Association between high sensitivity cardiac troponin and mortality risk in the non-diabetic population: findings from the National Health and Nutrition Examination Survey.

OBJECTIVE: We investigated the association of high-sensitivity cardiac troponin (Hs-cTn) with all-cause and cardiovascular mortality in non-diabetic individuals. METHODS: This study included 10,393 participants without known diabetes and cardiovascular disease from the US National Health and Nutrition Examination Survey (NHANES). Serum Hs-cTnI and Hs-cTnT concentrations were measured. Prediabetes was defined as fasting blood glucose between 100 and 125 mg/dL or HbA1c between 5.7 and 6.4%. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality risk. Time-dependent receiver operating characteristics (tROC) curves were utilized to measure the predictive performance of the biomarkers. Net Reclassification Improvement (NRI) were calculated to estimate the improvement in risk classification for adding Hs-cTnT or Hs-cTnI to the standard models based on Framingham risk factors. RESULTS: The mean age of the participants was 48.1 ± 19.1 years, with 53.3% being female and 25.8% being prediabetic. After multivariable adjustment, compared to those with Hs-cTnI concentration less than the limit of detection, the HRs (95% CIs) of the participants with Hs-cTnI concentration higher than the 99th upper reference limit were 1.74 (1.35, 2.24) for all-cause mortality and 2.10 (1.36, 3.24) for cardiovascular mortality. The corresponding HRs (95% CIs) for Hs-cTnT were 2.07 (1.53, 2.81) and 2.92 (1.47, 5.80) for all-cause and cardiovascular mortality. There was a significant interaction between prediabetes and Hs-cTnI on the mortality risk; a positive relationship was only observed in prediabetic individuals. No interaction was observed between prediabetes and Hs-cTnT on mortality risk. The Areas Under tROC indicated both Hs-cTnT and Hs-cTnI show better predictive performance in cardiovascular mortality than in all-cause mortality. NRI (95% CI) for adding Hs-cTnT to the standard model were 0.25 (0.21, 0.27) and 0.33 (0.26, 0.39) for all-cause and cardiovascular mortality. The corresponding NRI (95% CI) for Hs-cTnI were 0.04 (0, 0.06) and 0.07 (0.01, 0.13). CONCLUSIONS: Elevated blood levels of Hs-cTnI and Hs-cTnT are associated with increased mortality. Measurement of Hs-cTnT in non-diabetic subjects, particularly those with prediabetes, may help identify individuals at an increased risk of cardiovascular disease and provide early and more intensive risk factor modification.

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Hypertension and psychosis.

Hypertension, a prevalent component of metabolic syndrome (MetS), is a well-known risk factor for cardiovascular diseases (CVD). Psychosis is a feature in the schizophrenia spectrum. Meta-analysis suggests that the prevalence of hypertension in schizophrenia and related disorders is 39%. This may be explained by a unidirectional association between hypertension and psychosis, in that psychosis can be a causative factor of hypertension via antipsychotic medication, inflammation and irregular autonomic nervous system activity through multiple mechanisms. Obesity is a side effect of antipsychotic medication and is a risk factor for hypertension. Obesity leads to raised blood pressure, atherosclerosis, increased triglyceride concentration and decreased high-density lipoprotein concentration. Inflammation accompanies hypertension and obesity. In recent years, the role of inflammation in the onset of psychosis has been increasingly recognised. It underlies the immune dysregulation observed in both schizophrenia and bipolar disorder. Interleukin-6, a marker and driver of inflammation, is related to obesity and plays a role in the pathogenesis of MetS and hypertension. The lack of preventive care of hypertension and other MetS risk factors for patients on antipsychotic medication is reflected in the high incidence of CVD in this population. It is important to detect and treat MetS and hypertension in patients with psychosis in order to reduce cardiovascular morbidity and mortality in this population.

Intensive blood pressure control in older patients with hypertension-a STEP in the right direction?

In November 2022, the Clinical Practice Guidelines for the Management of Hypertension in China were updated; the definition of hypertension and the target of treatment was changed from 140/90 mm Hg to 130/80 mm Hg. This was prompted by the results of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) study, a large multicenter randomized controlled trial conducted in China. STEP echoed the results of the American Systolic Blood Pressure Intervention Trial (SPRINT), and confirmed that intense lowering of blood pressure is on the whole beneficial. This confirmation is important for the Chinese population, in which strokes outnumber myocardial infarctions. It is also reassuring to know that treating adults aged 60 years or older to achieve a systolic blood pressure of <130 mm Hg is safe, while reducing cardiovascular events, stroke and all-cause mortality. Nevertheless, further studies are needed to delineate the risks and benefits in subgroups, such as the elderly with diabetes or a history of stroke.

Prevalence of metabolic syndrome in the United States National Health and Nutrition Examination Survey 2011-18.

PURPOSE: To estimate the prevalence of metabolic syndrome (MetS) in the US National Health and Nutrition Examination Survey (NHANES) 2011-18. METHODS: This study included 8183 eligible nonpregnant participants aged ≥20 years from the NHANES 2011-18. MetS was defined as the presence of at least three of the following components: central obesity, reduced high-density lipoprotein cholesterol, elevated triglycerides, elevated blood pressure, and elevated fasting blood glucose. The prevalence of MetS was estimated taking into account the complex sampling. The time trend was evaluated using logistic regression. RESULTS: The total prevalence of MetS increased from 37.6% [95% confidence interval (CI): 34.0%-41.4%] in 2011-12 to 41.8% (95% CI: 38.1%-45.7%) in 2017-18 (P for trend = .028). Among the MetS components, the prevalence of elevated glucose increased from 48.9% (95% CI: 45.7%-52.5%) in 2011-12 to 64.7% (95% CI: 61.4%-67.9%) in 2017-18 (P for trend <.001). The prevalence of MetS in participants with low educational attainment increased from 44.4% (95% CI: 38.8%-50.1%) in 2011-12 to 55.0% (95% CI: 50.8%-59.1%) in 2017-18 (P for trend = .01). CONCLUSION: The prevalence of MetS increased during 2011-18, notably in participants with low educational attainment. Lifestyle modification is needed to prevent MetS and the associated risks of diabetes and cardiovascular disease. Key messages What is already known on this topic: Prevalence of metabolic syndrome is an index of the cardiometabolic health of a population. What this study adds: The prevalence of metabolic syndrome in US adults increased during 2011-18, notably in participants with low educational attainment. How this study might affect research, practice, or policy: Lifestyle modification is needed to prevent metabolic syndrome and the associated risks of diabetes and cardiovascular disease.

Diuretic-induced hypokalaemia: an updated review.

Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%-56% of hypokalaemia in patients taking thiazide diuretics. The clinical manifestations of hypokalaemia due to diuretics are non-specific, varying from asymptomatic to fatal arrhythmia. Diagnosis of hypokalaemia is based on the level of serum potassium. ECG is useful in identifying the more severe consequences. A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac arrhythmias can increase the risk of cardiovascular events and mortality. Thiazide-induced potassium depletion may cause dysglycaemia. The risk of thiazide-induced hypokalaemia is higher in women and in black people. Reducing diuretic dose and potassium supplementation are the most direct and effective therapies for hypokalaemia. Combining with a potassium-sparing diuretic or blocker of the renin-angiotensin system also reduces the risk of hypokalaemia. Lowering salt intake and increasing intake of vegetables and fruits help to reduce blood pressure as well as prevent hypokalaemia.

Knowledge and practice of home blood pressure monitoring 6 months after the risk and assessment management programme: does health literacy matter?

BACKGROUND: Little is known whether patients with lower health literacy could retain the practice and knowledge of home blood pressure monitoring (HBPM) after an educational programme. METHODS: A cluster randomised controlled trial in five primary care clinics recruited participants with uncontrolled hypertension. Clinics were randomised either to a HBPM group education (Risk Assessment and Management Programme (RAMP-group), or individual counselling of self-management (RAMP-individual). Health literacy was assessed by the Chinese Health Literacy Scale for Chronic Care. Practice and knowledge of HBPM were surveyed by a 10-item HBPM knowledge checklist and patient record review 6 months after interventions. Predictors for regular HBPM and good HBPM knowledge were assessed by multivariate logistic regression models. RESULTS: 287 participants (RAMP-group: 151; RAMP-individual: 136) were follow-up for 6 months. 272 participants completed the knowledge questionnaires (response rate 94.8%). 67.8% of the participants performed HBPM regularly, and there was no statistical difference between both interventions. Age more than 65 (adjusted odds ratios (aOR) 2.58, 95% CI 1.37 to 4.86, p=0.003), not working (aOR 2.34, 95% CI 1.10 to 4.97, p=0.027)and adequate health literacy (aOR 2.25, 95% CI 1.28 to 3.95, p=0.005) predicted regular HBPM. Participants in RAMP-group demonstrated a significant lower body weight than those in RAMP-individual (-0.3±2.0 kg vs +0.7 ±1.7 kg, p<0.001).The RAMP-group participants were eight times more likely to have full HBPM knowledge score than the RAMP-individual participants (aOR 8.46, 95% CI 4.68 to 15.28, p<0.001). CONCLUSION: Patients could retain HBPM knowledge better after RAMP-group than RAMP-individual. Older, retired and patients with adequate health literacy were more likely to continue weekly HBPM 6 months after education. TRIAL REGISTRATION NUMBER: NCT02551393.

Long-term Outcome of Short-course High-dose Glucocorticoids for Severe Acute Respiratory Syndrome (SARS): A 17-Year Follow-up in SARS Survivors.

Use of high-dose glucocorticoids for COVID-19 (caused by SARS-CoV-2) is controversial because of safety concerns. We examined the long-term consequences of glucocorticoid use in severe acute respiratory syndrome (caused by SARS-CoV-1) survivors. Results showed that high-dose glucocorticoids greatly increased the long-term risk of avascular necrosis but not other major diseases.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis.

BACKGROUND: Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD. METHODS: MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model. RESULTS: Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 [64.8%] of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70-0.96), embolic stroke (RR 0.32, 95% CI 0.12-0.85), AF/AFL (RR 0.82, 95% CI 0.71-0.95), and VT (RR 0.73, 95% CI 0.53-0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58-1.17) and cardiac arrest (RR 0.83, 95% CI 0.61-1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease [ASCVD] vs no ASCVD) and the SGLT2i used. CONCLUSIONS: SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.

Treatment with direct oral anticoagulants or warfarin and the risk for incident diabetes among patients with atrial fibrillation: a population-based cohort study.

BACKGROUND: Diabetes mellitus is a common comorbidity of atrial fibrillation (AF), which can complicate the management of AF. The pharmacology of oral anticoagulants (OACs) have been implicated in pathogenesis of diabetes, but the relationship between different OACs and risk of diabetes remains unexamined. This study aimed to evaluate the risk of diabetes with use of different OACs in AF patients. METHODS: Population-based retrospective cohort study using an electronic healthcare database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with AF from 2014 through 2018 and prescribed OACs were included and followed till December 31, 2019. Inverse probability of treatment weighting based on the propensity score (PS) is used to address potential bias due to nonrandomized allocation of treatment. The risks ofdiabetes were compared between different new OAC users using propensity score-weighted cumulative incidence differences (CID). RESULTS: There were 13,688 new users of OACs (warfarin: n = 3454; apixaban: n = 3335; dabigatran: n = 4210; rivaroxaban: n = 2689). The mean age was 75.0 (SD, 11.2), and 6,550 (47.9%) were women. After a median follow-up of 0.93 years (interquartile range, 0.21-1.92 years), 698 incident diabetes cases were observed. In Cox-regression analysis, dabigatran use was significantly associated with reduced risk of diabetes when compared with warfarin use [HR 0.69 (95% CI 0.56-0.86; P < 0.001)], with statistically insignificant associations observed for use of apixaban and rivaroxaban. The corresponding adjusted CIDs at 2 years after treatment with apixaban, dabigatran, and rivaroxaban users when compared with warfarin were - 2.06% (95% CI - 4.08 to 0.16%); - 3.06% (95% CI - 4.79 to - 1.15%); and - 1.8% (- 3.62 to 0.23%). In head-to-head comparisons between women DOAC users, dabigatran was also associated with a lower risk of diabetes when compared with apixaban and rivaroxaban. CONCLUSIONS: Among adults with AF receiving OACs, the use of dabigatran had the lowest risk of diabetes when compared with warfarin use.

The lipid-lowering effect of once-daily soya drink fortified with phytosterols in normocholesterolaemic Chinese: a double-blind randomized controlled trial.

PURPOSE: Phytosterols reduce intestinal cholesterol absorption and help to lower LDL-cholesterol. Many Chinese adults are lactose-intolerant and cannot tolerate bovine milk enriched with phytosterol. Soya-milk is a common beverage in Asia and it has beneficial effects on general health. We therefore conducted a randomized double-blind controlled trial to assess the effectiveness of a phytosterols-enriched soya drink in lowering serum LDL-cholesterol level (primary outcome) and other cardiovascular parameters (secondary outcomes). METHODS: One hundred and fifty-nine normocholesterolaemic participants (85 men and 74 women; aged 19-79) were randomized to daily intake of one serving of phytosterols-enriched soya drink (N = 82), equivalent to 2 g of phytosterol per day, or a matched soya drink without phytosterols (N = 77) for 3 weeks. Adverse events, withdrawal and compliance were documented. RESULTS: Among the treatment group (N = 82), phytosterols-enriched soya drink significantly decreased LDL-cholesterol by 5.96% (SE 1.48, 95% CI - 8.91%, - 3.00%) with a median of 6.74% compared with baseline, resulting in a significant reduction of 4.70% (95% CI - 8.89%, - 0.51%; p = 0.028) with a median of 5.20% compared with placebo (N = 77). In contrast, there were no significant changes in other lipid parameters, blood glucose, blood pressure, body weight or waist circumference. Remarkably, 95% of the participants randomized to the fortified drink reported no adverse events at all. CONCLUSIONS: Daily consumption of a phytosterols-enriched soya drink may be a simple and cost-neutral means of lowering LDL-cholesterol in individuals in China, with massive population and rising incidence of coronary heart disease (ClinicalTrials.gov identifier: NCT02881658; date of registration: 14 Aug 2016).

Vancomycin-associated acute kidney injury in Hong Kong in 2012-2016.

BACKGROUND: To study the incidence of vancomycin-associated acute kidney injury (VA-AKI) in Hong Kong and identify risk factors for VA-AKI. METHOD: Patients with vancomycin prescription and blood level measurement in 2012-2016 were identified using the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. Acute kidney injury was defined using KDIGO criteria. Patients without creatinine measurements, steady-state trough vancomycin level or who had vancomycin treatment < 3 days were excluded. Results were analyzed using SPSS version 22.0. Logistic regression was used to identify the predictors for VA-AKI. Odds ratio and 95% confidence interval were estimated. RESULTS: One thousand four hundred fifty patients were identified as VA-AKI from 12,758 records in Hong Kong in 2012-2016. The incidence was respectively 10.6, 10.9, 11.3, 12.2, 11.2% from 2012 to 2016. The incidence of VA-AKI was 16.3, 12.2, 11.3 and 6.2% in patients aged 1-12, 12-60, elderly aged > 60 and newborn and infants, respectively. Baseline creatinine, serum trough vancomycin level, systematic disease history including respiratory failure, hypertension, congestive heart failure, chronic renal failure, anemia and type II diabetes, and concomitant diuretics, piperacillin-tazobactam (PTZ) and meropenem prescription were significantly higher in VA-AKI patients older than 12 years. Logistic regression showed that older age group, higher baseline creatinine, serum trough vancomycin level, respiratory failure, chronic renal failure and congestive heart failure, concomitant diuretics, PTZ and meropenem prescription, and longer hospital stay were all associated with increased risk of VA-AKI. CONCLUSION: The incidence of VA-AKI in Hong Kong is low but shows no decline. Patients with higher baseline creatinine, multi-organ diseases and multiple drugs administration should have their vancomycin level monitored to decrease the risk of VA-AKI.

Prevalence of metabolic syndrome among ethnic groups in China.

BACKGROUND: Metabolic syndrome (MetS) is common in China, which has a multi-ethnic population of 1·3 billion. We set out to determine the prevalence of MetS and its components in different ethnic groups. METHODS: This nationwide cross-sectional survey involved 24,796 participants from eight ethnicities in six provinces in China from 2008 to 2011. MetS was defined using the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Results were analysed using SPSS version 22·0 in 2018. Logistic regression was used for deriving odds ratios and 95% confidence intervals of risk factors for the MetS. RESULTS: The prevalence of MetS increased with age from 3·60% to 21·68%. After age standardization, the prevalence of MetS, in descending order, was 35·42% (Korean), 22·82% (Hui), 19·80% (Han), 13·72% (Miao), 12·90% (Tujia), 12·04% (Li), 11·61% (Mongolian), 6·17% (Tibetan). Korean ethnicity was associated with a higher prevalence in five components of MetS, while Tibetan ethnicity was associated with lower prevalence except decreased HDL cholesterol. Logistic regression analyses showed that age, drinking and being non-Tibetan were associated with a higher risk of MetS. CONCLUSIONS: Within one country, albeit a large one, the prevalence of MetS can vary greatly. Chinese of Korean ethnicity had a much higher prevalence than Tibetan ethnicity. Measures to tackle MetS should be tailored to the ethnic groups within a population.

High-sensitivity troponin I and B-type natriuretic peptide biomarkers for prediction of cardiovascular events in patients with coronary artery disease with and without diabetes mellitus.

BACKGROUND: High-sensitivity troponin I (hs-Tnl) and B-type natriuretic peptide (BNP) are promising prognostic markers for coronary artery disease (CAD). This prospective cohort study investigated whether a combination of these cardiac biomarkers with conventional risk factors would add incremental value for the prediction of secondary major adverse cardiovascular events (MACEs) in patients with CAD, with and without type 2 diabetes mellitus (T2DM). METHODS: Baseline plasma level of hs-Tnl and BNP was measured in 2275 Chinese patients with stable CAD. Patients were monitored for new-onset of MACE over a median of 51 months. Cox proportional hazard model and area under the receiver operating characteristic curve (AUC) were used to assess the association of cardiac biomarkers with MACE and their predictive values in relationship with or without T2DM. RESULTS: During the follow up period 402 (18%) patients experienced a new-onset MACE with hs-Tnl and BNP level significantly higher than in those without MACE. In multivariable analyses, patients with elevated hs-Tnl (hazard ratio, 1.75 [95% CI 1.41-2.17]; P < 0.001) and BNP (hazard ratio, 1.42 [95% CI 1.15-1.75]; P = 0.001) were significantly associated with an increased risk of MACE after adjustment for variables of a risk factor model of age, sex, T2DM and hypertension. The risk factor model had an AUC of 0.64 for MACE prediction. The AUC significantly increased to 0.68 by the addition of hs-Tnl to the risk factor model. Subgroup analyses showed that hs-Tnl and BNP remained significant predictors of MACE in both patients with and without T2DM in multivariable models with higher risk of MACE evident in those without T2DM. Among patients without T2DM, addition of each biomarker yielded greater predictive accuracy than in T2DM patients, with AUC further increased to 0.75 when a combination of hs-Tnl and BNP was added to the risk factor model (age, sex and hypertension). CONCLUSIONS: Elevated hs-Tnl and BNP level are independent predictors of new-onset MACE in CAD patients, irrespective of diabetes status. Among CAD patients without T2DM, a combination of cardiac biomarkers hs-Tnl and BNP yield the greatest predictive value beyond conventional risk factors.

Age-Biomarkers-Clinical Risk Factors for Prediction of Cardiovascular Events in Patients With Coronary Artery Disease.

Objective- In patients with stable coronary artery disease, conventional risk factors provide limited incremental predictive value for cardiovascular events. We sought to investigate whether a panel of cardiometabolic biomarkers alone or combined with conventional risk factors would exhibit incremental value in the prediction of cardiovascular events. Approach and Results- In the discovery cohort, we measured serum adiponectin, A-FABP (adipocyte fatty acid-binding protein), lipocalin-2, FGF (fibroblast growth factor)-19 and 21, plasminogen activator inhibitor-1, and retinol-binding protein-4 in 1166 Chinese coronary artery disease patients. After a median follow-up of 35 months, 170 patients developed new-onset major adverse cardiovascular events (MACE). In the model with age ≥65 years and conventional risk factors, area under the curve for predicting MACE was 0.68. Addition of lipocalin-2 to the age-clinical risk factor model improved predictive accuracy (area under the curve=0.73). Area under the curve further increased to 0.75 when a combination of lipocalin-2, A-FABP, and FGF-19 was added to yield age-biomarkers-clinical risk factor model. The adjusted hazard ratio on MACEs for lipocalin-2, A-FABP, and FGF-19 levels above optimal cutoffs were 2.23 (95% CI, 1.62-3.08), 1.99 (95% CI, 1.43-2.76), and 1.65 (95% CI, 1.15-2.35), respectively. In the validation cohort of 1262 coronary artery disease patients with type 2 diabetes mellitus, the age-biomarkers-clinical risk factor model was confirmed to provide good discrimination and calibration over the conventional risk factor alone for prediction of MACE. Conclusions- A combination of the 3 biomarkers, lipocalin-2, A-FABP, and FGF-19, with clinical risk factors to yield the age-biomarkers-clinical risk factor model provides an optimal and validated prediction of new-onset MACE in patients with stable coronary artery disease.

Fast-tracking acute stroke care in China: Shenzhen Stroke Emergency Map.

China has the largest stroke population and at-risk population in the world. However, it has a lower thrombolytic therapy rate and longer onset-to-needle time/door-to-needle time for patients who had an acute stroke compared with developed countries, which might be due to redundant procedures or inefficient systems. Things are changing due to some new initiatives. Two years ago, a new emergency system in China, Stroke Emergency Map, was first launched as a regional emergency system in Shenzhen, the bustling metropolis just north of Hong Kong. As a result of the Stroke Emergency Map in Shenzhen, the number of thrombolytic cases increased in the last 2 years, from 568 to 809 annually. The Stroke Emergency Map, first pioneered in Shenzhen and now spreading to the rest of China, is a comprehensive and interdisciplinary system. The benefits are not just the immediate improvements in the acute stroke care because the continuous data collection and audit allows for improvements in logistics and future strategies.

Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.

AIMS/HYPOTHESIS: Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. METHODS: An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. RESULTS: In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery < 6.45 × 10-7). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta] = 3.74 × 10-15) in the combined analysis. CONCLUSIONS/INTERPRETATION: We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.

Serum fibroblast growth factor 21 is a superior biomarker to other adipokines in predicting incident diabetes.

OBJECTIVE: Fibroblast growth factor 21 (FGF21) improves glucose and lipid metabolism, but high circulating levels are found in type 2 diabetes, suggesting FGF21 resistance. Serum FGF21 predicts incident diabetes, but its performance compared to established and emerging predictors is not known. We aimed to study the performance of FGF21 in diabetes prediction, relative to other adipokines and established risk factors including 2-h plasma glucose (2hG) during the oral glucose tolerance test (OGTT). DESIGN/PARTICIPANTS/MEASUREMENTS: We studied 1380 nondiabetic subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study using the second visit (2000-2004) as baseline when serum levels of FGF21 and other adipokines were measured. Glycaemic status was assessed by OGTT. Incident diabetes was defined as fasting glucose level (FG) ≥ 7 mmol/l or 2hG ≥ 11·1 mmol/l or use of antidiabetic agents, at subsequent visits. RESULTS: A total of 123 participants developed diabetes over 9·0 years (median). On multivariable logistic regression analysis, FGF21 (P = 0·003), adipocyte fatty acid-binding protein (P = 0·003) and adiponectin (P = 0·035) were independent predictors of incident diabetes. FGF21 had the best change in log likelihood when added to a diabetes prediction model (DP) based on age, family history, smoking, hypertension, BMI, dyslipidaemia and FG. It also improved the area under ROC curve (AUROC) of diabetes prediction (DP) from 0·797 to 0·819 (P = 0·0072), rendering its performance comparable to the 'DP + 2hG' model (AUROC=0·838, P = 0·19). CONCLUSIONS: As a biomarker for diabetes prediction, serum FGF21 appeared to be superior to other adipokines and, on its own, could be considered as an alternative to the OGTT.