Diabetes in Women: Pathophysiology and Therapy (Contemporary Diabetes)

"Gender differences impact the pathophysiology and clinical burden of diabetes in women. Exploring the complex interplay between gender and diabetes, Diabetes in Women provides a state-of-the-art update from conception to menopause and beyond. Written by experts in the field, Diabetes in Women covers sex differences in cardiometabolic risk, the impact of diabetes on women's health, diabetes and pregnancy, offspring of the diabetic mother and the disease management of women with diabetes. Chapters include up to date information on cardiometabolic risk in women throughout the lifecycle and the differences between sexes in energy balance and body composition. Prominent authors also explore the impact of poverty and globalization on the emerging epidemic of obesity in developing countries. Designed for primary care and internal medicine physicians, endocrinologists, obstetricians and gynecologists, and trainees and basic scientists in these areas, Diabetes in Women is an invaluable resource and important contribution to the field."--BOOK JACKET. Tsatsoulis_FM1.pdf Tsatsoulis_Ch01.pdf 1 Sex Differences in Energy Balance, Body Composition, and Body Fat Distribution INTRODUCTION SEX DIFFERENCES IN ENERGY BALANCE SEX DIFFERENCES IN BODY COMPOSITION AND BODY FAT DISTRIBUTION FAT DEPOT-SPECIFIC CHARACTERISTICS: A KEY TO THE LINK BETWEEN VISCERAL FAT ACCUMULATION AND DISEASE OUTCOME Adipocyte Size Adipocyte Metabolism Adipokines Genomics and Gene Expression TELEOLOGICAL SIGNIFICANCE STEROID HORMONES AND BODY FAT DISTRIBUTION PATTERNS Cortisol Androgens Estrogens CONCLUSION REFERENCES Tsatsoulis_Ch02.pdf 2 Menopause and Diabetes Mellitus CHANGES IN GONADAL HORMONES AT MENOPAUSE SYMPTOMS OF MENOPAUSE AGE OF MENOPAUSE CHANGES IN BODY COMPOSITION AT MENOPAUSE Effects of Menopause on Body Composition Effects of Changes in Body Composition on Insulin Sensitivity in Postmenopausal Women RISK OF DIABETES IN POSTMENOPAUSAL WOMEN HORMONE REPLACEMENT THERAPY Effects of HRT on Glycemic Control in Women with Diabetes Effects of HRT on Risk of Developing Diabetes CONCLUSION REFERENCES Tsatsoulis_Ch03.pdf 3 Cardiovascular Disease in Women with Diabetes INTRODUCTION IMPACT AND BURDEN OF DIABETES ON CARDIOVASCULAR DISEASE IN WOMEN Gender-Specific Differences in CVD Loss of Estrogen Protection in Diabetic Women CVD Morbidity and Mortality in Diabetic Women: The Evidence Treatment of CVD Risk Factors in Diabetic Women: Are We Achieving the Goals? PLATELET AND COAGULATION ABNORMALITIES IN DIABETES Platelet Mechanism of Action Intrinsic Platelet Abnormalities Increased Platelet Surface Glycoproteins Decreased Production of NO and Prostacyclin Increased Advance Glycation End Products and Metabolic Alterations Insulin Action on Platelets Oxidative Stress Coagulation Abnormalities in Diabetes Mellitus Hemostatic Mechanism Fibrinolytic System in Diabetes Mellitus Plasminogen Activator Inhibitor Tissue Plasminogen Activator Alterations in Clotting Factor Levels Fibrinogen Factor VIIc Von Willebrand Factor and Factor VIII Thrombin–Antithrombin Complex Antithrombin III, Protein C, and Protein S Lipoprotein(a) [Lp(a)] ENDOTHELIAL DYSFUNCTION Normal Endothelial Cell Function NO as Mediator of Endothelial Cell Function Angiotensin II Regulation of Hemostasis Regulation of VSMC Growth and Inflammation Endothelial Dysfunction Measurement of Endothelial Dysfunction Endothelial Dysfunction and Diabetes Insulin Effects on the Endothelium Type 1 Diabetes and Endothelial Dysfunction Endothelial Dysfunction in DM2 Insulin Resistance: A Mediator of Endothelial Dysfunction Mechanisms Underlying Endothelial Dysfunction in Diabetes Hyperglycemia and Its Immediate Biochemical Sequelae Hyperglycemia and Sex-specific Differences in EC Dysfunction The DAG/PKC Pathway Hyperglycemia-Induced Oxidative Stress and Vascular Dysfunction Nonenzymatic Glycation The Role of Growth Factors and Cytokines SCREENING AND DIAGNOSIS OF CAD TREATMENT OF CVD IN WOMEN WITH DIABETES SUMMARY REFERENCES Tsatsoulis_Ch04.pdf 4 Insulin Resistance, Diabetes, and Cardiovascular Risk in Women and the Paradigm of the Polycystic Ovary Syndrome The Biology of Sex Difference in Health and Disease Insulin Resistance in the General Female Population The Metabolic Syndrome, Cardiovascular Risk Factors, and Cardiovascular Events in Women How the Definition of the Metabolic Syndrome Overlaps that of Insulin Resistance Diabetes and Cardiovascular Risk Factors in Women The Paradigm of Pcos Insulin Resistance in PCOS The Metabolic Syndrome in PCOS Obesity and the Abdominal Phenotype in PCOS Glucose Intolerance and DM2 in PCOS Cardiovascular Risk in PCOS Women Androgens and Risk for Cvd and Diabetes in the Female Population: Lessons From the Pcos Paradigm Summary and Conclusions References Tsatsoulis_Ch05.pdf 5 Developmental Programming of Polycystic Ovary Syndrome: Role of Prenatal Androgen Excess Introduction The Clinical and Molecular Phenotype of Pcos Evidence for the Developmental Origins of Pcos Prenatal Androgenization and PCOS Clinical Observations Prenatally Androgenized Animal Models Prenatal Growth Restraint and PCOS Potential Origin of Prenatal Androgen Excess in Humans The Placental Barrier to Excess Androgens Gestational Hyperandrogenism of Maternal Origin Environmental Influences on Prenatal Androgenization Plausible Genetic Contribution to Prenatal Androgenization Genetic Contribution to Placental Barrier Function Genetic Contribution to Hyperandrogenic Fetal Ovaries Plausible Biological Mechanisms Conclusions and Future Implications References Tsatsoulis_Ch06.pdf 6 An Anthropological View of the Impact of Poverty and Globalization on the Emerging Epidemic of Obesity The Big Three The Homo sapiens Genotype Activity Growing Availability The Food Production Subsidies EXPORT TAXES (OR “SLIDING SCALE DUTIES” OR “RETENTIONS”) Globalized Industry Good to Sell The Logic of Market Society: Slim Rich and Fat Poor Final Words References Tsatsoulis_Ch07.pdf 7 Eating Disorders and Depression in Women with Diabetes Eating Disorders and Depression: an Introduction Diabetes and Eating Disorders: Epidemiology and Clinical Features Depression and Diabetes Eating Disorders and Depression: Screening and Treatment Conclusion References Tsatsoulis_Ch08.pdf 8 Sexual Health in Women with Diabetes INTRODUCTION FEMALE SEXUAL DYSFUNCTION: DEFINITIONS, CLINICAL CLASSIFICATION, AND EPIDEMIOLOGY Sexual Disorders Among Women with Type 1 Diabetes Mellitus Sexual Disorders Among Women with Type 2 Diabetes Mellitus PREDICTORS OF SEXUAL DYSFUNCTION AMONG WOMEN WITH DIABETES Age Duration of Diabetes, Diabetes-Related Complications, and Diabetes Control Menopausal Status and the Androgen Milieu Menstrual Cycle and the Endocrine Profile Among Reproductive-Aged Women with Type 1 Diabetes Psychological Factors TREATMENT OF SEXUAL DISORDERS IN WOMEN WITH DIABETES Genital Sexual Arousal Disorders Among Women with Diabetes Hormonal Replacement Therapy, Women’s Sexual Health, and Diabetes Testosterone Substitution Therapy CONCLUSIONS REFERENCES Tsatsoulis_Ch09.pdf 9 Contraception for Women with Diabetes Introduction Counseling and Selecting A Method Barrier Methods Hormonal Contraception Question: Can She Use Hormonal Contraception? Question: Can She Use Estrogen-Containing Contraception? Question: What Progestin Dose and Formulation Should be Selected in Prescribing COC? Question: Should She Use Progestin-Only Contraception? Question: Can She Use Intrauterine Contraception? Question: Which Intrauterine Contraceptive Should She Use: The Copper-Containing Intrauterine Device or the Levonorgestrel-Cont Breastfeeding and Postpartum Contraception: Stepwise Questions Question: Does She Need Contraception During the Postpartum Period if She Is Breastfeeding? Question: Can Hormonal Contraception Be Used During Breastfeeding? Question: When Should Intrauterine Contraception Be Used After Delivery? Question: Which Methods Can Be Used in Postpartum Women with Diabetes? References Tsatsoulis_Ch10.pdf 10 The Effect of PCOS on Fertility and Pregnancy INTRODUCTION PATHOGENESIS OF INFERTILITY INFERTILITY TREATMENT IN PCOS Weight Loss Clomiphene Citrate Metformin Metformin, Clomiphene Citrate or Both for Ovulation Induction in PCOS Thiazolidenediones Gonadotropin Therapy Aromatase Inhibitors Laparoscopic Ovarian Drilling Gonadotropin Releasing Hormone In Vitro Fertilization PREGNANCY Early Pregnancy Loss LH and EPL Androgens and EPL Plasminogen Activator Inhibitor Activity and EPL Obesity, Hyperinsulinemia, and EPL Prevention of EPL with Metformin Metformin and Pregnancy Risks Gestational Diabetes Polycystic Ovaries and GDM BMI and GDM PCOS and GDM Prevention of GDM with Metformin Pregnancy-Induced Hypertension Hyperinsulinemia and PIH PCOS and PIH Androgens and PIH Prevention of PIH in PCOS CONCLUSION REFERENCES Tsatsoulis_Ch11.pdf 11 The Effect of Pregnancy on Energy Metabolism, Body Composition, and Endothelial Function INTRODUCTION ENERGY METABOLISM IN PREGNANCY The Energy Cost of Pregnancy Basal Metabolic Rate in Pregnancy The Impact of Maternal Obesity on the Energy Cost of Pregnancy The Energy Cost of Pregnancy in Gestational Diabetes Mellitus BODY COMPOSITION Assessment of Body Composition in Pregnancy Weight Gain in Pregnancy Changes in Body Composition Associated with Pregnancy Location of Fat Deposition in Pregnancy Fat Deposition in Obese Pregnancy Gestational Diabetes Mellitus and Fat Deposition INSULIN RESISTANCE IN PREGNANCY Insulin Resistance in Obese Pregnancy Insulin Resistance in Glucose Intolerance and GDM Pregnancy LIPID METABOLISM IN PREGNANCY Lipid Changes in Normal Pregnancy Lipid Changes in Obesity Lipid Changes in Diabetes and GDM ENDOTHELIAL FUNCTION Background Change in Normal Pregnancy Changes in Plasma Markers Changes in Endothelial Function in Obese Pregnancy Potential Mechanisms for Vascular Function Changes in Pregnancy Endothelial Function in Diabetic Pregnancy SUMMARY References Tsatsoulis_Ch12.pdf 12 The Epidemiology of Diabetes in Women and the Looming Epidemic of GDM in the Third World The prevalence of diabetes in women in third world countries The prevalence of gestational diabetes in women in third world countries Screening for gestational diabetes in third world countries: do we need ethnic and national specific criteria? Challenges to heath care delivery in third world countries Medical Aspects Economic Aspects Medical impact of gdm in the third world Short- and Long-Term Consequences of Fetal Complications Short- and Long-Term Consequences of Maternal Complications and Consequences Postpartum consequences of gestational diabetes on the prevalence of subsequent diabetes Medical Aspects Economic Aspects Can we reduce the future risk of diabetes in women with gestational diabetes? Conclusion References Tsatsoulis_Ch13.pdf 13 Gestational Diabetes Mellitus: Diagnosis, Maternal and Fetal Outcomes, and Management Diagnostic Criteria and Screening Procedures for Gestational Diabetes Mellitus Diagnostic Criteria Three-Hour Oral Glucose Tolerance Test Thresholds Two-Hour Oral Glucose Tolerance Test Thresholds Screening Procedures Universal vs. Selective Screening One-Step vs. Two-Step Protocols Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study management of Gestational Diabetes Medical Nutritional Therapy and Exercise Blood Glucose Monitoring Medications Insulin Oral Antihyperglycemic Agents Glyburide Metformin postpartum Care: Postpartum Diabetes Screening and Diabetes Risk Maternal Diabetes and Cardiovascular Disease Risk Diagnostic Criteria and Screening Procedures for Postpartum Diabetes Mellitus Performance of Postpartum Screening Risk Factors for Maternal Postpartum Diabetes Among Women with GDM conclusions References Tsatsoulis_Ch14.pdf 14 Nutrition and Pregnancy Introduction Preconception Counseling Nutrition Requirements and Meal Planning with Pregnancy and Preexisting Diabetes Calories for Pregnancy Weight Gain Meal Plan Recommendations Physical Activity Cautions During Physical Activity Carbohydrates Dietary Fiber Carbohydrate Counting Glycemic Response to Foods Protein Fat Heart Healthy Fats Seafood Recommendations During Pregnancy Food-borne Illness Sweeteners Micronutrients Iron Folic Acid Calcium and Vitamin D Record Keeping Alcohol Caffeine Breastfeeding Nutrition and Meal Planning in Gestational Diabetes Follow-up Postpartum Care/clinical Implications Celiac Disease Gluten-free Diet Grains and Grain Products Milk and Milk Products Meat and Meat Alternatives Fruits and Vegetables Soups Fats Desserts Miscellaneous Resources for Celiac Disease and the Gluten-free Diet Celiac Medical Centers in the USA Associations and Organizations References Tsatsoulis_Ch15.pdf 15 Preconception Care for Women with Diabetes Mellitus Introduction: What is Preconception Care? Efficacy of Preconception Care at Reducing Pregnancy Complications: Why Do I Need Preconception Care? The Three Cs: Contraception, Counseling and Care Contraception: Why Should I Use Contraception if I Want to Get Pregnant? Counseling and Preconception Care Recommendations to Reduce Maternal and Fetal Risks of Preexisting Diabetes: What Are the Risk Fertility: Will We Have Trouble Getting Pregnant? Maternal Hypoglycemia: Will Low Blood Sugars Hurt My Baby? Diabetic Ketoacidosis and Intrauterine Fetal Demise (IUFD): How High Is Dangerous? Hypertension/Nephropathy/Preeclampsia and Prematurity Hypertension: How Does Hypertension Effect a Pregnancy? Are My Blood Pressure Medications Safe in Pregnancy? Nephropathy: Does Pregnancy Increase My Risk of Kidney Disease? Does My Kidney Disease Affect My Pregnancy? Preeclampsia: What Is the Danger of Preeclampsia? Prematurity/Preterm Delivery: Will I Deliver Full Term? Retinopathy: Why Do I Have to Have an Eye Exam? Hyperlipidemia: When Should I Stop My Cholesterol Medication? Macrovascular Disease: Should I Have a Stress Test Before Becoming Pregnant? IUGR: Why Do I Have to Worry About Small Babies Too? Thyroid Disease: Does My Thyroid Disease Affect My Pregnancy? Congenital Malformations: What Congenital Malformations Are Associated with Diabetes? Spontaneous Abortion: Am I At Risk for Miscarriage? Macrosomia: What Is Wrong with Having a Big Baby? Cesarean Delivery: Will I Have to Have a Cesarean Delivery? Neonatal Hypoglycemia: Will My Baby Need a NICU? Genetic Risk: Will My Baby Have Diabetes? Perinatal Mortality and Morbidity: What Is the Chance My Baby Will Die? Nutrition: What Should I Eat? Glycemic Control: What Do I Have to Do? Adoption of Preconception Care Programs: Why Did I Not Know About this with My Last Pregnancy? Summary References Tsatsoulis_Ch16.pdf 16 Obstetric Care of the Woman with Diabetes First Trimester (0–12 Weeks) Second Trimester (13–24 Weeks) Third Trimester (25–40 Weeks) Labor and Delivery Postpartum Final Postpartum Visit Summary References Tsatsoulis_Ch17.pdf 17 Medical Management of Preexisting Diabetes in Pregnancy Nutrition Exercise Insulin Therapy Glucose Monitoring Self-Monitoring of Blood Glucose Continuous Glucose Monitoring Alternative Site Testing Optimal Timing and Frequency Hemoglobin A1C Medical Management of Complications During Diabetic Pregnancy Diabetic Retinopathy in Pregnancy Nephropathy Hypertension Neuropathy Lipid Changes During Pregnancy and Preexisting Diabetes Thyroid Disease in Preexisting Diabetic Pregnancy Management of Diabetic Ketoacidosis During Pregnancy Summary References Tsatsoulis_Ch18.pdf 18 Use of Ultrasound in the Metabolic Management of Gestational Diabetes and Preexisting Diabetes Mellitus in Pregnancy introduction Features of Fetal Growth in Diabetic Pregnancies Management of Gdm Based on Maternal Glucose Control Combined with Fetal Growth The Weiss Concept: Management of Diabetes Based on Maternal Glucose Combined with Amniotic Fluid Insulin Management of GDM Based on Maternal Glucose Control Combined with Fetal Growth Management of Preexisting Diabetes Based on Maternal Glucose Control Combined with Fetal Growth References Tsatsoulis_Ch19.pdf 19 Preeclampsia Epidemiology of Preeclampsia Definition of Preeclampsia (1) Prevalence of Preeclampsia Preeclampsia Worldwide Risk Factors for Preeclampsia Pathophysiology of Preeclampsia Normal Placental Development (Fig. 1) Abnormal Placental Development in Preeclampsia (Fig. 1) Maternal Endothelial Dysfunction Circulating Angiogenic Factors Soluble fms-like Tyrosine Kinase-1 (sFlt-1) (Fig. 1) Soluble Endoglin (Fig. 2) Immunologic Factors Renin-Angiotensin System Genetic Factors Oxidative Stress and Inflammation Evolution of Preeclampsia Prediction and Diagnosis of Preeclampsia Diagnosis of Preeclampsia Predicting Preeclampsia Diabetic Nephropathy and Superimposed Preeclampsia Complications of Preeclampsia Summary References Tsatsoulis_Ch20.pdf 20 The Infant of the Diabetic Mother: Metabolic Imprinting Diabetes in Pregnancy Epidemiological Studies Fetal Growth and Metabolic Consequences Abnormal Glucose Tolerance, Insulin Sensitivity and Insulin Secretion Type 2 Diabetes Cardiovascular Abnormalities Genetic Factors vs. Environment Maternal Diabetes: Does It Matter Which Type? Animal Data Mechanisms Adipoinsular Axis Defective Insulin Secretion Public Health and Clinical Implications Public Health Consequences Clinical Health Care Concerns References Tsatsoulis_Ch21.pdf 21 The Genetic Basis of Diabetes Introduction Genetic Variations Genetic Variations and Diabetes Type 1 Diabetes The HLA Locus The INS Locus The CTLA4 Locus The PTPN22 Locus The IL2RA Locus The IFIH1 Locus The KIAA0350 Locus The Vitamin D Metabolism Gene CYP27B1 Other Loci Type 2 Diabetes Pparg KCNJ11 and ABCC8 Tcf7l2 Other DM2 Loci Maturity Onset Diabetes of the Young Other Monogenic Forms of Diabetes Special Issues in Women Related to the Genetics of Diabetes Gestational Diabetes Mellitus The Genetics of Polycystic Ovarian Syndrome Conclusion References Tsatsoulis_Ch22.pdf 22 Breastfeeding and Diabetes Introduction Definitions Recommendations for Infant Nutrition Breastfeeding Rates in the USA Breastfeeding Rates Among Women with Diabetes Breastfeeding and Maternal Health Maternal Obesity, Diabetes and Perinatal Complications Hospital Support for Breastfeeding Among Diabetic Mothers Postpartum Issues for Breastfeeding Women with Diabetes Effect of Breastfeeding on Maternal Glucose Tolerance and Future Diabetes Risk Summary of Maternal Health Issues Breastfeeding and Pediatric Health Associations Between Breastfeeding and Pediatric Outcomes Obesity Type 1 Diabetes Type 2 Diabetes Gestational Diabetes Mellitus Children of Mothers with Diabetes Breast Milk Composition Short-Term Issues Long-Term Issues Summary of Pediatric Health Issues Pharmacologic Treatment Options for Breastfeeding Women with Diabetes Pharmacokinetics of Human Milk Specific Medications Used for Treating Diabetes and Related Conditions Insulin Metformin Sulfonylureas Alpha-Glucosidase Inhibitors Meglitidines Thiazoladinediones New Agents for Diabetes ACE Inhibitors Angiotensin Receptor Blockers Aspirin Cholesterol-Lowering Agents Contraception for Breastfeeding Women with Diabetes Clinical Resources on Medications in Breastfeeding Women Future Research References Tsatsoulis_Ch23.pdf 23 Management of Disease in Women with Diabetes Introduction Macrovascular or cardiovascular disease Cigarette and Tobacco Abuse Prevalence Association with Disease Impact of Smoking Cessation and Effectiveness of Smoking Cessation Interventions Recommendations Hypertension Prevalence Association with Disease Effectiveness of Interventions Recommendations Dyslipidemia Prevalence Association with Disease Effectiveness of Interventions Recommendations Physical Activity or Exercise Prevalence Association with Disease Effectiveness of Interventions Recommendations Aspirin Prevalence Association with Disease and Effectiveness of Interventions Recommendations for Aspirin Glycemic Control Prevalence Randomized Studies of Glycemic C Recommendations Microvascular complications Nephropathy Screening and Treatment Prevalence Effectiveness of Interventions Recommendations Retinopathy Screening and Treatment Prevalence Effectiveness of Interventions Recommendations Neuropathy Prevalence Effectiveness of Interventions and Treatment Recommendations Other disease management recommendations Vaccinations Preconception Care Depression and Anxiety Eating Disorders Healthcare delivery for diabetes Multifactorial Interventions Health System Characteristics Individual Interventions References Tsatsoulis_Index.pdf Annotation This book is devoted to women with diabetes. The primary aim is to provide cutting edge knowledge pertaining to diabetes in women from conception to menopause and beyond. The whole notion of the book arises from the understanding that there is a complex interplay between gender and diabetes. Gender differences may differentially affect energy metabolism, body composition and cardiovascular risk and therefore the pathophysiology and clinical burden of diabetes in women. Events in the reproductive lifecycle of women cause both special treatment considerations for diabetes and pose unique risks from diabetes. For example, during pregnancy, an adverse intrauterine environment may program fetal metabolism towards the development of cardiometabolic disease and diabetes in adult life. On the other hand, maternal diabetes may influence fetal development and postnatal outcome. The beneficial effects of endogenous sex steroids during reproductive age appear to be lost in women with diabetes, and the withdrawal of estrogens after the menopause may increase cardiovascular risk. Finally, gender has certain psychological, social and cultural dimensions, which may affect a personâs risk for and ability to treat diabetes. This book aims to explore the spectrum of issues specific to diabetes in women. The book is designed for generalists, physicians with an interest in diabetes, endocrinologists, obstetricians and gynecologists, and those training in these areas of health care. It is hoped that the topics in the book will help improve the knowledge of diabetes in women