabetic Ketoacidosis
		5 Short-Term Follow-Up
		References
	Chapter 19: Long-Term Maternal Complications
		1 Maternal Complications in Women with Gestational Diabetes Mellitus
			1.1 Dysglycemia
				1.1.1 Recurrence of Gestational Diabetes in a Subsequent Pregnancy
				1.1.2 Impaired Glucose Tolerance
				1.1.3 Metabolic Syndrome
				1.1.4 Type 2 Diabetes
				1.1.5 Type 1 Diabetes
			1.2 Cardiovascular Disease
			1.3 Chronic Kidney Disease
			1.4 Retinopathy
			1.5 Cancer
		2 Maternal Complications in Women with Pre-gestational Diabetes Mellitus
			2.1 Exacerbation of Microvascular Disease
			2.2 Diabetic Retinopathy
			2.3 Diabetic Kidney Disease
			2.4 Cardiovascular Disease
		3 Long-Term Follow-Up and Prevention of Subsequent Diabetes
			3.1 Women with Prediabetes
			3.2 Women with Overt Diabetes
				3.2.1 Breastfeeding
				3.2.2 Preconception Care
			3.3 Women with Normal Test Results
			3.4 Follow-Up of Women Not Screened for Gestational Diabetes Mellitus
		References
Part VI: Special Issues
	Chapter 20: Diabetes Mellitus and Infertility
		1 Introduction
		2 Menarche
			2.1 Menarche in T1DM
			2.2 Menarche in T2DM
		3 Menstrual Disorders
			3.1 Menstrual Disorders in T1DM
			3.2 Menstrual Disorders in T2DM
		4 Hormonal Disturbances
			4.1 Hormonal Disturbances in T1DM
			4.2 Hormonal Disturbances in T2DM
		5 PCOS
			5.1 PCOS in T1DM
			5.2 PCOS in T2DM
		6 Ovarian Reserve
			6.1 Ovarian Reserve in Girls with T1DM
			6.2 Ovarian Reserve in Women with T1DM
			6.3 Ovarian Reserve in T2DM
		7 Sexual Dysfunction
		8 Time of Menopause
			8.1 Time of Menopause in T1DM
			8.2 Time of Menopause in T2DM
		9 Pregnancy
			9.1 Gestational Diabetes Mellitus and Infertility
			9.2 Pre-Existing T1DM/T2DM in Pregnancy and Infertility
		10 Preconception Care
		11 Conclusion
		References
	Chapter 21: Diabetes Mellitus and Contraception
		1 Introduction
		2 Access to Contraception
			2.1 The Importance of Contraception
			2.2 Epidemiologic Evidence
			2.3 Barriers to Contraception Access
		3 Hormonal Contraception and Glucose Metabolism
			3.1 Women Without Diabetes
				3.1.1 Perimenopausal Women
				3.1.2 Polycystic Ovary Syndrome (PCOS)
				3.1.3 Different Administration Routes
				3.1.4 Risk of Developing Diabetes
			3.2 Women with Diabetes
				3.2.1 Diabetes Mellitus
				3.2.2 Gestational Diabetes Mellitus (GDM)
		4 The WHO Medical Eligibility Criteria for Contraceptive Use
			4.1 Hormonal Contraception
				4.1.1 Long-Acting Reversible Contraception (Tables 21.3, 21.4 and 21.5)
				4.1.2 Cardiovascular Risk Factors and T2DM
			4.2 Sterilization
			4.3 Barrier Methods
		5 Non-Contraceptive Advantages
		References
	Chapter 22: Diabetes in Pregnancy and Breastfeeding
		1 Introduction
		2 Lactation Practices in Women After Diabetes in Pregnancy
		3 Physiology of Lactogenesis and Diabetes During Pregnancy
		4 Lactation and Short-Term Metabolic Implications in Women with Diabetes in Pregnancy
			4.1 Milk Composition in Women with Pre-Existing Diabetes
			4.2 Milk Composition in Women with GDM
		5 Lactation and Long-Term Metabolic Implications in Women With and Without Diabetes in Pregnancy
		6 Lactation and Long-Term Risk of Future Diabetes Mellitus: Εvidence from Meta-Analyses
		7 Lactation After Pregnancy with Diabetes: The Benefits for the Offspring
		8 Clinical Implications
		References
	Chapter 23: Biomedical Technology and Gestational Diabetes Mellitus
		1 Introduction
		2 Sensing and Actuators
			2.1 Medical Imaging in GDM
			2.2 Cardiotocography, Cardiac Sounds, and Fetal Heart Rate
			2.3 Automated Insulin Delivery Systems
		3 Monitoring
		4 Decision Support Systems and Artificial Intelligence
			4.1 Introduction
			4.2 Prediction, Diagnosis, and Prognosis of GDM
				4.2.1 Early Diagnosis and Prediction
				4.2.2 Prognosis
			4.3 GDM Treatment and Management
				4.3.1 Clinical Guidelines for Decision Support
				4.3.2 DSS in Daily Life Support Systems
				4.3.3 BG Control and Closed-Loop Systems
		5 Discussion
		6 Conclusions
		References
	Chapter 24: Issues to be Solved: Future Perspectives
		1 Introduction
		2 Pre-Existing Diabetes Mellitus
		3 Gestational Diabetes Mellitus
		4 Conclusions
		References
Index