Genetic epidemiology of type 1 diabetes

The evidence that there is clinical heterogeneity of type 1 diabetes is reviewed and the implications for genetic studies are discussed. In the past year, genome-wide linkage analysis of 1435 multiplex families was reported. Additionally, confirmed evidence for association of specific markers at two loci (PTPN22, OAS1) as well as failure to replicate three others (IL12B, SUMO4, PAX4) is discussed. Some common themes are identified and suggestions for improvements are made. We look forward to the results from genome-wide association studies.     

The epidemiology and management of diabetes mellitus in Indonesia

Predications indicate a potentially explosive increase in the prevalence of diabetes worldwide, especially in developing countries such as Indonesia. Studies of people living in rural areas of East Java and Bali show a prevalence rate of 1.5% in 1982 to 5.7% in 1995 among the urban population. Ujung Pandnag also experienced an increase, and recent studies in Manado found a dramatically high rate of 6.1% in urban areas. Preliminary results indicate varying prevalence between those living in urban and rural areas. Currently, Indonesia has an estimated 1.2-2.3% prevalence among people over 15 years. Geographically variation appears to be an influential factor, due to differences in ethnics, race, culture and lifestyle. Studies of diabetic families show a significantly high prevalence and, clinically speaking, the mode of treatment indicates the type of diabetes. Those who respond well to OHA among young diabetics (<40) are assumed to have the MODY variation of the disease. The level of obesity among the general population has increased, due partly to increased calorie intake and is a significant factor in the increased rate of diabetes. It is also more common among the elderly, as our results will show. The new types of the disease are clinically more difficult to assess than the classical types 1 and 2, as they require relatively costly genetic and immunological studies. The rate of LADA type diabetes was found to be relatively high (>20% for ICA and IAA and 2.3% for GAOA). A concensus on diabetes management has now been formulated in Indonesia and these guidelines are now used by all Indonesian health care professionals.     

Genetic epidemiology of type 1 diabetes mellitus in Taiwan

Some environmental and genetic factors play important roles in etiopathogenesis of type 1 or insulin-dependent diabetes mellitus (IDDM). HLA genes, the IDDM1 locus located the human chromosome 6, were found to be associated with insulin-dependent diabetes mellitus. However, the incidence of IDDM varied greatly among various populations. To evaluate the pathogenetic factors contributing to the development of IDDM in Taiwan, HLA typing was performed in a group of IDDM unrelated individuals and IDDM pedigrees along with the normal controls from the northern Taiwan. DNA genotypes of class II HLA were done by polymerase-chain-reaction based oligotyping techniques. We confirmed that class II HLA genes were significantly associated with IDDM in Taiwan. To study detailed molecular structure of class II HLA molecules and disease association, we examined several amino acid residues on DQalpha and DQbeta chains and the molecular mechanisms to explain the heterozygotic effect of the DR3/DR4 and DR3/DR9 in the Chinese population. Linkage analysis in our pedigrees confirmed the association between HLA and IDDM in population association studies. Among the several class II alleles, a closer segregation of HLA-DQB1*0401 to the affected persons might suggest that HLA-DQB1*0401 itself or an allele closely linked to the DQB1 locus was the IDDM-predisposing allele in Taiwanese. For IDDM2 (INS) region, association with IDDM was not found due to that more than 90% of the population carried class I alleles. In our collection of IDDM, we found few cases (2.4%) carried mitochondrial DNA mutation. Our studies in Taiwanese confirm a multigenetic nature for IDDM.     

早期干预改变糖尿病

研究者不仅要把注意力放在2型糖尿病的治疗上,更要注重糖尿病的预防.2009年国际糖尿病联盟(IDF)第20次学术会议上,报道了2型糖尿病的早期干预--"早期干预改变糖尿病",共包括4个部分:生活方式干预在糖尿病预防中的作用,药物干预在糖尿病预防中的作用,英国前瞻性糖尿病研究(UKPDS)早期血糖控制的远期效果及改善和保存现有胰岛功能的潜能.     

流行病学方法在糖尿病研究中的应用

随着流行病学的发展,流行病学的定义也在不断地演化.目前较为公认的流行病学定义是,研究特定人群中健康相关状态与事件的分布情况和决定因素以及这种研究结果在健康问题控制中的应用[1].由此可见流行病学是研究疾病的分布(时间、空间和人群)和致病因素以及疾病防治的科学.随着人类疾病谱的改变,流行病学的研究重点也应随之发生变化.研究显示中国的主要死因已经从呼吸系统疾病和传染病转变为心血管疾病和恶性肿瘤等慢性疾病[2].糖尿病是心血管疾病和肾脏疾病的重要危险因素.     

A review of the epidemiology of diabetes in rural India

Objective

To describe the extent of problem of diabetes in rural India based on review of available literature and examine the secular trends over a period of 15 years i.e. from 1994 to 2009.

Methods

A systematic search was performed using electronic as well as manual methods. Studies providing details of sample size, age group of participants, criteria used for diagnosis, along with the prevalence of any of the three outcomes of interest i.e. diabetes mellitus, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), were included.

Results

Analysis of secular trends reveals an increase in diabetes prevalence among rural population at a rate of 2.02 per 1000 population per year. The rate of increase was high in males (3.33 per 1000 per year) as compared to females (0.88 per 1000 per year). High prevalence of IFG and IGT has been observed in southern and northern parts of the country.

Conclusion

The prevalence of diabetes is rising in rural India. There is a large pool of subjects with IFG and IGT at high risk of conversion to overt diabetes. Population-level and individual-level measures are needed to combat this increasing burden of diabetes.     

The changing epidemiology of diabetic microangiopathy in type 1 diabetes

Diabetic microvascular complications in the kidney and the eye are a major burden for diabetic patients due to increased morbidity and mortality. Furthermore, diabetic nephropathy is the leading cause of end-stage renal disease and diabetic retinopathy is the leading cause of blindness in younger patients, representing a major public health concern. During the past two decades beneficial effects of, in particular, aggressive antihypertensive control and strict glycaemic control have been demonstrated in randomised controlled clinical trials. Technological improvements in diabetes care have made good metabolic control easier to achieve. Has this led to an improved prognosis? In observational studies from dedicated centres, a decrease from 47 to 13% has been reported in the incidence of proliferative diabetic retinopathy after 20–25 years of diabetes, and the incidence of overt diabetic nephropathy after 20 years has decreased from 28 to 5.8%. Even functional and morphological remission of diabetic nephropathy has been reported. Despite this, recent population-based studies have failed to demonstrate a decrease in the incidence of blindness caused by diabetes, and the incidence of end-stage renal disease has progressively increased. This may, in part, be the result of a combination of increasing numbers of diabetic patients and a lag phase between improvement in management and a decline in end-stage complications. It is of concern, however, that the results from specialised centres may not apply to routine diabetes care. It is, therefore, mandatory that the beneficial effects of pharmacological and non-pharmacological interventions demonstrated in clinical trials and recommended by treatment guidelines are translated into clinical practice to ensure a widespread improvement in prognosis.     

The epidemiology of neuropathic foot ulcers in individuals with diabetes

There is now substantial evidence that diabetic neuropathy is a major etiologic factor for diabetic foot ulcers. Epidemiologic data show a very strong association between foot ulcers and indicators of sensorimotor neuropathy. Additionally, a causal pathway (sensorimotor neuropathy, which leads to increased pressures at foot surfaces, which then leads to foot ulcers) has been postulated. Evidence suggests that other factors also contribute to foot ulcer risk through an interaction with neuropathy such as foot deformity, footwear, and body weight. There has been an effort to optimize modalities for screening diabetic patients for hypoesthesia in order to prevent foot ulcers; however, there have not been definitive prospective studies that have compared the effectiveness of available tests.     

The epidemiology of diabetes mellitus in the United Kingdom: The Yorkshire regional childhood diabetes register

Summary A register of the incidence of Type 1 (insulin-dependent) diabetes mellitus in the Yorkshire region of the United Kingdom has been completed. A total of 1,490 subjects aged between 0 and 16 years were identified from 1978 to 1990, giving an incidence of 13.7 per 100,000 (ages 0–14) or 13.6 per 100,000 (ages 0–16), comparable to other recent studies in the United Kingdom. An age-period-cohort analysis shows evidence for a modest drift effect of 1.75% per year (95% confidence interval 0.28 to 3.25%). There is a marked epidemic pattern with peaks at 4-year intervals. The age-incidence curve is similar to that reported elsewhere, having peaks in early childhood and puberty. Girls have an earlier pubertal peak than boys. There is substantial seasonal variation in incidence confined to those over 5 years of age. Ascertainment is believed to be very complete, and is estimated to be 97.6% (95% confidence interval 97.2% to 98.1%).     

Molecular pathological epidemiology in diabetes mellitus and risk of hepatocellular carcinoma

Molecular pathological epidemiology (MPE) is a multidisciplinary and transdisciplinary study field, which has emerged as an integrated approach of molecular pathology and epidemiology, and investigates the relationship between exogenous and endogenous exposure factors, tumor molecular signatures, and tumor initiation, progression, and response to treatment. Molecular epidemiology broadly encompasses MPE and conventional-type molecular epidemiology. Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated death worldwide and remains as a major public health challenge. Over the past few decades, a number of epidemiological studies have demonstrated that diabetes mellitus (DM) is an established independent risk factor for HCC. However, how DM affects the occurrence and development of HCC remains as yet unclearly understood. MPE may be a promising approach to investigate the molecular mechanisms of carcinogenesis of DM in HCC, and provide some useful insights for this pathological process, although a few challenges must be overcome. This review highlights the recent advances in this field, including: (1) introduction of MPE; (2) HCC, risk factors, and DM as an established independent risk factor for HCC; (3) molecular pathology, molecular epidemiology, and MPE in DM and HCC; and (4) MPE studies in DM and risk of HCC. More MPE studies are expected to be performed in future and I believe that this field can provide some very important insights on the molecular mechanisms, diagnosis, personalized prevention and treatment for DM and risk of HCC.     

The worldwide epidemiology of type 2 diabetes mellitus--present and future perspectives

Over the past three decades, the number of people with diabetes mellitus has more than doubled globally, making it one of the most important public health challenges to all nations. Type 2 diabetes mellitus (T2DM) and prediabetes are increasingly observed among children, adolescents and younger adults. The causes of the epidemic of T2DM are embedded in a very complex group of genetic and epigenetic systems interacting within an equally complex societal framework that determines behavior and environmental influences. This complexity is reflected in the diverse topics discussed in this Review. In the past few years considerable emphasis has been placed on the effect of the intrauterine environment in the epidemic of T2DM, particularly in the early onset of T2DM and obesity. Prevention of T2DM is a 'whole-of-life' task and requires an integrated approach operating from the origin of the disease. Future research is necessary to better understand the potential role of remaining factors, such as genetic predisposition and maternal environment, to help shape prevention programs. The potential effect on global diabetes surveillance of using HbA(1c) rather than glucose values in the diagnosis of T2DM is also discussed.     

The epidemiology of low-grade chronic systemic inflammation and type 2 diabetes

The fattening of the human species and the accompanying emergence of the metabolic syndrome and of type 2 diabetes as remarkably frequent clinical entities are among the major epidemiologic events of our time. Control of the diabetes epidemic requires a greater understanding of the pathophysiologic processes underlying these phenomena. Many epidemiologic studies have now shown associations between inflammation markers and diabetes, with the most consistent being for leukocytes and the strongest being for C-reactive protein. Consistent protective associations have also been reported for adiponectin, an adipocyte secretory protein with antiinflammatory actions. Although great variability is seen between reported associations, as a whole these studies suggest a role for inflammation linked to obesity. The variability reported is in part due to differences in model adjustment, in how diabetes was ascertained, and in the different means used to operationalize the concept of low-grade chronic systemic inflammation. It is also due, in part, to sample characterization, as findings are heterogeneous across some subgroups, such as those defined by smoking. Consistent with their association with type 2 diabetes, inflammation markers have also be shown to predict conditions present in the prediabetes state such as weight gain, hypertension, gestational diabetes, and decline in insulin sensitivity.     

The epidemiology of left ventricular hypertrophy in type 2 diabetes mellitus

Aims/hypothesis Patients with type 2 diabetes mellitus are at greater cardiovascular risk than the general population. Although it is widely acknowledged that diabetes is a risk factor for coronary artery disease, the increased prevalence of potentially lethal left ventricular abnormalities in this population is less well appreciated.Methods We carried out an echocardiographic study of 500 subjects with type 2 diabetes mellitus to assess the prevalence of left ventricular hypertrophy (LVH) and left ventricular systolic dysfunction (LVSD). We also assessed whether abnormalities in diastolic filling parameters were present.Results Of the 371 patients in whom left ventricular mass could be successfully assessed, 264 had LVH (71%). Left ventricular systolic dysfunction was much less common, being present in 16/385 patients (4.2%). Long axis contraction was abnormal in 29/429 patients (6.8%). Diastolic filling abnormalities were present in 178/435 (41%) of patients who could be classified using the selected criteria.Conclusions We conclude that left ventricular abnormalities are common in type 2 diabetic patients. As medical therapy is available for both LVH and LVSD and has been demonstrated to reduce cardiovascular death, these left ventricular abnormalities could be ideal targets for screening, followed by selective therapeutic intervention.Electronic Supplementary Material Supplementary material is available for this article at .