Table of Contents
BENTHAM SCIENCE PUBLISHERS LTD.
End User License Agreement (for non-institutional, personal use)
Usage Rules:
Disclaimer:
Limitation of Liability:
General:
PREFACE
FOREWORD
List of Contributors
Diabetes Epidemic, Epidemiology, Statistics and Trends
Abstract
INTRODUCTION
Epidemiology of Diabetes Mellitus
Epidemiology of Diabetic Retinopathy
Screening of Diabetic Retinopathy
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Recent Developments in Diabetes Evaluation and Management: Implications for the Practicing Clinicians
Abstract
INTRODUCTION
RISK FACTORS OF DIABETES MELLITUS
Non-modifiable Risk Factors (Table 1)
Genetics
Susceptibility Loci
Modifiable Risk Factors (Table 1)
Lifestyle
Vitamins
Vitamin K
Vitamin D
Gut Bacteria
COMPLICATIONS OF DIABETES MELLITUS
Macrovascular Complications
Cardiovascular Diseases
Cancer
Cerebrovascular Accident
Peripheral Vascular Disease
Microvascular Complications
Neuropathy
Retinopathy
Diabetic Kidney Disease
NEW THERAPEUTIC MODALITIES FOR TREATING DIABETES MELLITUS
DPP-4 and SGLT2 Inhibitors: The Next Second Line Oral Agents
DPP-4 Inhibitors Compared to Sulfonylurea
The Search for Superior Insulin as Demand for Higher Doses Rises
Insulin Degludec
GPR40 Agonist
Lixisenatide
Anti-Inflammatory Treatment
Nitrates and Nitrites
Antioxidant Therapy
NEW TECHNOLOGIES FOR TREATMENT OF DIABETES MELLITUS
Glucose Monitoring
The Artificial Pancreas (Closed-loop Monitoring System)
Components of the Closed-loop Monitoring System
The Three-body Access Routes
The Efficacy of the Closed-loop System
Bi-hormonal Therapy and the Closed-loop System
Adjunctive Therapies and the Closed-loop System
The Outlook of the Closed-loop Monitoring System
Pancreas Allotransplantation
Islet Cell Allotransplantation
Becoming Insulin Free with Stem Cells (Table 2)
PREVENTION OF DIABETES MELLITUS
Screening
Lifestyle Modification
Pharmacological Agents
Motivational Interviewing
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Blurred Vision in the Diabetic Patient – Reversible and Non-reversible Causes – General Classification of Diabetic Eye Disease
Abstract
INTRODUCTION
CLASSIFICATION SYSTEM
REVERSIBLE AND NON-REVERSIBLE CAUSES OF VISION LOSS IN DIABETIC RETINOPATHY
Diabetic Macular Edema
Complications from Proliferative Diabetic Retinopathy
Vitreomacular Traction and Epiretinal Membrane
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Diabetes and Ocular Infections
Abstract
INTRODUCTION
RHINO-ORBITAL-CEREBRAL MUCORMYCOSIS
Case 1
PRE-SEPTAL & ORBITAL CELLULITIS
Case 2
Case 3
INFECTIOUS KERATITIS
Case 4
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Neuro-Ophthalmic Complications of Diabetes Mellitus
Abstract
INTRODUCTION
DIABETES AND NEURO-OPHTHALMOLOGIC COMPLICATIONS
Cranial Nerve Palsies in Diabetes
Case 1: Diabetic Patient Presents with an Oculomotor Nerve Palsy
Cases 2 and 3: Botulinum Toxin A as a Treatment of Diplopia from Diabetic Abducens Nerve Palsy
Non-Arteritic Anterior Ischemic Optic Neuropathy
Optic Neuropathy in Young Patients with Diabetes
Pupils in Diabetes
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Overview of Anterior and Posterior Segment Complications
Abstract
INTRODUCTION
Anterior Segment Complications
Ocular Surface Diseases
Dry Eye Syndrome (DES)
Diabetic Keratopathy
Refractive Changes
Cataracts
Ocular Movement Disorders
Neovascular Glaucoma
Posterior Segment Complications
Diabetic Retinopathy
Diabetic Papillopathy
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Diabetes and the Cornea
Abstract
CORNEAL EPITHELIUM
Increase in Epithelial Thickness
Abnormal Basement Membrane Formation
Impaired Epithelial Barrier Function
Increased Epithelial Fragility
Poor Healing Capacity of Epithelial Defects
CORNEAL INFECTIONS
CORNEAL STROMA
Altered Collagen Synthesis
CORNEAL ENDOTHELIUM
Morphological Abnormalities
Functional Abnormalities Leading to Increased Water Content in the Atroma and Folds in Descement’s Membrane
CORNEAL NERVES
Reduced Corneal Sensation
Loss of the Subbasal Nerve Plexus
Loss of Neurotrophic Support
TEAR DYNAMICS AND TEARING
Tear Film Dysfunction
Decreased Reflex Tearing
CORNEA CONSIDERATIONS IN OCULAR SURGERY
Cataract Surgery
Refractive Surgery: PRK
Refractive Surgery: LASIK
Penetrating Keratoplasty
Pterygium
Closed Pars Plana Vitrectomy
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
References
Diabetes, Cataract, and Glaucoma
Abstract
CATARACT
Anatomy
Risk Factors
Pathophysiology
Clinical Evaluation
Treatment
Glaucoma
Definition and Epidemiology
Diabetes and Glaucoma Risk
Diabetes and Neovascular Glaucoma
Clinical Examination
Treatment
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
References
Optical Coherence Tomography and Fluorescein Angiography in Diabetic Retinopathy
Abstract
OPTICAL COHERENCE TOMOGRAPHY
Diabetic Macular Edema
Morphological Patterns of Diabetic Macular Edema
Retinal Thickness and Individual Layer Integrity in Diabetic Macular Edema
Retinal Thickness
Disorganization of the Retinal Inner Layers (DRIL)
Ellipsoid Zone
Hard Exudates
Hyperreflective Foci and an External Limiting Membrane
Macular Cube and Cystic Macular Edema
Choroidal Thickness
Summary
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Diabetic Macular Edema
Macular Ischemia
Increased FAZ
Perfusion and Vessel Density
Microaneurysms
Peripheral Ischemia
Proliferative Diabetic Retinopathy
Summary
FLUORESCEIN ANGIOGRAPHY
Diabetic Ischemia
Diabetic Leakage
WIDE FIELD FLUORESCEIN ANGIOGRAPHY
Summary
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Classification of Proliferative and Non-Proliferative Diabetic Retinopathy and its Implications
Abstract
BACKGROUND
CLINICAL MANIFESTATIONS OF NONPROLIFERATIVE DIABETIC RETINOPATHY
NONPROLIFERATIVE DIABETIC RETINOPATHY
Mild Nonproliferative Diabetic Retinopathy
Moderate and Severe Nonproliferative Diabetic Retinopathy
PROLIFERATIVE DIABETIC RETINOPATHY
Panretinal Laser Photocoagulation
Anti-Vascular Endothelial Growth Factor (anti-VEGF) Therapy
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Current Treatment for Diabetic Retinopathy
Abstract
INTRODUCTION
Diabetic Retinopathy
Treatment of Diabetic Macular Edema
Anti-VEGF Therapy for DME
Comparison of Anti-VEGF Agents for DME
Anti-VEGF Treatment Regimens for DME
Safety and Potential Side Effects of Anti-VEGF Therapy
Future Developments in Anti-VEGF Therapy for DME
Laser Photocoagulation for DME
Micropulse Laser Treatment for DME
Targeted Peripheral Laser Photocoagulation for DME
Corticosteroids for DME
Vitrectomy for DME
Treatment of Proliferative Diabetic Retinopathy
Vitrectomy for PDR
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Future Direction in Diabetic Eye Disease
Abstract
INTRODUCTION
Standard of Care Treatment
Addressing Risk Factors
Anti-Vascular Endothelial Growth Factor (VEGF) Therapy
Future Directions in Anti-VEGF
Brolucizumab
Faricimab
Conbercept
OPT-302
Port Delivery System (PDS)
Gene Therapy
Growth Factor Inhibition
Inflammatory Response Inhibition
THR-149-001
THR-687
OCS-01
Risuteganib
AKB-9778 Tie2 Mediators
XipereTM
Photobiomodulation (PBM)
Targeting Neurodegeneration and Other Potential Targets
Future Treatment Strategies for Proliferative Diabetic Retinopathy (PDR)
Protocol S
Adjuvant Anti-VEGF Usage
Hybrid-Gauge Surgery
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Diabetes: Current and Future
Developments
(Volume 2)
(Diabetes and the Eye:
Latest Concepts and Practices)
Edited by
Douglas R. Lazzaro
Department of Ophthalmology,
NYU Langone Health,
NYU Grossman School of Medicine,
USA
&
Samy I. McFarlane
Department of Medicine,
Division of Endocrinology,
State University of New York-Downstate Medical Center,
Brooklyn, New York,
USA
BENTHAM SCIENCE PUBLISHERS LTD.
End User License Agreement (for non-institutional, personal use)
This is an agreement between you and Bentham Science Publishers Ltd. Please read this License Agreement carefully before using the ebook/echapter/ejournal (“Work”). Your use of the Work constitutes your agreement to the terms and conditions set forth in this License Agreement. If you do not agree to these terms and conditions then you should not use the Work.
Bentham Science Publishers agrees to grant you a non-exclusive, non-transferable limited license to use the Work subject to and in accordance with the following terms and conditions. This License Agreement is for non-library, personal use only. For a library / institutional / multi user license in respect of the Work, please contact: [email protected].
Usage Rules:
All rights reserved: The Work is the subject of copyright and Bentham Science Publishers either owns the Work (and the copyright in it) or is licensed to distribute the Work. You shall not copy, reproduce, modify, remove, delete, augment, add to, publish, transmit, sell, resell, create derivative works from, or in any way exploit the Work or make the Work available for others to do any of the same, in any form or by any means, in whole or in part, in each case without the prior written permission of Bentham Science Publishers, unless stated otherwise in this License Agreement.You may download a copy of the Work on one occasion to one personal computer (including tablet, laptop, desktop, or other such devices). You may make one back-up copy of the Work to avoid losing it.The unauthorised use or distribution of copyrighted or other proprietary content is illegal and could subject you to liability for substantial money damages. You will be liable for any damage resulting from your misuse of the Work or any violation of this License Agreement, including any infringement by you of copyrights or proprietary rights.
Disclaimer:
Bentham Science Publishers does not guarantee that the information in the Work is error-free, or warrant that it will meet your requirements or that access to the Work will be uninterrupted or error-free. The Work is provided "as is" without warranty of any kind, either express or implied or statutory, including, without limitation, implied warranties of merchantability and fitness for a particular purpose. The entire risk as to the results and performance of the Work is assumed by you. No responsibility is assumed by Bentham Science Publishers, its staff, editors and/or authors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products instruction, advertisements or ideas contained in the Work.
Limitation of Liability:
In no event will Bentham Science Publishers, its staff, editors and/or authors, be liable for any damages, including, without limitation, special, incidental and/or consequential damages and/or damages for lost data and/or profits arising out of (whether directly or indirectly) the use or inability to use the Work. The entire liability of Bentham Science Publishers shall be limited to the amount actually paid by you for the Work.
General:
Any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims) will be governed by and construed in accordance with the laws of Singapore. Each party agrees that the courts of the state of Singapore shall have exclusive jurisdiction to settle any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims).Your rights under this License Agreement will automatically terminate without notice and without the need for a court order if at any point you breach any terms of this License Agreement. In no event will any delay or failure by Bentham Science Publishers in enforcing your compliance with this License Agreement constitute a waiver of any of its rights.You acknowledge that you have read this License Agreement, and agree to be bound by its terms and conditions. To the extent that any other terms and conditions presented on any website of Bentham Science Publishers conflict with, or are inconsistent with, the terms and conditions set out in this License Agreement, you acknowledge that the terms and conditions set out in this License Agreement shall prevail.
Bentham Science Publishers Pte. Ltd.
80 Robinson Road #02-00
Singapore 068898
Singapore
Email: [email protected]
PREFACE
Diabetic eye disease is a heterogeneous group of disorders that affect the diabetic population and include diabetic retinopathy, cataract, macular edema, glaucoma, as well as other manifestations of the anterior and posterior segments of the eye. Among these manifestations, diabetic retinopathy and cataract are the most common cause of visual impairment and blindness. In fact people with diabetes are 25 times more likely to develop blindness compared to the general population, and diabetes is the most common cause of blindness among adults 20-74 years of age.
While diabetic retinopathy affects nearly 60% of patients with type 2 diabetes, in type 1 diabetes it is almost universal to develop diabetic retinopathy 15- 20 years after the diagnosis of diabetes is made.
With the rapid rise of obesity, diabetes has become the modern-day epidemic with its attendant complications including diabetic eye disease that leaves millions of people visually disabled, significantly decreasing the quality of life and markedly increasing the risk of injury.
In this volume on Diabetes and the Eye: Latest Concepts and Practices, we have assembled a group of renowned scholars with special expertise in diabetic eye disease, addressing a wide range of topics in a highly scientific, yet easy to read format that will benefit the generalist as well as the specialist and will appeal to the student, the graduate and the practicing physician who commonly encounter diabetic eye disorders, putting practical, yet cutting edge information at their fingertips.
Topics covered in this volume include the epidemiology and trends of the diabetes epidemic and diabetic eye disorders, the pathophysiologic mechanisms of diabetic eye disease and the various manifestations of diabetic complications in the eye. We highlight the latest research findings, the cutting edge diagnostic methods and the most recent developments in the management of retinopathy and other complications. We also discuss future directions and the latest developments in this exciting and rapidly developing field.
Douglas R. Lazzaro
Department of Ophthalmology
NYU Langone Health
NYU Grossman School of Medicine
USA
&Samy I. McFarlane
Department of Medicine
State University of New York-Downstate Medical Center
Brooklyn, New York
FOREWORD
Diabetes mellitus is certainly one of the most important public health problems of the 21st century. Its protean impacts on the eye are well known to all ophthalmologists, who deal with diabetic ocular complications virtually every day. Diabetic eye disease still accounts for much preventable blindness in working age adults, despite the many advances in understanding of pathophysiology and treatment over the last three decades. It is therefore a great pleasure for me to write a foreword to this comprehensive textbook on diabetes and the eye, edited by my colleagues, Douglas R. Lazzaro, and Samy I. McFarlane. Of interest to a wide audience, this book will enhance education of trainees in ophthalmology, and will serve as a definitive resource for practicing ophthalmologists and other physicians who manage diabetes for years to come. This text not only sheds light on the current state of our understanding of ocular manifestations of diabetes, but also looks towards the future when a better understand of the risk factors for diabetic eye disease and improved treatments will reduce the burden of this disease on our society, truly a noble goal. Happy reading!
Kathryn Colby
Elisabeth J Cohen Professor and Chairman
Department of Ophthalmology
NYU Grossman School of Medicine
NYU Langone Health System
New York
USA
List of Contributors
Steven Agemy, New York Eye and Ear Infirmary of Mount SinaiNYUSAAlessandro Albano, SUNY Downstate College of MedicineBrooklyn, NYUSAFerhina S. Ali, The Retina Service of Wills Eye HospitalProfessor of Ophthalmology Thomas Jefferson University 840 Walnut StreetSuite 1020 Philadelphia, PA 19107USASruthi Arepalli, The Cole Eye InstituteCleveland Clinic, Cleveland, OHUSAZaki Azam, SUNY-Downstate College of MedicineBrooklyn, NYUSAFrank Cao, SUNY Downstate College of MedicineSUNY Downstate Medical CenterBrooklyn, NYUSAJohn Danias, SUNY Downstate College of MedicineSUNY Downstate Medical CenterBrooklyn, NYUSAJulie DeBacker, NYU School of MedicineNYU Langone HealthNY, USAJustis P. Ehlers, The Cole Eye InstituteCleveland ClinicCleveland, OHUSASunir J. Garg, The Retina Service of Wills Eye HospitalProfessor of Ophthalmology Thomas Jefferson University 840 Walnut StreetSuite 1020 Philadelphia, PA 19107USARony Gelman, Department of OphthalmologyState University of New York, Downstate Medical CenterNYUSAAnna Y. Groysman, Department of MedicineDivision of Endocrinology, State University of New YorkDownstate-Medical Center, Brooklyn, NYUSAAndrew M Hendrick, Department of OphthalmologyEmory UniversityAtlanta, GAUSABogaard Joseph, Department of Ophthalmology and Visual SciencesMedical College of WisconsinMilwaukeeUSAPeter K. Kaiser, The Cole Eye InstituteCleveland ClinicCleveland, OHUSAJudy E. Kim, Department of Ophthalmology and Visual SciencesMedical College of WisconsinMilwaukeeUSADouglas R. Lazzaro, Department of OphthalmologyNYU Langone HealthNYUSALina Soni, Department of MedicineDivision of Endocrinology, State University of New YorkDownstate-Medical Center, Brooklyn, NYUSAJennifer Lopez, Medical CenterNYU LangoneNY, USASamy I. McFarlane, Department of MedicineDivision of Endocrinology, State University of New YorkDownstate-Medical Center, Brooklyn, NYUSAAllison E. Rizzuti, Medical CenterNYU LangoneNYUSAGaurav K. Shah, The Retina InstituteSaint Louis, MissouriUSAEric Shrier, SUNY- Downstate College of MedicineBrooklyn, NYUSASamara Skwiersky, Department of MedicineDivision of Endocrinology, State University of New YorkDownstate-Medical Center, Brooklyn, NYUSALucy Sun, SUNY Downstate Medical CenterNYUSAGautam Vangipuram, The Retina InstituteSaint Louis, MissouriUSA
Diabetes Epidemic, Epidemiology, Statistics and Trends
Andrew M. Hendrick*
Department of Ophthalmology, Emory University, Atlanta, GA, USA
Abstract
The incidence of diabetes mellitus is increasing worldwide. Over time, diabetes is associated with the development of diabetic retinopathy, a major cause of vision loss globally. Research has demonstrated factors associated with the onset and progression of the disease. Despite advancements in understanding the importance of optimizing care, the cases of vision loss due to diabetic retinopathy are also increasing. The epidemic of this systemic disease and the retinal manifestations will be discussed in detail in this chapter.
Keywords: Diabetes mellitus, Diabetic retinopathy, Epidemic, Epidemiology, Population, Type 1 Diabetes mellitus, Type 2 Diabetes mellitus.
*Corresponding Author Andrew M. Hendrick: Department of Ophthalmology, Emory University, Atlanta GA, USA; E-mail:
[email protected]INTRODUCTION
Diabetes mellitus (DM) is a chronic health condition defined by the presence of impaired glucose regulation leading to hyperglycemia. Normal blood sugar levels depend on the effective use of insulin, a peptide hormone responsible for triggering glucose uptake into cellular spaces (among many other critical metabolic effects). In people with diabetes mellitus, insulin is not used effectively; this is either due to underproduction as seen in type 1 diabetes mellitus (T1DM), or end-tissue resistance to the effects of insulin as seen in type 2 diabetes mellitus (T2DM). Longstanding and/or poorly controlled elevated blood sugar levels are major determinants of complications from DM such as cardiovascular disease, nerve damage, renal disease, and eye disease including retinopathy [1].
The two major subdivisions of diabetes mellitus have several distinguishing characteristics. T1DM results from an auto-immune attack of the insulin-producing pancreatic islet cells, typically during childhood. The onset of T1DM can be dramatic with diabetic ketoacidosis but can be more insidious, characterized by poor growth. T1DM requires insulin injections as the fulcrum of
therapy to normalize blood sugar levels and are required for survival. In contrast, T2DM results from dysfunction of insulin response, such that circulating glucose levels remain elevated [2]. It is often unclear when T2DM onset begins and symptoms can be poorly recognized for years in some cases. Although previous nomenclature described T2DM as adult-onset, children are increasingly affected [3]. Therapies are directed at lifestyle improvement, weight and dietary manage-ment, along with medicines taken both orally and injectable insulin [2].
Our world is in the midst of a diabetes mellitus epidemic with rising rates of people affected across the globe. Factors driving the increase include population aging, economic development, increased urbanization, sedentary lifestyle, and increased consumption of unhealthy foods [2]. Diabetes is a major driver of healthcare costs, morbidity and mortality worldwide [2]. The risk of developing complications is tied directly to the adequacy of medical management. Managing the disease and associated health-related consequences, such as blinding complications of retinopathy, is becoming increasingly important as all societies struggle with this burden. This chapter will discuss the epidemiology of diabetes mellitus, with a focus on diabetic retinopathy (DR) and the implications for vision loss.
Epidemiology of Diabetes Mellitus
T1DM accounts for nearly 10% of DM cases and the incidence has slightly increased over time, with considerable variation by region and sampling technique [3]. Data from US based studies indicate the incidence of T1DM increased from 14.8/100,000 (95% CI 14.0 – 15.6) from 1978-1988 to 23.9/100,000 (95% CI 22.2-25.6) from 2002-2004 and was noted to increase in both Hispanic and non-Hispanic youth [4]. The prevalence of T1DM for adults in the US is estimated to be 0.55% (95% CI 0.46-0.66) [5].
90% of all people with DM have T2DM, also known as adult-onset diabetes. As a result, global estimates of diabetes are predominantly reflective of change due to T2DM. T2DM is increasingly more common - likely due to the strong association with obesity, population aging, inactive lifestyle and poor dietary habits [6]. Fig. (1) demonstrates a graphical estimate of worldwide numbers of people with diabetes over since 2000. These estimates represent a compilation of best-available data sources, but high-quality data are not universally available. In 2015, the International Diabetes Federation estimated that the worldwide burden of diabetes mellitus (DM) affected 415 million people and would increase to 642 million globally by the year 2040 [2]. Current estimates demonstrate a global prevalence of ~9% of all adults with only half of individuals being formally diagnosed with DM [2]. The International Diabetes Federation predicts that low- and middle-income countries will be disproportionately affected by this epidemic and are expected to have the greatest increase in prevalence [2]. This is critical because of the magnitude of impact: Approximately 75% of all individuals with T2DM live in low- and middle-income countries [2].
Fig. (1))
Estimated number of people with diabetes over time worldwide (in millions) [2].
The fallout from chronic hyperglycemia on the human body is accumulative over time. Morbidity and disability that arises from serious complications of diabetes include cardiovascular disease, kidney disease, neuropathy, limb amputation, and retinopathy. These complications, in turn, lead to an increased demand for medical care, reduce the quality of life, and place stress on families including financial burden. Altogether, diabetes-related care incurs an estimated $673 billion (12%) of global healthcare expenditure and 8% of all-cause mortality [7]. The presence of T2DM increases the risk of heart attack comparable to the risk attributable to having had a prior heart attack [8]. Actual risk varies by study, but the prevalence of coronary heart disease in T2DM is around 21% (ranges between 12-32%) [8]. Similarly, stroke risk is also increased nearly three-fold in people with diabetes compared to those without [8]. Interestingly, the presence of diabetic retinopathy serves as an independent risk factor predicting a higher likelihood of systemic comorbidities such as both stroke and heart disease [9-11]. Furthermore, T2DM is a leading cause of renal failure and lower limb amputation [12, 13]. It is estimated that T2DM accounts for estimated up to 21-54% of all cases of end-stage renal disease [12, 14], and the prevalence of end-stage renal disease is 10-fold greater in people with diabetes compared to those without [7]. Similarly, lower limb amputations are estimated 10 to 20 times more likely in people with diabetes compared to those without [13].
Epidemiology of Diabetic Retinopathy
Ocular complications of diabetes include a spectrum of pathologies that range from refractive error and increased risk of cataract formation to cranial nerve palsies and blindness from diabetic retinopathy (DR) [15]. DR results from damage to the retinal neurons and microvasculature that occurs more commonly in individuals with longstanding DM [16]. Retinopathy is the most serious ocular complication of diabetes and is a leading cause of significant vision loss globally [17]. Importantly, most DR is largely preventable [18] and affects working age adults [19]. As a result, screening and treatment of DR contributes to taking otherwise productive individuals from the workplace, creating economic burden and impacting quality of life. Both the onset and progression of DR is mitigated with blood glucose control [20] and blood pressure management [1]. Other factors commonly associated with DR progression include the socioeconomic status of the individual, degree of dietary compliance, level of physical activity, and geographic location [10].
Earliest estimates on the epidemiology of DR came from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). The WESDR was a population-based study conducted on a predominantly Caucasian cohort with both T1DM and T2DM in the 1980’s. In this study, which has now accrued decades of follow up, it became possible to understand the increased risk of diabetic retinopathy progression over time [16, 21]. At 4 years, 10 year, and 14 years, the cumulative incidence of DR in people with T1DM was 59%, 89%, and 96%, respectively. After 25 years, 97% of people with type 1 DM had DR, 43% of them PDR, and 29% had DME [22, 23]. People with T2DM have an estimated cumulative incidence of DR that is lower than people with T1DM, but due to the greater prevalence, the impact in the overall population is greater. Studies in the UK report the 4-year cumulative incidence of DR at 26% [24], 6 years at 38-41% [1, 25], and 66% at 10 years [26]. Similar results are seen in US based studies with reports of the 4-year cumulative incidence of DR at 22-34% [27, 28] and 72% at 14 years [29]. In contrast, a study based in urban China demonstrated a higher 5 year cumulative incidence of DR at 46.9%, which was attributed to a longer disease duration in their cohort [30].
At the time of WESDR, it was not yet established that euglycemia was critical for risk factor modification in preventing retinopathy progression [1, 31]. Despite advances in pharmacotherapy and knowledge regarding the importance of lifestyle, glycemic control and comorbidity management, data from the WESDR remains pertinent, as it demonstrates the natural history of diabetic retinopathy is to progress through advancing severity stages. More recent studies indicate declining rates of DR, PDR, and DME in patients with T1DM, which is likely significantly improved by advancements in systemic management [25, 32].
The prevalence of DR is widely varied due to variations in timing and characteristics of the snapshot of the defined population [19]. A multitude of studies examining diverse populations report wide variations in prevalence of diabetic retinopathy and are summarized in (Fig. 2). Global estimates indicate over one third of people with DM have DR, and that one third of those have visually threatening diabetic retinopathy (VTDR) [33]. VTDR represents a higher risk category of ‘severe NPDR’ or worse and includes all eyes with DME. This study further concluded that the global prevalence of PDR is 7.5%, and DME is 6.8% [33]. Prevalence of any DR and PDR was higher in people with T1DM, compared to individuals with type 2 diabetes (77.3 vs. 25.2% for any DR, 32.4 vs. 3.0% for PDR) [33].
Fig. (2))
The prevalence of diabetic retinopathy varies depending on the population characteristics and sampling techniques employed [34-42].
The epidemiology of DME is of great interest due to its impact on quality of vision, but difficult to compare due to variations in definition of the disease. Studies vary with use of clinical examination, fundus photography and optical coherence tomography based definitions [43]; in addition, variations in subject selection and population characteristics make cross study comparisons less robust in their validity. WESDR reported the 14 year cumulative incidence of DME in people with T1DM was 26.1%, which increased to 29% by 25 years of follow up [22, 44]. Among population-based studies of DME, the prevalence of DME in people with T1DM ranges between 4.2 and 7.9% [33]. In people with T2DM, prevalence of DME is reported between 1.4 and 12.8% [33].
Racial and ethnic impact on the epidemiology of DR is of great interest because of the wide differences in the reported rates of DR prevalence and the implications for environmental versus genetic influence. From the US, the third National Health and Nutrition Examination Survey (NHANES III) was a cross sectional study from the Center for Disease Control and Prevention from 1988-1994 to determine if racial and or ethnic differences modulated the risk of developing DR. This study demonstrated that Mexican-American participants had higher rates of DR compared to non-Hispanic white participants (33.4% vs 18.2%) [45]. In general, trends are seen in most studies such that Western societies have higher prevalence of DR than Eastern societies [19]. Of great concern is the impact that Westernization has on development of DM and DR. As evidenced in the Singapore Indian Eye Study, increased industrialization and urbanization in an Asian country was associated with rates of DR in Asian eyes that are similar to rates reported in Western populations [46]. Interestingly, in the same study, three major ethnic groups in Singapore had differing prevalence of DR. The Malays and Indians have a higher prevalence of DR (33.4% in Malays, 33.0% in Indians) compared to the Chinese (25.4%). Urban and rural differences in DR prevalence also indicate an important impact of the environment on health outcomes [47, 48].
Genetics also contribute to susceptibility of DR onset and severity. Analysis of the Diabetes Control and Complications Trial (DCCT) indicates that glycemic control, as was reflected by hemoglobin A1c levels, was beneficial in reducing the incidence of DR [31]. It also showed a significant association for an inheritable tendency to developing advanced severity of DR in families with both type 1 and T2DM, independent of shared risk factors [49]. Similar findings were demonstrated in a study that included Mexican Americans with both T1DM and T2DM and severe DR [50-53]. A meta-analysis confirming the presence of variations in a gene that affects the aldose reductase pathway (AKR1B1) was found to be significantly associated with DR onset in T1DM, regardless of ethnicity [54]. Other genes of interest include the adipose most abundant gene transcript-1 (apM-1) which encodes for adiponectin [55], vascular endothelial growth factor (VEGF) gene polymorphisms [56-59], The overall importance of genetics in determinants of diabetes related complications is an ongoing area of investigation.
Screening of Diabetic Retinopathy
Due to the asymptomatic nature of DR, individuals with diabetes should be properly screened for signs of DR and the progressive stages of DR. At a minimum, screening guidelines suggest a dilated fundus examination on an annual basis for T2DM and T1DM, beginning 5 years after diagnosis [18]. People with evident DR need more frequent follow up to determine if treatment may become indicated, thereby requiring more exams as disease severity worsens. Screening for and timely treatment of DR reduces the likelihood of developing severe vision loss by up to 94% and are also highly cost-effective [60].
Studies suggest that there is poor adherence to recommended guidelines such that an estimated nearly half of people with diabetes do not routinely receive an eye exam [61]. Screening can alternatively be considered remotely using telemedicine in some systems. Telemedicine involves the use of remote interpretation of point of care fundus photography. While remote screening does not fully replace a comprehensive eye exam, it improves access to individuals who have limited access to ophthalmic care, such as in resource poor or geographically remote locations. Research has consistently validated telemedicine-based screening efforts as both effective and cost-effective tools with substantial cost savings to healthcare systems [62].
CONCLUSION
Overall, type 1 diabetes represents a minority of cases of diabetes mellitus with indications that the disease is becoming slightly more common over time. Although people with T1DM have higher rates of ocular complications than people with T2DM, incident retinopathy has reduced with improved control of systemic management. In contrast, type 2 diabetes is much more prevalent, and the prevalence is increasing over time worldwide with substantial regional variation. Similar increasing trends are noted when examining the epidemiology of diabetic retinopathy.
Detecting, diagnosing, and managing diabetes mellitus and the associated retinopathy is an increasingly important societal burden of great public health importance that current projections indicate will only worsen without change. The increased potential for death and disability, due to associations of DR with stroke, heart attack, amputation and kidney failure, supports a multifaceted approach to management and treatment. Glycemic control is fundamental to optimizing the health-related morbidity in the diabetic patient, but the duration disease over time remains an important driver of complications. Racial, ethnic, genetic and environmental influences are increasingly understood as contributors of disease status. Screening programs are critical to detect disease and provide framework to connect the patient to treatment when indicated.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The author declares no conflict of interest, financial or otherwise.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1]Stratton IM, Kohner EM, Aldington SJ, et al. UKPDS 50: risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis. Diabetologia 2001; 44(2): 156-63.[http://dx.doi.org/10.1007/s001250051594] [PMID: 11270671][2]International Diabetes FederationIDF Diabetes Atlas, eB 2015.[3]Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am 2010; 39(3): 481-97.[http://dx.doi.org/10.1016/j.ecl.2010.05.011] [PMID: 20723815][4]Vehik K, Hamman RF, Lezotte D, et al. Increasing incidence of type 1 diabetes in 0- to 17-year-old Colorado youth. Diabetes Care 2007; 30(3): 503-9.[http://dx.doi.org/10.2337/dc06-1837] [PMID: 17327312][5]Bullard KM, Cowie CC, Lessem SE, et al. Prevalence of Diagnosed Diabetes in Adults by Diabetes Type - United States, 2016. MMWR Morb Mortal Wkly Rep 2018; 67(12): 359-61.[http://dx.doi.org/10.15585/mmwr.mm6712a2] [PMID: 29596402][6]van Dieren S, Beulens JW, van der Schouw YT, Grobbee DE, Neal B. The global burden of diabetes and its complications: an emerging pandemic. Eur J Cardiovasc Prev Rehabil 2010; 17 (Suppl. 1): S3-8.[http://dx.doi.org/10.1097/01.hjr.0000368191.86614.5a] [PMID: 20489418][7]Group IDFDA. IDF Diabetes Atlas GroupUpdate of mortality attributable to diabetes for the IDF Diabetes Atlas: Estimates for the year 2013. Diabetes Res Clin Pract 2015; 109(3): 461-5.[http://dx.doi.org/10.1016/j.diabres.2015.05.037] [PMID: 26119773][8]Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol 2018; 17(1): 83.[http://dx.doi.org/10.1186/s12933-018-0728-6] [PMID: 29884191][9]Cheung N, Wang JJ, Rogers SL, et al. ARIC (Atherosclerosis Risk In Communities) Study InvestigatorsDiabetic retinopathy and risk of heart failure. J Am Coll Cardiol 2008; 51(16): 1573-8.[http://dx.doi.org/10.1016/j.jacc.2007.11.076] [PMID: 18420100][10]Cheung N, Wang JJ, Klein R, Couper DJ, Sharrett AR, Wong TY. Diabetic retinopathy and the risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Diabetes Care 2007; 30(7): 1742-6.[http://dx.doi.org/10.2337/dc07-0264] [PMID: 17389333][11]Cheung N, Rogers S, Couper DJ, Klein R, Sharrett AR, Wong TY. Is diabetic retinopathy an independent risk factor for ischemic stroke? Stroke 2007; 38(2): 398-401.[http://dx.doi.org/10.1161/01.STR.0000254547.91276.50] [PMID: 17194880][12]Bell S, Fletcher EH, Brady I, et al. Scottish diabetes research network and scottish renal registryEnd-stage renal disease and survival in people with diabetes: a national database linkage study. QJM 2015; 108(2): 127-34.[http://dx.doi.org/10.1093/qjmed/hcu170] [PMID: 25140030][13]Moxey PW, Gogalniceanu P, Hinchliffe RJ, et al. Lower extremity amputations--a review of global variability in incidence. Diabet Med 2011; 28(10): 1144-53.[http://dx.doi.org/10.1111/j.1464-5491.2011.03279.x] [PMID: 21388445][14]Lok CE, Oliver MJ, Rothwell DM, Hux JE. The growing volume of diabetes-related dialysis: a population based study. Nephrol Dial Transplant 2004; 19(12): 3098-103.[http://dx.doi.org/10.1093/ndt/gfh540] [PMID: 15507475][15]Jeganathan VS, Wang JJ, Wong TY. Ocular associations of diabetes other than diabetic retinopathy. Diabetes Care 2008; 31(9): 1905-12.[http://dx.doi.org/10.2337/dc08-0342] [PMID: 18753669][16]Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 1984; 102(4): 527-32.[http://dx.doi.org/10.1001/archopht.1984.01040030405011] [PMID: 6367725][17]Leasher JL, Bourne RR, Flaxman SR, et al. Vision loss expert group of the global burden of disease studyGlobal estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis from 1990 to 2010. Diabetes Care 2016; 39(9): 1643-9.[http://dx.doi.org/10.2337/dc15-2171] [PMID: 27555623][18]American Academy of Ophthalmology Retina/Vitreous Panel.Preferred Practice Pattern®Guidelines. Diabetic Retinopathy C.A.A.o.O.A.a.w.a.o.p[19]Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond) 2015; 2: 17.[http://dx.doi.org/10.1186/s40662-015-0026-2] [PMID: 26605370][20]Nathan DM, Genuth S, Lachin J, et al. Diabetes Control and Complications Trial Research GroupThe effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977-86.[http://dx.doi.org/10.1056/NEJM199309303291401] [PMID: 8366922][21]Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology 1984; 91(12): 1464-74.[http://dx.doi.org/10.1016/S0161-6420(84)34102-1] [PMID: 6521986][22]Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. Ophthalmology 2009; 116(3): 497-503.[http://dx.doi.org/10.1016/j.ophtha.2008.10.016] [PMID: 19167079][23]Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 2008; 115(11): 1859-68.[http://dx.doi.org/10.1016/j.ophtha.2008.08.023] [PMID: 19068374][24]Thomas RL, Dunstan F, Luzio SD, et al. Incidence of diabetic retinopathy in people with type 2 diabetes mellitus attending the Diabetic Retinopathy Screening Service for Wales: retrospective analysis. BMJ 2012; 344e874[http://dx.doi.org/10.1136/bmj.e874] [PMID: 22362115][25]Younis N, Broadbent DM, Harding SP, Vora JP. Incidence of sight-threatening retinopathy in Type 1 diabetes in a systematic screening programme. Diabet Med 2003; 20(9): 758-65.[http://dx.doi.org/10.1046/j.1464-5491.2003.01035.x] [PMID: 12925058][26]Jones CD, Greenwood RH, Misra A, Bachmann MO. Incidence and progression of diabetic retinopathy during 17 years of a population-based screening program in England. Diabetes Care 2012; 35(3): 592-6.[http://dx.doi.org/10.2337/dc11-0943] [PMID: 22279031][27]Varma R. Four-year incidence and progression of diabetic retinopathy and macular edema: the Los Angeles Latino Eye Study. Am J Ophthalmol 2010; 149(5): 752-61.e1-3.[http://dx.doi.org/10.1016/j.ajo.2009.11.014][28]Tudor SM, Hamman RF, Baron A, Johnson DW, Shetterly SM. Incidence and progression of diabetic retinopathy in Hispanics and non-Hispanic whites with type 2 diabetes. San Luis Valley Diabetes Study, Colorado. Diabetes Care 1998; 21(1): 53-61.[http://dx.doi.org/10.2337/diacare.21.1.53] [PMID: 9538971][29]Lee ET, Lee VS, Kingsley RM, et al. Diabetic retinopathy in Oklahoma Indians with NIDDM. Incidence and risk factors. Diabetes Care 1992; 15(11): 1620-7.[http://dx.doi.org/10.2337/diacare.15.11.1620] [PMID: 1468294][30]Tam VH, Lam EP, Chu BC, Tse KK, Fung LM. Incidence and progression of diabetic retinopathy in Hong Kong Chinese with type 2 diabetes mellitus. J Diabetes Complications 2009; 23(3): 185-93.[http://dx.doi.org/10.1016/j.jdiacomp.2008.03.001] [PMID: 18479945][31]Group, DRThe effect of intensive treatment of diabetes on the development and progression of long-term complications in insulindependent diabetes mellitus. N Engl Med 1993; 329: 977-86.[http://dx.doi.org/10.1056/NEJM199309303291401][32]Kytö JP, Harjutsalo V, Forsblom C, Hietala K, Summanen PA, Groop PH. FinnDiane Study GroupDecline in the cumulative incidence of severe diabetic retinopathy in patients with type 1 diabetes. Diabetes Care 2011; 34(9): 2005-7.[http://dx.doi.org/10.2337/dc10-2391] [PMID: 21868777][33]Yau JW, Rogers SL, Kawasaki R, et al. Meta-analysis for eye disease (META-EYE) study groupGlobal prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35(3): 556-64.[http://dx.doi.org/10.2337/dc11-1909] [PMID: 22301125][34]Varma R, Wen G, Jiang X, et al. Chinese American Eye Study GroupPrevalence of diabetic retinopathy in adult chinese american individuals: the Chinese American eye study. JAMA Ophthalmol 2016; 134(5): 563-9.[http://dx.doi.org/10.1001/jamaophthalmol.2016.0445] [PMID: 27055063][35]Kovarik JJ, Eller AW, Willard LA, Ding J, Johnston JM, Waxman EL. Prevalence of undiagnosed diabetic retinopathy among inpatients with diabetes: the diabetic retinopathy inpatient study (DRIPS). BMJ Open Diabetes Res Care 2016; 4(1)e000164[http://dx.doi.org/10.1136/bmjdrc-2015-000164] [PMID: 26925238][36]Rodriguez NM, Aguilar S. Prevalence of diabetic retinopathy in a clinic population from puerto rico. Optom Vis Sci 2016; 93(7): 750-3.[http://dx.doi.org/10.1097/OPX.0000000000000854] [PMID: 27046091][37]Park DW, Mansberger SL. Eye disease in patients with diabetes screened with telemedicine. Telemed J E Health 2017; 23(2): 113-8.[http://dx.doi.org/10.1089/tmj.2016.0034] [PMID: 27328169][38]Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 2005-2008. JAMA 2010; 304(6): 649-56.[http://dx.doi.org/10.1001/jama.2010.1111] [PMID: 20699456][39]Lim A, Stewart J, Chui TY, et al. Prevalence and risk factors of diabetic retinopathy in a multi-racial underserved population. Ophthalmic Epidemiol 2008; 15(6): 402-9.[http://dx.doi.org/10.1080/09286580802435179] [PMID: 19065433][40]Kempen JH, O’Colmain BJ, Leske MC, et al. Eye Diseases Prevalence Research GroupThe prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol 2004; 122(4): 552-63.[http://dx.doi.org/10.1001/archopht.122.4.552] [PMID: 15078674][41]Varma R, Torres M, Peña F, Klein R, Azen SP. Los Angeles Latino Eye Study GroupPrevalence of diabetic retinopathy in adult Latinos: the Los Angeles Latino eye study. Ophthalmology 2004; 111(7): 1298-306.[http://dx.doi.org/10.1016/j.ophtha.2004.03.002] [PMID: 15234129][42]West SK, Klein R, Rodriguez J, et al. Proyecto VERDiabetes and diabetic retinopathy in a Mexican-American population: Proyecto VER. Diabetes Care 2001; 24(7): 1204-9.[http://dx.doi.org/10.2337/diacare.24.7.1204] [PMID: 11423503][43]Virgili G, Menchini F, Murro V, Peluso E, Rosa F, Casazza G. Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy. Cochrane Database Syst Rev 2011; (7)CD008081[http://dx.doi.org/10.1002/14651858.CD008081.pub2] [PMID: 21735421][44]Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 1995; 102(1): 7-16.[http://dx.doi.org/10.1016/S0161-6420(95)31052-4] [PMID: 7831044][45]Harris MI, Klein R, Cowie CC, Rowland M, Byrd-Holt DD. Is the risk of diabetic retinopathy greater in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites with type 2 diabetes? A U.S. population study. Diabetes Care 1998; 21(8): 1230-5.[http://dx.doi.org/10.2337/diacare.21.8.1230] [PMID: 9702425][46]Zheng Y, Lamoureux EL, Lavanya R, et al. Prevalence and risk factors of diabetic retinopathy in migrant Indians in an urbanized society in Asia: the Singapore Indian eye study. Ophthalmology 2012; 119(10): 2119-24.[http://dx.doi.org/10.1016/j.ophtha.2012.04.027] [PMID: 22709419][47]Liu L, Wu X, Liu L, et al. Prevalence of diabetic retinopathy in mainland China: a meta-analysis. PLoS One 2012; 7(9)e45264[http://dx.doi.org/10.1371/journal.pone.0045264] [PMID: 23028893][48]Rema M, Premkumar S, Anitha B, Deepa R, Pradeepa R, Mohan V. Prevalence of diabetic retinopathy in urban India: the Chennai Urban Rural Epidemiology Study (CURES) eye study, I. Invest Ophthalmol Vis Sci 2005; 46(7): 2328-33.[http://dx.doi.org/10.1167/iovs.05-0019] [PMID: 15980218][49]The Diabetes Control and Complications Trial Research GroupClustering of long-term complications in families with diabetes in the diabetes control and complications trial. Diabetes 1997; 46(11): 1829-39.[http://dx.doi.org/10.2337/diab.46.11.1829] [PMID: 9356033][50]Hallman DM, Huber JC, Jr, Gonzalez VH, Klein BE, Klein R, Hanis CL. Familial aggregation of severity of diabetic retinopathy in Mexican Americans from Starr County, Texas. Diabetes Care 2005; 28(5): 1163-8.[http://dx.doi.org/10.2337/diacare.28.5.1163] [PMID: 15855583][51]Arar NH, Freedman BI, Adler SG, et al. Family investigation of nephropathy and diabetes research groupHeritability of the severity of diabetic retinopathy: the FIND-Eye study. Invest Ophthalmol Vis Sci 2008; 49(9): 3839-45.[http://dx.doi.org/10.1167/iovs.07-1633] [PMID: 18765632][52]Hietala K, Forsblom C, Summanen P, Groop PH. FinnDiane Study GroupHeritability of proliferative diabetic retinopathy. Diabetes 2008; 57(8): 2176-80.[http://dx.doi.org/10.2337/db07-1495] [PMID: 18443200][53]Monti MC, Lonsdale JT, Montomoli C, Montross R, Schlag E, Greenberg DA. Familial risk factors for microvascular complications and differential male-female risk in a large cohort of American families with type 1 diabetes. J Clin Endocrinol Metab 2007; 92(12): 4650-5.[http://dx.doi.org/10.1210/jc.2007-1185] [PMID: 17878250][54]Abhary S, Hewitt AW, Burdon KP, Craig JE. A systematic meta-analysis of genetic association studies for diabetic retinopathy. Diabetes 2009; 58(9): 2137-47.[http://dx.doi.org/10.2337/db09-0059] [PMID: 19587357][55]Zietz B, Buechler C, Kobuch K, Neumeier M, Schölmerich J, Schäffler A. Serum levels of adiponectin are associated with diabetic retinopathy and with adiponectin gene mutations in Caucasian patients with diabetes mellitus type 2. Exp Clin Endocrinol Diabetes 2008; 116(9): 532-6.[http://dx.doi.org/10.1055/s-2008-1058086] [PMID: 18680072][56]Wang H, Cheng JW, Zhu LS, et al. Meta-analysis of association between the -2578C/A polymorphism of the vascular endothelial growth factor and retinopathy in type 2 diabetes in Asians and Caucasians. Ophthalmic Res 2014; 52(1): 1-8.[http://dx.doi.org/10.1159/000357110] [PMID: 24751925][57]Han L, Zhang L, Xing W, et al. The associations between VEGF gene polymorphisms and diabetic retinopathy susceptibility: a meta-analysis of 11 case-control studies. J Diabetes Res 2014; 2014805801[http://dx.doi.org/10.1155/2014/805801] [PMID: 24868559][58]El-Shazly SF, El-Bradey MH, Tameesh MK. Vascular endothelial growth factor gene polymorphism prevalence in patients with diabetic macular oedema and its correlation with anti-vascular endothelial growth factor treatment outcomes. Clin Exp Ophthalmol 2014; 42(4): 369-78.[http://dx.doi.org/10.1111/ceo.12182] [PMID: 23927080][59]Kaidonis G, Burdon KP, Gillies MC, et al. Common Sequence Variation in the VEGFC Gene Is Associated with Diabetic Retinopathy and Diabetic Macular Edema. Ophthalmology 2015; 122(9): 1828-36.[http://dx.doi.org/10.1016/j.ophtha.2015.05.004] [PMID: 26072347][60]Schoenfeld ER, Greene JM, Wu SY, Leske MC. Patterns of adherence to diabetes vision care guidelines: baseline findings from the Diabetic Retinopathy Awareness Program. Ophthalmology 2001; 108(3): 563-71.[http://dx.doi.org/10.1016/S0161-6420(00)00600-X] [PMID: 11237912][61]Javitt JC, Aiello LP. Cost-effectiveness of detecting and treating diabetic retinopathy. Ann Intern Med 1996; 124(1 Pt 2): 164-9.[http://dx.doi.org/10.7326/0003-4819-124-1_Part_2-199601011-00017] [PMID: 8554212][62]Avidor D, Loewenstein A, Waisbourd M, Nutman A. Cost-effectiveness of diabetic retinopathy screening programs using telemedicine: a systematic review. Cost Eff Resour Alloc 2020; 18: 16.[http://dx.doi.org/10.1186/s12962-020-00211-1] [PMID: 32280309]
Recent Developments in Diabetes Evaluation and Management: Implications for the Practicing Clinicians
Anna Y. Groysman,Lina Soni,Samara Skwiersky,Samy I. McFarlane*
Department of Medicine, Division of Endocrinology, State University of New York, Downstate-Medical Center, Brooklyn, NY, USA
Abstract
Diabetes is a major public health problem affecting millions of people around the globe. In the United States alone, over 7.5 million have type 2 diabetes and an alarming 78 million adults have prediabetes and remain largely undiagnosed. This epidemic was ushered in by the ongoing epidemic of obesity and is caused in-part by sedentary life style and aging population. In this chapter we discuss the diabetes epidemic highlighting the major risk factor of diabetes, particularly type 2. We also discuss the complications of diabetes including microvascular complications as well as macrovascular disease including coronary heart disease and stroke, the major cause of morbidity and mortality in the diabetic population. Finally, we present the major therapeutic advances in diabetes including modern pharmacologic agents and their potential effects on cardiovascular risk. We also outline the recent technological advances in diabetes management including closed loop systems, artificial pancreas, stem cell therapy among other ongoing research bound to prevent and/or alleviate the effects of this ongoing epidemic.
Keywords: Complications, Diabetes, Glucose monitoring technology, Modern therapy, Risk factors.
*Corresponding Author Samy I. McFarlane: Department of Medicine, Division of Endocrinology, State University of New York, Downstate-Medical Center, Brooklyn, NY, USA; Tel: 718-270- 3711; Fax: 718-270- 6358;
E-mail:
[email protected]INTRODUCTION
Diabetes mellitus is a progressively debilitating condition resulting in vascular complications, including cardiovascular, cerebrovascular, and peripheral vascular disease. This disease, together with microvascular diseases, including retinopathy, nephropathy, and peripheral neuropathy, lead to devastating complications and increased mortality. Although adults are generally afflicted with this condition, rising numbers of children, teenagers, and adolescents are also affected [1].
Driven mainly by a continuous rise in type 2 diabetes, the global epidemic of diabetes, according to data from the World Health Organization, reached over 422 million adults worldwide in 2014, exceeding the previous forecast of 439 million worldwide by 2030 [2].