Genetics of cardiovascular and renal complications in diabetes

The development of debilitating complications represents a major heathcare burden associated with the treatment of diabetes. Despite advances in new therapies for controlling hyperglycemia, the burden associated with diabetic complications remains high, especially in relation to cardiovascular and renal complications. Furthermore, an increasing proportion of patients develop type 2 diabetes at a younger age, putting them at higher risk of developing complications as a result of the increased exposure to hyperglycemia. Diabetes has become the main contributing cause to end‐stage renal disease in most countries. Although there has been important breakthroughs in our understanding of the genetics of type 1 and type 2 diabetes, bringing important insights towards the pathogenesis of diabetes, there has been comparatively less progress in our understanding of the genetic basis of diabetic complications. Genome‐wide association studies are beginning to expand our understanding of the genetic architecture relating to diabetic complications. Improved understanding of the genetic basis of diabetic cardiorenal complications might provide an opportunity for improved risk prediction, as well as the development of new therapies.     

Monogenic diabetes: Implementation of translational genomic research towards precision medicine

Various forms of early onset non‐autoimmune diabetes are recognized as monogenic diseases, each subtype being caused by a single highly penetrant gene defect at the individual level. Monogenic diabetes (MD) is clinically and genetically heterogeneous, including maturity onset diabetes of the young and infancy‐onset and neonatal diabetes mellitus, which are characterized by functional defects of insulin‐producing pancreatic β‐cells and hyperglycemia early in life. Depending on the genetic cause, MD differs in the age at diabetes onset, the severity of hyperglycemia, long‐term diabetic complications, and extrapancreatic manifestations. In this review we discuss the many challenges of molecular genetic diagnosis of MD in the face of a substantial genetic heterogeneity, as well as the clinical benefit and cost‐effectiveness of an early genetic diagnosis, as demonstrated by simulation models based on lifetime complications and treatment costs. We also discuss striking examples of proof‐of‐concept of genomic medicine, which have enabled marked improvement in patient care and long‐term clinical management. Recent advances in genome editing and pluripotent stem cell reprogramming technologies provide new opportunities for in vitro diabetes modeling and the discovery of novel drug targets and cell‐based diabetes therapies. A review of these future directions makes the case for exciting translational research to further our understanding of the pathophysiology of early onset diabetes.     

RD Lawrence Lecture 2013 Stratified approaches to the management of diabetes

A stratified approach to medicine aims to identify subgroups of patients who should be managed differently from others. Diabetes is a condition that offers considerable potential for stratification, in areas of drug response, complication risk and rate of progression amongst others. Approaches to stratification can be simple, using clinical phenotyping, or more complex involving genomic and other ‘–omic’ technologies. In this review, I will highlight the utility of measuring endogenous insulin production to aid in diagnosis and appropriate treatment; outline key advances in monogenic diabetes where determining genetic aetiology can result in dramatic changes in treatment, and describe the developments in the field of pharmacogenetics in Type 2 diabetes.     

Understanding the role of the gut ecosystem in diabetes mellitus

Diabetes mellitus is a type of metabolic disorder whereby patients are unable to regulate glycemia. It is currently a worldwide public health issue, and is a burden to society because of its disabling and common complications. Diabetes is multifactorial, and also induces the onset of other diseases. In the present report, we review the labyrinth encompassing the gut microbiota and gut microbiota‐derived metabolites in type 1 diabetes and type 2 diabetes pathogenesis. There have been exceptional improvements in deoxyribonucleic acid sequencing and mass spectrometry technologies throughout these past years, and these have allowed the comprehensive collection of information on our unique gut ecosystem. We would like to advocate incorporating metagenome and metabolome information for a comprehensive perspective of the complex interrelationships between the gut environment, host metabolism and diabetes pathogenesis. We hope that with this improved understanding we would be able to provide exciting novel therapeutic approaches to engineer an ideal gut ecosystem for optimal health.     

Panvascular risk factor – Diabetes

Diabetes mellitus is the metabolic bed rock on which macrovascular and microvascular complications develop, hence diabetes is often regarded as a panvascular risk factor. Diabetes, a major risk factor of coronary artery disease (CAD), is also a maker for systemic atherosclerosis. Macrovascular complications include CAD, cerebrovascular disease and peripheral arterial disease (PAD), while microvascular complications include retinopathy, nephropathy and neuropathy. The underlying pathophysiological mechanism of diabetic vasculopathy is complex and multi-factorial, which requires an active research for potential therapeutic targets. The Achilles heel of diabetes related morbidity and mortality is diabetic vasculopathy and its related complications. Hence the management of diabetes per se is often translated into managing its vascular complications. A comprehensive understanding of diabetes as a panvascular risk factor is important. This review has briefly addressed the pathophysiology of diabetic vasculopathy and its complications.     

An algorithm for the treatment of type 2 diabetes in Latin America

Diabetes is a principal and growing health concern in Latin America, accounting for significant mortality and morbidities. Large, randomized, prospective trials of various interventional therapies in patients with both type 1 and type 2 diabetes have demonstrated that reductions in hyperglycaemia and management of diabetes-related risk factors can significantly reduce the micro- and macrovascular complications of diabetes. Therefore, patients with type 2 diabetes will benefit from more aggressive treatment regimens to help decrease the occurrence and rate of progression of diabetic complications. Given the many complexities of diabetes management, it is often difficult for general practice physicians to stay abreast of emerging treatment strategies and therapies. Owing to the high prevalence of type 2 diabetes in Latin America, the majority of patients with diabetes are treated by generalists rather than specialists. This article was intended to assist physicians and other healthcare professionals in developing and using effective treatment strategies to stem the growing epidemic of diabetes and its complications in Latin America.     

Socioeconomic factors relating to diabetes and its management in India

Diabetes is an escalating problem in India and has major socioeconomic dimensions. Rapid dietary changes coupled with decreased levels of physical activity have resulted in increases in obesity and diabetes in rural and semi‐urban areas, as well as in urban‐based people living in resettlement colonies. Increasing risk has also been recorded in those who suffered from poor childhood nutrition and in rural‐to‐urban migrants. Social inequity manifests in disparities in socioeconomic status (SES), place of residence, education, gender, and level of awareness and affects prevention, care, and management. All these population subsets have major socioeconomic challenges: low levels of awareness regarding diabetes and prevention, inadequate resources, insufficient allotment of healthcare budgets, and lack of medical reimbursement. Unawareness and delays in seeking medical help lead to complications, resulting in many‐fold increased costs in diabetes care. These costs plunge individuals and households into a vicious cycle of further economic hardship, inadequate management, and premature mortality, resulting in more economic losses. At the societal level, these are massive losses to national productivity and the exchequer. Overall, there is an immediate need to strengthen the healthcare delivery system to generate awareness and for the prevention, early detection, cost‐effective management, and rehabilitation of patients with diabetes, with a focus on people belonging to the lower SES and women (with a particular focus on nutrition before and during pregnancy). Because of an enhanced awareness campaign spearheaded through the National Program on Prevention of Cardiovascular Disease, Cancer, Diabetes and Stroke (NCPCDS) initiated by Government of India, it is likely that the level of awareness and early detection of diabetes may increase.     

Educational program for diabetic patients in Korea--multidisplinary intensive management

The socioeconomic burden of type 2 diabetes and its complications has become a big social issue in Korea. And so, the proper management of diabetes in terms of its prevention and management of complications are considered the most important tasks in our healthcare system and these can be accomplished through the multidisciplinary program. Our program is composed of separate educational programs for in-patients and out-patients, individualized teaching, and group teaching. In order to maintain such a program, there need systemic interactions among the team members, including endocrinologists, nurses, dieticians, pharmacists, and social workers. The optimal way to control diabetes can be achieved through interactions between members of the diabetes management team and the patient. For the patient, this is expected to lead to a better glycemic control, prevention of diabetes complications, and sparing of medical expenses as well. As for the healthcare providers, physicians are able to treat their patients more efficiently. Thus, both the patient and the healthcare centers can benefit from this multidisciplinary educational program. Diabetes educational program should be a basis for the management of diabetes.     

Counseling patients with type 2 diabetes and insulin resistance in the outpatient setting

Insulin resistance is a major health concern. Besides being a leading risk factor for type 2 diabetes, it is also associated with hypertension, dyslipidemia, obesity, and cardiovascular disease. Making lifestyle changes can reduce insulin resistance and help prevent the onset of diabetes. For those with type 2 diabetes, treatment with insulin-sensitizing drugs, such as the TZDs and biguanides, can improve glycemic control and prevent some of the adverse consequences of the disease. Adherence to both lifestyle and medication regimens is very important and should be actively supported by all members of the healthcare team. Diabetes educators, including pharmacists, can increase awareness of the underlying pathophysiology and clinical implications of insulin resistance. Diabetes educators also play a vital role in counseling patients with type 2 diabetes on strategies that reduce their risk of hyperglycemic complications and in providing support, education, and guidance. By understanding the disease and its management, diabetes educators can contribute to improved outcomes and help to reduce the impact of this worldwide epidemic.     

西药联合中药汤剂治疗糖尿病并发症的临床进展综述

中国疾病预防控制中心2017年发布数据显示:我国成人糖尿病患病率为10.9%。男性发病率高于女性,并且患者逐渐年轻化。糖尿病是由遗传和环境因素共同作用而形成一组以高血糖为特征的常见代谢综合征,目前尚无有效治愈糖尿病方案,近年来糖尿病并发症已严重影响到患者生活与健康,对医疗服务行业造成不小冲击,所以目前研究治疗糖尿病并发症已刻不容缓。中西药联用为治疗糖尿病提供一种新的思路,推动扩大治疗糖尿病方法路径的研究进展。因此,该文将对西药联合中药汤剂治疗糖尿病并发症的临床进展展开综述。     

Validity and reliability of the Turkish version of the Diabetes Self-Care Scale

The purpose of this study was to evaluate the validity and reliability of the Turkish version of the Diabetes Self-Care Scale. Self-care in diabetes is influenced by various factors, and it is important that the diabetes healthcare providers evaluate the efficacy of self-care activities. Accurate and careful measurements of diabetes self-care activities/levels provide important information both for healthcare providers and researchers to enable deeper understanding of appropriate management of and attitude towards self-care in patients with diabetes. Language properties of a Turkish adaptation of the Diabetes Self-Care Scale were ensured with the translation-backtranslation method, content validity by soliciting specialist opinions. Reliability, consistency over time (test-retest reliability), item-total item correlation analysis, and internal consistency were also analyzed. Data were collected between May and July 2007. The Cronbach’s alpha reliability coefficient was 0.81. The Diabetes Self-care Scale is a valid and reliable scale to evaluate self-care activities of diabetics.     

Diabetes management. Analysis of the American Diabetes Association's clinical practice recommendations

Type 2 diabetes generally develops in persons older than age 45 and comprises more than 90% of the estimated 15 million diabetes cases identified in the United States. Due to the burgeoning population of older Americans and the increased prevalence of obesity and sedentariness, type 2 diabetes is nearing epidemic proportions. Tight glycemic control combined with good diet and regular exercise can reduce the incidence of complications associated with unchecked disease. To help physicians and patients achieve such objectives, the American Diabetes Association publishes clinical practice recommendations that propose the most effective methods for screening, diagnosis, and disease management. The position statements presenting the standard of care for treatment of diabetes are reviewed and critiqued from an evidence-based medicine perspective.     

NIDDK encourages technology research in diabetes

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) actively supports technology-related research directed at development of new therapies for prevention and treatment of diabetes and its complications. Identification of the genetic and environmental contributors to diabetes and the molecular mechanisms through which they act will yield new targets for therapeutic development. Major efforts are also directed at development of beta-cell replacement therapy; improved methods for sensing glucose and delivering insulin; imaging technologies and other surrogate markers to detect disease progression; improved animal models for study of diabetes and its complications; and clinical trials to evaluate the safety and efficacy of new therapies. Application of genomic, proteomic and other new technologies to diabetes research, collaborations between diabetes researchers and researchers with technologies relevant to diabetes, and bench to bedside translational research are particularly encouraged. A variety of funding mechanisms are available to prospective researchers.     

耳穴压豆疗法在2型糖尿病及其并发症治疗中的应用概况

糖尿病是一种以糖代谢紊乱为特征的慢性综合性疾病,属中医"消渴"范畴.目前临床治疗DM以口服降糖药和注射胰岛素,以及日常饮食控制、运动为主.该文主要从糖尿病中医学认知,阐述耳穴压豆疗法作为一种传统的中医外治法,可以显著改善早期2型糖尿病、糖尿病合并失眠、糖尿病合并便秘及其他并发症的临床症状,体现耳穴压豆治疗糖尿病的特色与...     

Diabetes,healthcare cost and loss of productivity in Sweden 1987 and 2005—a register‐based approach

Aim The aim of this study was to estimate healthcare cost and productivity losses as a result of diabetes and diabetes‐related chronic complications in Sweden in 1987 and 2005. Research design and methods Published estimates on relative risks and Swedish age‐specific diabetes‐prevalence rates were used to calculate the proportions of diabetes‐related chronic complications that are attributable to diabetes. These attributable risks were applied to cost estimates for diabetes‐related chronic complications based on data from Swedish population registers. Results The estimated total costs for Sweden in 1987 and 2005 were EUR439m and EUR920m, respectively. The increase of 110% was as a result of a 69% increase in the estimated prevalence from 150 000 (1.8% of the population) to 254 000 (2.8%) and of an increase in the estimated annual cost per person diagnosed with diabetes by 24%. Healthcare accounted for 45% of the estimated cost in 1987 and for 37% in 2005. The estimated diabetes‐related healthcare cost accounted for approximately 1.0% of total healthcare cost in Sweden in 1987 and for 1.4% in 2005. Diabetes per se accounted for 57% of the healthcare cost in 1987 and for 50% in 2005. The most important chronic complication was cardiovascular disease. Conclusions The cost of diabetes is substantial and increasing even in a fairly low‐prevalence country such as Sweden. Measures to curb the increase in prevalence and to improve individual control of his or her diabetes seem to be the most important challenges.     

Resourcing issues

Diabetes is a chronic, progressive disease and achieving appropriate control of glycaemia and the other associated cardiovascular risk factors is essential to prevent its long-term complications. Currently, recovery and rehabilitation from the cardiovascular complications of diabetes are the major focus of diabetes care rather than primary and secondary prevention of diabetes and its complications. This focus, coupled with limited funding and other resource issues, means that diabetes care and outcomes are generally suboptimal. More efficient and effective management strategies, primarily based upon a broad educational approach including both those with diabetes and their care-givers will be essential in reducing the cost of diabetes and diabetes-related complications. Continuous education of patients and providers increases the quality of care and improves clinical and metabolic outcomes as well as reducing the cost of care and optimising human and financial resources. Thus, education will be a key strategy in minimising the growing burden of diabetes on society. Making these changes will require the co-operation of patients, their families, the community, healthcare policy makers, national governments and the pharmaceutical industry. Medical schools must also place more emphasis on educating doctors about chronic disease management using not only recovery and rehabilitation, but also prevention strategies, emphasising the importance of helping patients to participate in the control of their disease.     

Importance of long‐term care of diabetic women starting in pregnancy

Large scale, multi‐center, controlled studies have demonstrated the importance of glycemic control, as indicated by HbA_1c levels, in reducing the incidence and progression of diabetic complications. However, Yasue Omori, who began practicing medicine in Tokyo 60 years ago, in 1957, has the vantage point of long‐term continuing care for women with type 2 diabetes, some for several decades. An internist who specializes in diabetic pregnancy, Dr Omori began caring for many of her patients during their pregnancies and continued to care for them following their deliveries, some now more than 50 years. Surprisingly, despite lack of optimal HbA_1c levels, they have suffered relatively few diabetic complications. As reported in “The importance of nonstop treatment after delivery for pregnant women with type 2 diabetes” in Diabetes/Metabolism Research and Reviews , Omori and colleagues present a historical perspective that provides evidence that a long‐term patient‐care giver relationship following pregnancy can be valuable in reducing the onset and progression of diabetic complications.     

An epidemiological perspective of personalized medicine: the Estonian experience

The Estonian Biobank and several other biobanks established over a decade ago are now starting to yield valuable longitudinal follow‐up data for large numbers of individuals. These samples have been used in hundreds of different genome‐wide association studies, resulting in the identification of reliable disease‐associated variants. The focus of genomic research has started to shift from identifying genetic and nongenetic risk factors associated with common complex diseases to understanding the underlying mechanisms of the diseases and suggesting novel targets for therapy. However, translation of findings from genomic research into medical practice is still lagging, mainly due to insufficient evidence of clinical validity and utility. In this review, we examine the different elements required for the implementation of personalized medicine based on genomic information. First, biobanks and genome centres are required and have been established for the high‐throughput genomic screening of large numbers of samples. Secondly, the combination of susceptibility alleles into polygenic risk scores has improved risk prediction of cardiovascular disease, breast cancer and several other diseases. Finally, national health information systems are being developed internationally, to combine data from electronic medical records from different sources, and also to gradually incorporate genomic information. We focus on the experience in Estonia, one of several countries with national goals towards more personalized health care based on genomic information, where the unique combination of elements required to accomplish this goal are already in place.     

Diabetes and Hypertension: A Comparative Review of Current Guidelines

Cardiovascular disease plays a major role in the morbidity and mortality of patients with diabetes mellitus. In turn, hypertension is a major risk factor for cardiovascular disease, and its prevalence is increased in diabetes mellitus. Therefore, the detection and management of elevated blood pressure (BP) is a critical component of the comprehensive clinical management of diabetics. Despite significant advances in our understanding of the pathogenesis and treatment of hypertension, there continues to be debate regarding the pharmacologic treatment of hypertension, especially in high‐risk groups such as in patients with diabetes mellitus with and without chronic kidney disease (CKD). This debate largely involves at what BP (ie, treatment threshold BP) to initiate pharmacologic antihypertensive therapy and subsequently what treatment target BP should be achieved (ie, goal BP). Presently, there are several guidelines that address hypertension in diabetes mellitus, including the recently released guideline from the Eighth Report of the Joint National Committee (JNC 8). Therefore, this review will compare and contrast these current guidelines, as they relate to the management and treatment of hypertension in diabetes mellitus. Since diabetes mellitus and CKD are significantly inter‐related, the presence of CKD as it relates to patients with diabetes mellitus will also be addressed.