Decreased cortical bone density and mechanical strength with associated elevated bone turnover markers at peri-pubertal peak height velocity: a cross-sectional and longitudinal cohort study of 396 girls with adolescent idiopathic scoliosis.

Decreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS. INTRODUCTION: As part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls. METHODS: 396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). RESULTS: Cohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1-3 (724.99 ± 32.09 mg/mm3 (p < 0.001), 0.79 ± 0.11 mm (p < 0.001) and 1910.88 ± 374.75 N/mm2 (p < 0.001), respectively) and (b) those at TOCI-8 (732.28 ± 53.75 mg/mm3 (p < 0.001), 0.84 ± 0.14 mm (p < 0.001), 1889.11 ± 419.37 N/mm2 (p < 0.001), respectively). Cohort-B included 217 girls (12.22 ± 0.89 years old). Subjects at TOCI-4 had higher levels of C-terminal telopeptide of type 1 collagen (1524.70 ± 271.10 pg/L) and procollagen type 1 N-terminal propeptide (941.12 ± 161.39 µg/L) than those at TOCI-8 (845.71 ± 478.55 pg/L (p < 0.001) and 370.08 ± 197.04 µg/L (p < 0.001), respectively). CONCLUSION: AIS girls had decreased cortical bone density and bone mechanical strength with elevated BTMs at PHV. Coupling of PHV with decreased cortical and FEA parameters could provide the link to the previously reported observation that low BMD could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.

Association of serum 25(OH)Vit-D levels with risk of pediatric fractures: a systematic review and meta-analysis.

The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children. INTRODUCTION: This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results. METHODS: Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = - 3.51 nmol/L; 95% confidence interval (CI): - 5.60 to - 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of - 4.35 nmol/L (95% CI: - 6.64 to - 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%). CONCLUSION: This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.

Hong Kong College of Physicians Position Statement and Recommendations on the 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension Guidelines for the Management of Arterial Hypertension.

The American College of Cardiology/American Heart Association released guidelines for the prevention, detection, evaluation, and management of high blood pressure (BP) in adults in 2017. In 2018, the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) published new guidelines for the management of arterial hypertension. Despite the many similarities between these two guidelines, there are also major differences in the guidelines in terms of diagnosis and treatment of hypertension. A working group of the Hong Kong College of Physicians (HKCP) convened and conducted a focused discussion on important issues of public interest, including classification of BP, BP measurement, thresholds for initiation of antihypertensive medications, BP treatment targets, and treatment strategies. The HKCP concurs with the 2018 ESC/ESH guideline on BP classification, which defines hypertension as office systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. The HKCP also acknowledges the growing evidence of home BP monitoring and ambulatory BP monitoring in the diagnosis and monitoring of hypertension and endorses the wider use of both methods. The HKCP also supports the direction of a risk-based approach for initiation of antihypertensive medications and the specification of a treatment target range for both systolic and diastolic BP with consideration of different age-groups and specific disease subgroups. Non-pharmacological interventions are crucial, both at the societal and individual patient levels. The recent guideline publications provide good opportunities to increase public awareness of hypertension and encourage lifestyle modifications among the local population.

Young-onset diabetes, nutritional therapy and novel insulin delivery systems: a report from the 21st Hong Kong Diabetes and Cardiovascular Risk Factors - East Meets West Symposium.

The prevalence and incidence of young-onset diabetes are increasing in many parts of the world, with the most rapid increase occurring in Asia, where one in five people with diabetes are diagnosed below the age of 40 years. Accumulation of glycaemic burden from an early age significantly increases the lifetime risks of developing complications from diabetes. Despite impending health threats, young people fare worse in the control of blood glucose and other metabolic risk factors. Challenges in the management of young-onset diabetes are compounded by heterogeneity of the underlying causes, pathophysiology and clinical phenotypes in this group. Effective characterization of people with diabetes has implications in steering the choice of glucose-lowering drugs, which, in turn, determines the clinical outcome. Medical nutritional therapy is key to effective management of people with diabetes but dietary adherence is often suboptimal among younger individuals. A recently published consensus report on nutritional therapy addresses dietary management in people with prediabetes as well as diabetes, and summarizes clinical evidence regarding macronutrient and micronutrient composition as well as eating patterns in people with diabetes. For people with type 1 diabetes, automated insulin delivery systems have rapidly evolved since the concept was first introduced at the National Institute of Health and the Juvenile Diabetes Research Foundation in 2005. The subsequent development of a type 1 diabetes simulator, developed using detailed human physiology data on carbohydrate metabolism replaced the need for pre-clinical animal studies and facilitated the seamless progression to artificial pancreas human clinical trials.

High risk of conversion to diabetes in first-degree relatives of individuals with young-onset type 2 diabetes: a 12-year follow-up analysis.

AIM: Family history of diabetes is an established risk factor for Type 2 diabetes, but the impact of a family history of young-onset diabetes (onset < 40 years) on future risk of diabetes among first-degree relatives is unclear. In this prospective study, we examined the influence of family history of late- versus young-onset diabetes on the development of diabetes in a young to middle-aged Chinese population. METHODS: Some 365 siblings identified through probands with Type 2 diabetes and 452 participants from a community-based health awareness project (aged 18-55 years) who underwent metabolic assessment during the period 1998-2002 were followed to 2012-2013 to determine their glycaemic status. Multivariate logistic regression was performed to investigate the association of family history of diabetes presented at different age categories with development of diabetes. RESULTS: In this cohort, 53.4% (n = 167) of participants with a family history of young-onset diabetes, 30.1% (n = 68) of those with a family history of late-onset diabetes and 14.4% (n = 40) of those without a family history developed diabetes. Using logistic regression, family history of diabetes presented at ages ≥ 50, 40-49, 30-39 and < 30 years, increased conversion to diabetes with respective odds ratios of 2.4, 5.8, 9.4 and 7.0 (P < 0.001 for all), after adjustment for socio-economic status, smoking, obesity, hypertension and dyslipidaemia. Among participants without diabetes at baseline, risk association of family history of late-onset diabetes with incident diabetes was not sustained, whereas that of family history of young-onset diabetes remained robust on further adjustment for baseline glycaemic measurements. CONCLUSIONS: First-degree relatives of people with Type 2 diabetes, especially relatives of those with young-onset diabetes, are at high risk for diabetes.

A multicentre demonstration project to evaluate the effectiveness and acceptability of the web-based Joint Asia Diabetes Evaluation (JADE) programme with or without nurse support in Chinese patients with Type 2 diabetes.

AIMS: To test the hypothesis that delivery of integrated care augmented by a web-based disease management programme and nurse coordinator would improve treatment target attainment and health-related behaviour. METHODS: The web-based Joint Asia Diabetes Evaluation (JADE) and Diabetes Monitoring Database (DIAMOND) portals contain identical built-in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow-up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND (n = 1728) or JADE, plus nurse-coordinated follow-up visits (n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving ≥ 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l). RESULTS: Of 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow-up of 12.5 (4.6) months. The proportion of participants attaining ≥ 2 treatment targets increased in both groups (JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [DIAMOND -8 mmol/mol vs JADE -7 mmol/mol (-0.69 vs -0.62%)] and LDL cholesterol (DIAMOND -0.32 mmol/l vs JADE -0.28 mmol/l), with no between-group difference. The JADE group was more likely to self-monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001). CONCLUSIONS: Integrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self-care. (Clinical trials registry no.: NCT01274364).

Radiofrequency ablation compared with laparoscopic adrenalectomy for aldosterone-producing adenoma.

BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for primary aldosteronism owing to aldosterone-producing adenoma. Whether RFA could be an alternative treatment to laparoscopic adrenalectomy is unknown. METHODS: This was a retrospective comparative study in patients with aldosterone-producing adenoma undergoing either laparoscopic adrenalectomy or CT-guided percutaneous RFA between 2004 and 2012. Short-term outcomes and long-term resolution rates of primary aldosteronism (normalized aldosterone to renin ratio), hypokalaemia and hypertension (BP lower than 140/90 mmHg without antihypertensive medical therapy) were evaluated. RESULTS: Some 63 patients were included, 27 in the laparoscopic adrenalectomy group and 36 in the RFA group. RFA was associated with shorter duration of operation (median 12 versus 124 min; P < 0·001), shorter hospital stay (2 versus 4 days; P < 0·001), lower analgesic requirements (13 of 36 versus 23 of 27 patients; P < 0·001) and earlier resumption of work (median 4 versus 14 days; P = 0·006). Morbidity rates were similar in the two groups. With median follow-up of 5·7 (range 1·9-10·6) years, resolution of primary aldosteronism was seen in 33 of 36 patients treated with RFA and all 27 patients who had laparoscopic adrenalectomy (P = 0·180). Hypertension was resolved less frequently after treatment with RFA compared with laparoscopic adrenalectomy (13 of 36 versus 19 of 27 patients; P = 0·007). Hypokalaemia was resolved in all patients. CONCLUSION: For patients with aldosterone-producing adenoma the efficacy of resolution of primary aldosteronism and hypertension was inferior after treatment with RFA compared with laparoscopic adrenalectomy.

Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. RESULTS: In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). CONCLUSIONS: The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia.

Early gene-diet interaction between glucokinase regulatory protein (GCKR) polymorphism, vegetable and fish intakes in modulating triglyceride levels in healthy adolescents.

BACKGROUND AND AIMS: The benefits of dietary vegetable and fish consumptions on improving glucose and lipid metabolism have been well established. Recently, the T-allele of a common genetic variant rs780094 at glucokinase regulatory protein (GCKR) was reported to be associated with elevated triglyceride (TG) levels but reduced fasting plasma glucose (FPG) and type 2 diabetes risk. However, the dietary modulation on genetic risk is not clearly understood. METHODS AND RESULTS: A cohort of 2095 Chinese adolescents (mean age 15.6 ± 2.0 years, 45.3% male) recruited from a population-based school survey for cardiovascular risk factor assessment, with dietary data including weekly vegetable and fish consumptions as well as clinical data were genotyped for the GCKR rs780094 polymorphism. In the linear regression analysis with adjustment for sex, age, body mass index, and socioeconomic status (school banding, paternal and maternal education levels), the frequency of vegetable intake per week was inversely associated with FPG (P = 0.044). Individuals with low fish intake generally had elevated TG levels but reduced TC, HDL-C and LDL-C (0.006 < P < 0.029). We also observed significant associations of the minor T-allele of GCKR rs780094 with decreased FPG (P = 0.013) and increased TG levels (P = 2.7 × 10(-8)). There were significant gene-diet interactions between rs780094 and vegetable consumption (P(interaction) = 0.009), and between rs780094 and fish consumption (P(interaction) = 0.031) in modulating TG levels. The T-allele of GCKR locus was associated with higher TG levels amongst individuals with ≥7 vegetable meals per week (P = 6.4 × 10(-9)), and among individuals with <7 fish meals per week (P = 0.020 and 7.0 × 10(-7) for 4-6 and ≤3 meals per week, respectively). High intake of vegetable exerted a reduction in TG levels only among CC genotype carriers (Ptrend = 0.020), while high intake of fish was associated with reduced TG levels only among TT genotype carriers (Ptrend = 0.026). CONCLUSIONS: In summary, our data indicated that the favorable associations of higher vegetable and fish intakes on TG levels are dependent on the genetic background of an individual. In particular, at-risk TT- genotype carriers of the GCKR variant may derive more benefits from a high fish intake, while the CC-genotype carriers may find further benefits from a high consumption of vegetable.

Non-linear relationship between birthweight and cardiometabolic risk factors in Chinese adolescents and adults.

AIM: To investigate the relationship between birthweight and cardiometabolic traits in two cohorts: one of Chinese adolescents and one of Chinese adults. METHODS: Birthweight and clinical data, including anthropometric traits, fasting plasma glucose and fasting plasma insulin levels, blood pressure and lipid profiles were collected from 2035 adolescents and 456 adults. A subset of 735 subjects underwent an oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min. RESULTS: Among adolescents, birthweight showed U-shaped relationships with larger body size, obesity, abdominal obesity in girls, insulin resistance and worse lipid profiles (0.0013 < P(quadratic) < 0.0499), as well as an inverse association with fasting plasma glucose (P(linear) = 0.0368). After further adjustment for adiposity, decreasing birthweight was associated with elevated fasting plasma glucose levels, greater insulin resistance and worse lipid profiles (3.1 × 10⁻5 < P(linear) < 0.0058). Among adults, high birthweight was associated with larger body size and abdominal obesity in men, while low birthweight was associated with elevated glucose levels at 15, 30, 60 and 120 min and a greater area under the curve at 0-120 min, as well as with ß-cell dysfunction (6.5 × 10⁻5 < P(linear) < 0.0437). Adjustment for adult adiposity did not substantially change the relationships. There was significant interaction between birthweight and abdominal obesity in elevating fasting plasma insulin and homeostasis model assessment of insulin resistance (P > 0.05), with abdominally obese adolescents in the lowest birthweight category (≤ 2.5 kg) having the highest risk of insulin resistance. CONCLUSIONS: Both high and low birthweights are associated with an increased risk of cardiometabolic abnormalities including obesity, abdominal obesity, hyperglycaemia, dyslipidaemia and insulin resistance, as well as with ß-cell dysfunction.

Eczema phenotypes are associated with multiple vitamin D pathway genes in Chinese children.

BACKGROUND: Vitamin D is increasingly recognized to play crucial roles in cutaneous immunity, and vitamin D treatment improved eczema control in small clinical trials. Several vitamin D-related genes were associated with asthma, but there are no data for eczema. METHODS: Twenty-three single-nucleotide polymorphisms (SNPs) of five vitamin D-related genes (CYP27A1, CYP2R1, CYP27B1, GC and VDR) were genotyped in 1442 Chinese children with eczema and 1231 non-allergic controls. SNPs that followed Hardy-Weinberg equilibrium and yielded ≥ 95% genotyping call-rate were included. Haplotypic associations and SNP-SNP interactions for eczema diagnosis and subphenotypes were analysed. RESULTS: Atopic eczema was associated with rs4674343 of CYP27A1 (odds ratio 0.66, 95% confidence interval 0.53-0.83, P = 0.0004). Increased eosinophil percentage was associated with CYP2R1 rs2060793A (P = 0.001) and rs1933064A (P = 0.001). Two CYP2R1 haplotypes increased eczema risk whereas one VDR haplotype lowered eczema risk. GC rs7041 and CYP2R1 rs7935792 interacted to modulate total IgE (cross-validation consistency 10/10, P = 0.047). Specifically, high-risk eczema patients had higher log-transformed total IgE than low-risk patients (2.76 ± 0.76 vs 2.60 ± 0.80, P = 0.002). CONCLUSION: A vitamin D-related SNP rs4674343 on CYP27A1 was found to be protective against atopic eczema. CYP2R1 and VDR haplotypes altered eczema susceptibility and eosinophil percentage, and GC and CYP2R1 interacted to determine total IgE among eczema patients.

Maternal history of diabetes is associated with increased cardiometabolic risk in Chinese.

OBJECTIVE: Positive family history is associated with increased type 2 diabetes (T2D) risk, and reflects both genetic and environmental risks. Several studies have suggested an excess maternal transmission of T2D, although the underlying mechanism is unknown. We aimed to examine the association between maternal diabetes and cardiometabolic risk in the offspring. METHODS: Parental history of diabetes and clinical data including anthropometric traits, fasting plasma glucose and insulin (FPG, FPI), blood pressure and lipid profile were collected from 2581 unrelated Chinese offspring (2026 adolescents from a population-based school survey and 555 adults from a community-based health screening programme). A subset of subjects (n=834) underwent oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min for evaluation of the areas under the curve (AUC) of glucose and insulin at 0-120 min, homoeostasis model assessment of insulin resistance (HOMA-IR) and bell-cell function, insulinogenic index, insulin sensitivity index (ISI) and oral disposition index (DI). RESULTS: A positive parental history of diabetes was associated with increased risk of obesity (odd ratios (OR) (95% confidence interval (CI))=1.48 (1.10-2.00)), central obesity (OR (95% CI)=1.67 (1.21-2.32)), higher FPI, HOMA-IR, 2-h insulin, AUC of glucose at 0-120 min, triglycerides, reduced ISI and DI. Compared with individuals without parental diabetes, offspring with diabetic mother had significantly increased risk of obesity (OR (95% CI)=1.59 (1.07-2.35)), central obesity (OR (95% CI)=1.88 (1.23-2.88)), higher glucose levels and BP, were more insulin resistant but also had impaired first-phase insulin response and worse lipid profile. However, paternal history of diabetes had no effect on any of the studied traits, except higher body mass index, waist circumference in females and FPG. CONCLUSIONS: Our findings suggested that maternal history of diabetes conferred increased risk of cardiometabolic abnormalities, and was associated with both insulin resistance and impaired first-phase insulin secretion. Further investigation into the mechanism of transgenerational diabetes is warranted.

Genetic variants for type 2 diabetes and new-onset cancer in Chinese with type 2 diabetes.

BACKGROUND: Diabetes is associated with an increased risk of cancer. This study aimed to evaluate associations between recently reported type 2 diabetes (T2D) susceptibility genetic variants and cancer risk in a prospective cohort of Chinese patients with T2D. METHODS: Seven single nucleotide polymorphisms (SNP) in IGF2BP2, CDKAL1, SLC30A8, CDKN2A/B, HHEX and TCF7L2, all identified from genome-wide association studies of T2D, were genotyped in 5900 T2D patients [age mean ± SD = 57 ± 13 years, % males = 46] without any known cancer at baseline. Associations between new-onset of cancer and SNPs were tested by Cox proportional hazard models with adjustment of conventional risk factors. RESULTS: During the mean follow-up period of 8.5 ± 3.3 years, 429 patients (7.3%) developed cancer. Of the T2D-related SNPs, the G-alleles of HHEX rs7923837 (hazard ratio [HR] (95% C.I.) = 1.34 (1.08-1.65); P = 6.7 ×10(-3) under dominant model) and TCF7L2 rs290481 (HR (95% C.I.) = 1.16 (1.01-1.33); P = 0.040 under additive model) were positively associated with cancer risk, while the G-allele of CDKAL1 rs7756992 was inversely associated (HR (95% C.I.) = 0.80 (0.65-1.00); P = 0.048 under recessive model). The risk alleles of these significant SNPs exhibited combined effect on increasing cancer risk (per-allele HR (95% C.I.) = 1.25 (1.12-1.39); P = 4.8 × 10(-5)). The adjusted cancer risk was 2.41 (95% C.I. 1.23-4.69) for patients with four risk alleles comparing to patients without risk allele. CONCLUSIONS: T2D-related variants HHEX rs7923837, TCF7L2 rs290481 and CDKAL1 rs7756992 increased cancer risk in patients with diabetes. IMPACT: Our findings provide novel insights into the pathogenesis of cancer in diabetes.

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.

Associations of uric acid and gamma-glutamyltransferase (GGT) with obesity and components of metabolic syndrome in children and adolescents.

BACKGROUND: The combined effect of uric acid, gamma-glutamyltransferase (GGT) and cardiovascular risk factors clustering in the youth remains under-explored. OBJECTIVE: The objective of this study was to examine the association between uric acid, GGT, obesity and the individual components of metabolic syndrome in children and adolescents. METHODS: We performed a cross-sectional observational study of 2067 children and adolescents (875 boys and 1192 girls) aged 6-20 years who were healthy volunteers and were recruited from primary and secondary schools in Hong Kong between 2007 and 2008. Subjects were divided into two strata (75th percentile as cut-off) for comparison between odds of cardiovascular risk factors. RESULTS: After adjustment by multivariable logistic regression, subjects in upper stratum, i.e., >75th percentile, of either serum uric acid or GGT levels were associated with obesity, low high-density lipoprotein cholesterol (HDL-C) level and high blood pressure (adjusted odds ratios [AOR] ranged from 1.63 to 5.82, all P < 0.005) compared with those in the lower stratum. There were combined effect for upper stratum of both uric acid and GGT in the association with obesity, low HDL-C and high blood pressure (AOR ranged from 2.60 to 10.69, all P < 0.05) after adjustment for age, sex and body mass index z-score (except for obesity status) as well as body height (for high blood pressure). CONCLUSION: Uric acid and GGT have combined effect in association with obesity and other cardiovascular risk factors in children and adolescents.

Self-reported waist circumference: a screening tool for classifying children with overweight/obesity and cardiometabolic risk factor clustering.

OBJECTIVES: The objectives of this study were twofold - (i) to assess the agreement between self-reported waist circumference (SRWC) and assessor measured waist circumference (MWC) and (ii) to evaluate the diagnostic ability of SRWC for classifying (i) a clustering of cardiometabolic risk factors (CMRFs) and (ii) overweight/obese status in Hong Kong Chinese children aged 6-18 years. METHODS: A cross-sectional study with cluster random sampling was conducted. A self-administrated questionnaire, which included demographic data, body weight, body height and waist circumference, was given to children to bring home for completion. Children were asked to return the questionnaire and fast themselves for at least 8 h on the day of the survey. Anthropometric measurements and blood pressure were taken by trained research staff and fasting blood samples were collected for measurements of fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. RESULTS: A total of 515 boys and 711 girls were included in the data analysis. Agreement between SRWC and MWC was assessed by intra-class correlation coefficient and it ranged from 0.77 to 0.87. The ability of sex-specific SRWC values to classify children with a clustering of CMRFs and overweight/obesity exhibited moderately high to high sensitivity and specificity, and the area under the receiver operating characteristics ranged from acceptable to excellent (from 0.76 to 0.84). CONCLUSIONS: SRWC has good agreement with MWC and could be used as a screening tool to classify children with a clustering of CMRFs and overweight/obesity status in Hong Kong Chinese children.

Long-term outcomes and predictors of chronic insomnia: a prospective study in Hong Kong Chinese adults.

OBJECTIVES: We aimed to determine the longitudinal course and outcome of chronic insomnia in a five-year prospective study in Hong Kong Chinese adults. METHODS: Two thousand three hundred and sixteen middle-aged adults (53.3% females, 46.3 ± 5.1 years old at follow-up) were recruited at baseline and follow-up. Participants were divided into three groups: non-insomnia, insomnia symptoms, and insomnia syndrome (insomnia symptoms plus daytime symptoms). Upper airway inflammatory diseases, mental problems, and medical problems were additionally assessed at follow up. RESULTS: The incidence of insomnia (symptoms and syndrome) was 5.9%. The persistence rate of insomnia syndrome was 42.7% for insomnia syndrome and 28.2% for insomnia symptoms. New incidence of insomnia was associated with younger age, unemployment, and daytime symptoms, while persistence of insomnia was associated with female sex, lower education level, and daytime symptoms at the baseline (p<0.05). Baseline insomnia syndrome was significantly associated with upper airway inflammatory diseases (including asthma and laryngopharyngitis; adjusted OR=1.97-17.9), mental problems, and medical conditions (including arthritis, psychiatric disorders, chronic pain, and gastroesophageal reflux disease; AOR=2.29-3.77), whereas baseline insomnia symptoms were associated with poor mental health (AOR=2.43), psychiatric disorders (AOR=2.39), and chronic pain (AOR=2.95). CONCLUSIONS: Chronic insomnia is a common problem with considerable persistence and incidence rates among middle-aged Chinese adults. Insomnia syndrome has a higher persistence rate with more mental and medical comorbidities when compared with insomnia symptoms without daytime consequences.

Circulating LL-37 is a biomarker for eczema severity in children.

BACKGROUND: Eczema lesions are characterized by impaired expression of antimicrobial peptides such as cathelicidin, which play crucial roles in the innate immune defence against cutaneous infections. LL-37 corresponds to amino acids 134-170 of human cathelicidin and is a multifunctional host defence molecule essential for normal immune responses to infection and tissue injury. OBJECTIVES: The aim of this study was to investigate the relationship between childhood eczema and circulating LL-37 levels. METHODS: One hundred and forty-four eczema children and 36 controls were recruited. Eczema severity was assessed by SCORing Atopic Dermatitis (SCORAD) and serum LL-37 concentration measured using enzyme immunoassay. Patients' skin hydration and transepidermal water loss at forearms were measured using Corneometer and Tewameter. RESULTS: Patients' mean SCORAD was 49.2 and their disease was classified as mild (n=28; 12.8%), moderate (n=95; 43.6%) and severe (n=95; 43.6%). Serum LL-37 concentrations did not differ between eczema patients and controls (mean: 832 pg/mL vs. 952 pg/mL, P=0.471). However, serum LL-37 concentrations increased with increasing eczema severity among the patients (P=0.005 for trend). This biomarker shows weakly positive correlation with patients' objective SCORAD (r=0.207, P=0.013) and age (r=0.170, P=0.041), but not skin hydration or transepidermal water loss (P>0.09). Linear regression confirmed significant association between objective SCORAD and serum LL-37 when adjusted for age and gender as covariates (ß=0.171, P=0.038). On the other hand, serum LL-37 did not differ between patients with and without heavy growth of staphylococci (P=0.151). CONCLUSIONS: Circulating LL-37 may be a biomarker for severity of childhood eczema, which supports the importance of innate immunity in eczema pathogenesis.