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Objective: Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK) pathways-two pathways proposed as the link between CLAIS and insulin resistance.Research Design and Methods: Adiposity (dual-energy X-ray absorptiometry), waist-to-hip ratio (WHR), and insulin sensitivity (M, hyperinsulinemic-euglycemic clamp) were measured in 22 healthy nondiabetic volunteers (aged 29 +/- 11 years, body fat 28 +/- 11%). NF-kappaB activity (DNA-binding assay) and JNK1/2 activity (phosphorylated JNK) were assessed in biopsies of the vastus lateralis muscle and subcutaneous adipose tissue and in peripheral blood mononuclear cell (PBMC) lysates.Results: NF-kappaB activities in PBMCs and muscle were positively associated with WHR after adjustment for age, sex, and percent body fat (both P < 0.05). NF-kappaB activity in PBMCs was inversely associated with M after adjustment for age, sex, percent body fat, and WHR (P = 0.02) and explained 16% of the variance of M. There were no significant relationships between NF-kappaB activity and M in muscle or adipose tissue (both NS). Adipose-derived JNK1/2 activity was not associated with obesity (all P> 0.1), although it was inversely related to M (r = -0.54, P < 0.05) and explained 29% of its variance. When both NF-kappaB and JNK1/2 were examined statistically, only JNK1/2 activity in adipose tissue was a significant determinant of insulin resistance (P = 0.02).Conclusions: JNK1/2 activity in adipose tissue but not NF-kappaB activity in PBMCs is an independent determinant of insulin resistance in healthy individuals. [ABSTRACT FROM AUTHOR]

Objective: The aim of this work was to study the frequency of examining for diabetic eye and foot complications in an Australian population and to study factors associated with regular screening.Research Design and Methods: The Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based study of 11,247 people from randomly selected areas of Australia. Participants identified as having previously diagnosed diabetes (n=475) were invited to participate in the complications study. Measures included foot examination, retinopathy photography, and self-report use of health care services.Results: Seventy-seven percent of participants reported having an eye examination within the previous 2 years, and 50% reported having their feet examined by a health professional in the previous year. Type of diabetes treatment (odds ratio 1.46, 95% CI 0.85-2.50 for tablets versus diet alone and 4.17, 1.71-10.17 for insulin or insulin and tablets versus diet alone) and visiting a diabetes nurse educator in the previous 12 months (2.14, 1.18-3.87) were independent predictors of having had an eye examination. Duration of diabetes (1.33, 1.06-1.67 per year) and visiting a diabetes nurse educator in the previous 12 months (1.89, 1.20-2.95) were independent predictors of a foot examination.Conclusions: This study has shown that retinopathy screening is performed more frequently than foot screening in Australia. This may be due to the implementation of eye screening programs and awareness campaigns. Foot screening appears to be poor, with less than one-half of the population reporting a regular examination for foot complications. In Australia, diabetes nurse educators play a key role in promoting screening for diabetes complications. [ABSTRACT FROM AUTHOR]

That people with serious mental illness have poor physical health and face a significant life expectancy gap compared with the general population is well known. Despite considerable policy focus in some countries, the gap in life expectancy remains. Tackling complex and persistent health problems such as this requires a systems-based approach, recognising the complexity of interacting components and their effects on the problem and on each other and applying collaborative analysis, design and implementation by those with knowledge of and expertise in the problem and the context. This paper describes the methods used to develop the Australian Being Equally Well National Policy Roadmap for better physical health care and longer lives for people with severe mental illness. Whilst recognising that high rates of physical health comorbidities are caused by many factors including lifestyle, access to high-quality healthcare and medication side effects, the work was focused on what could be done within Australian primary care to improve the physical health of this cohort. A Clinical Microsystem Approach was applied to synthesise clinical evidence with professional and lived experience, and an innovative policy development process was established, creating trust across all system levels. Participants with different kinds of knowledge and experience worked in discrete groups according to their professional or expert role whilst also being supported to participate in an intensive cross-collaboration. The potential value of this methodology for tackling other complex problems in health policy is discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Duggan, Dunbar, Morgan, Mc Namara, de Courten and Calder.)

The impact of COVID-19 on the mental health and wellbeing of adolescents is a major concern. Most research has been conducted only in more economically developed countries. Using data from two similar surveys administered during July-September, 2020 in Australia (a high-income country) and Cambodia (a low-middle income country), this paper examined the impact early in the pandemic on the mental health and wellbeing of adolescents in the two countries. We found that COVID-19 had mostly negative impacts on participants' mental health; threats to personal safety; education; support for schooling; basic necessities such as food, income, employment, and housing; and responsibilities at home. This finding suggests that even short-term disasters may have negative repercussions, and regardless of differences in wealth, culture, and government response. We found that threats to personal safety appeared to be more prevalent in Cambodia than in Australia, the impact on mental health of the Cambodian participants may have been greater than reported, and that, in both countries, support for online or distance schooling during periods of lockdown was wanting, particularly at the state and school levels. This study will contribute to our understanding of the impact of major disruptive global events on young people in both more economically developed and developing countries., Competing Interests: The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Van Dyke, Keo and de Courten.)

Background: Interrelated chronic vascular diseases (chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease (CVD)) are common with high morbidity and mortality. This study aimed to assess if an electronic-technology-based quality improvement intervention in primary care could improve detection and management of people with and at risk of these diseases., Methods: Stepped-wedge trial with practices randomised to commence intervention in one of five 16-week periods. Intervention included (1) electronic-technology tool extracting data from general practice electronic medical records and generating graphs and lists for audit; (2) education regarding chronic disease and the electronic-technology tool; (3) assistance with quality improvement audit plan development, benchmarking, monitoring and support. De-identified data analysis using R 3.5.1 conducted using Bayesian generalised linear mixed model with practice and time-specific random intercepts., Results: At baseline, eight included practices had 37,946 active patients (attending practice ≥3 times within 2 years) aged ≥18 years. Intervention was associated with increased OR (95% CI) for: kidney health checks (estimated glomerular filtration rate, urine albumin:creatinine ratio (uACR) and blood pressure) in those at risk 1.34 (1.26-1.42); coded diagnosis of CKD 1.18 (1.09-1.27); T2D diagnostic testing (fasting glucose or HbA1c) in those at risk 1.15 (1.08-1.23); uACR in patients with T2D 1.78 (1.56-2.05). Documented eye checks within recommended frequency in patients with T2D decreased 0.85 (0.77-0.96). There were no significant changes in other assessed variables., Conclusions: This electronic-technology-based intervention in primary care has potential to help translate guidelines into practice but requires further refining to achieve widespread improvements across the interrelated chronic vascular diseases., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Multiple authors have been involved in a further study, Future Health Today which builds upon the concepts explored within this study but uses a quality improvement platform which differs from this one. CLN and J-AM-N are lead investigators on the Future Health Today program and EDJ, PSH, JLJ and NL are investigators. J-AM-N is an investigator in the Data for Decisions research initiative www.gp.unimelb.edu.au/datafordecisions which uses the GRHANITE research data collection tool. All other authors have declared no relevant conflicts of interest., (© The Author(s) 2023.)

Introduction: Congestive heart failure (CHF) causes significant morbidity and mortality. It is an epidemic, and costs are escalating. CHF is a chronic disease whose trajectory includes stable phases, periods of decompensation, and finally palliation. Health services and medical therapies must match the various patient needs. Chronic disease self-management (CDSM) programmes that are patient-focused, identify problems and set actionable goals that appear as a logical, cost-friendly method to navigate patient journeys. There have been challenges in standardising and implementing CHF programmes., Methods and Analysis: SELFMAN-HF is a prospective, observational study to evaluate the feasibility and validity of the SCRinHF tool, a one-page self-management and readmission risk prediction tool for CHF, with an established, comprehensive CDSM tool. Eligible patients will have CHF with left ventricular ejection fraction <40% and commenced sodium glucose co-transporter-2 inhibitors (SGLT2-i) within 6 months of recruitment. The primary endpoint is the 80% concordance in readmission risk predicted by the SCRinHF tool. The study will recruit >40 patients and is expected to last 18 months., Ethics and Dissemination: This study has been approved by the St Vincent's ethics committee (approval no. LRR 177/21). All participants will complete a written informed consent prior to enrolment in the study. The study results will be disseminated widely via local and international health conferences and peer-reviewed publications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Iyngkaran, Hanna, Andrew, Horowitz, Battersby and De Courten.)

Introduction: It has been estimated that congestive heart failure (CHF) will reach epidemic proportions and contribute to large unsustainable impacts on health budgets for any cardiovascular condition. Against other major trends in cardiovascular outcomes, readmission and disease burden continue to rise as the demographics shift., Methods: The rise in heart failure with preserved ejection fraction (HFpEF) among elderly women will present new challenges. Gold standard care delivers sustainable and cost-effective health improvements using organised care programs. When coordinated with large hospitals, this can be replicated universally., Results: A gradient of outcomes and ambulatory care needs to be shifted from established institutions and shared with clients and community health services, being a sizeable proportion of CHF care., Conclusion: In this review, we explore health technologies as an emerging opportunity to address gaps in CHF management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Heart failure (HF) is predominately a chronic disease. There are overlaps in HF and chronic disease research and care. Chronic disease and HF research are conducted with multiple goals. The overarching goal is "optimized patient outcomes at maximum costeffectiveness". However, observations on patients can come with many variables; thus, we see differences in clinical translation. This document discusses an argument for three important gaps common to HF and chronic disease, i.e., screening, self-management, and patient-reported outcomes (PRO), and provides a glance of how it could fit into the evidence tree. Pertinent arguments for a framework for health services and models of care are provided as a prelude to future consensus., Methodology: 1) A preliminary literature review to identify a taxonomy for cardiovascular research, and 2) a review of the published literature describing the translation of research studies into clinical practice for cardiovascular disorders. A spectrum from observational to large randomized controlled trials to post-marketing studies were identified., Discussion: A brief discussion on traditional research and differences focusing on screening, mixed methods research concepts, and chronic diseases models of care. Six steps to facilitate this: 1) Research design; 2) Research application (translation) i. routine ii. challenges; 3. Transforming research to translational level; 4. Funding and infrastructure; 5. Clinical Centres of Research Excellence (CCRE) and collaboration; 6. Governance and cost-effectiveness., Conclusion: Implementation research that aims to link research findings to improved patient outcomes in an efficient and effective way is a neglected area. Skills required to perform implementation research are complex. Ways to maximize translational impacts for chronic disease research to clinical practice are described in a HF context., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Enhancing community based Chronic Disease Management (CDM) will make significant impacts on all major chronic disease management outcome measures. There are no successful models of community hubs to triage and manage chronic diseases that significantly reduce readmissions, cost and improve chronic disease knowledge. Chronic heart failure (CHF) management foundations are built on guideline derived medical therapies (GDMT). These consensuses evidenced building blocks have to be interwoven into systems and processes of care which create access, collaboration and coordinate effective and innovative health services., Methods: Perspective and short communication., Conclusions: This review explores: (i) conventional chronic disease management in Australia; (ii) Possible options for future chronic diseases models of care that deliver key components of CHF management., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Objectives: To evaluate the capacity of general practice (GP) electronic medical record (EMR) data to assess risk factor detection, disease diagnostic testing, diagnosis, monitoring and pharmacotherapy for the interrelated chronic vascular diseases-chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease., Design: Cross-sectional analysis of data extracted on a single date for each practice between 12 April 2017 and 18 April 2017 incorporating data from any time on or before data extraction, using baseline data from the Chronic Disease early detection and Improved Management in PrimAry Care ProjecT. Deidentified data were extracted from GP EMRs using the Pen Computer Systems Clinical Audit Tool and descriptive statistics used to describe the study population., Setting: Eight GPs in Victoria, Australia., Participants: Patients were ≥18 years and attended GP ≥3 times within 24 months. 37 946 patients were included., Results: Risk factor and disease testing/monitoring/treatment were assessed as per Australian guidelines (or US guidelines if none available), with guidelines simplified due to limitations in data availability where required. Risk factor assessment in those requiring it: 30% of patients had body mass index and 46% blood pressure within guideline recommended timeframes. Diagnostic testing in at-risk population: 17% had diagnostic testing as per recommendations for CKD and 37% for T2D. Possible undiagnosed disease: Pathology tests indicating possible disease with no diagnosis already coded were present in 6.7% for CKD, 1.6% for T2D and 0.33% familial hypercholesterolaemia. Overall prevalence: Coded diagnoses were recorded in 3.8% for CKD, 6.6% for T2D, 4.2% for ischaemic heart disease, 1% for heart failure, 1.7% for ischaemic stroke, 0.46% for peripheral vascular disease, 0.06% for familial hypercholesterolaemia and 2% for atrial fibrillation. Pharmaceutical prescriptions: the proportion of patients prescribed guideline-recommended medications ranged from 44% (beta blockers for patients with ischaemic heart disease) to 78% (antiplatelets or anticoagulants for patients with ischaemic stroke)., Conclusions: Using GP EMR data, this study identified recorded diagnoses of chronic vascular diseases generally similar to, or higher than, reported national prevalence. It suggested low levels of extractable documented risk factor assessments, diagnostic testing in those at risk and prescription of guideline-recommended pharmacotherapy for some conditions. These baseline data highlight the utility of GP EMR data for potential use in epidemiological studies and by individual practices to guide targeted quality improvement. It also highlighted some of the challenges of using GP EMR data., Competing Interests: Competing interests: J-AM-N is an investigator in the Data for Decisions research initiative www.gp.unimelb.edu.au/datafordecisions which uses the GRHANITE research data collection tool. She is a lead investigator on the Future Health Today program which includes a quality improvement platform which differs to the one used in this study. All other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Congestive heart failure (CHF) management has proven devastating on morbidity, mortality, quality of life and also costly to health systems. Therapeutics for CHF have advanced and benefited greatly due to large multicentre randomised controlled trials and the evidence obtained from them. Management for chronic diseases and nonpharmaceutical therapies such as chronic disease self-management has lagged, and for CHF the evidence base has even been questioned., Methods: Perspective and non systematic mini review., Conclusions: Advancing translational research standards is important to achieve optimal cost effectiveness. Importantly is understanding evidence generation in medicine, identifying the primary roots for management and its translation., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Congestive Heart Filur is an epidemic and its trajectory apppears to be escaling. Undoubtly tremendous gains have seen improvement in life expectancy and quality of life, however, hospital readmissions, resource utilization and health system cost continue to create challenges. In this short perspective, we raise the prospect of extending the research phases the community and real world setting. Logistic have supported service supply chains during the COVID-19 pandemic and there are lesson here to be learned., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Plants that are primarily used as a food source commonly have undervalued biological properties beyond the basic supply of nutrients. One important example of this are the antimicrobial properties of plants. Inclusion of natural and food grade antimicrobial ingredients in recipes to prevent food spoilage and disease transmission, or in cosmetic products to prevent transient and pathogenic bacteria would have world-wide public health implications. A patented natural polyphenol rich sugar cane extract (PRSE), is marketed as a high anti-oxidant and polyphenol ingredient, but its anti-microbial activity has not been reported previously. We determined the anti-bacterial properties of PRSE on common human pathogens relating to a range of diseases including food poisoning, tooth decay, acne and severe skin infections using disc/well diffusion experiments. Our findings indicate that PRSE is an efficient antimicrobial, which could be included at differing dosages to target a range of food borne and environmental pathogens.

Carnosine has been shown to reduce oxidation and glycation of low density lipoprotein hence improving dyslipidaemia in rodents. The effect of carnosine on human plasma lipidome has thus far not been investigated. We aimed to determine whether carnosine supplementation improves the plasma lipidome in overweight and obese individuals. Lipid analysis was performed by liquid chromatography mass spectrometry in 24 overweight and obese adults: 13 were randomly assigned to 2 g carnosine daily and 11 to placebo, and treated for 12 weeks. Carnosine supplementation maintained trihexosylceramide (0.01 ± 0.19 vs -0.28 ± 0.34 nmol/ml, p = 0.04), phosphatidylcholine (77 ± 167 vs -81 ± 196 nmol/ml, p = 0.01) and free cholesterol (20 ± 80 vs -69 ± 80 nmol/ml, p = 0.006) levels compared to placebo. Trihexosylceramide was inversely related with fasting insulin (r = -0.6, p = 0.002), insulin resistance (r = -0.6, p = 0.003), insulin secretion (r = -0.4, p = 0.05) and serum carnosinase 1 activity (r = -0.3, p = 0.05). Both phosphatidylcholine and free cholesterol did not correlate with any cardiometabolic parameters. Our data suggest that carnosine may have beneficial effects on the plasma lipidome. Future larger clinical trials are needed to confirm this.

Type 2 diabetes mellitus (T2DM) is a complex chronic disease affecting over 400 million people worldwide. Managing T2DM and its associated complications in individual patient consultations poses substantial challenges to physicians due to limited time and resources and lack of access to multidisciplinary teams. Shared medical appointments (SMAs) are consecutive medical consultations provided by a physician in a group setting, where integrated medical care and patient education are delivered in a single session. SMAs allow physicians to deliver the same level of care to multiple patients at the same time, thereby maximizing available resources. However, the effectiveness and practicality of SMAs in the management of T2DM remains unknown. This narrative review summarizes current and emerging evidence regarding the effectiveness of SMAs in improving clinical outcomes in patients with T2DM, as well as whether SMAs are associated with reduced costs and improved diabetes-related behavioral and lifestyle changes. An extensive literature search was conducted on major electronic databases including PubMed and Google Scholar using keywords, including SMAs, group visits, and T2DM to identify all studies of SMAs in patients with T2DM. Studies in type 1 diabetes or mixed or unspecified populations were excluded, as well as studies where SMAs did not involve a physician since these do not meet the classical definition of a SMA. Nineteen studies were identified and are included in this review. Overall, current evidence suggests that SMAs delivered regularly over time may be effective in improving glycemic outcomes, diabetes knowledge, and some diabetes-related behaviors. However, the main limitation of existing studies was the paucity of comparisons with standard care which limits the ability to draw conclusions regarding whether SMAs are superior to standard care in T2DM management. Moreover, the small number of studies and substantial heterogeneity in study designs, populations, and interventions creates difficulties in establishing the practicality and efficiency of SMAs in the clinical care setting. We conclude that there remains a need for larger studies to identify populations who may or may not benefit from the SMA model of care and to clarify the potential benefits and barriers to implementing SMAs into routine diabetes care.

Introduction: Carnosine, an over-the-counter food supplement, has a promising potential for the prevention and treatment of chronic diseases such as type 2 diabetes (T2DM), cardiovascular and neurodegenerative diseases through its anti-inflammatory, antiglycation, antioxidative and chelating effects. We have previously shown that supplementation with carnosine preserves insulin sensitivity and secretion in non-diabetic overweight and obese individuals. The effect of carnosine on cardiometabolic risk and related cognitive outcomes in patients with pre-diabetes and T2DM has thus far not been studied. We therefore aim to investigate whether supplementation with carnosine improves cardiometabolic health and cognitive function in patients with pre-diabetes and T2DM., Methods and Analysis: We will employ a parallel design randomised controlled trial. Fifty participants with pre-diabetes (impaired fasting glycaemia and impaired glucose tolerance) and T2DM (with HbA1c level < 8%) aged between 18 to 70 years will be randomly assigned to the intervention or control group. At baseline, participants will undergo a medical review and series of tests including anthropometric measurements (body mass index, a dual X-ray absorptiometry and peripheral quantitative computed tomography scan), an oral glucose tolerance test, cardiovascular measurements (central blood pressure, endothelial function and arterial stiffness), cognitive function, physical activity measurement, heart rate variability and liver fibroscan as well as questionnaires to assess dietary habits, sleep quality, depression and quality of life. The intervention group will receive 2 g of carnosine daily in two divided doses while the control group will receive identical placebo capsules for 14 weeks. All baseline measurements will be repeated at the end of the intervention. The change in glycaemic, cardiovascular and cognitive parameters as well as other measures will be compared between the groups., Ethics and Dissemination: This study is approved by the Human Research Ethics Committee of Monash Health and Monash University, Australia. The findings will be disseminated via peer-reviewed publications and conference presentations., Trial Registration: NCT02917928; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Diets high in advanced glycation end products (AGEs) are thought to be detrimental to cardiovascular health. However, there remains uncertainty about the beneficial effect of a low AGE diet on cardiovascular risk factors and inflammatory markers in overweight individuals. We thus performed a randomised, double blind, crossover trial to determine whether consumption of low AGE diets reduce inflammation and cardiovascular risks in overweight and obese otherwise healthy adults. All participants (n = 20) consumed low and high AGE diets alternately for two weeks and separated by a four week washout period. Low AGE diets did not change systolic (p = 0.2) and diastolic blood pressure (p = 0.3), mean arterial pressure (p = 0.8) and pulse pressure (p = 0.2) compared to high AGE diets. Change in total cholesterol (p = 0.3), low-density lipoprotein (p = 0.7), high-density lipoprotein (p = 0.2), and triglycerides (p = 0.4) also did not differ and there was no difference in inflammatory markers: interleukin-6 (p = 0.6), monocyte chemoattractant protein-1 (p = 0.9), tumour necrosis factor α (p = 0.2), C-reactive protein (p = 0.6) and nuclear factor kappa beta (p = 0.2). These findings indicate that consumption of low AGE diets for two weeks did not improve the inflammatory and cardiovascular profiles of overweight and obese adults.

Background: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion. Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo. Design: Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)]. Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m 2 ): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg -1 · min -1 , respectively; P = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary vitamin D intake ( P > 0.1). Conclusions: Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults, despite using high-dose vitamin D supplementation and robust endpoint measures. Therefore, it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient populations. This trial was registered at clinicaltrials.gov as NCT02112721., (© 2017 American Society for Nutrition.)

Background: The consumption of advanced glycation end products (AGEs) has increased because of modern food processing and has been linked to the development of type 2 diabetes in rodents., Objective: We determined whether changing dietary AGE intake could modulate insulin sensitivity and secretion in healthy, overweight individuals., Design: We performed a double-blind, randomized, crossover trial of diets in 20 participants [6 women and 14 men; mean ± SD body mass index (in kg/m(2)): 29.8 ± 3.7]. Isoenergetic- and macronutrient-matched diets that were high or low in AGE content were alternately consumed for 2 wk and separated by a 4-wk washout period. At the beginning and end of each dietary period, a hyperinsulinemic-euglycemic clamp and an intravenous glucose tolerance test were performed. Dietary, plasma and urinary AGEs N(€)-(carboxymethyl)lysine (CML), N(€)-(carboxyethyl)lysin (CEL), and methylglyoxal-derived hydroimadazolidine (MG-H1) were measured with the use of mass spectrometry., Results: Participants consumed less CML, CEL, and MG-H1 during the low-AGE dietary period than during the high-AGE period (all P < 0.05), which was confirmed by changes in urinary AGE excretion. There was an overall difference in insulin sensitivity of -2.1 mg · kg(-1) · min(-1) between diets (P = 0.001). Insulin sensitivity increased by 1.3 mg · kg(-1) · min(-1) after the low-AGE diet (P = 0.004), whereas it showed a tendency to decrease by 0.8 mg · kg(-1) · min(-1) after the high-AGE diet (P = 0.086). There was no difference in body weight or insulin secretion between diets (P = NS)., Conclusions: A diet that is low in AGEs may reduce the risk of type 2 diabetes by increasing insulin sensitivity. Hence, a restriction in dietary AGE content may be an effective strategy to decrease diabetes and cardiovascular disease risks in overweight individuals. This trial was registered at clinicaltrials.gov as NCT00422253., (© 2016 American Society for Nutrition.)

Objective: Carnosine is a naturally present dipeptide in humans and an over-the counter food additive. Evidence from animal studies supports the role for carnosine in the prevention and treatment of diabetes and cardiovascular disease, yet there is limited human data. This study investigated whether carnosine supplementation in individuals with overweight or obesity improves diabetes and cardiovascular risk factors., Methods: In a double-blind randomized pilot trial in nondiabetic individuals with overweight and obesity (age 43 ± 8 years; body mass index 31 ± 4 kg/m(2) ), 15 individuals were randomly assigned to 2 g carnosine daily and 15 individuals to placebo for 12 weeks. Insulin sensitivity and secretion, glucose tolerance (oral glucose tolerance test), blood pressure, plasma lipid profile, skeletal muscle ((1) H-MRS), and urinary carnosine levels were measured., Results: Carnosine concentrations increased in urine after supplementation (P < 0.05). An increase in fasting insulin and insulin resistance was hampered in individuals receiving carnosine compared to placebo, and this remained significant after adjustment for age, sex, and change in body weight (P = 0.02, P = 0.04, respectively). Two-hour glucose and insulin were both lower after carnosine supplementation compared to placebo in individuals with impaired glucose tolerance (P < 0.05)., Conclusions: These pilot intervention data suggest that carnosine supplementation may be an effective strategy for prevention of type 2 diabetes., (© 2016 The Obesity Society.)

A number of approaches have been utilized in the prevention, management, and treatment of obesity, including, surgery, medication, diet, exercise, and overall lifestyle changes. Despite these interventions, the prevalence of obesity and the various disorders related to it is growing. In obesity, there is a constant state of chronic low-grade inflammation which is characterized by activation and infiltration of pro-inflammatory immune cells and a dysregulated production of high levels of pro-inflammatory cytokines. This pro-inflammatory milieu contributes to insulin resistance, type-2 diabetes, cardiovascular disease, and other related co-morbidities. The roles of the innate (macrophages, neutrophils, eosinophils, mast cells, NK cells, MAIT cells) and the adaptive (CD4 T cells, CD8 T cells, regulatory T cells, and B cells) immune responses and the roles of adipokines and cytokines in adipose tissue inflammation and obesity are discussed. An understanding of the crosstalk between the immune system and adipocytes may shed light in better treatment modalities for obesity and obesity-related diseases., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists., Methods and Results: Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body fat (bioimpedance), abdominal subcutaneous and visceral adiposity (magnetic resonance imaging), insulin sensitivity (euglycaemic hyperinsulinemic clamp), resting energy expenditure (REE, indirect calorimetry), free-living ambulatory physical activity (accelerometers) and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years) with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04) and subcutaneous (r = 0.38, p = 0.02) but not visceral fat (r = 0.17, p = 0.33). Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008), REE (r = -0.58, p<0.001) and HDL-cholesterol levels (r = -0.34, p = 0.048). Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity., Conclusion: Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

Obesity, type 2 diabetes, and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. Insulin resistance, which is a shared feature in these conditions, is also strongly linked to the development of polycystic ovary syndrome (PCOS), which is the most common endocrine disease in women of reproductive age and a major cause of infertility. Vitamin D deficiency has reached epidemic proportions worldwide, primarily due to the shift to sedentary, indoor lifestyles and sun avoidance behaviours to protect against skin cancer. In recent years, vitamin D deficiency has been implicated in the aetiology of type 2 diabetes, PCOS and CVD, and has been shown to be associated with their risk factors including obesity, insulin resistance, hypertension, as well as chronic low-grade inflammation. Treating vitamin D deficiency may offer a feasible and cost-effective means of reducing cardiometabolic risk factors at a population level in order to prevent the development of type 2 diabetes and CVD. However, not all intervention studies show that vitamin D supplementation alleviates these risk factors. Importantly, there is significant heterogeneity in existing studies with regards to doses and drug regimens used, populations studied (i.e. vitamin D deficient or sufficient), and the lengths of supplementation, and only few studies have directly examined the effect of vitamin D on insulin secretion and resistance with the use of clamp methods. Therefore, there is a need for well-designed large scale trials to clarify the role of vitamin D supplementation in the prevention of type 2 diabetes, PCOS, and CVD.

Background: Despite Australia's sunny climate, low vitamin D levels are increasingly prevalent. Sun exposure is limited by long working hours, an increase in time spent indoors, and sun protection practices, and there is limited dietary vitamin D fortification. While the importance of vitamin D for bone mineralization is well known, its role as a protective agent against chronic diseases, such as type 2 diabetes and cardiovascular disease, is less understood. Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion, mainly via its anti-inflammatory properties, thereby decreasing the risk of development and progression of type 2 diabetes. The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D (25(OH)D), obtained through vitamin D supplementation, will increase insulin sensitivity and insulin secretion. A secondary aim is to determine whether these relationships are mediated by a reduction in underlying subclinical inflammation associated with obesity., Methods/design: Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old, with low vitamin D levels (25(OH)D < 50 nmol/l), will be randomly assigned to intervention or placebo. At baseline, participants will undergo a medical review and anthropometric measurements, including dual X-ray absorptiometry, an intravenous glucose tolerance test, muscle and fat biopsies, a hyperinsulinemic euglycemic clamp, and questionnaires assessing diet, physical activity, sun exposure, back and knee pain, and depression. The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D (cholecalciferol) daily, while the placebo group will receive apparently identical capsules, both for a period of 16 weeks. All measurements will be repeated at follow-up, with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group. Secondary outcome measures will compare changes in anthropometry, cardiovascular risk factors, and inflammatory markers., Discussion: The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms, which are relevant for the prevention and management of type 2 diabetes., Trial Registration: Clinicaltrials.gov ID: NCT02112721 .

Background: Advanced glycation end products (AGEs) are formed during the processing, storage, and cooking of foods. As part of a western diet, AGEs are consumed in excess and impair glucose metabolism in patients with type 2 diabetes. In the absence of diabetes, AGE-mediated decreases in insulin sensitivity and signaling have been postulated. However, randomized studies to test this relationship in humans are limited., Objective: The primary aim of this trial is to determine whether dietary consumption of AGEs will decrease insulin sensitivity in healthy overweight adults. A secondary aim is to determine the effects of dietary AGEs on insulin secretion, circulating soluble receptor for AGEs (sRAGE), and inflammation markers., Methods: Overweight, but otherwise healthy, non-diabetic adults (N=20) aged 18-50 years old will complete a randomized cross-over design intervention study alternating low and high (4-fold increase) AGE diets (2-week duration). At baseline, participants will undergo a medical review including an intravenous glucose tolerance test (IVGTT), a hyperinsulinemic-euglycemic clamp, and anthropometric measures and questionnaires assessing diet, physical activity, and general wellness. Each test diet will be followed for 14 days, followed by a 4-week washout period before commencement of the second alternate dietary period. Energy, macronutrient, and AGE intake will be calculated for each dietary period. Additionally, the AGE content of foods used in the study will be measured by ultra performance liquid chromatography mass spectrometry. All measurements will be repeated at the beginning and end of each dietary period. Primary and secondary outcomes will be expressed as a change over the dietary period for insulin sensitivity, secretion, anthropometric parameters, sRAGE, and inflammation markers and compared by paired t test and analysis of variance (ANOVA)., Results: The study will be completed in early 2016., Conclusion: The proposed trial will provide much needed clinical evidence on the impact of excess dietary AGE consumption on insulin sensitivity and will indicate whether lowering dietary AGE intake can improve insulin sensitivity and/or secretion, thereby decreasing risk for type 2 diabetes., Trial Registration: Clinicaltrials.gov NCT00422253; https://clinicaltrials.gov/ct2/show/NCT00422253 (Archived by Webcite at http://www.webcitation.org/6ZXLhT89c).

It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p < 0.05) and lower 2-h glucose concentrations during OGTT (r = -0.31; p < 0.05). In addition, fasting (r = -0.36; p < 0.05) and 2-h glucose concentrations were negatively related to circulating levels of soluble receptor for AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.

Background: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals., Methods: We measured body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males). Carboxymethyl-lysine (CML) was measured by ELISA as a marker for circulating AGEs and NF-κB p65 activity as an inflammatory marker by DNA-binding in peripheral blood mononuclear cells lysates (PBMC)., Results: Plasma CML concentrations were related to diastolic blood pressure (r=-0.51, p<0.01) independently of age, sex, BMI and WHR (p<0.05). Diastolic blood pressure was also related to NF-κB activity in PBMC (r=0.47, p<0.01) before and after adjustment for age, sex, BMI and WHR (p<0.05). Plasma CML concentrations were related to the pulse pressure before (r=0.42; p<0.05) and after adjustment for age, sex, BMI and waist (p<0.05). Neither CML nor NF-κB activity were related to systolic blood pressure (both p=ns). Plasma CML concentrations were not associated with plasma lipid or glucose concentrations (all p=ns)., Conclusions: Plasma AGE levels and NF-κB activity in PBMC were independent determinants of diastolic and pulse pressure in healthy normotensive individuals. This association suggests a role for AGEs in the etiology of hypertension, possibly via the initiation of CLAIS and aortic stiffening.

Objective: Plasma Hepatocyte Growth Factor (HGF) is significantly elevated in obesity and may contribute to vascular disease, metabolic syndrome or cancer in obese individuals. The current studies were done to determine if hyperinsulinemia increases plasma HGF., Materials/methods: Twenty-two participants (10 women/12 men, BMI 20.6-34.5 kg/m(2), age 18-49 years) underwent a hyperinsulinemic euglycemic clamp with measurement of HGF at baseline and steady state. Relationships between baseline HGF, anthropometrics, triglycerides, liver enzymes, c-reactive protein and adiponectin were also evaluated., Results: Fasting HGF was positively correlated (P<0.050) with weight (r=0.63), BMI (r=0.55), waist circumference (r=0.68), WHR (r=0.48), triglycerides (r=0.44), alanine aminotransferase (r=0.74) and γ-glutamyl transpeptidase (r=0.56), but not c-reactive protein or adiponectin. In stepwise regression, alanine aminotransferase and insulin sensitivity accounted for significant variation in fasting HGF. A significant effect of insulin to suppress HGF during the clamp (P=0.029) was found after adjustment for BMI. HGF was reduced 7% at steady state in the lean subjects only (437.1 ±57.8 vs 405.4±72.0 pg/ml; P=0.030)., Conclusions: The positive correlation of HGF with hepatic enzymes suggests liver may be a significant source of circulating HGF in lean subjects. The strong correlation of plasma HGF with adiposity and the lack of an effect of insulin to increase HGF during the clamp in obese subjects suggest that adiposity, rather than elevated insulin levels, may be the major contributor to plasma HGF in obese subjects. Thus, a reduction in plasma HGF through weight loss is likely the best way to decrease comorbidities mediated by this angiogenic and mitogenic factor., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Obesity is highly prevalent in Western populations and is considered a risk factor for the development of renal impairment. Interventions that reduce the tissue burden of advanced glycation end-products (AGEs) have shown promise in stemming the progression of chronic disease. Here we tested if treatments that lower tissue AGE burden in patients and mice would improve obesity-related renal dysfunction. Overweight and obese individuals (body mass index (BMI) 26-39 kg/m(2)) were recruited to a randomized, crossover clinical trial involving 2 weeks each on a low- and a high-AGE-containing diet. Renal function and an inflammatory profile (monocyte chemoattractant protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF)) were improved following the low-AGE diet. Mechanisms of advanced glycation-related renal damage were investigated in a mouse model of obesity using the AGE-lowering pharmaceutical, alagebrium, and mice in which the receptor for AGE (RAGE) was deleted. Obesity, resulting from a diet high in both fat and AGE, caused renal impairment; however, treatment of the RAGE knockout mice with alagebrium improved urinary albumin excretion, creatinine clearance, the inflammatory profile, and renal oxidative stress. Alagebrium treatment, however, resulted in decreased weight gain and improved glycemic control compared with wild-type mice on a high-fat Western diet. Thus, targeted reduction of the advanced glycation pathway improved renal function in obesity.

Decreased gene expression of heat shock protein 72 (HSP72) in skeletal muscle is associated with insulin resistance in humans. We aimed to determine whether HSP72 protein expression in insulin-sensitive tissues is related to criterion standard measures of adiposity and insulin resistance in a young healthy human population free of hyperglycemia. Healthy participants (N = 17; age, 30 ± 3 years) underwent measurement of body composition (dual-energy x-ray absorptiometry), a maximum aerobic capacity test (VO(2max)), an oral glucose tolerance test, and a hyperinsulinemic-euglycemic clamp (M) to access insulin sensitivity. Skeletal muscle and subcutaneous adipose tissue biopsies were obtained by percutaneous needle biopsy. HSP72 protein expression in skeletal muscle was inversely related to percentage body fat (r = -0.54, P < .05) and remained significant after adjustment for age and sex (P < .05). Insulin sensitivity was also related to HSP72 protein expression in skeletal muscle (r = 0.52, P < .05); however, this relationship disappeared after adjustment for percentage body fat (P = .2). In adipose tissue, HSP72 protein expression was not related to adiposity or insulin sensitivity. Physical activity and aerobic fitness did not show any association with HSP72 protein expression in either tissue studied. A lower expression of HSP72 protein in human skeletal muscle was associated with increased adiposity and decreased insulin sensitivity in healthy individuals. These findings are consistent with rodent data suggesting that HSP72 stimulates fat oxidation with consequent reduction in fat storage and adiposity., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: People with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) compared with the general population. We investigated the relative contribution of traditional cardiovascular risk factors to this elevated risk., Methods: Fifty RA subjects and 150 age and sex matched controls attended a cardiovascular risk assessment clinic betweenMarch and July 2006. Traditional cardiovascular risk factors and the absolute risks of CVD (calculated from application of a Framingham risk equation) were compared between the 2 groups., Results: Compared with the controls, RA subjects were more likely to smoke (p<0.001), be physically inactive (p=0.006), and have higher mean measurements of body mass index (p=0.040) and waist circumference (p=0.049). No significant differences were found in mean levels of plasma lipid or glucose, or in the prevalences of diabetes and hypertension. Overall, the mean absolute risk of CVD was higher in the RA group, even after excluding smokers (p=0.036)., Conclusion: Smoking and physical inactivity are important risk factors in the management of cardiovascular risk among patients with RA. Subjects with RA seem to have higher absolute risks of CVD compared with controls, even independently of smoking. This highlights the importance of treating all modifiable risk factors in those with RA although, individually, few may be conspicuous.

Aim: We examined the association of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG) and HbA1c with retinopathy and microalbuminuria using both deciles of glycaemia and change point models, to validate current diagnostic criteria for diabetes and to identify therapeutic thresholds for glycaemic control., Methods: The Australian Diabetes Obesity and Lifestyle study (AusDiab), conducted in 1999-2000, included adults aged > or =25 years from 42 randomly selected areas of Australia. Retinopathy and albuminuria were assessed in participants identified as having diabetes (based on self report and oral glucose tolerance test), impaired fasting glucose, impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,182 participants with retinal photographs and 2,389 with urinary albumin/creatinine results., Results: The prevalence of retinopathy in the first 8 deciles of FPG and HbA1c and the first 9 deciles of 2hPG were 7.2, 6.6, and 6.3%, respectively and showed no variation with increasing glucose or HbA1c. Above these levels, the prevalence rose markedly to 18.6% in the top 2 deciles of FPG, 21.3% in the top 2 deciles of HbA1c and 10.9% in the top decile of 2hPG. The thresholds for increasing prevalence of retinopathy were 7.1 mmol/l for FPG, 6.1% for HbA1c and 13.1 mmol/l for 2hPG. The prevalence of microalbuminuria rose gradually across deciles of each glycaemic measure. Thresholds were less clear than for retinopathy, but were seen at a FPG of 7.2 mmol/l and HbA1c of 6.1%, with no evidence of a threshold effect for 2hPG., Conclusions: The prevalence of retinopathy rose dramatically in the highest deciles of each glycaemic measure, while for microalbuminuria the increase of prevalence was more gradual. The FPG values corresponded well with the WHO diagnostic cut-point for diabetes, however the 2hPG value did not. HbA1c thresholds were similar for both retinopathy and microalbuminuria and compared well to values shown in other studies. These results support current targets for FPG and HbA1c in preventing microvascular complications.

Objective: To examine gender differences in the characteristics and prevalence of various categories of glucose tolerance in a population study in Mauritius., Research Design and Methods: In 1998, a community-based cross-sectional survey was conducted in Mauritius. Categories of glucose metabolism were determined in 5388 adults, with an oral glucose tolerance test given to those who did not have previously diagnosed diabetes (n=4036). Other cardiovascular risk factors were assessed among those without known diabetes., Results: For men and women the prevalence of diabetes (22.0 vs. 21.8%, respectively) and the prevalence of coexisting impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (3.2 vs. 2.9%) were similar. However, men were twice as likely as women to have isolated IFG [5.1% (4.2-6.0) vs. 2.9% (2.3-3.5)], despite being younger, thinner and with lower plasma insulin but higher lipids. Conversely, the prevalence of isolated IGT was lower in men [9.0% (7.9-10.2) vs. 13.9% (12.6-15.1)]. Among non-diabetic individuals, fasting glucose was higher in men than women, whereas 2-h glucose was higher in women. In people without diabetes, women had significantly higher body mass index, beta cell function (HOMA-B), fasting and 2-h insulin than men and significantly lower waist-hip ratios, waist circumference, insulin sensitivity (HOMA-S) and triglycerides., Conclusion: In Mauritius, the distribution of impaired glucose metabolism differs by sex. The observation that IFG is more prevalent in men and IGT more prevalent in women raises important questions about their underlying aetiology and the ability of the current glucose thresholds to equally identify men and women at high-risk of developing diabetes. IFG should be seen as a complimentary category of abnormal glucose tolerance, rather than a replacement for IGT.

Objective: To determine the prevalence and factors associated with diabetic retinopathy in the Australian population and to estimate the time difference between disease onset and clinical diagnosis of type 2 diabetes., Research Design and Methods: The Australian Diabetes, Obesity and Lifestyle study (AusDiab) included 11,247 adults aged > or =25 years in 42 randomly selected areas of Australia. Retinopathy was assessed in participants identified as having diabetes (based on self-report and oral glucose tolerance test), impaired fasting glucose, and impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,177 participants., Results: Overall, 15.3% of those with diabetes had retinopathy. The prevalence of retinopathy was 21.9% in those with known type 2 diabetes (KDM) and 6.2% in those newly diagnosed (NDM). The prevalence of proliferative diabetic retinopathy (PDR) was 2.1% in those with KDM. No cases of PDR were found in those with NDM. Untreated vision threatening retinopathy (presence of PDR or macular edema) was present in 1.2% (n = 4). Factors associated with retinopathy were duration of diabetes, HbA(1c), and systolic blood pressure. Using linear extrapolation of the prevalence of retinopathy with diabetes duration, the onset of diabetes in this population was approximately the time of diagnosis., Conclusions: This is one of the first national studies of diabetic retinopathy in a developed country. The prevalence of retinopathy was similar to that in other population-based studies. Vision threatening retinopathy was relatively rare; however, four untreated cases were identified. Regular screening for diabetic retinopathy and more aggressive management of modifiable risk factors could reduce the numbers of people who develop vision-threatening retinopathy.

Aims: To determine the prevalence and risk factors for neuropathy and peripheral vascular disease (PVD) in the Australian diabetic population and identify those at high risk of foot ulceration., Methods: The Australian Diabetes Obesity and Lifestyle study included 11 247 adults aged >or= 25 years in 42 randomly selected areas of Australia. Neuropathy and PVD were assessed in participants identified as having diabetes (based on self report and oral glucose tolerance test), impaired fasting glucose, impaired glucose tolerance and in a random sample with normal glucose tolerance (total n = 2436)., Results: The prevalence of peripheral neuropathy was 13.1% in those with known diabetes (KDM) and 7.1% in those with newly diagnosed (NDM). The prevalence of PVD was 13.9% in KDM and 6.9% in NDM. Of those with diabetes, 19.6% were at risk of foot ulceration. Independent risk factors for peripheral neuropathy were diabetes duration (odds ratio (95% CI) 1.73 (1.33-2.28) per 10 years), height (1.42 (1.08-1.88) per 10 cm), age (2.57 (1.94-3.40) per 10 years) and uric acid (1.59 (1.21-2.09) per 0.1 mmol/l). Risk factors for PVD were diabetes duration (1.64 (1.25-2.16) per 10 years), age (2.45 (1.86-3.22) per 10 years), smoking (2.07 (1.00-4.28)), uric acid (1.03 (1.00-1.06) per 0.1 mmol/l) and urinary albumin/creatinine ratio (1.11 (1.01-1.21) per 1 mg/mmol)., Conclusions: The prevalence of neuropathy and PVD was lower in this population than has been reported in other populations. This may reflect differences in sampling methods between community and hospital-based populations. Nevertheless, a substantial proportion of the diabetic population had risk factors for foot ulceration.

Objective: To determine the population-based prevalence of diabetes and other categories of glucose intolerance (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) in Australia and to compare the prevalence with previous Australian data., Research Design and Methods: A national sample involving 11,247 participants aged > or =25 years living in 42 randomly selected areas from the six states and the Northern Territory were examined in a cross-sectional survey using the 75-g oral glucose tolerance test to assess fasting and 2-h plasma glucose concentrations. The World Health Organization diagnostic criteria were used to determine the prevalence of abnormal glucose tolerance., Results: The prevalence of diabetes in Australia was 8.0% in men and 6.8% in women, and an additional 17.4% of men and 15.4% of women had IGT or IFG. Even in the youngest age group (25-34 years), 5.7% of subjects had abnormal glucose tolerance. The overall diabetes prevalence in Australia was 7.4%, and an additional 16.4% had IGT or IFG. Diabetes prevalence has more than doubled since 1981, and this is only partially explained by changes in age profile and obesity., Conclusions: Australia has a rapidly rising prevalence of diabetes and other categories of abnormal glucose tolerance. The prevalence of abnormal glucose tolerance in Australia is one of the highest yet reported from a developed nation with a predominantly Europid background.

Objective: Physical activity and insulin sensitivity are related in epidemiological studies, but the consistency of this finding among populations that greatly differ in body size is uncertain. The present multiethnic epidemiological study examined whether physical activity was related to insulin concentrations in two populations at high risk for diabetes that greatly differ by location, ethnic group, and BMI., Research Design and Methods: The study populations consisted of 2,321 nondiabetic Pima Indian men and women aged 15-59 years from Arizona and 2,716 nondiabetic men and women aged 35-54 years from Mauritius. Insulin sensitivity was estimated by mean insulin concentration (average of the fasting and postload insulin), and total (i.e., leisure and occupational) physical activity was assessed by questionnaire., Results: Pima men and women who were more active had significantly (P < 0.05) lower mean insulin concentrations than those less active (BMI and age-adjusted means were 179 vs. 200 and 237 vs. 268 pmol/l). Similar findings were noted in Mauritian men and women (94 vs. 122 and 127 vs. 148 pmol/l). In both populations, activity remained significantly associated with mean insulin concentration controlled for age, BMI, waist-to-thigh or waist-to-hip ratio, and mean glucose concentrations., Conclusions: Physical activity was negatively associated with insulin concentrations both in the Pima Indians, who tend to be overweight, and in Mauritians, who are leaner. These findings suggest a beneficial role of activity on insulin sensitivity that is separate from any influence of activity on body composition.

Objectives: To describe changes in the prevalence of cigarette smoking in the middle income country of Mauritius from 1987 to 1998, and to relate these changes to legislative and health promotion efforts over the same period., Design: Questionnaire survey., Setting: Mauritius, an island in the Indian Ocean with a population of about 1.2 million (about 70% south Asian, 2% Chinese, and 28% Creole)., Participants: Data were obtained from 5072 participants in 1987, 6573 in 1992, and 6281 in 1998., Main Outcome Measures: Prevalence of current smoking in 1987, 1992, and 1998, sales of cigarettes in Mauritius, and information on activities for control of tobacco., Results: Self reported cigarette smoking has been decreasing in Mauritius since 1987, with the largest decrease between 1987 and 1992. From 1987 to 1998 smoking prevalence decreased by 23% in men and 61% in women. Smoking decreased across all age and ethnic groups and across different levels of income and education. Sales of cigarettes also decreased in line with smoking prevalence., Conclusions: The introduction of cigarette taxes, a limited health promotion programme, and the absence of massive promotional campaigns by the sole tobacco company on Mauritius have led to a striking and continued decrease in smoking prevalence and cigarette consumption on the island.

Objective: To investigate the relationship between polymorphisms in the OB-R and OB genes and metabolic markers for obesity and glucose intolerance in a population of Nauruan men. In addition, we examined the effect of the simultaneous presence of the three polymorphisms on the phenotype of individuals in this population., Design and Subjects: This study was conducted in a population from the Pacific Island of Nauru. Populations in this region have some of the highest recorded rates of obesity and type 2 diabetes and are therefore of great interest in the genetic analysis of these diseases. Two hundred and thirty-two male subjects were examined in this cross-sectional study. All subjects were non-diabetic and the group had a mean age of 31 y and a mean body weight of 104 kg., Measurements: Several phenotypic measures of body fatness and fat distribution (anthropometry), fasting plasma insulin, glucose and leptin concentrations, blood pressure and 2 h plasma glucose concentration, genotypes of subjects for the Gln223Arg, PRO1019pro (OB-R gene) and OB gene polymorphisms., Results: Individually, the OB gene and Gln223Arg OB-R polymorphisms were not associated with the obese or glucose-intolerant phenotype in this population. Individuals with the PRO1019pro polymorphism were found to have elevated insulin concentrations and diastolic blood pressure (Pc = 0.04). In addition, individuals found to simultaneously exhibit homozygosity of the common allele of all three polymorphisms (genotypes: Arg/Arg, pro/pro and II/II) exhibited significantly elevated fasting insulin levels (Pc = 0.03)., Conclusions: Pacific Island populations exhibit a remarkably high prevalence rate of obesity and type 2 diabetes and represent a unique population for genetic studies of obesity. In the present study we have revealed that a specific combination of alleles in OB and OB-R, two candidate genes for obesity, may confer an increased risk for the development of insulin resistance in Nauruan males.