Joel Rodriguez-Saldana Editor The Diabetes Textbook Clinical Principles, Patient Management and Public Health Issues 123 The Diabetes Textbook Joel Rodriguez-Saldana Editor The Diabetes Textbook Clinical Principles, Patient Management and Public Health Issues Editor Joel Rodriguez-Saldana Multidisciplinary Diabetes Center Mexico City Mexico ISBN 978-3-030-11814-3 ISBN 978-3-030-11815-0 (eBook) https://doi.org/10.1007/978-3-030-11815-0 © Springer Nature Switzerland AG 2019 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface This book is the result of three decades of endeavors in outpatient diabetes management, starting with the creation of a diabetes clinic in a public hospital in Mexico City Shortly afterward, we had the privilege of meeting Donnell Etzwiler and his colleagues from the International Diabetes Center in Minneapolis Don was one of the pioneering supporters of structured diabetes care, the importance of teamwork between health professionals and patients, with a patient-centered approach at the center He was also aware of the need to improve the quality of diabetes care based on the principles established by Shewhart, Deming, Juran, and many other brilliant minds in the history and evolution of quality in industry, and he guided us to develop and implement a model of diabetes management based on these principles Starting in 1991, we have presented a diabetes conference in which we have had the opportunity of meeting more than a hundred experts from multiple areas of diabetes from all over the world, from basic science to clinical management Many of them are collaborators of this book or have supported its creation We have also came to understand and respect the importance of the multidisciplinary approach to confront, in the words of Professor Paul Zimmet, “the largest epidemic in human history” [1] in a globalized world where social determinants of health are crucially linked to clinical outcomes The Diabetes Textbook was conceived to address and recognize the expertise and efforts of countless people, from multiple disciplines and from all over the world, devoted to improve the life of persons with diabetes I am extremely grateful for the contributions and enthusiasm of more than a hundred experts from five continents Their leadership and experience in the most diverse professional areas reflect the importance of diabetes and the multiple needs arisen for its management All the coauthors of The Diabetes Textbook are kindly and forever recognized, but special thanks are for Barry Ginsberg, Maggie Powers, and Sanjay Kalra Their guidance and support were essential to achieve the final work Thank you so much to all We should never ignore the patients [2] Above and beyond, this book is dedicated to persons with diabetes and their families Our greatest challenge is to honor the compromise and the privilege to support them Mexico City, Mexico Joel Rodriguez-Saldana References Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history? Clin Diabetes Endocrinol 2017;31:1 Etzwiler DD. Don’t ignore the patients Diabetes Care 2001;24:1840–41 v Contents 1 Preface: A New Disease?�������������������������������������������������������������������������������������������� 1 Joel Rodriguez-Saldana Part I Magnitude of the Problem from an Individual and Social Context 2 The Dynamics of Diabetes Prevalence, Morbidity, and Mortality������������������������� 11 Edward W Gregg and Paula Bracco 3 Economic Costs, from Individuals to Health Systems: Evidence from a Middle-Income Country�������������������������������������������������������������������������������� 23 Armando Arredondo, Emanuel Orozco, Maria Beatriz Duarte, Silvia Magali Cuadra, Ana Lucía Recamán, and Alejandra Azar 4 The Ecological Approach to Self-Management in Diabetes ����������������������������������� 33 Edwin B Fisher, Paul Bloch, and William Sherlaw 5 Social Determinants of Health and Diabetes Outcomes����������������������������������������� 61 Hideki Hashimoto 6 Definition, Diagnostic Criteria, Screening, Diagnosis, and Classification of Diabetes and Categories of Glucose Intolerance������������������������������������������������� 71 Lakshmana Perumal Nandhini, Sadishkumar Kamalanathan, and Jayaprakash Sahoo Part II Diagnosis, Classification and Mechanisms of Disease 7 Pathophysiology of Type Diabetes ������������������������������������������������������������������������� 89 Rita A Gómez-Díaz 8 Pathophysiology of Type Diabetes ������������������������������������������������������������������������� 101 Jothydev Kesavadev, Fatema Jawad, Asma Deeb, Ankia Coetzee, M A Jalil Ansari, Dina Shrestha, Noel Somasundaram, and Sanjay Kalra 9 Genetic Determinants of Type Diabetes����������������������������������������������������������������� 117 Miguel Cruz, Adán Valladares-Salgado, Eugenia Flores-Alfaro, and José de Jesús Peralta Romero 10 Gene Expression Modifications in Type Diabetes������������������������������������������������� 127 Fernando Suarez-Sanchez and Jaime Gomez-Zamudio 11 The Immune System and Inflammation in Type Diabetes����������������������������������� 145 Rebeca García Macedo 12 Dysfunction and Death of Pancreatic Beta Cells in Type Diabetes��������������������� 169 Clara Ortega-Camarillo vii viii 13 Obesity in the Pathophysiology of Diabetes����������������������������������������������������������� 185 Juan Antonio Paniagua González and Antonio Vidal-Puig 14 Pathogenesis of Gestational Diabetes Mellitus��������������������������������������������������������� 215 Evangelia Kintiraki, Gesthimani Mintziori, and Dimitrios G Goulis 15 Non-alcoholic Fatty Liver in the Pathogenesis of Diabetes������������������������������������� 227 Cristiane A Villela Nogueira and Nathalie Carvalho Leite Part III Examples of Global Experiences in Diabetes Care 16 Diabetes Management in Asia����������������������������������������������������������������������������������� 239 Roopa Shivashankar, Kavita Singh, L R Aravind, and Nikhil Tandon 17 Diabetes Management in the United States ������������������������������������������������������������� 255 Mohammed K Ali, Megha K Shah, and Tannaz Moin 18 Diabetes Management in Africa ������������������������������������������������������������������������������� 273 Simeon Pierre Choukem, Christian Akem Dimala, Camille Maadjhou, and Jean Claude Mbanya Part IV Basic Components of Management: Patient Centeredness, Evidence-Based Medicine and Outcomes Challenges for Implementation 19 The Patient-Centered Medical Home, Primary Care, and Diabetes��������������������� 291 Joel Rodriguez-Saldana 20 Outpatient Diabetes Management and the Chronic Care Model��������������������������� 305 Joel Rodriguez-Saldana 21 Clinical Practice Guidelines, Evidence-Based Medicine, and Diabetes����������������� 333 Joel Rodriguez-Saldana 22 Measuring Diabetes Quality of Care: Clinical Outcomes, Cost-Effectiveness, and Patient Experience of Care����������������������������������������������� 357 Patrick J O’Connor, Jo Ann M Sperl-Hillen, and Todd P Gilmer 23 Clinical Inertia: The Role of Physicians in Diabetes Outcomes����������������������������� 367 Joel Rodriguez-Saldana 24 Patient Adherence: Challenges, Myths, and Realities��������������������������������������������� 381 Joel Rodriguez-Saldana Part V Resources of Support for Persons with Diabetes 25 Challenges and Opportunities in Diabetes Education��������������������������������������������� 403 Jane K Dickinson, Melinda Downie Maryniuk, and Margaret Powers 26 Diabetes and Mental Health: From Distress to Depression ����������������������������������� 417 Gerhard Heinze, Diana Guizar-Sánchez, and Napoleón Bernard-Fuentes 27 Tools of Self-Care: Self-Monitoring of Blood Glucose and Tele-Health Resources����������������������������������������������������������������������������������������� 429 Barry H Ginsberg 28 Continuous Glucose Monitoring in Clinical Practice: Ambulatory Glucose Profile and the Application of Advanced Glucose Sensing Technologies to Clinical Decision-Making��������������������������������������������������������������������������������������� 451 Roger S Mazze Contents Contents ix 29 Type Diabetes and Lifestyle Medicine������������������������������������������������������������������� 463 Karla I Galaviz and Mohammed K Ali 30 Evidence and Implementation of Medical Nutrition Therapy in Persons with Diabetes��������������������������������������������������������������������������������������������� 477 Melinda Downie Maryniuk, Alison Evert, and Jo-Anne Rizzotto 31 Evidence and Implementation of Physical Activity and Exercise��������������������������� 485 Edtna Jáuregui-Ulloa and Juan López-Taylor Part VI Drug Therapy 32 The “Old” Oral Antidiabetics ����������������������������������������������������������������������������������� 501 Susanne Buhse and Ingrid Mühlhauser 33 Incretin Therapies: Current Use and Emerging Possibilities��������������������������������� 515 Haiko Schlögl and Michael Stumvoll 34 Sodium-Glucose Cotransporter Inhibitors����������������������������������������������������������� 531 George Dailey III, Lauren H S Clarine, and Renil Marie Rodriguez-Martinez 35 Use of Insulin in Outpatient Diabetes Management����������������������������������������������� 541 Raquel N Faradji, Ana Paula Díaz Barriga-Menchaca, and María Elena Sainz de la Maza Viadero 36 Insulin Pump Therapy����������������������������������������������������������������������������������������������� 555 Raquel N Faradji and María Elena Sainz de la Maza Viadero Part VII Cardiovascular Risk Factors 37 Diabetes and Hypertension ��������������������������������������������������������������������������������������� 573 D Khangura, J Hong, R Kurukulasuriya, and James R Sowers 38 Diabetes and Atherogenic Dyslipidemia������������������������������������������������������������������� 587 Arshag D Mooradian 39 Obesity and Diabetes ������������������������������������������������������������������������������������������������� 597 Sean Wharton, Christy Costanian, Talia Gershon, and Rebecca A G Christensen 40 Diabetes and Smoking: The Burden of Evidence��������������������������������������������������� 611 Sameer Aggarwal, Deepak Khandelwal, Deep Dutta, Sanjay Kalra, and Yatan Pal Singh Balhara Part VIII Acute Complications 41 Diabetic Ketoacidosis������������������������������������������������������������������������������������������������� 619 Guillermo E Umpierrez 42 Hypoglycemia: Diagnosis, Management, and Prevention��������������������������������������� 629 Raquel N Faradji, Ana C Uribe-Wiechers, and María Elena Sainz de la Maza Viadero 43 Inpatient Management of Diabetes and Hyperglycemia����������������������������������������� 655 William B Horton 44 Diabetes and Infection ����������������������������������������������������������������������������������������������� 669 Atulya Atreja, Sanjay Kalra, and Joel Rodriguez-Saldana x Part IX Chronic Complications 45 Biochemical Mechanisms of Vascular Complications in Diabetes������������������������� 695 Margarita Díaz-Flores and Luis Arturo Baiza-Gutman 46 Diabetes and Cardiovascular Disease����������������������������������������������������������������������� 709 Daniel Coutiño-Castelán, Arturo Abundes-Velasco, Félix Damas de los Santos, Eduardo A Arias Sánchez, Celso Mendoza González, Arturo Méndez Ortiz, José L Morales, José Luis Briseño de la Cruz, César Eduardo Hernández Fonseca, and Piero Custodio Sánchez 47 Diabetes and Stroke: The Role of Glucose Regulation ������������������������������������������� 731 Forrest Lowe and Wuwei (Wayne) Feng 48 Peripheral Arterial Disease and Diabetes Mellitus ������������������������������������������������� 747 Tracy J Cheun, Georges M Haidar, and Boulos Toursarkissian 49 Ophthalmic Disease in Diabetes ������������������������������������������������������������������������������� 765 José Henriques, Sara Vaz-Pereira, João Nascimento, Marco Medeiros, Susana Henriques, and Paulo Caldeira Rosa 50 Diabetes and Oral Health������������������������������������������������������������������������������������������� 777 Rosa Maria Díaz-Romero and Manuel Salvador Robles-Andrade 51 Renal Disease in Diabetes������������������������������������������������������������������������������������������� 791 Carlos A Garza-García, Virgilia Soto-Abraham, and Magdalena Madero 52 Peripheral Diabetic Neuropathies����������������������������������������������������������������������������� 809 Gergely Feher 53 Diabetic Cardiac Autonomic Neuropathy����������������������������������������������������������������� 825 Viktoria Serhiyenko and Alexandr Serhiyenko 54 Autonomic Visceral Neuropathy and Gastrointestinal Disorders ������������������������� 851 Anne Mohr Drewes, Christina Brock, and Asbjørn Mohr Drewes 55 Urologic Complications in Patients with Diabetes��������������������������������������������������� 863 Stephania Casco, Jose Carlos Arroyo-Kuribreña, and Elena Soto-Vega 56 Musculoskeletal Complications of Diabetes Mellitus ��������������������������������������������� 873 Rajiv Singla, Deep Dutta, Meha Sharma, and Aarti Sharma 57 Diabetes and the Skin������������������������������������������������������������������������������������������������� 883 Justine Mestdagh, J Damman, and H Bing Thio 58 Foot Complications��������������������������������������������������������������������������������������������������� 899 Lawrence B Harkless, Jarrod Shapiro, and Lisa D Breshars 59 Diabetes and Cancer��������������������������������������������������������������������������������������������������� 919 Joanna Krajewska (Wojciechowska), Wojciech Krajewski, and Tomasz Zatoński Part X Diabetes in Special Populations 60 Diabetes in Children and Adolescents����������������������������������������������������������������������� 941 América Liliana Miranda Lora, Martha Beauregard Paz, and Miguel Klünder Klünder 61 Pregnancy: Pregestational and Gestational Management ������������������������������������� 967 María Isabel García-Argueta and Maricela González-Espejel Contents Contents xi 62 The Elderly with Diabetes ��������������������������������������������������������������������������������������� 977 Willy Marcos Valencia-Rodrigo Part XI Novel Therapeutic Approaches: Evidence-Based and Others 63 The Artificial Pancreas��������������������������������������������������������������������������������������������� 993 Barry H Ginsberg and Richard Mauseth 64 Unproven Therapies for Diabetes��������������������������������������������������������������������������� 999 Jothydev Kesavadev, Lakshmy Ramachandran, and Sanjay Kalra Index����������������������������������������������������������������������������������������������������������������������������������� 1015 1026 Health systems (cont.) morbidity and mortality, 24 out-of-pocket expense, 31 perspectives, 31 productivity and efficiency, 28, 29 quality of care, 24, 25 relative weight, 29 resources and strategic planning, 24 risk factors, 28 social impact, 28 treatment cost, 24 trustworthiness, validity and relevance, 28, 29 uninsured population, 27 use of resources, 28 Healthy diabetes plate, 278 Heart failure (HF) aortic aneurysm, 721 aortic dissection, 721 aortic stenosis, 721 arrhythmias, 721–722 diastolic dysfunction, 720 empagliflozine, 720 epidemiology, 719 left ventricular hypertrophy, 719 pathophysiology, 719 pharmacological treatment, 720 Heart Outcomes Prevention Evaluation trial (HOPE), 733 Heart rate turbulence (HRT), 832 Heart rate variability (HRV) components, 831 during 24-h recordings, 832 frequency domain, 831 mechanisms, 831 R-R interval low-frequency spectral data, 832 time- and frequency-domain analysis, 831 time domain measures, 831 Hematogenous spread osteomyelitis, 902 Hemodynamic pathway, 791 Hemoglobin A (HbA), 73 Hemoglobin A1c (HbA1c), 39, 277, 283, 503, 531, 656, 780 Hepatic glucose production (HGP), 101 Hepatic insulin resistance, 231 Hepatic steatosis, 228, 231 Hepatocellular carcinoma (HCC), 227, 228, 232, 923 Hepatocyte Nuclear Factor 1-Alpha (HNF1A) gene, 121, 122 Hereditary hemochromatosis (HH), 108 Hexosamine pathway, 698, 792 Hexosamine signaling pathway, 698 High density lipoprotein (HDL) cholesterol, 587–590, 592, 593 Higher high-sensitivity CRP (hs-CRP), 421 High-sensitivity C-reactive protein (hsCRP), 421 Hip ratio (HR), 186 Homoeopathy, 1004 Hospital diabetes programs, 305 Housing Development Board (HDB) public housing, 49 Human placental lactogen (HPL), 215 Hybrid close loop system, 568 Hygiene hypothesis, 671 Hypercholesterolemia, 593 Hyperglucagonemia, 105 Hyperglycemia, 197, 198, 503, 546, 547, 549, 563, 580, 749, 853, 854, 883, 921, 922 with blood ketones >0.6 mmol/L or positive urine ketones, 950 corticosteroid therapy, 663 EN/PN therapy, 663 glucocorticoid therapy, 663 glycemic control (see Inpatient glycemic control) Index hemoglobin A1c, 656 hospital discharge, 661, 664 initial BG measurement, 655 inpatient management, 655 insulin infusion (pump) therapy, 663, 664 malnutrition, 663 with negative ketones, 950 nutritional state, 663 vascular complications, 695 Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, 75, 968 Hyperglycemia, management of KPD, 281 lifestyle modification components of, 277 medical nutrition therapy, 277, 278 physical activity and other lifestyle measures, 278 pharmacologic therapy, 279 combination therapy with oral antidiabetic medications and insulin, 280 insulin therapy, 279, 280 OAD/OHA, 279, 280 treatment targets, 279 screening and diagnosis, 275, 277 Hyperglycemic emergencies management, 623 pathogenesis, 620 Hyperglycemic hyperosmolar state, 952 Hyperglycemic process, 900 Hyperinsulinemia, 230, 231, 921 Hyperinsulinemia: the Outcome of its Metabolic Effects (HOME) trial, 504 Hypertension (HTN), 385, 386, 494, 710, 742, 954, 959 Ambulatory BP monitoring (ABPM), 580, 581 antihypertensive medications, 579–581 definition, 573 DM medications, 578, 579 evidence of, 575 fellowship training programs, 581 guidelines and blood glucose targets, 575, 576 internal medicine and related residency, 581 large scale trials, 575 lifestyle modifications aerobic exercise, 577 DASH diet, 577 intensive lifestyle modification, 576, 578 Mediterranean diet, 577, 578 moderate-intensity physical activity, 578 National Institutes of Health (NIH) clinical guidelines, 576 sodium impacts, 576 non-dipping pattern, 580 pathophysiology of, 573, 574 peripheral arterial disease (PAD), 752 PWV, 580 Hypertriglyceridemia, 587, 588, 590, 593 Hypertrophy, 894 Hypo-compass, 648 Hypoglycemia, 245, 282, 305, 361, 362, 456, 461, 506, 526, 533, 542, 544, 546, 549, 556, 558, 563, 564, 568, 664, 854 ACCORD study, 644 ADVANCE study, 644 cardiac arrhythmias, 644 and cardiovascular disease, 643 causes, 640 classification, 949 clinical characteristics, 644 Index clinical classification, 630 cognitive function and dementia, 644 critical illness and hospitalization, 646 dead-in-bed syndrome, 645 definition, 664, 949 with diabetes, 629–630 without diabetes, 629 diagnosis and detection, 640 fear of hypoglycemia, 645 insulin combined therapies, 637–639 degludec, 637 detemir, 637 fast-acting insulin analogues, 637 glargine, 637 oral agents medications alpha-glucosidase inhibitors, 636 amylin, 636 DPP-4 inhibitors, 637 metformin, 636 SGLT2 inhibitors, 637 sulphonylureas, 636 pathophysiology associated autonomic failure, 633–635 hypoglycemia unawareness, 633 physiological mechanisms cortisol and growth hormone, 631 endogenous insulin secretion, inhibition of, 630 epinephrine, increased release of, 631 glycemic mechanisms, 631–632 glycemic thresholds, 631 increased glucagon release, 630 prevention, 647, 648, 950, 984, 985 quality of life, 645 reduction, 649 risk factors and determinants, 641 alcohol, 641, 642 children and adolescents, 643 congestive heart failure, 642 elderly, 643 exercise, 641 glucose variability, 642 medications, 642 nocturnal hypoglycemia, 643 physical activity, 641 pregnancy, 643 renal insufficiency, 642 sepsis, trauma, and burns, 642 self-monitoring of blood glucose, 439 signs and symptoms, 949 spontaneous and iatrogenic, 664 sudden death, 645 symptoms, 639, 640 treatment after exercise, 647 glucagon, 646 intravenous glucose, 647 mild, 646 moderate, 646 severe, 646 type diabetes, 635, 949 epidemiology, 635, 636 pathophysiology, 632 type diabetes, 442 epidemiology, 636 pathophysiology, 632, 633 urgency, 949 1027 VADT study, 644 varenicline, 616, 617 Hypoglycemia–associated autonomic failure (HAAF), 633 Hypoglycemia unawareness, 633 Hyposalivation, 783, 784 Hypothalamic-pituitary adrenal (HPA) axis dysfunction, 420 I Impaired fasting glucose (IFG), 814 Impaired glucose tolerance (IGT), 246, 602 acute pancreatitis, 77 ADA, 72 antipsychotic medications, 79 antiretroviral therapy, 79 asymptomatic adults, 72 beta blockers, 79 chronic inflammation, 77 complications, 72 definition, 71 endocrinopathies acromegaly, 77, 78 Cushing’s syndrome, 78 FCPD, 77 GDM, 74–76 genetic defect, 76 glucagonoma, 78 glycated hemoglobin, 73 HbA1c, 74 monogenic diabetes syndromes, 76 NDDG, 72 neonatal diabetes, 76 NODAT, 79 one-step strategy, 76 pathophysiology, 72 PDAC, 77 pregnancy, 76 screening, 73 somatostatinomas, 78 statins, 78, 79 thiazide diuretics, 78 two-step strategy, 76 type DM, 74, 75 type DM, 74, 75 Incretin therapies DPP-4 inhibitors, 526 GIP, mechanism of, 520 GLP-1 albiglutide, 522 central nervous system, effects on, 517, 519, 520 clinical data from trial and clinical effects, 523 dulaglutide, 522 exenatide, 520 exenatide LAR, 520, 522 intestinal motility, effects on, 517 liraglutide, 520 lixisenatide, 522, 523 pancreas, effects on, 517 receptor agonists, 525 secretion, stimulation of, 516, 517 semaglutide, 523 side effects of, 525 history of discovery of, 515, 516 first clinical usage, 516 Indian Diabetes Prevention Program (IDPP), 247 Inducible nitric oxide synthase (iNOS), 701 1028 Infection abdomen acute emphysematous cholecystitis, 675 psoas and spinal epidural abscess, 675 pyogenic liver abscess, 675 awareness, 671 choice of antimicrobial therapy, 671, 683–686 common infections, 671 empirical therapy, 671, 680–682 genitourinary tract acute pyelonephritis, 676 asymptomatic bacteriuria, 676 bacterial cystitis, 676 balanoposthitis, 677 candiduria, 676 emphysematous cystitis, 677 emphysematous pyeloneprhitis, 676 Fournier´s gangrene, 678 fungal cystitis, 676 necrotizing fasciitis, 677 perinephric abscess, 676 vulvovaginal candidiasis, 677 glycaemic control, 686 head and neck herpes zoster opthalmicus, 672 malignant external otitis, 673 oral candidiasis, 673 periodontal infections, 673 rhino-orbital or rhino-cerebral sinusitis, 673 hospital-acquired infections, 679 hygiene hypothesis, 671 innate and adaptive immune function, 670 intestinal parasites, 671 magnitude of risk, 669 metabolic consequences, 671 pathogenesis, 670 principles of management, 671 respiratory system community-acquired pneumonia, 674 influenza, 674 pulmonary coccidioidomycosis, 675 pulmonary mucormycosis, 675 pulmonary tuberculosis, 675 source control, 686 therapeutic interventions, 671 therapeutic measures and prognosis, 686–688 uncommon infections, 671 upper and lower extremities, skin and appendages cellulitis, 678 cutaneous zygomycosis, 678, 679 foot ulcer infections, 678 hand ulceration and infection, tropical diabetic hand syndrome, 678 herpes zoster, 679 onychomicosis, 679 tinea pedis, intertrigo, 679 Inflammatory cytokines, 702 Inflammatory pathway, 793 Inflammatory stress, 697 Ang II, 701 EMT, 702 MCP-1, 701 monocyte chemotactic protein 1, 701 TGFβ, 702 TNFα, 701 Infrapopliteal lesions, 755 Innate immune response, 231, 670 Inpatient glycemic control, 659 glycemic monitoring Index critically ill patient, 660 non-critically ill patient, 657 perioperative patient, 662 glycemic target values critically ill patient, 660, 661 non-critically ill patient, 658 perioperative patient, 662 management approach critically ill patient, 661 non-critically ill patient, 658, 659 perioperative patient, 662, 663 therapeutic agents and regimens, 656 Inpatient hyperglycemia, 655 Institute of Medicine (IOM), 334, 346 Instrumental activities of daily living (IADLs), 982 Insulin, 188, 971 acquisition costs, 362 degludec, 637 detemir, 637 fast-acting insulin analogues, 637 glargine, 637 with other therpies basal insulin analogues and continuation with sulphonylurea therapy, 637 beta-cell replacement, 638 closed loop system, 638 continuous glucose monitoring, 638 continuous subcutaneous insulin infusion, 637, 638 Glucagon-like-peptide-1 (GLP-1) mimetic, 637 sensor augmented pumps, 638 Insulin bolus delivery, 558 Insulin dose calculators, 447 Insulin infusion (pump) therapy, 663, 664 Insulin like growth factor 1, 189 Insulin lipodystrophy, 894 Insulin neuritis, 818 Insulin pump therapy, 550, 994 basal rate fine tuning, 558–561 calculate initial dose, 558 candidates, 556 CGM, 567 correction bolus, 556 CSII therapy advantages of, 556 disadvantages of, 556 food bolus, 556 ICR fine tuning, 561 initial bolus calculation, 557, 558 initial pump settings, 562–563 initial total and basal insulin dose, 557 integrated systems, 567, 568 ISF fine tuning, 562 patient requirements, 556 patient’s BG registry, 558–560 pump settings after fine tuning adjustments, 562–563 special situations alcohol, 566 exercise, response to, 563, 564 fasting, 564 hospitalizations, 565 menstruation, 565 pregnancy, 565, 566 sick days, 564 surgery, 565 travel, 566, 567 types of, 556 on vacation going back on the pump, 567 Index going off the pump, 567 Insulin receptor (InsR), 121, 133, 231 Insulin resistance (IR), 195, 196, 230, 231 Insulin sensitivity factor (ISF), 435, 557, 558, 561, 562 Insulin therapy, 244, 260, 279, 280, 623, 624, 946 adjustment phase, 546 adverse effects, 550 basal insulin regimen, 546 clinical guidelines, 542, 543 glycemic control, 542 glycemic targets, 542 indications for insulin, 542 inhaled, 545 initial doses, 552–553 insulin preparations used in Africa, 280 intensification of, 543 intensive regimen, 546 basal-bolus, 548–550 basal-plus, 547, 548 basal plus GLP-1ra, 548 conventional insulin regimen, 546, 547 premixed insulins, 547 patient selection, 542 SMBG, 542 storage and application techniques, 550, 551 times of action, 543 type diabetes, 279 type diabetes, 279 types and time of action, 543–545 Insulin to carb ratio (ICR), 557, 558, 561 Insulinotropic effects, 516 Integrated care model, 246 Intensive blood glucose lowering therapy, 503 Intensive insulin therapy (IIT), 438, 441, 445, 446 Intensive lifestyle modification (ILI), 576, 578 Inter-decile range (IDR), 453, 459 Interferon-stimulated genes (ISGs), 92 Interleukin 1β (IL-1β), 196, 701 Interleukin (IL-6), 191, 196, 230, 421, 733 Interleukin-10, 196 Intermediate-acting insulin, 546 International Association of Diabetes and Pregnancy Study Groups (IADPSG) criterion, 75 International Diabetes Educator E-Learning, 412 International Diabetes Federation (IDF), 3, 239, 240 International Diabetes Federation Global Guideline for Type Diabetes, 465 International Diabetes Federation management practice study (IDMPS), 243 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), 74 Inter-quartile range (IQR), 453 Interstitial fluid, 451 Intestinal parasites, 671 Intracellular adhesion molecule-1 (ICAM-1), 701 Intracellular metabolic process, 697 Intuity Pogo®, 435 Invariant natural killer T (iNKT), 150, 151 Ipsilateral limb amputation, 914 Ischemic heart disease acute coronary syndromes clinical manifestations and diagnosis, 715 medical treatment, 716, 717 revascularization therapy (see Revascularization therapy) risk stratification, 716 antiplatelet treatment, 711, 712 ASCVD risk evaluation, 714 atherosclerosis 1029 pathophysiology, 710 progression / regression, 709 epidemiology, 710 hyperglycemia treatment, 712–713 hypertension treatment, 710–711 lipid treatment, 712 SIHD clinical manifestation, 714 definition, 714 diagnosis, 714 optimal medical treatment, 714, 715 revascularization treatment, 715 Islet amyloid polypeptide (IAPP) amylin, 176 apoptosis, 176 p53 protein, 176 Islet β cell exhaustion, 199 Islet transplantation, 949 IStar BG®, 431 J Janus kinase-signal transducer and activator of transcription (JAK- STAT) pathway, 805 Joint and connective tissue diseases, 875 Joint Asia Diabetes Evaluation (JADE) Program, 241 K Kaiser Permanente (KP), 470 Kerala Diabetes Prevention Program (K-DPP), 43 Keratinocyte function, 884 Keratosis pilaris, 891 Ketogenesis, 536 Ketosis-prone type diabetes (KPD), 281 Kidney cancer, 924 L Lactic acidosis, 504 Laryngeal cancer, 924 Laser-evoked potentials (LEPs), 815 Laser therapy, 769, 770 Latent autoimmune diabetes in adults (LADA), 240, 542 Latin American Diabetes Association Consensus Statement, 465 Left ventricular hypertrophy, 719 Leptin, 189, 197, 198, 601 Lichen planus, 889, 895 Lifescan®, 430 Lifestyle medicine ABCD goals, 472 clinic-community linkages, 469, 470 community barrier, 467 continued engagement, 470 definition, 463, 472 diabetes management, 463–465 DSME, 465 family barrier, 466 family support, 468 incentivizing adoption, 470 individual barrier, 466 multidisciplinary care teams, 468, 469, 472 patient empowerment, 468, 472 peer support, 468 provider barrier, 466, 467 strategies for self-management, 471 system barrier, 467 technology, 470, 471 1030 Limited joint mobility (LJM), 876 Linagliptin, 533 Lipid effects on β cell function, 199 Lipotoxicity syndrome, 193 Liraglutide, 520, 523, 524, 545, 603 Liver biopsy, 228, 229 Liver cancer, 923 Liver insulin-resistance, 197, 198 Liver steatosis, 228 Lixisenatide, 522, 523, 545 Lomitapide, 593 Long non-coding RNAs (lncRNAs), 132 Long-acting insulin, 544, 546, 547 Look AHEAD study, 464, 470 Lorcaserin (Belviq), 603 Lovastatin, 592 Low- and middle- income countries (LMICs), 239 Low density lipoprotein (LDL) cholesterol, 421, 587–590, 593, 594, 752 Lower extremity bypass, 758, 759 Lower urinary tract dysfunction benign prostatic hyperplasia diagnosis, 866 pathophysiology, 865 treatment, 866 bladder dysfunction/cystopathy clinical manifestation, 864 diagnosis, 864, 865 pathophysiology, 863, 864 treatment, 865 Low-grade microtrauma, 900 M Macroalbuminuria, 241 Macrovascular complications, 281, 358, 477, 491, 734 Major adverse cardiovascular events (MACE), 506 Major histocompatibility complex (MHC), 89 Malnutrition, 663 Massachusetts Department of Public Health1, Massachusetts Male Aging Study (MMAS), 107 Maturity-onset diabetes of the young (MODY), 920, 942, 943 Measure of instability, 456 Medial arterial calcification (MAC), 748 Medical care, 292, 456 Medical nutrition therapy (MNT), 38, 274, 277, 278, 658, 659 alcohol, 479 behavioral therapy, 480 calories per meal, 481 carbohydrate per meal, 481 dyslipidemia, 589 eating patterns, 480, 481 evidence, 477–478 fiber, 479 individualized assessment, 480, 481 lifestyle interventions, 477 macronutrient, 478 micronutrients, 480 nutrition interventions, 477 nutrition teaching priorities, 478 physical activity, 480 protein intake, 479 reasonable weight loss goals, 480 registered dietitian nutritionist (RDN), 477 total fat, 479 unsaturated fats, 479 very low calorie/carbohydrate (ketogenic) diets, 480 vitamin/mineral supplements, 479 Index Medicare’s Hospital Re-admissions Reduction Program, 264 Medication possession ratio (MPR), 390 Medisense®, 430 Mediterranean diet, 577, 578, 589 Meglitinides, 501, 502, 506, 507 Metabolic control, 770, 771, 785 Metabolic equivalents (METs), 486, 487 Metabolic pathway AGES pathway, 792 hexosamine pathway, 792 polyol pathway, 792 protein kinase C pathway, 792 Metabolic stress, 695 AGEs, 699 diacylglycerols and protein kinase C Activation, 698 dicarbonyl stress, 700 glycation, 698 hexosamine pathway, 698 hexosamine signaling pathway, 698 methylglyoxal, 699 nuclear factor kappa B, 699 O-GlcNAcylation, 698 polyol pathway, 697 Metabolic syndrome, 194, 227, 240, 576, 577 Metformin, 357, 362, 407, 501–507, 526, 533, 603 digestive system, 926 direct impact, 926 genitourinary system, 926 head and neck cancers, 926 indirect impact, 925 lung cancer, 926 Methylglyoxal, 699, 700 Metiglinides, 442 Microalbuminuria, 241 Microalbuminuria Prevalence (MAP) survey, 241 MicroRNAs (miRNAs), 132, 138 Microvascular complications, 281, 357, 358, 477 advanced glycation end products, 732 AGE/RAGE complex, 733 chronic hyperglycemia, 731 electron transport chain, 732 IL-6, 733 monocyte chemoattractant protein-1, 733 RAGE independent endothelial dysfunction, 732 vascular endothelial growth factor, 733 vascular smooth muscle cells, 733 vasculature endothelium, 733 Miglitol, 280, 502 Mineralocorticoid receptor (MR) blocker, 580 Mipomersen, 593 Mitochondrial diabetes, 942 Mitochondrial dysfunction, 196, 197 Mitochondrial dysfunction and reactive oxygen species, 199 Mobile phone based technology (mHealth), 616 Model Predictive Controllers (MPC), 994, 995 Monocyte chemoattractant protein-1 (MCP-1), 733 Monocyte chemotactic protein (MCP-1), 701 Monogenic diabetes, 942 Monounsaturated fatty acids (MUFA), 479 Morisky Medication Adherence Scale (MMAS), 386 Morisky Medication Scale, 390 Morphometric analysis, 814 Motivational interviewing, 389 Multi-Ethnic Study of Atherosclerosis (MESA), 230 Multi-morbidity (MM), 313, 318 definitions of, 313 epidemiology of, 314–317 in management, 320–321 Index in patients, 320 Multiple Risk Factor Intervention Trial (MRFIT), 107 Muscle sympathetic nerve activity (MSNA), 833 Musculoskeletal complications adhesive capsulitis, 876 bone effects, 874 calcific shoulder periarthritis, 877 calcific tendinitis, 878 calciphylaxis, 877 Carpal Tunnel syndrome, 877 Charcot’s arthropathy, 878, 879 diabetic amyotrophy, 875 diabetic foot, 879 diabetic myonecrosis, 874, 875 diffuse idiopathic skeletal hyperostosis, 878 dupuytren contracture, 876, 877 gout, 878 joint and connective tissue diseases, 875 limited joint mobility, 876 muscle effects, 874 osteoarthritis, 878 reflex sympathetic dystrophy, 878 stenosing flexor tenosynovitis, 877 My Fitness Pal, 447 N Nateglinide, 502 Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial (NAVIGATOR), 735 National and local Government policy, 47, 48 National Committee for Quality Assurance (NCQA), 257 National Diabetes Data Group (NDDG), 72 National Health and Nutrition Education Survey (NHANES), 109 National Quality Forum, 257 Natural killer T (NKT) cells, 89, 94 Naturopathy, 1000 NAVIGATOR study, 107 Necrobiosis lipoidica, 889, 890, 896 Necrolytic migratory erythema, 78 Neonatal diabetes mellitus, 942 Nephropathology albuminuric and non albuminuric pathway, 795 biopsy, 796 glomerular stages, 796 glycolisis, 792 interstitial and vascular lesions, 796, 797 KDIGO classification, 796 kidney biopsy, 800 stages, 794 Nephropathy, 954, 959 Network-based systems, Neural growth factor (NGF), 864 Neuronal apoptotic processes, 826 Neuro-ophthalmic disorders, 771, 772 Neuropathic pain (NP), 702, 703, 813, 814 Neuropathy, 258 Neurotrophic therapy, 840 New-onset diabetes after transplantation (NODAT), 79 Niacin, 591, 592, 712, 837 NICE diabetes management guidelines, 465 Nicotine replacement therapy, 616 Nitric oxide (NO) deficiency, 702, 865 Nociceptive matrix, 813 Nocturnal hypoglycemia, 643 Non-adherent patients, 381 Non-alcoholic fatty liver disease (NAFLD), 923, 960 clinical manifestations, 228 1031 definition of, 227 diagnosis, 228 diagnostic performance of serologic scores, 229 endoplasmic reticulum stress response, 231 epidemiology, 227, 228 genetics in pathogenesis, 231 hepatic insulin resistance, 231 hyperinsulinemia, 230, 231 innate immune response, 231 insulin resistance, 230 liver biopsy, 228, 229 non-invasive markers of fibrosis, 228, 229 pathogenesis, 230 T2DM interplay, 229, 230 Non-alcoholic steatohepatitis (NASH), 227, 229, 960 Non-arteritic ischemic optic neuropathy, 772 Non-communicable diseases (NCDs), 321, 485 Non-critically ill patient glycemic monitoring, 657 glycemic target values, 658 management approach, 658 Non-dipping pattern, 580, 829 Non-esterified fatty acids (NEFAs), 230 Non-Exercise Activity Thermogenesis (NEAT), 486 Non-invasive markers of fibrosis, 228, 229 Non-obese diabetic mouse models (NOD), 94 Non-proliferative diabetic retinopathy (NPDR), 766, 768 Non-reflux phenomenon, 717 Non-retinal manifestations cornea, 771 cystalline lens, 771 eyelid, 771 glaucoma, 771 neuro-ophthalmic disorders, 771, 772 Non ST-elevated myocardial infarction (NSTEMI), 717, 718 Normal glucose tolerance, 451, 456–458, 460–461 Notified Body, 434 No-wipe strip, 430 Nuclear factor kappa B (NFκB), 699 Nuclear respiratory factor-1 (NRF-1), 135 Nutritional management, 946–948 Nutritional state, 663 O Obesity, 284, 573, 574, 576, 577 adipocytes, types and differentiation, 186–188 adipogenesis and glucose metabolism adiponectin, 189, 191 asprosin, 191 chemokine molecules, 191 fatty acid metabolism effects, 191, 192 glucocorticoids and sexual hormones, 189 growth hormones, 189 IL-6, 191 insulin, 188 insulin like growth factor 1, 189 leptin, 189 obestatin, 191 omentin 1, 191 RBP4, 191 resistin, 191 thyroid hormones, 189 TNF-α, 191 visfatin, 191 body circumference waist circumference, 598 waist-to-hip ratio, 598 1032 Obesity (cont.) body fat BIA, 599 DEXA, 599 four compartment model, 599 skinfold thickness, 599 subcutaneous fat, 598 visceral fat, 598 body mass index (BMI), 597, 598 cancers, 185 causes of, 599 characterization, 185 CVD, 185 definition of, 185 direct healthcare costs, 597 environmental factors diet, 600 physical activity, 600, 601 glucose metabolism adult-obesity on, 193 fetal develop on adult, 192 hereditable factors, 600 inflammation and insulin resistance, 195, 196 lipotoxicity syndrome, 193 liver insulin-resistance and hyperglycemia, 197, 198 measurements and assessment, 186 obesity-induced insulin resistance ER stress, 197 mitochondrial dysfunction, 196, 197 oxidative stress, 197 pathogenesis of type diabetes, 192, 193, 195 peripheral arterial disease (PAD), 753 in pregannacy, 967 skeletal muscle glucose- and lipid metabolism, 197 T2D, 185, 601, 602 β-cells dysfunction, 198 differentiation of undifferentiated cells to pancreatic β-cells, 200 glucotoxicity and glycation stress, 198 islet β cell exhaustion and ER stress, 199 lifestyle intervention, 602 lipid effects on β cell function, 199 mitochondrial dysfunction and reactive oxygen species, 199 pharmacological intervention, 603 surgical intervention, 603, 604 type diabetes, 597 in United States, 185 worldwide prevalence of, 597 Obestatin, 191 Obstructive sleep apnea, 960 Ocular ischemic syndrome (OIS), 771 Ocular manifestations of DM, 770 non-retinal manifestations cornea, 771 cystalline lens, 771 eyelid, 771 glaucoma, 771 neuro-ophthalmic disorders, 771, 772 vitreoretinal manifestations, 770–771 Oculomotor nerve palsy, 771–772 Older adults available devices, 997 Beta Bionics, 997 Bigfoot Biomedical, 997 clinical trials, 996, 997 cyber-security, 997 effectiveness, 997 food insecurity, 984 Index functional domain falls, 982 impaired mobility, 982 self-care deficit and functional decline, 982 urinary incontinence, 982, 983 geriatric syndromes, 980, 981 geriatrics approach, 978, 979 healthy older adult, 980 hypoglycemia, 984, 985 management, 980 medical domain malnutrition, 981 multimorbidity, 981 nutritional status, 981 polypharmacy, 981 pharmacotherapy, 985–986 psychological domain dementia, 983 depression, 983 poor quality of life, 983 safety, 996 with severe complex health scenario, 980 social domain, 983 Type Zero device, 997 Omarigliptin, 526 Omentin 1, 191 O-N-acetylglucosamination (O-GlcNAc), 177 Oncogenesis, 921 One touch monitoring system, 430 Opiramate, 603 Optical coherence tomography (OCT), 766 Oral antidiabetic medications (OAD), 279, 280 Oral cancer, 925 Oral glucose tolerance test (OGTT), 72, 137, 230, 277 Oral health, 778 candidiasis, 784, 785 clinical management in dental office, 786, 787 definition, 778 dental caries, 782, 783 guidelines the physician, 787 hyposalivation, 783, 784 periodontal disease systemic interaction models, 778–781 treatment and diagnosis, 781, 782 quality of health, 777, 778 wound healing and changes in mucosa, 785 xerostomia, 783, 784 Oral hypoglycemic agents (OHA), 279, 280 Oral hypoglycemic medication, 894 Orlistat (Xenical), 603 Orthostatic hypotension (OH) syndrome, 826, 828, 842, 843 Orthostatic intolerance, 826 Oscillate, 453 Osteoarthritis, 878 Outpatient diabetes management CCM (see Chronic care model (CCM)) co-morbidity, 313 classification, 318 in clinical practice, 320 definitions of, 313 epidemiology of, 314–317 in patient with diabetes, 318–319 worldwide prevalence of, 313 complex problems, 323 complexities of diabetes management, 324 complicated problems, 323 diabetes clinics, ongoing story of, 305, 306 effectiveness of, 307 Index experiences of, 307–312 factors affecting, 324 multi-morbidity, 313, 318 definitions of, 313 epidemiology of, 314–317 in management, 320–321 in patients, 320 PAM, 324 self-care management, 324–325 simple problems, 323 support, 325 transforming diabetes care, 306 of type diabetes, 313 Oxidative phosphorylation (OXPHOS) pathway, 133, 135 Oxidative stress, 197, 697, 700, 701 P Palen’s test, 877 Palmer erythema, 891, 892 Pancreatic cancer (PaC), 923 Pancreatic ductal adenocarcinoma (PDAC), 77 Pancreatic exocrine insufficiency, 856 Pancreatic β-cell apoptosis, 421 Panretinal photocoagulation (PRP) technique, 768 Partial toe amputations, 909 Patch pumps, 556 Pathogen associated molecular patterns (PAMPs), 129 Patient Activation Measure (PAM), 324 Patient adherence, 394 adherence aids, 390 behavioral characteristics, 383 clinical outcomes and costs, 381 complexities of diabetes self-management, 386–388 compliance, 392, 393 concordance, 392, 393 definition of, 381 depression, 388, 389 diabetes empowerment, 389–390 drug compliance, 381 emotional distress, 389 emphatic engagement, 390 evidence of interventions, 383 hypertension, 385, 386 impact of, 393 measurement, 390, 391 medical perspective, 392 medical recommendations, 382 meta-analysis and reviews of interventions, 384–385 motivational interviewing, 389 noncompliance, 382, 383 noncompliant, 381 patient-centered counseling, 393 predictors, 392 psychological issues, 388 World Health Organization report, 393, 394 Patient Aligned Care Teams (PACTs), 262 Patient Assessment of Chronic Illness Care (PACIC), 321 Patient-centered approach, 273 Patient centered care, 293, 346, 361 attributes of, 295, 296 components of sickness, 292 definitions of, 295 pathological model of disease, 292 and primary care, 293, 294 western health systems, 292 Patient-centered counseling, 393 Patient-centered medical homes (PCMH), 38, 262, 263 1033 barriers to implementation, 294 behavioral health care, 297 in diabetes management, 298–300 effectiveness of, 297 evidence, 297–300 primary care, transitioning from, 295 principles of, 300 Patient centered medicine, 293 Patient-centeredness, 291, 292, 297 Patient education, 410 Pay-for-performance programs, 264 PCSK9 inhibitors, 590, 591, 593 Perceived treatment efficacy (PTE), 388 Percutaneous balloon angioplasty, 757 Percutaneous coronary intervention (PCI) NSTEMI, 717, 718 STEMI, 717 Percutaneous therapy, 757, 758 Perindropril Protection Against Recurrent Stroke (PROGRESS), 742 Periodontal disease and systemic interaction models, 778–781 treatment and diagnosis, 781, 782 Periodontal probing, 779 Periodontitis, 613, 779–782, 787 Perioperative patient glycemic monitoring, 662 glycemic target values, 662 management approach, 662, 663 Peripheral arterial disease (PAD), 615, 617, 901 diagnostic challenge, 747–748 epidemiology, 747 foot amputations, 907 management, 751 natural history, 748, 750, 751 outcomes, 748, 750, 751 pathophysiology, 748, 750, 751 revascularization endovascular versus open, 755, 756 indications, 754, 755 interventional challenges, 755 open surgery, 758, 759 percutaneous therapy, 757, 758 risk factor modification antiplatelet therapy, 753, 754 diabetes, 751 dyslipidemia, 752, 753 exercise, 753 hypertension, 752 obesity, 753 pharmacologic treatment of claudication, 754 smoking, 751, 752 Peripheral blood mononuclear cells (PBMCs), 136 Peripheral neuropathy, 614, 878 Peripheral vascular disease, 901 Periungual telangiectasia, 891 Perivascular fat, 146 Peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1 (PGC-1α) gene, 135 Personal plaque control (PPC), 778, 779 Pharmacologic therapy, 279 insulin therapy, 279, 280 OAD/OHA, 279, 280 oral antidiabetic medications and insulin, 280 treatment targets, 279 Pharyngeal cancer, 925 Phenformin, 503 Phentermine, 603 1034 Phlorizin, 531 Phlorozin, 531 3-phosphoinositide-dependent protein kinase (PDK1), 733 Physical activity, 485, 486 action plan of, 493–495 biochemical benefits, 488 clinical practice setting, implementation anthropometric and nutritional assessment, 492 assessment, 492 cardiovascular assessment, 491, 492 medical assessment of individual, 490, 491 physical fitness assessment, 492 team, 489 clinical recommendation of, 491 definition, 486 domains, 486 evidence of benefits, 487–489 five "A" of general counseling, 489 human movement, 486 intensity, 486 METs and behaviors, 486 obesity, 600, 601 in persons, 494 recommendations for, 487 recommendations of, 487, 490, 492–494 type of, 486 Physical fitness, 487, 492 Physical inactivity, 486 Physical work capacity (PWC), 486 Phytotherapy, 273 PI3K/Akt/mTOR signalling pathway, 921 Pioglitazone, 280, 502, 506, 507, 579 Point of care (POC) glucose meters, 640 Point of care testing (POCT), 657 Poly (ADP-ribose) polymerase (PARP), 178 Poly (ADP-ribose) polymerase (PARP-1), 701 Polycystic ovarian syndrome (PCOS), 228, 959 Polyneuropathy, 614 Polyol pathway, 697, 792 Polyol pathway hyperactivity, 810 Polyunsaturated fatty acids (PUFAs), 129, 479 Poor oral health, 777 Post- Stroke Antihypertensive Treatments Study (PATS), 742 Post-traumatic stress disorder, 35 Potassium, 624 PPARγ-independent antineoplastic activity, 927 Pramilintide, 442 Prediabetes, 71 PREDIMED trial, 464 Premixed insulins, 547 Preulcerative digital erythema, 901 Prevencion Dieta Mediterranea trial (PREDIMED), 577 Primary care, 320, 321, 360, 361 attributes of, 292 patient-centered care, 293, 294 PCMH, transitioning to, 295 site of medical home, 292 for type diabetes, 313 Problem Areas in Diabetes Questionnaire (PAID), 423 Proinflammatory cytokines, 421 Proliferative diabetic retinopathy (PDR), 766, 768–770 Prolonged-acting insulin analogue, 544 Proportional integral derivative (PID), 994, 995 Proportion of days covered (PDC), 390 Prospective Study of Pravastatin in the Elderly at Risk trial (PROSPER), 78 Prostate cancer (PC), 925 Protein kinase C pathway (PKC), 792 Index Pruritus, 891 Psoriasis vulgaris, 890, 891 Pupillary abnormalities, 771 Pyruvate dehydrogenase (PDH), 702 Pyruvate dehydrogenase kinase (PDK)-lactic acid axis, 702 Q Qsymia, 603 QTi prolongation, 828 Quality improvement (QI) interventions, 261, 262 Quality of care measurement affordability and cost effectiveness, 362, 363 outpatient diabetes care, clinical outcomes in accountability measures, 359 aspirin, 358 clinical inertia, 359 composite measure, 358, 359 Diabetes Prevention Program, 357 diagnostic measures, 359, 360 evidence-based components of diabetes care, 360 microvascular complications, 357 patient education, 360 prevent retinopathy, 360 primary care providers, 360 providers feedback, 360 quality measures, 357, 358 patient experience of care, 361, 362 Quality of life (QOL), 485 R Racial and Ethnic Approaches to Community Health (REACH) program, 261 Radiculoplexus neuropathies, 816 RAGE independent endothelial dysfunction, 732 Ramipril, 752 Ranibizumab, 769 Rapid-acting insulin, 547 Ray amputation, 909, 910 Reactive oxygen species (ROS), 133, 731 Real time-continuous glucose monitoring (RT-CGM), 638 Receptor activator of NF-κB ligand (RANKL), 902 Redistributing transferrin receptor (TfR), 109 Referral diabetic retinopathy (RDR), 766 Reflex sympathetic dystrophy, 878 Refractive error, 771 Regular-acting insulin, 543 Renal cell cancer (RCC), 924 Renin-angiotensin-aldosterone antagonists, 716 Renin angiotensin aldosterone system (RAS), 574, 579, 720, 791, 801–803 Renin-angiotensin system (RAS), 106, 107, 701 Repaglinide, 280, 502, 507 Resistin, 191 Resources and Supports for Self Management, 36 Retinal arterial occlusions (RAO), 771 Retinal vein occlusions, 770 Retinol-binding protein (RBP4), 191 Retinopathy, 360, 614 Revascularization therapy coronary artery bypass grafting, 718 fibrinolytic therapy, 718 percutaneous coronary intervention NSTEMI, 717, 718 STEMI, 717 Reverse dipping patterns, 829 Right foot Lisfranc amputation, 913 Index Risk Evaluation and Mitigation Strategy (REMS), 506 Rosiglitazone, 280, 502, 503, 506, 507 Roux-en-Y gastric bypass (RYGB), 130, 604 Rrifampicin, 243 Rubeosis faciei, 891 S Saturated fatty acids (SFAs), 479 Saxagliptin, 526, 533 Scleredema diabeticorum, 892 Sedentary behavior, 487 Selective serotonin reuptake inhibitors (SSRIs), 422, 424, 820 Self-care management, 324–325 Self-monitoring of blood glucose (SMBG), 451, 452, 542, 546, 638 BGM strip channel, 433 cover, 432 electrodes, 433 layer, 432 well, 433 early meters, 429, 430 enzymes glucose dehydrogenase, 432 glucose oxidase, 431, 432 limitations altitude, 443 BGM accuracy, 443 humidity, 443 interfering substances, 443 temperature, 443 meter bounceback elimination, 434 function, 433 lancing devices, 433 shallower depth of lancing, 434 thinner lancets, 433 wobble elimination, 434 monitoring system alternate site testing, 437 averages, 438 BG value, 435 blood transfer, 436 data entry, 436 error grid, 435 error readings, 437, 438 hand washing, 436 ISO 15193, 434 lancing for blood drop, 436 MARD, 434, 435 memory, 438 setting up monitor, 435 tools preparation, 435 whole blood versus plasma, 437 sensors, 430, 431 smart meters, 431 tele-health basic data, 444 BGM apps, 447 disease management, 447 food apps, 447 glucagon apps, 447 graphics, 446, 447 “How am I doing?” charts, 444 insulin dose calculator, 447 regulation of diabetes apps, 447 statistics, 444–446 1035 type hypoglycemia, 439 insulin dose using blood glucose values, 438, 439 long term changes, 440 pattern recognition, 440, 441 type hypoglycemia, 442 hypoglycemic agents, 442 insulin, 441 non-hypoglycemic agents, 442 SMBG therapy, 442 urine testing, 429 Semaglutide, 523, 525 Sensor augmented pumps (SAP), 638 Sensorimotor neuropathy acute diabetic mononeuropathies, 816 DCRPN, 816 distal sensory diabetic polyneuropathy, 816 DLRPN, 816 DTRN, 816 insulin neuritis, 818 radiculoplexus neuropathies, 816 Sensors, 430, 431 Sex hormone binding globulin (SHBG), 107 Sexual dysfunction, 866–868 Shared decision making (SDM), 501 Silent ischemic heart disease, 714 Silent myocardial ischemia (SMI), 827, 829 Silent nephropathy, 794 Simple steatosis, 227, 228 Simvastatin, 591 Sitagliptin, 516, 526, 532, 579, 592 Skeletal muscle glucose- and lipid metabolism, 197 Skin diseases acanthosis nigricans, 884, 895 acquired perforating dermatosis, 885, 886, 895 acrochordon, 885 bullosis diabeticorum, 885, 886, 895 clinical manifestations, 883 diabetic cheiroarthropathy, 887 diabetic dermopathy, 887, 895 disseminated granuloma annulare, 887, 888, 895 eruptive xanthomas, 888 fibroepithelial polyp, 885 infections, 888 insulin lipodystrophy, 894 keratosis pilaris, 891 lichen planus, 889, 895 necrobiosis lipoidica, 889, 890, 896 oral hypoglycemic medication, 894 palmer erythema, 891, 892 pathogenesis, 883, 884 periungual telangiectasia, 891 prevalence, 883 pruritus, 891 psoriasis vulgaris, 890, 891 rubeosis faciei, 891 scleredema diabeticorum, 892 skin thickening, 891 ulcers, 892 vitiligo, 892, 893, 896 xerosis cutis, 890, 891 yellow nails, 892, 893 Skinfold thickness, 599 Skin phototypes, 891 Skin thickening, 891 Skin-to-liver capsule distance (SCD), 229 Sleeve Gastrectomy, 604 1036 Sliding scale insulin (SSI), 656 Smart meters, 431 Smartphone app, 438, 447 Smoking cerebrovascular accident/stroke, 615 coronary heart disease, 615, 617 counseling and behavior therapy, 616 diabetes, increased risk, 617 diabetic nephropathy, 614, 616 diabetic neuropathy, 614 diabetic retinopathy, 614 incidence, 613 inflammatory and oxidative pathway mechanisms, 613 internet, 616 macrovascular complications, 615 microvascular complications, 614 mobile phone based technology, 616 mortality risks, 615 nicotine replacement therapy, 616 non-micro and macro vascular complication, 613 peripheral artery disease, 615, 617 pharmacological agents, 617 weight gain, 617 Social determinants of health, socioeconomic conditions, 61 Socioeconomic disparities, 261 Sodium-glucose cotransporter inhibitors (SGLT inhibitors), 501, 579, 620, 637, 713, 720, 737, 803, 804, 928–929 canagliflozin, 532 cardiovascular benefits, 533 dapagliflozin, 532, 533 empagliflozin, 533 ketogenesis, 536 mechanism of action, 531, 532 phlorizin, 531 renal effects, 534, 536 Sodium-glucose transporter (SGLT-1), 803, 804 Soluble form of the adhesion protein ICAM (sICAM-1), 702 Soluble intercellular adhesion molecule (sICAM)-1, 421 Somatostatin agonists (SSA), 77–78 Spaghetti map, 599 Spatial independent component analysis (sICA), 814 Specific, Measurable, Attainable, Realistic, Timely (SMART), 493 Spinal disinhibition, 813 Stable ischemic heart disease (SIHD) clinical manifestation, 714 definition, 714 diagnosis, 714 optimal medical treatment, 714, 715 revascularization treatment, 715 Staged Diabetes Management (SDM), 313 Statins, 591, 592, 712, 752 Steatosis, 228–230, 232 Steatosis, Activity, Fibrosis (SAF), 229 ST-elevated myocardial infarction (STEMI), 717 Stem cell therapy, 949 Stenosing flexor tenosynovitis, 877 Stepped-care approach, 343 Stress hyperglycemia, 655 Stroke antidiabetic drug classes alpha-glucosidase inhibitor, 736 biguanides, 736 bile acid sequestrants, 737 dipeptidyl peptidase inhibitors, 736 glucagon-like peptide 1, 737 Index insulin, 735, 736 meglitinides, 736 sodium glucose co-transporter-2, 737 sulfonylureas, 736 thiazolidinediones, 737 antihyperglycemic drug classes, 741–742 diabetes mellitus, 740, 741 macrovascular complications, 734 microvascular complications advanced glycation end products, 732 AGE/RAGE complex, 733 chronic hyperglycemia, 731 electron transport chain, 732 IL-6, 733 monocyte chemoattractant protein-1, 733 RAGE independent endothelial dysfunction, 732 vascular endothelial growth factor, 733 vascular smooth muscle cells, 733 vasculature endothelium, 733 optimization of DM control, 742 prevalence, 731 primary prevention, 734–735 recurrent stroke prevention, 741–743 secondary stroke prevention, 738, 743 atherosclerosis, 739 atrial fibrillation, 738, 739 hyperlipidemia, 739, 742 hypertension, 738, 739, 742 uncontrolled diabetic mellitus, 731 Stromal vascular fraction (SVF), 149 Subcutaneous (SC) insulin regimen, 656 Subcutaneous fat, 598 Sulfonylurea (SU), 279, 280, 501, 502, 504–506, 713 Superfuel, 536 Supersonic Shear Imaging (SWE), 229 Supervised exercise therapy (SET), 753 Supplemental insulin adjustment, 657 Supplemental insulin orders, 657 Sympathetic nervous system (SNS), 420, 421 Sympathoadrenal system, 639 SYNTAX score, 716 Systemic interaction models, 778–781 T Tai chi, 1006 Target glucose/target range, 435 Targeted retinal photocoagulation (TRP), 768 Teneligliptin, 526 Therasense®, 437 Thiazolidinediones (TZD), 280, 501, 502, 504, 506, 507 3-phosphoinositide-dependent protein kinase (PDK1), 733 Thyroid hormones, 189 Time- and frequency-domain analysis, 831 Tinel’s sign, 877 Toe-brachial index (TBI), 748 Toe systolic blood pressure (TSBP), 748 Tolazomide, 280 Tolbutamide, 280, 504 Tonsillectomy, 333 Total body phosphate deficiency, 624 Total contact casting (TCC), 905 Total daily basal dose, 557 Total daily insulin dose (TDD), 557 Traditional Chinese medicine, 1000 Index Transcription start site (TSS), 132 Transcutaneous electric nerve stimulation (TENS), 821 Transcutaneous oxygen pressure measurements (TCOM), 755 Transient elastography (TE), 229 Transient receptor potential V1 (TRPV1), 813 Transmetatarsal amputation, 909, 911, 912 Treatment intensification, 374 Treatment-induced neuropathy in diabetes (TIND), 818 Trelagliptin, 526 Tricyclic antidepressants (TCA), 820 Triglyceride, 587–590, 592, 593 Tropical chronic pancreatitis, 77 Tuberculosis, 243 Tumor necrosis factor α (TNFα), 191, 196, 230, 421 Two dimension shear wave elastography (2D-SWE), 229 Type diabetes mellitus (T1DM), 531 Asia, diabetes management in, 240 autoimmune activation, 89 autoimmunity and inflammation, 94 cancer, 920 children autoimmune thyroid disease, 953 blood glucose monitoring, 945, 946 cardiovascular risk factors, 954, 955 celiac disease, 953 classification, 942 clinical presentation, 945 diabetes self-management education and support, 945 diabetic ketoacidosis, 952 environmental risk factors, 945 epidemiology, 944 exercise management, 948 genetic risk factor, 945 glucagon, 949 glycemic control, 945 health-related quality of life, 955 honeymoon phase, 948 hypoglycemia, 949 insulin therapy, 946 islet transplantation, 949 metformin, 949 nutritional management, 946–948 pathogenesis, 944 pre-pregnancy prevention, 954 psychosocial issues, 954 sickness, 950, 951 stem cell therapy, 949 surgical procedure, 951, 952 vaccination, 954 Class II MHC molecules, 95 Colombian patients, 94 CRTAM, 95 environmental risk factors, 89, 92, 93 epidemiology, 635, 636 genetic factors Caucasian population, 90 DIAMOND Project, 90 genome scanning (IDDM3-15), 91 HLA genes, 89, 90 I-Ag-7 molecule, 91 IDDM12, 91 IL-10 production, 91 Mexican-American population, 90, 91 MHC, 89 non-HLA genes, 91 1037 glucose counterregulation, 632 health impacts, 255 HTN, 580 IDD9 and IDD6 genes, 94 immune system, 94 immunological factors, 91, 92 innate and adaptive immune systems, 89 insulin pump therapy, 556, 563–565, 567 insulin therapy, 279 intestinal microbiota, 93, 94 MNT, 477, 478 NKT, 94 non-HLA genes, 95 obesity, 597 outpatient diabetes management, 313 pathogenesis, 89 stages, 89 technological advances, 95 therapeutic agents and regimens, 656 Type diabetes mellitus (T2DM), 345, 347, 348, 477, 502, 515, 524, 531, 587 adipocyte size, 145 adiponectin, 156–158 adipose tissue, 145, 146, 159 adolescents bariatric surgery, 958 cigarette smoking, 957 depression, 960 diagnosis, 955 dyslipidemia, 959 exercise management, 957 glycemic monitoring, 957 health problems, 960 hypertension, 959 incidence, 955 nephropathy, 959 non-alcoholic fatty liver disease, 960 nutritional management, 957 obesity, 959 obstructive sleep apnea, 960 pathophysiology, 956 pharmacological treatment, 958 polycystic ovarian syndrome, 959 prevalence, 955 tobacco use, 957 transition care, 960 alpha cells, 104, 105 Asia, diabetes management in, 240, 241, 243 β-cell dysfunction, 102 age and genes, 103 dedifferentiated cells, 103 IGT, 103 insulin secretion, 103 insulin sensitivity, 103 IR index, 103 multiple abnormalities, 102 pathogenic factors, 103 plasma insulin response, 102 β-cells, 102 cancer, 920 child abuse experience, 62 chronic inflammation, 63 comorbidity, 61 culture, 63 diabetes-related mortality, 62 1038 Type diabetes mellitus (T2DM) (cont.) diabetes-related risk factors, 62 dietary requirements alcohol, 277 carbohydrate, 277 fats, 277 healthy diet, 277 proteins, 277 salts, 277 vitamins and minerals, 277 dopamine, 106 ecological perspective, 63, 64 ectopic lipid accumulation, 146 epidemiology, 636 European cross-country panel survey, 61 F4/80+, 159 factors, 102 gene expression (see Gene expression) general population, 62 genetic determinants ABCC8, 120 Admixture Mapping method, 119 Amerindian ancestry, 119 biological validation studies, 122 CAPN10, 120 CDKN2A/B gene, 121 diploid, 117 FTO gene, 121 GWAS, 118–119 heterogeneous nuclear RNA, 117 HNF1A, 121, 122 human haploid genome, 117 insulin resistance and dyslipidemia, 122 IRS-1 gene, 121 KCNJ11 E23K, 120 PPARγ, 120 SLC30A8, 122 SNPs, 117, 118 TCF7L2 gene, 119, 120 glucose counterregulation, 632, 633 glucose homeostasis, 101 glycemic targets for adults, 345 gut, 107, 108 gut microbiome, 108 health care sectors, 64 health impacts, 255 high-income countries, 67 histamine and serine proteases, 158, 159 HTN, 580 IL-1 family, 152 IL-1Ra, 155, 156 IL-4, 156 IL-6, 152, 153 IL-10, 156 IL-18, 153 immune cells, 158 B-cells, 150 dendritic cells, 151 eosinophils, 149 iNKT cells, 150, 151 innate and adaptive immunity, 147 lymphocytes, 149, 150 macrophages, 148 mast cells, 148 natural killer (NK) T cells, 150 immunotherapy, 157, 158 Index incretin effect, 105 incidence, 67 individual-level factors, 63 inflammation, 146 iNKT cells, 158 insulin pump therapy, 556 insulin resistance adipose tissue insulin resistance, 104 GDM, 103 hepatic insulin resistance, 104 high insulin levels, 103 insulin sensitivity, 103 muscle insulin resistance, 104 insulin therapy, 145, 279 interferon and interleukins, 159 iron overload β-thalassemia, 108 body iron stores, 109 DNP, 109 Friedreich ataxia, 108 impaired insulin secretion, 109 iron depletion, 109 pathologic iron overload disease conditions, 108 pathophysiology, 109, 110 redox-active transitional metal, 109 risk factor for, 108 TfR, 109 kidney’s adaptive response, 105 leptin, 154, 155 life-course perspective, 64 lifestyle behaviors, 62, 63 low-middle income countries, 67 macro-social mechanisms, 63 management, 280 MNT, 477–481 mortality, 61 NAFLD, 229, 230 normal insulin sensitivity, 102 obesity, 147, 158, 185, 192, 193, 195, 601, 602 β-cells dysfunction, 198 differentiation of undifferentiated cells to pancreatic β-cells, 200 glucotoxicity and glycation stress, 198 islet β cell exhaustion and ER stress, 199 lifestyle intervention, 602 lipid effects on β cell function, 199 mitochondrial dysfunction and reactive oxygen species, 199 pharmacological intervention, 603 surgical intervention, 603, 604 outpatient diabetes management, 306 policy intervention, 67 prevalence, 66, 671 proportionate universalism approach, 67 quality of care measurement, 357, 358, 363 quality of diabetes care, 63 RAS, 106, 107 resistin, 154 screening, 275 self-care activities, 63 social determinants of health, 64–66 social relationships, 63 social stigma, 63, 67 socioeconomic position, 61, 62 sympathetic and parasympathetic nervous systems, 105, 106 T cells, 159 Index testosterone, 107 TGF-β, 153 therapeutic agents and regimens, 656 TNF-α, 151, 152 treatment for, 333 triumvirate, 102 unequal distribution of the incidence, 61 United States-based cohort study, 62 United States National Health and Nutrition Examination Survey, 62 universal public health insurance coverage, 63 vitamin D, 106 TypeZero device, 997 U Ulcers, 892 Ultra long-acting insulin, 544, 547 United kingdom prospective diabetes study (UKPDS), 73 United States, diabetes management in clinical care models and practice re-design application, 262, 263 conceptual basis, 262 evidence, 263 disparities in diabetes prevention and management demographic disparities, 260, 261 in care delivery, 261 socioeconomic disparities, 261 evolution of guidelines and care targets, 259 health impacts, 255, 256 implementation sciences, 265 national trends cardio-metabolic risks, management of, 257 complications, incidence of, 259 diabetes complications, screening for, 257–259 screening, 256, 257 outpatient setting hospital-based care, 259 patient, 259, 260 provider, 260 system-level factors, 260 PCMH and applications in diabetes care, 263 polices and incentives on accountability and quality in diabetes care DQIP measures, 264 electronic health records (EHR) policies, 265 HEDIS measures, 264 pay-for-performance programs, 264 population-based interventions, 265 prevalence and cost burdens, 255 quality improvement initiatives in outpatient diabetes care, 261, 262 Unproven therapies, see Complementary and alternative medicine (CAM) Urethral obstruction, 865 Urinary incontinence, 982, 983 Urinary tract infections (UTI) clinical manifestation, 868 diagnosis, 868 pathophysiology, 868 prevalence, 868 treatment, 869 Urine testing, 429 US National Diabetes Surveillance System, 17 U.S. National Health Interview Survey (NHIS), 14, 15 US Preventive Services Task Force (USPSTF), 256 1039 V Vascular cell adhesion molecule-1 (VCAM-1), 701 Vascular claudication, 747 Vascular complications anaerobic glycolysis, 702 anaerobic metabolism, 702 dicarbonyl stress, 697 dyslipidemia, 701 endogenous glication, 700 endothelial dysfunction, 695, 702 hyperglycemia/chronic elevation, 695 inflammatory stress, 697 Ang II, 701 EMT, 702 MCP-1, 701 monocyte chemotactic protein 1, 701 TGFβ, 702 TNFα, 701 lipid accumulation, 701 metabolic stress, 695 AGEs, 699 diacylglycerols and protein kinase C Activation, 698 dicarbonyl stress, 699 glycation, 698 hexosamine pathway, 698 hexosamine signaling pathway, 698 nuclear factor kappa B, 699 O-GlcNAcylation, 698 polyol pathway, 697 methylglyoxal, 700 NADH overproduction/reductive stress, 700 neuropathic pain, 702, 703 nitric oxide deficiency, 702 oxidative stress, 697, 700, 701 pathophysiological mechanisms, 696 reductive/oxidative stress, 697 Vascular endothelial growth factor (VEGF), 733 Vascular risk spectrum, 901 Vascular smooth muscle cells (VSMCs), 733 Ventromedial hypothalamus (VMH), 106 Vertical bony defect, 781 Very low density lipoprotein (VLDL) cholesterol, 231, 587 Veterans Administration (VA) Healthcare System, 262 Veterans Affairs Diabetes Trial (VADT), 346 Vibration test, 815 Vicious cycle, 648 Victoza, 603 Vildagliptin, 526 Visceral adipose tissue (VAT), 146 Visceral fat, 420, 598 Visfatin, 191 Vitiligo, 892, 893, 896 Vitreoretinal manifestations, 770–771 Volanesorsen, 593 W Wagner’s Chronic Care Model, 38 Waist circumference (WC), 186, 598 Waist-HR (WHR) ratio, 186 Waist-to-hip ratio, 598 Wavesense Diabetes Manager, 447 Weight management, 597, 600, 602, 603 Well-Being Index, 423 WellDoc app, 447 Whipple’s Triad, 640 1040 White adipose tissue (WAT), 146, 186, 188 Whole blood cells (WBC) biological process, 137 ceramide and adipocytokine signaling pathways, 137 early detection of, 137, 138 JNK, 137 miRNAs, 138 OLETF rats, 137 OXPHOS pathway, 137 PBMCs, 136 stress response, 137 Wired enzyme sensors, 452 Wobble, 434 Index World Health Organization’s Tobacco Free Initiative, 42 Wound healing and changes in mucosa, 785 X Xerosis cutis, 891 Xerostomia, 783, 784, 787 Y Yellow nails, 892, 893 Yoga, 1000, 1006 ... the projected demand for the year 2015 as point of cutoff On the average of the costs to the pocket of the users, it is noteworthy the high relative weight of the origin of the expenses for diabetes. .. up the ladder of complexity, one can see the same kind of reciprocity in the influence of: • The group on the individual and the individual on the group • The organization on the division and the. .. consequences of diabetes would be of greater impact for the IMSS, following in order of relevance the SSA and finally the ISSSTE. On the other hand, the financial requirements for the treatment of diabetes,