Ex-vivo systems for neuromodulation: A comparison of ex-vivo and in-vivo large animal nerve electrophysiology.

BACKGROUND: Little research exists on extending ex-vivo systems to large animal nerves, and to the best of our knowledge, there has yet to be a study comparing these against in-vivo data. This paper details the first ex-vivo system for large animal peripheral nerves to be compared with in-vivo results. NEW METHOD: Detailed ex-vivo and in-vivo closed-loop neuromodulation experiments were conducted on pig ulnar nerves. Temperatures from 20 °C to 37 °C were evaluated for the ex-vivo system. The data were analysed in the time and velocity domains, and a regression analysis established how evoked compound action potential amplitude and modal conduction velocity (CV) varied with temperature and time after explantation. MAIN RESULTS: Pig ulnar nerves were sustained ex-vivo up to 5 h post-explantation. CV distributions of ex-vivo and in-vivo data were compared, showing closer correspondence at 37 °C. Regression analysis results also demonstrated that modal CV and time since explantation were negatively correlated, whereas modal CV and temperature were positively correlated. COMPARISON WITH EXISTING METHODS: Previous ex-vivo systems were primarily aimed at small animal nerves, and we are not aware of an ex-vivo system to be directly compared with in-vivo data. This new approach provides a route to understand how ex-vivo systems for large animal nerves can be developed and compared with in-vivo data. CONCLUSION: The proposed ex-vivo system results were compared with those seen in-vivo, providing new insights into large animal nerve activity post-explantation. Such a system is crucial for complementing in-vivo experiments, maximising collected experimental data, and accelerating neural interface development.

Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study.

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Cardiovascular Mortality, Habitual Exercise, and Particulate Matter 2.5 Exposure: A Longitudinal Cohort Study.

INTRODUCTION: Habitual exercise may amplify the respiratory uptake of air pollutants in the lung, exacerbating the adverse effects of air pollution. However, it is unclear whether this can reduce the health benefits of habitual exercise (referred to as leisure-time exercise). Thus, the combined effects of habitual exercise and chronic exposure to ambient fine particulate matter 2.5 on cardiovascular mortality were examined among adults in Taiwan. METHODS: A total of 384,128 adults were recruited between 2001 and 2016 and followed up to May 31, 2019. Participants' vital status was obtained by matching their unique identification numbers with records of cardiovascular death in the National Death Registry of Taiwan. A time-varying Cox regression model was used to analyze the data. Analyses were conducted in 2021. RESULTS: Cardiovascular death risks were inversely associated with habitual exercise and positively associated with chronic exposure to particulate matter 2.5. The beneficial effects of habitual exercise on cardiovascular mortality were not modified by chronic exposure to particulate matter 2.5. Inactive participants with high particulate matter 2.5 exposure exhibited a 123% higher risk of cardiovascular death than high-exercise-group participants exposed to low levels of particulate matter 2.5 (95% CI=89, 163). CONCLUSIONS: High level of habitual exercise combined with low exposure level of ambient particulate matter 2.5 is associated with the lowest risk of cardiovascular death. A higher level of habitual exercise is associated with a lower risk of cardiovascular death at all levels of particulate matter 2.5 exposure studied. The results indicate that habitual exercise is a safe health promotion strategy even for people residing in relatively polluted regions.

Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Patient and Public Involvement and Engagement (PPIE): first steps in the process of the engagement in research projects in Brazil.

Patient and Public Involvement and Engagement (PPIE) - sometimes called Community Engagement and Involvement (CEI) - comes as a big challenge but one that can be very helpful for health care professionals and stakeholders in planning better health policies for attending to the main needs of the community. PPIE involves three pillars: public involvement, public engagement, and participation. Public involvement occurs when members of the general population are actively involved in developing the research question, designing, and conducting the research. Public engagement tells people about new studies, why they are important, the impact of results, the possible implication of the main findings for the community, and the possible impact of these new findings in society, as well as, in the dissemination of knowledge to the general population. Participation is being a volunteer in the study. Our experience with PPIE, to the best of our knowledge the first initiative in Brazil, is a partnership with the University of Birmingham, the University of Liverpool, and the NIHR Global Health Group on Atrial Fibrillation (AF) Management focusing on the AF care pathway exploring the important aspects of diagnosis and treatment in the primary care system from a low-middle income area in São Paulo. The involvement of patients/public in the research represents a new step in the process of inclusion of all segments of our society based on patient illness and the gaps in knowledge aiming to open new horizons for continuous improvement and better acceptance of research projects.

Patient and Public Involvement and Engagement (PPIE): first steps in the process of the engagement in research projects in Brazil

Patient and Public Involvement and Engagement (PPIE) - sometimes called Community Engagement and Involvement (CEI) - comes as a big challenge but one that can be very helpful for health care professionals and stakeholders in planning better health policies for attending to the main needs of the community. PPIE involves three pillars: public involvement, public engagement, and participation. Public involvement occurs when members of the general population are actively involved in developing the research question, designing, and conducting the research. Public engagement tells people about new studies, why they are important, the impact of results, the possible implication of the main findings for the community, and the possible impact of these new findings in society, as well as, in the dissemination of knowledge to the general population. Participation is being a volunteer in the study. Our experience with PPIE, to the best of our knowledge the first initiative in Brazil, is a partnership with the University of Birmingham, the University of Liverpool, and the NIHR Global Health Group on Atrial Fibrillation (AF) Management focusing on the AF care pathway exploring the important aspects of diagnosis and treatment in the primary care system from a low-middle income area in São Paulo. The involvement of patients/public in the research represents a new step in the process of inclusion of all segments of our society based on patient illness and the gaps in knowledge aiming to open new horizons for continuous improvement and better acceptance of research projects.

Risk of cardiovascular outcomes among women with endometriosis in the United Kingdom: a retrospective matched cohort study.

OBJECTIVE: To describe the prevalence and incidence of endometriosis and to estimate the risk of cardiovascular outcomes in women with endometriosis. DESIGN: Population-based cohort study using The Health Improvement Network database. SETTING: UK primary care. POPULATION: Women aged 16-50 years were followed from 1995 to 2018. METHODS: Adjusted hazard ratios (aHR) for cardiovascular outcomes comparing women with endometriosis with those without endometriosis were estimated using multivariable Cox regression models. Prevalence and incidence of endometriosis were estimated using annual (1998-2017) sequential cross-sectional and cohort studies, respectively. MAIN OUTCOME MEASURE: The primary outcome was composite cardiovascular disease (CVD) including, ischaemic heart disease (IHD), heart failure (HF) and cerebrovascular disease. Secondary outcomes were arrhythmia, hypertension and all-cause mortality. RESULTS: In all, 56 090 women with endometriosis and 223 669 matched controls without endometriosis were included in the analysis of cardiovascular risk. Compared with women without endometriosis, the aHR for cardiovascular outcomes among women with endometriosis were: composite CVD 1.24 (95% CI 1.13-1.37); IHD 1.40 (95% CI 1.22-1.61); cerebrovascular disease 1.19 (95% CI 1.04-1.36); HF 0.76 (95% CI 0.54-1.07); arrhythmia 1.26 (95% CI 1.11-1.43); hypertension 1.12 (95% CI 1.07-1.17) and all-cause mortality 0.66 (95% CI 0.59-0.74). The incidence of endometriosis was 12.3 per 10 000 person-years in 1998 and 11.5 per 10 000 person-years in 2017. The prevalence of endometriosis increased from 119.7 per 10 000 population in 1998 to 201.3 per 10 000 population in 2017. CONCLUSION: Endometriosis is associated with an increased risk of cardiovascular outcomes. Young women with endometriosis are a potential target for CVD risk assessment and prevention. TWEETABLE ABSTRACT: Endometriosis is associated with increased risk of cardiovascular outcomes: a UK retrospective matched cohort study.

Impact of obesity and metabolic health status in the development of non-alcoholic fatty liver disease (NAFLD): A United Kingdom population-based cohort study using the health improvement network (THIN).

BACKGROUND: With the obesity epidemic reaching crisis levels, there has been attention around those who may be resilient to the effects of obesity, termed metabolically healthy obesity (MHO), who initially present without associated metabolic abnormalities. Few longitudinal studies have explored the relationship between MHO and non-alcoholic fatty liver disease (NAFLD), which we address using over 4 million primary care patient records. METHODS: A retrospective population-based longitudinal cohort was conducted using The Health Improvement Network (THIN) database incorporating adults with no history of NAFLD or alcohol excess at baseline. Individuals were classified according to BMI category and metabolic abnormalities (diabetes, hypertension and dyslipidaemia). Diagnosis of NAFLD during follow-up was the primary outcome measure. NAFLD was identified by Read codes. RESULTS: During a median follow-up period of 4.7 years, 12,867 (0.3%) incident cases of NAFLD were recorded in the cohort of 4,121,049 individuals. Compared to individuals with normal weight and no metabolic abnormalities, equivalent individuals who were overweight, or obese were at significantly greater risk of incident NAFLD (Adjusted HR 3.32 (95%CI 2.98-3.49), and 6.92 (6.40-7.48, respectively). Metabolic risk factors further increased risk, including in those with normal weight and 1 (2.27, 1.97-2.61) or = < 2 (2.39, 1.99-2.87) metabolic abnormalities. CONCLUSIONS: MHO individuals are at greater risk of developing NAFLD compared to those with normal weight. This finding supports that the MHO phenotype is a temporary state, and weight must be considered a risk factor even before other risk factors develop. Being normal weight with metabolic abnormalities was also associated with risk of NAFLD.

The double burden of malnutrition among adolescents: analysis of data from the Global School-Based Student Health and Health Behavior in School-Aged Children surveys in 57 low- and middle-income countries.

Background: Adults and young children in countries experiencing the nutrition transition are known to be affected simultaneously by undernutrition and overnutrition. Adolescence is a critical period for growth and development. Yet, it is unknown to what extent this double burden of malnutrition affects adolescents in low- and middle-income countries (LMICs) and the macrolevel contextual factors associated with the double burden of malnutrition. Objective: The aim was to quantify the magnitude of the double burden of malnutrition among adolescents and to examine the potential sources of heterogeneity in prevalence estimates across LMICs. Design: We used individual-participant data from the Global School-Based Student Health and Health Behavior in School-Aged Children surveys conducted in 57 LMICs between 2003 and 2013, comprising 129,276 adolescents aged 12-15 y. Pooled estimates of stunting, thinness, or both; overweight or obesity; and concurrent stunting and overweight or obesity were calculated overall, by regions, and stratified by sex, with random-effects meta-analysis. Guided by UNICEF's conceptual framework for child malnutrition, we used ecological linear regression models to examine the association between macrolevel contextual factors (internal conflict, lack of democracy, gross domestic product, food insecurity, urbanization, and survey year) and stunting, thinness, and overweight and obesity prevalence, respectively. Results: The prevalence of stunting was 10.2% (95% CI: 8.3%, 12.2%) and of thinness was 5.5% (95% CI: 4.3%, 6.9%). The prevalence of overweight or obesity was 21.4% (95% CI: 18.6%, 24.2%). Between 38.4% and 58.7% of the variance in adolescent malnutrition was explained by macrolevel contextual factors. The prevalence of concurrent stunting and overweight or obesity was 2.0% (95% CI: 1.7%, 2.5%). Conclusions: The double burden of malnutrition among adolescents in LMICs is common. Context-sensitive implementation and scale-up of interventions and policies for the double burden of malnutrition are needed to achieve the Sustainable Development Goal to end malnutrition in all of its forms by 2030. This trial was registered at clinicaltrials.gov as NCT03346473.

Adiposity and incident diabetes within 4 years of follow-up: the Guangzhou Biobank Cohort Study.

AIM: Whether different adiposity measures predict incident diabetes differentially in general Chinese populations is unclear. We investigated this in Chinese people aged 50+ years in the Guangzhou Biobank Cohort Study. METHODS: Waist circumference and BMI were measured at baseline, and fasting glucose was measured at both baseline and follow-up examinations. Incident diabetes was defined as fasting glucose ≥ 7.0 mmol/l, glucose after 2-h oral glucose tolerance test ≥ 11.1 mmol/l, and/or self-reported physician-diagnosed diabetes during the follow-up period. RESULTS: Of 15 752 people without diabetes at baseline from 2003 to 2008, 1779 (11.3%) developed incident diabetes during the follow-up from 2008 to 2012 (mean = 3.6 years, sd = 1.0). After mutually adjusting each other and adjusting for other potential confounders, waist circumference showed a higher predictive value than BMI. The odds ratio (OR) (95% confidence interval (CI) was 1.50 (95% CI 1.37-1.64) for a 1 sd increment in waist circumference and 1.21 (95% CI 1.11-1.33), for a 1 sd increment in BMI. Similarly, after mutual adjustment, abdominal obesity was associated with an almost twofold odds of incident diabetes (OR 1.93, 95% CI 1.71-2.17), which was higher than that for general obesity (OR 1.76, 95% CI 1.50-2.06). The area under receiver operating characteristic curve (AUC) for waist circumference was higher than that for BMI [AUC = 0.676 (95% CI 0.660-0.686) vs. 0.665 (95% CI 0.651-0.678), P = 0.02]. CONCLUSION: Abdominal obesity predicted incident diabetes in older people better than general obesity. Our findings may be an early warning signal for local government or public health practitioners to develop and investigate more effective intervention programmes for diabetes, and should also be disseminated to the public to pay more attention to this important public health issue.

All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based, open cohort study.

AIM: The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. METHODS: We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n=8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n=16,541). RESULTS: Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56-0.74, P-value<0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53-0.76, P -value=0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83-1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories. CONCLUSIONS: GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.

Outcomes of levator advancement and Müller muscle-conjunctiva resection for the repair of upper eyelid ptosis.

Both the Müller muscle-conjunctiva resection (MMCR) and levator advancement (LA) procedures can be used to manage ptosis in patients with good levator function. The aim of this article is to evaluate the efficacy and cosmetic outcomes of the two procedures. The clinical records of 29 consecutive eyelids of 26 patients undergoing MMCR and 30 eyelids of 23 patients undergoing LA were analysed. Eleven (42%) in the LA group and 9 (39%) in the MMCR group were male. The preoperative eyelid measurements were significantly different in the LA compared to the MMCR groups, in terms of palpebral aperture (PA) (6.3 vs 7.4, p = 0.01), marginal reflex distance 1 (MRD1) (-0.1 vs 1.5, p < 0.001) and levator function (LF) (12.1 vs 13.4, p = 0.03). The MRD1 1 month post-surgery was slightly less in the LA group compared to the MMCR group (2.6 vs 3.18 mm, p = 0.047) but not significantly different at months 3 and 6. The final change in MRD1 was significantly higher in the LA group (2.93 vs 1.76, p = 0.004). The MMCR group had a lower incidence of lid contour abnormalities (0% vs 20%, p = 0.01) and overcorrection (0% vs 13%, p = 0.04). There was no statistically significant difference in the rates of undercorrection in either group. Both the MMCR as well as LA procedures are effective for mild to moderate ptosis in patients with good levator function. Patients undergoing MMCR had higher success rates, better preservation of the natural lid contour, and a lower incidence of overcorrection than patients undergoing LA.

Effect of obstructive sleep apnoea on diabetic retinopathy and maculopathy: a systematic review and meta-analysis.

AIMS: To summarize the association between obstructive sleep apnoea and diabetic retinopathy and diabetic maculopathy, and to examine the effects of oxygen desaturation index, mean and minimum oxygen saturation and time spent with < 90% oxygen saturation on diabetic retinopathy and diabetic maculopathy. METHODS: A systematic search was performed for papers published from inception to January 2014 in MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews using indexed terms and free text. Additional searches were carried out for grey literature. Two authors conducted the study selection and quality assessment. Data extraction was performed by the main author and checked by the other authors. RESULTS: One cohort study and 15 cross-sectional studies were included for narrative synthesis and three for meta-analyses. There was no convincing evidence that obstructive sleep apnoea was associated with diabetic retinopathy, although some evidence suggested that obstructive sleep apnoea was associated with greater severity of diabetic retinopathy and advanced diabetic retinopathy in people with Type 2 diabetes. Only six studies examined the impact of obstructive sleep apnoea on diabetic maculopathy and our narrative review suggests there is an association in Type 2 diabetes. Oxygen desaturation index, mean oxygen saturation or time spent with < 90% oxygen saturation were not associated with diabetic retinopathy, and insufficient evidence was available to draw conclusions on their effects on diabetic maculopathy; however, there was evidence from both narrative synthesis and meta-analysis that minimum oxygen saturation had an impact on diabetic retinopathy (pooled odds ratio 0.91, 95% CI 0.87-0.95; I(2) = 0%). CONCLUSIONS: There is a need for large cohort studies with long-term follow-up data to examine the long-term effects of obstructive sleep apnoea and other sleep variables on advanced retinal disease in diabetes.

Overall obesity is leveling-off while abdominal obesity continues to rise in a Chinese population experiencing rapid economic development: analysis of serial cross-sectional health survey data 2002-2010.

BACKGROUND: Obesity epidemic is related to industrialization and urbanization that have lead to changes in nutrition, lifestyle and socio-economic status. However, information on the trajectory of the obesity epidemic in populations experiencing rapid economic development is limited. We therefore investigate trends in obesity from 2002 to 2010 in a southern Chinese population experiencing world's fastest economic development. METHODS: Between 2002 and 2010 four standardized surveys were conducted in a population of 85 million residents in Guangdong, China. Multistage cluster sampling was adopted to recruit representative samples. Weight, height and waist circumference of the participants were measured in a standardized way. The analysis included residents aged between 18 and 69 years. The number of participants included in the present analysis for Surveys conducted in 2002, 2004, 2007 and 2010 were 13058, 7646, 6441 and 8575, respectively. RESULTS: From year 2002 to 2010, the age-standardized Body mass index (BMI) insignificantly changed from 21.7 kg m(-2) to 22.3 kg m(-2), and the prevalence of overweight and overall obesity from 15.8 to 16.6% (both P>0.05). The age-standardized waist circumference increased from 73.7 to 78.4 cm, and prevalence of abdominal obesity increased from 12.9 to 23.7% (both P<0.001). In urban areas, BMI and overall obesity changed little during the 8-year period (BMI increased from 22.6 to 22.7 kg m(-2) and overall obesity changed from 23.7 to 21.4%), whereas there were slight increases of the same in rural areas (BMI increased from 20.8 to 22.1 kg m(-2)and overall obesity increased from 8.2 to 13.3%). Waist circumference and abdominal obesity increased significantly in both areas, but the increase was more pronounced in rural areas (in urban area, waist circumference increased from 75.1 to 78.5 cm and abdominal obesity from 16.8 to 26.5%; in rural area, waist circumference from 72.2 to 78.3 and abdominal obesity from 8.8 to 22.0%). CONCLUSIONS: BMI and overall obesity in this population, which has experienced the world's fastest economic development over the past three decades, has been leveling-off, while waist circumference and abdominal obesity, independent predictors of cardiovascular risk, have continued to rise. Our findings suggest that obesity epidemic transition in rapidly developing populations may be much faster than what has been observed in Western countries.

Glycaemia is associated with cognitive impairment in older adults: the Guangzhou Biobank Cohort Study.

AIMS: an association between T2DM and cognitive impairment has been reported among Western populations, but data are limited in other settings. We investigated the cross-sectional association between fasting blood glucose (FBG) and cognition in an older Chinese population. METHODS: the Guangzhou Biobank Cohort Study included 27,971 individuals (50-96 years, mean age 61.5 years, 72% female) with measures of cognitive function assessed using modified Delayed Word Recall Test (DWRT) and Mini-Mental State Examination (MMSE). Fasting glucose and lipids, and potential confounders were measured. RESULTS: after adjustment for potential confounders, the risk for cognitive impairment as measured by DWRT, significantly increased [odds ratio (OR) = 1.18, 95% CI 1.00-1.40] but the association was of borderline significance when measured by MMSE (OR = 1.04, 95% CI 0.73-1.47) in those with diabetes relative to those without diabetes. Fasting blood glucose was significantly negatively associated with cognitive function as measured by DWRT but not MMSE, with an increase of 1 mmol/l of FBG associated with a decrease of 0.02 in DWRT (P < 0.05, 95% CI -0.03 to -0.002) and 0.03 in MMSE score (P = 0.114, 95% CI -0.06-0.01). CONCLUSIONS: an FBG level indicative of T2DM was associated with increased risk for cognitive impairment. The findings also demonstrate that glycaemia is continuously associated with cognitive impairment, suggesting that dysfunction is associated with increasing glucose levels even in the normoglycaemic range.

Anthropometric indices predicting incident type 2 diabetes in an Iranian population: the Isfahan Cohort Study.

BACKGROUND: The link between adiposity and type 2 diabetes (T2D) is well known. However, it remains controversial as to which index and cutoff point is the best predictor in different populations. METHODS: A total of 2981 urban and rural Iranian adults over 35 years of age, and free of cardiovascular disease and diabetes were followed for 7 years. Anthropometric indices included body mass index (BMI), body adiposity index [BAI=(hip circumference/height¹·5)-18], waist-to-height ratio (WHtR), waist-to-hip ratio (WHpR), and waist and hip circumferences. T2D was defined as fasting plasma glucose ≥ 126 mg/dL or 2-h post-prandial plasma glucose ≥ 200 mg/dL, or the use of antidiabetic agents. Receiver operating characteristic curve analysis determined the best cutoff point for each adiposity index. RESULTS: After 7 years of follow-up, 389 new cases of diabetes were found. Most indices were linearly associated with increased risk of diabetes but the best continuous predictor was WHtR in men [odds ratio: 1.10 (95% confidence interval: 1.07-1.12) for one unit] and BMI in women [1.08 (1.04-1.11) for 0.1 kg/m²]. BMI cutoffs of 26 kg/m² in men and 30 kg/m² in women were the best binary predictors in adjusted models, and showed increased T2D risks of 2.91 (2.06-4.12) and 1.94 (1.42-2.66) times, respectively. All central-obesity indices in men and WHpR in women were also significantly associated with T2D independent of BMI. BAI was significantly associated with T2D in men but not in women. CONCLUSION: BMI at the appropriate cutoffs in both genders and WHtR in men and BMI in women as continuous factors were the best predictors of incident T2D in this Iranian population.

Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4.

AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians. METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations. RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10(-5) from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (p meta = 2.6 × 10(-8); OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (p meta = 2.3 × 10(-10)) and a population of European descent (p = 8.6 × 10(-3)). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians. CONCLUSIONS/INTERPRETATION: Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.