Latent autoimmune diabetes in adults (LADA)--more than a name.
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Autoantibodies↗
Biomedical subjects
P Zimmet
Publications and source records attributed to P Zimmet.
Is grand multiparity associated with an increased risk of dysglycaemia?
AIMS/HYPOTHESIS: We sought to determine the risk of diabetes and IGT/IFG with grand multiparity. SUBJECTS, MATERIALS AND METHODS: Women, aged > or =25 years, from the Australian Diabetes, Obesity and Lifestyle Study and the Crossroads Undiagnosed Disease Study (a rural study in Victoria, Australia), participated in a household census (response 67 and 70%, respectively), subsequently attending a biomedical examination that included an oral glucose tolerance test (58% [6198] and 69% [819]). RESULTS: After adjusting for age, obesity and socio-economic status, diabetes, but not IGT/IFG, was less common among women with a parity of 1 to 2 (odds ratio [OR]=0.64 [0.48-0.84]) and 3 to 4 (OR=0.72 [0.53-0.96]) than in grand multiparous women. This relationship was unrelated to past hysterectomy, use of the oral contraceptive pill or menopausal status. CONCLUSIONS/INTERPRETATION: Grand multiparity is associated with an increased risk of diabetes but not of IGT/IFG. We postulate that parity accelerates transition from IGT/IFG to diabetes, more than it does transition from normal glucose tolerance to IGT/IFG.
Adult↗
The metabolic syndrome: time to reflect.
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Body Size↗
Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation.
AIMS: To establish a unified working diagnostic tool for the metabolic syndrome (MetS) that is convenient to use in clinical practice and that can be used world-wide so that data from different countries can be compared. An additional aim was to highlight areas where more research into the MetS is needed. PARTICIPANTS: The International Diabetes Federation (IDF) convened a workshop held 12-14 May 2004 in London, UK. The 21 participants included experts in the fields of diabetes, public health, epidemiology, lipidology, genetics, metabolism, nutrition and cardiology. There were participants from each of the five continents as well as from the World Health Organization (WHO) and the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III). The workshop was sponsored by an educational grant from AstraZeneca Pharmaceuticals. CONSENSUS PROCESS: The consensus statement emerged following detailed discussions at the IDF workshop. After the workshop, a writing group produced a consensus statement which was reviewed and approved by all participants. CONCLUSIONS: The IDF has produced a new set of criteria for use both epidemiologically and in clinical practice world-wide with the aim of identifying people with the MetS to clarify the nature of the syndrome and to focus therapeutic strategies to reduce the long-term risk of cardiovascular disease. Guidance is included on how to compensate for differences in waist circumference and in regional adipose tissue distribution between different populations. The IDF has also produced recommendations for additional criteria that should be included when studying the MetS for research purposes. Finally, the IDF has identified areas where more studies are currently needed; these include research into the aetiology of the syndrome.
Adipose Tissue↗
IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71).
AIMS/HYPOTHESIS: Established autoimmune markers of type 1 diabetes, including islet cell autoantibodies (ICA) and autoantibodies to glutamic acid decarboxylase (GADA) have been used to screen people presenting with type 2 diabetes for latent autoimmune diabetes in adults. We have examined the prevalence of autoantibodies to protein tyrosine phosphatase isoforms IA-2 (IA-2A) and IA-2beta/phogrin (IA-2betaA) in a cohort of adult UKPDS patients thought to have type 2 diabetes, and investigated the possible role of these autoantibodies in predicting requirement for insulin therapy. METHODS: IA-2A and IA-2betaA were measured by a validated radioimmunoassay with human recombinant autoantigens in 4,169 white Caucasian patients aged 25-65 years and newly diagnosed with type 2 diabetes. The clinical requirement for insulin therapy within 6 years was examined in 2,556 patients not randomised to insulin. RESULTS: IA-2A and IA-2betaA were present in 2.2 and 1.4%, respectively, of these patients. IA-2A were more prevalent in younger patients (p for trend <0.00001), more often associated with the HLA-DR4 allele (26.3 vs 8.0%, p<0.0001), and their presence increased the likelihood of insulin therapy requirement within 6 years from diagnosis [relative risk (95%CI) 12.2 (9.8-15.3)]. The presence of IA-2A together with GADA increased the relative risk of requiring insulin therapy from 5.4 (4.1-7.1) for GADA alone to 8.3 (3.7-18.8) and the corresponding positive predictive value from 33 to 50%. CONCLUSIONS/INTERPRETATION: In type 2 diabetes, the presence of IA-2A is infrequent, associated with the HLA-DR4 haplotype, and highly predictive of future need for insulin therapy. The measurement of IA-2betaA does not provide additional information.
Adult↗
The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes.
AIMS/HYPOTHESIS: This study aimed to identify genes that are expressed in skeletal muscle, encode proteins with functional significance in mitochondria, and are associated with type 2 diabetes. METHODS: We screened for differentially expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and prioritised these on the basis of genomic localisation and bioinformatics analysis for proteins with likely mitochondrial functions. RESULTS: We identified a mitochondrial intramembrane protease, known as presenilins-associated rhomboid-like protein (PSARL) that is associated with insulin resistance and type 2 diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic Psammomys obesus, and restored after exercise training to successfully treat the diabetes. PSARL gene expression in human skeletal muscle was correlated with insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic-euglycaemic clamp. In 1,031 human subjects, an amino acid substitution (Leu262Val) in PSARL was associated with increased plasma insulin concentration, a key risk factor for diabetes. Furthermore, this variant interacted strongly with age to affect insulin levels, accounting for 5% of the variation in plasma insulin in elderly subjects. CONCLUSIONS/INTERPRETATION: Variation in PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.
Amino Acid Sequence↗
Choice and availability of takeaway and restaurant food is not related to the prevalence of adult obesity in rural communities in Australia.
OBJECTIVES: To establish whether choice and availability of takeaway and restaurant food consumption are associated with increased obesity. DESIGN: Crossroads Undiagnosed Disease Study: a cross-sectional study undertaken between June 2001 and March 2003. SETTING: A regional centre and six shire capitals of variables size in rural Victoria, Australia. PARTICIPANTS: In total, 1454 residents of randomly selected households. MEASUREMENTS: Obesity (by body mass index (BMI) or waist circumference), weekly recreational activity, self-reported frequency of takeaway consumption, number of local takeaway and restaurant food outlets in the area. RESULTS: The prevalence of obesity ranged from 25.5-30.8% and was higher than the general Australian population among both men and women. Those in the regional centre were less likely than those in large and small shire capitals to participate in recreational activity of 150 min or more (39.7 vs 48.4%, 46.0% respectively, P=0.023) and yet reported better access to facilities and amenities for physical activity. Recreational activity of > or =150 min/week was associated with 0.75 (0.58-0.97) fold less risk of obesity. BMI was unrelated to takeaway consumption. Waist circumference was significantly lower among those eating no takeaways, but similar whether takeaways were consumed <1/month or > or =1/week. Increased takeaway consumption was associated with increased consumption of higher fat preparations of dairy and meat products. Availability of takeaway outlets and restaurants was unrelated to obesity. CONCLUSION: The obesity epidemic exists among those without significant consumption of or availability to takeaway foods. In a setting of easy availability of food, the obesity epidemic relates strongly to reduced physical activity, but not to consumption of takeaway food.
Age Factors↗
Dietary Westernisation: conceptualisation and measurement in Mauritius.
OBJECTIVES: The aims of the study were to provide information that will contribute to conceptualising what is called "dietary Westernisation", and to provide an example of measuring it on an individual level. DESIGN: Food consumption frequency and demographic data on adults in Mauritius were examined in 1988, 1992 and 1998. In 1992, a 24-hour recall was also included. The cross-sectional samples consisted of 1115 (age 25-74 years) Mauritians in 1987/88, 1917 (age 30-74 years) in 1992 and 2239 (age 20-74 years) in 1998. Principal components analysis was carried out on daily consumption frequencies of 10 indicator foods (white rice, white bakery bread, pulses, processed meat, poultry, fresh/frozen fish, butter, margarine, whole milk and skimmed/low-fat milk). Correlations between dietary patterns and selected food consumption frequencies were examined in each survey year. RESULTS: Four dietary patterns were identified as being related to dietary Westernisation. The Traditional dietary pattern was characterised by higher consumption frequencies of Indian breads, salted/smoked fish and sugar-sweetened tea. The Western dietary pattern was characterised by higher consumption frequencies of cakes/pastries, meat and many Western fast foods like burgers, but, surprisingly, also by brown bread, breakfast cereals and salad. The Bread/butter dietary pattern predominantly described more frequent consumption of bread compared with rice. The Margarine/milk dietary pattern was inconsistently related with staple foods. Younger, educated and wealthier Mauritians appeared to adopt Western dietary patterns earlier. CONCLUSIONS: This study suggests that relatively few indicator foods are needed for measuring dietary Westernisation. Dietary Westernisation in a non-Western country may also include shifts towards voluntary consumption of healthier foods.
Adult↗
Increasing prevalence of Type 2 diabetes mellitus in all ethnic groups in Mauritius.
AIMS: To describe the prevalence of different stages of glucose intolerance in a population from Mauritius followed over 11 years. METHODS: Population-based surveys were undertaken in the multiethnic nation of Mauritius in 1987, 1992 and 1998, with 5083, 6616, and 6291 participants, respectively. Questionnaires, anthropometric measurements, and a 2-h 75-g oral glucose tolerance test were included. Subjects aged between 25 and 75 years with classifiable data were identified; 4991, 6463 and 5392 from 1987, 1992 and 1998, respectively. Glucose tolerance was classified according to WHO 1999 criteria. RESULTS: The prevalence of Type 2 diabetes increased significantly during the period studied, from 12.8% in 1987, to 15.2% in 1992, and 17.9% in 1998. The increasing prevalence was seen in both men and women, and in all age groups. The prevalence of known diabetes (KDM) increased progressively, and more markedly than the increase in newly diagnosed diabetes (NDM). A diagnosis of impaired glucose tolerance (IGT) was more prevalent amongst women whereas impaired fasting glucose (IFG) was more common amongst men. The prevalences of IGT and IFG did not change markedly during the period. The prevalence of diabetes and IGT was similar for participants of Indian, Creole and Chinese background in each survey, and the increasing prevalence of diabetes was seen in all ethnic groups. CONCLUSION: In this study, we report an increasing prevalence of diabetes over an 11-year period in Mauritius. This increase was seen in both sexes, and in all age and ethnic groups, and was mainly due to an increase in the numbers of those with known diabetes.
Adult↗
Improving glucose management: ten steps to get more patients with type 2 diabetes to glycaemic goal.
Despite increasingly stringent clinical practice guidelines for glycaemic control, the implementation of recommendations has been disappointing, with over 60% of patients not reaching recommended glycaemic goals. As a result, current management of glycaemia falls significantly short of accepted treatment goals. The Global Partnership for Effective Diabetes Management has identified a number of major barriers that can prevent individuals from achieving their glycaemic targets. This article proposes 10 key practical recommendations to aid healthcare providers in overcoming these barriers and to enable a greater proportion of patients to achieve glycaemic goals. These include advice on targeting the underlying pathophysiology of type 2 diabetes, treating early and effectively with combination therapies, adopting a holistic, multidisciplinary approach and improving patient understanding of type 2 diabetes. Implementation of these recommendations should reduce the risk of diabetes-related complications, improve patient quality of life and impact more effectively on the increasing healthcare cost related to diabetes.
Blood Glucose Self-Monitoring↗
Diet, nutrition and the prevention of type 2 diabetes.
OBJECTIVES: The overall objective of this study was to evaluate and provide evidence and recommendations on current published literature about diet and lifestyle in the prevention of type 2 diabetes. DESIGN: Epidemiological and experimental studies, focusing on nutritional intervention in the prevention of type 2 diabetes are used to make disease-specific recommendations. Long-term cohort studies are given the most weight as to strength of evidence available. SETTING AND SUBJECTS: Numerous clinical trials and cohort studies in low, middle and high income countries are evaluated regarding recommendations for dietary prevention of type 2 diabetes. These include, among others, the Finnish Diabetes Prevention Study, US Diabetes Prevention Program, Da Qing Study; Pima Indian Study; Iowa Women's Health Study; and the study of the US Male Physicians. RESULTS: There is convincing evidence for a decreased risk of diabetes in adults who are physically active and maintain a normal body mass index (BMI) throughout adulthood, and in overweight adults with impaired glucose tolerance who lose weight voluntarily. An increased risk for developing type 2 diabetes is associated with overweight and obesity; abdominal obesity; physical inactivity; and maternal diabetes. It is probable that a high intake of saturated fats and intrauterine growth retardation also contribute to an increased risk, while non-starch polysaccharides are likely to be associated with a decreased risk. From existing evidence it is also possible that omega-3 fatty acids, low glycaemic index foods and exclusive breastfeeding may play a protective role, and that total fat intake and trans fatty acids may contribute to the risk. However, insufficient evidence is currently available to provide convincing proof. CONCLUSIONS: Based on the strength of available evidence regarding diet and lifestyle in the prevention of type 2 diabetes, it is recommended that a normal weight status in the lower BMI range (BMI 21-23) and regular physical activity be maintained throughout adulthood; abdominal obesity be prevented; and saturated fat intake be less than 7% of the total energy intake.
Clinical Trials as Topic↗
High incidence of type 2 diabetes and increasing conversion rates from impaired fasting glucose and impaired glucose tolerance to diabetes in Mauritius.
OBJECTIVE: To describe the incidence of different stages of glucose intolerance in a population from Mauritius followed over 11 years. RESEARCH DESIGN, METHODS AND SUBJECTS: Population-based surveys were undertaken in the multi-ethnic nation of Mauritius in 1987, 1992 and 1998 with 5083, 6616 and 6291 participants, respectively. Questionnaires, anthropometric measurements, and a 2-h 75-g oral glucose tolerance test were included. Three cohorts aged between 25 and 79 years with classifiable glucose tolerance data were identified; 3680 between 1987 and 1992, 4178 between 1992 and 1998, and 2631 between 1987 and 1998. Glucose tolerance was classified according to WHO 1999 criteria. RESULTS: The incidence rate of type 2 diabetes was higher between 1992 and 1998 than between 1987 and 1992. In men, the incidence was similar between cohorts (24.5 and 25.4 per 1000 person-years) whereas the incidence increased in women (23.3 and 16.4 per 1000 person-years). The incidence of diabetes peaked in the 45-54 year age group and then plateaued or fell. The incidences of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) decreased in both men and women. Of normoglycaemic subjects at baseline, more women than men developed IGT and more men than women developed IFG. Of those labelled as IFG in 1987, 38% developed diabetes after 11 years. The corresponding figure for IGT was 46%. CONCLUSIONS: In this study, we report changes in incidence rates of glucose intolerance over a 11-year period. In particular, differences between men and women were observed. The increased incidence of IGT in women compared with men, and increased incidence of IFG in men compared with women was consistent with, and explains the sex biases seen in the prevalences of these states.
Adult↗
Epidemiology of childhood type 2 diabetes in the developing world.
Type 2 diabetes in the young is an increasing problem with potentially serious outcomes. Our understanding of the worldwide burden of this condition is incomplete, with many studies adopting different methodologies to assess the condition and reporting on specific communities or ethnic groups. Most of the data come from developed nations, with few studies from developing nations. The purpose of this review is to bring together the available data on type 2 diabetes in the young from the developing world, in order to highlight deficiencies in the knowledge of the condition and also to promote strategies to deal with it. Noted also are some of the factors associated with the condition, such as family history, genetic influences, intrauterine environment as well as the importance of birth weight, insulin resistance, obesity, and development of complications. These are of relevance in both developed and developing nations.
Acanthosis Nigricans↗
Metabolic, immunological and clinical characteristics in newly diagnosed Asian diabetes patients aged 12-40 years.
AIM: To describe the clinical, biochemical and immunological characteristics of young-onset diabetes in Asia. METHODS: Clinical, biochemical and immunological variables were assessed in 919 newly diagnosed (duration less than 12 months) young onset Asian diabetic patients aged between 12 and 40 years. The subjects constituted 57% Chinese, 29% Indians and 14% Malays, recruited from diabetes centres in China, Hong Kong, India, Malaysia and Singapore. RESULTS: The mean age (+/- sd) was 31.6 +/- 7.2 years, with the majority (66%) in the 31-40 years age group. Mean body mass index (BMI) (+/- sd) was 25.3 +/- 5.0 kg/m2 with 47% exceeding the suggested Asian cut-off point for obesity (BMI > or = 25). Ethnic difference in clinical characteristics included BMI, blood pressure, mode of treatment and degree of insulin resistance. Most patients had a clinical presentation of Type 2 diabetes. About 10% had a classical combination of ketotic presentation, presence of autoimmune-markers and documented insulin deficiency indicative of Type 1 diabetes. Forty-eight percent were receiving oral hypoglycaemic agents (OHAs) while 31% were on diet only, 18% were receiving insulin and 2% were on a combination of insulin and OHA. CONCLUSION: Young onset diabetes patients in Asia represent a heterogeneous group in terms of their clinical and biochemical characteristics and classical Type 1 diabetes is relatively uncommon. The 5-year follow up study will determine the progress of these patients and help to clarify the natural history.
Administration, Oral↗
The burden of type 2 diabetes: are we doing enough?
Increasing levels of obesity, arising from energy-rich diets and sedentary lifestyles, are driving a global pandemic of type 2 diabetes. The prevalence of type 2 diabetes worldwide is set to increase from its present level of 150 million, to 225 million by the end of the decade and to as many as 300 million by 2025. Shocking as they are, these figures represent only clinically diagnosed diabetes, and many more cases of diabetes remain undiagnosed and untreated. In addition, up to one-quarter of western populations have impaired glucose tolerance or the dysmetabolic syndrome, which are considered to represent pre-diabetic states. Type 2 diabetes is appearing increasingly in children and adolescents, and the frequency of diagnosis of paediatric type 2 diabetes is outstripping that of type 1 diabetes in some areas. The long-term complications associated with type 2 diabetes carries a crushing burden of morbidity and mortality, and most type 2 diabetic patients die prematurely from a cardiovascular event. Diabetic patients are more than twice as costly to manage as non-diabetic patients, due mainly to the high costs associated with management of diabetic complications. Indeed, diabetes care already accounts for about 2-7% of the total national health care budgets of western European countries. Controlling the type 2 diabetes epidemic will require changes to the structure of healthcare delivery. Well-resourced interventions will be required, with effective co-ordination between all levels of government, health care agencies, multidisciplinary health care teams, professional organisations, and patient advocacy groups. Above all, intervention is needed today.
Adolescent↗
Genotype, obesity and cardiovascular disease--has technical and social advancement outstripped evolution?
Teleologically, our ancestors were highly adapted hunter-gatherers. In recent history, the environment in which Homo sapiens exists has altered drastically and humans are exposed to environments for which the hunter-gatherer genotype is ill-suited. The adoption of a sedentary Western lifestyle, and the case of obtaining food of a high calorific content imposed upon a thrifty genotype, have resulted in the current global epidemic of obesity, Type 2 diabetes and the Metabolic Syndrome. The ramification of this epidemic is that cardiovascular disease is becoming a global healthcare problem, which will have its greatest impact on the developing nations. A global strategy is required to reduce the impact of the Western lifestyle on the health of developing nations and prevent obesity and Type 2 diabetes. Such an approach needs to be culturally sensitive, integrated, and multidisciplinary and involve a range of interventions that work at the individual and community levels. If lifestyle measures fail, then pharmacological intervention may be necessary. For this, novel agents such as dual PPARalpha/gamma agonists may be the therapy of the future.
Adaptation, Physiological↗
Preventing Type 2 diabetes and the dysmetabolic syndrome in the real world: a realistic view.
The last two decades have seen an explosive increase in the number of people with diabetes globally. There is now an urgent need for strategies to prevent the emerging global epidemic. Several recent successful intervention studies, both lifestyle and pharmacological, targeting subjects with impaired glucose tolerance (IGT) have stimulated enthusiasm for prevention of Type 2 diabetes. Lifestyle interventions reduced the incidence of diabetes by over 50% in the Finnish Diabetes Prevention Study and the Diabetes Prevention Program. Can the findings of these two studies be applied globally? Underpinning the enthusiasm, there needs to be a realistic approach to interventions in both developed and developing nations, and in ethnic groups where a better understanding of the socio-economic, cultural and demographic issues and perceptions surrounding chronic diseases such as diabetes is required. Whether the strategies used in these two studies can be translated into a 'real world' scenario is doubtful. In practice, it is more than likely that a number of strategies will be needed to compliment the lifestyle approach. These will include pharmacological approaches with metformin, acarbose and other agents used to treat diabetes and its complications, currently under investigation. Longer-term follow-up studies will also clarify whether both lifestyle and pharmacological interventions actually prevent Type 2 diabetes, or merely delay its onset.
Diabetes Mellitus, Type 2↗
The Taq IA and Ser311 Cys polymorphisms in the dopamine D2 receptor gene and obesity.
Dopamine D2 receptors (DRD2) in the central nervous system are involved in the regulation of feeding. It remains to be elucidated if mutations in the DRD2 gene contribute to the development of obesity. The aim of the present study was to investigate whether the Taq IA and Ser311Cys polymorphisms in the DRD2 gene are associated with obesity in Nauruan and Australian subjects. Subjects were selected based on extremes of the body mass index (BMI) distribution. Two groups of Australian women were selected. The leanest group had a mean BMI of 22.5 kg/m2 (range: 20.3-24.3) and the heaviest group had a mean of 36.1 kg/m2 (32.5-44.1). Four groups of Nauruan subjects were selected. Leanest men had a mean BMI of 33.0 kg/m2 (28.4-36.9), heaviest men had a mean of 52.8 kg/m2 (46.5-69.2), leanest women had a mean of 34.8 kg/m2 (28.2-41.8) and heaviest women had a mean of 55.1 kg/m2 (49.3-73.8). Subjects were genotyped for the Taq IA and Ser311Cys polymorphisms using polymerase chain reaction (PCR) restriction fragment length polymorphism analysis and allelic discrimination Taqman PCR respectively. Leanest and heaviest groups were examined for differences in genotype frequency. Taq IA and Ser311Cys genotype frequencies did not differ significantly between leanest and heaviest Nauruan groups, or between leanest and heaviest Australians. Haplotype frequencies of these polymorphisms did not differ between leanest and heaviest groups. The Taq IA and Ser311Cys polymorphisms in the DRD2 gene are unlikely to be common causes of obesity in these populations.
Adult↗