Juliana Chung Ngor Chan

Prince of Wales Hospital, Hong Kong, Chiu-lung, Kowloon City, Hong Kong

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Publications (15)54.59 Total impact

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    ABSTRACT: A significant proportion of patients with type 2 diabetes mellitus have a low testosterone level relative to reference ranges based on healthy young men. Only a small number of these patients suffer from classical hypogonadism as a result of recognizable hypothalamic–pituitary–gonadal axis pathology. The cut-off value of the serum testosterone level in men without obvious hypothalamic–pituitary–gonadal axis pathology is controversial. It is unclear to what extent a low serum testosterone level causally leads to type 2 diabetes and/or the metabolic syndrome. From a theoretical standpoint, there can be complex interactions among the hypothalamic–pituitary–gonadal axis, body composition and insulin resistance, which can be further influenced by intrinsic and extrinsic factors to give rise to metabolic syndrome, glucose intolerance, and low-grade inflammation to increase the risk of cardiovascular disease. Although a low serum testosterone level frequently coexists with cardiometabolic risk factors and might serve as a biomarker, more studies are required to clarify the causal, mediating or modifying roles of low serum testosterone level in the development of adverse clinical outcomes. Currently, there are insufficient randomized clinical trial data to evaluate the effects of testosterone replacement therapy on meaningful clinical outcomes. The risk-to-benefit ratio of testosterone therapy in high-risk subjects, such as those with type 2 diabetes, also requires elucidation. The present article aims to review the current evidence on low serum testosterone levels in patients with type 2 diabetes, and its implications on cardiovascular risk factors, metabolic syndrome and adverse clinical outcomes.
    Journal of Diabetes Investigation. 10/2014;
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    ABSTRACT: Objective Short sleep duration is a contributing factor for decreased insulin sensitivity and hyperglycemia. Sleep architecture represents a cyclical pattern of sleep which shifts between sleep stage N1, N2, N3 (slow wave sleep) and stage R (rapid eye movement sleep). We aimed to examine the association between sleep architecture and glucose and insulin metabolism in children and adolescents. MethodsA total of 118 subjects participated in this study. They underwent an overnight polysomnography (PSG) when percentage of total sleep time (TST) spent at each sleep stage were recorded. Oral glucose tolerance test together with assay of insulin levels was carried out after overnight PSG. We assessed glucose tolerance, insulin sensitivity and pancreatic β-cell function by 2-h glucose level, Matsuda index (ISOGTT) and insulin secretion-sensitivity index-2 (ISSI-2) respectively. ResultsAfter adjustment for age, gender, BMI z-score, pubertal status and obstructive apnea hypopnea index, stage N3 (%TST) was positively associated with ISOGTT, while stage N1 (%TST) exerted an opposite effect on ISOGTT. High sleep efficiency and long TST were independently associated with low 2-h glucose level, high ISSI-2 and/or high ISOGTT. Conclusions Stage N3, sleep efficiency and TST were protective factors in maintaining glucose and insulin homeostasis; however, stage N1 functioned in the opposite direction.
    Journal of Diabetes 02/2014; · 2.94 Impact Factor
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    ABSTRACT: In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57-3.96, P = 8.4×10(-5)). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02-1.12, Pmeta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07-2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19-9.19, P = 0.0214) and 3.27(1.25-11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese.
    PLoS ONE 01/2014; 9(1):e84770. · 3.53 Impact Factor
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    ABSTRACT: Type 2 diabetes (T2D) is a complex disease characterized by beta cell dysfunctions. Islet amyloid polypeptide (IAPP) is highly conserved and co-secreted with insulin with over 40% of autopsy cases of T2D showing islet amyloid formation due to IAPP aggregation. Dysregulation in IAPP processing, stabilization and degradation can cause excessive oligomerization with beta cell toxicity. Previous studies examining genetic associations of pathways implicated in IAPP metabolism have yielded conflicting results due to small sample size, insufficient interrogation of gene structure and gene-gene interactions. In this multi-staged study, we screened 89 tag single nucleotide polymorphisms (SNPs) in 6 candidate genes implicated in IAPP metabolism and tested for independent and joint associations with T2D and beta cell dysfunctions. Positive signals in the stage-1 were confirmed by de novo and in silico analysis in a multi-centre unrelated case-control cohort. We examined the association of significant SNPs with quantitative traits in a subset of controls and performed bioinformatics and relevant functional analyses. Amongst the tag SNPs, rs1583645 in carboxypeptidase E (CPE) and rs6583813 in insulin degrading enzyme (IDE) were associated with 1.09 to 1.28 fold increased risk of T2D (P Meta = 9.4×10(-3) and 0.02 respectively) in a meta-analysis of East Asians. Using genetic risk scores (GRS) with each risk variant scoring 1, subjects with GRS≥3 (8.2% of the cohort) had 56% higher risk of T2D than those with GRS = 0 (P = 0.01). In a subcohort of control subjects, plasma IAPP increased and beta cell function index declined with GRS (P = 0.008 and 0.03 respectively). Bioinformatics and functional analyses of CPE rs1583645 predicted regulatory elements for chromatin modification and transcription factors, suggesting differential DNA-protein interactions and gene expression. Taken together, these results support the importance of dysregulation of IAPP metabolism in T2D in East Asians.
    PLoS ONE 06/2013; 8(6):62378-. · 3.53 Impact Factor
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    ABSTRACT: Background Increased renal arterial resistance is associated with various types of chronic renal parenchymal diseases. A resistance index (RI) > 0.8 predicts deterioration in renal function in diabetic subjects. However, the association between renal RI and other diabetic complications has not been investigated. In this study, we examined the association between intrarenal arterial RI and diabetic complications in Chinese type 2 diabetic subjects.Methods Three hundred and eighty-seven Chinese type 2 diabetic patients were recruited from a structured assessment programme to evaluate their risk factors and complications as a part of the quality improvement programme at the Prince of Wales Hospital. All subjects underwent ultrasound examinations for the assessment of intrarenal arterial RI of both kidneys. Clinical and biochemical parameters, including diabetes-related microvascular complications (nephropathy, retinopathy and sensory neuropathy) and macrovascular diseases, were examined.ResultsThe mean RI of patients with any microvascular complications (0.70 ± 0.09 versus 0.65 ± 0.06) such as nephropathy (0.71 ± 0.09 versus 0.66 ± 0.06), retinopathy (0.71 ± 0.08 versus 0.67 ± 0.08) and sensory neuropathy (0.75 ± 0.07 versus 0.68 ± 0.08) and with any macrovascular complications (0.71 ± 0.09 versus 0.68 ± 0.08) was higher than those without (P < 0.05). On multivariate analysis, after controlling for confounding variables, an RI ≥0.75 was associated with microvascular complications, nephropathy, retinopathy and sensory neuropathy, with odds ratio of 4.02 [95% confidence interval (CI) 1.72-9.4], 4.99 (2.61-9.56), 2.78 (1.52-5.09) and 5.74 (1.8-18.3), respectively. The association of RI with macrovascular complications was not significant in multivariate analysis.Conclusion Increased intrarenal arterial resistance was independently associated with an increased risk of microvascular complications including diabetic nephropathy, diabetic retinopathy and diabetic sensory neuropathy in Chinese type 2 diabetic patients.
    Nephrology Dialysis Transplantation 12/2012; · 3.37 Impact Factor
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    ABSTRACT: Aims:  To study the prediction of abnormal glucose tolerance (AGT), diabetes mellitus (DM), hypertension (HT) and metabolic syndrome (MetS) among Chinese women using glycemic indices in the mid-trimester of pregnancy. Methods:  A cohort of Chinese women who had had either normal glucose tolerance or gestational diabetes mellitus (GDM) during a pregnancy were assessed at a median of 8 and 15 years post-delivery. All women underwent a 50-g glucose challenge test (GCT) and a 75-g oral glucose tolerance test in the mid-trimester of the index pregnancy. A receiver operating characteristic curve was used to assess the prediction of AGT, DM, HT and MetS. Results:  All glycemic indices were significant predictors of AGT and DM, and the 2-h plasma glucose (PG) and GCT were predictive of HT, at both 8 and 15 years post-delivery. MetS can only be predicted by the fasting plasma glucose (FPG) and was confined to 15 years post-delivery. After adjustment for confounding variables, all glycemic indices were still independent predictors of AGT and DM at both 8 and 15 years post-delivery, except for FPG in predicting DM at 8 years, while only the 2-h PG remains an independent predictor of HT at 15 years. The optimal cut-off values for FPG, 2-h PG and GCT are 4.2 mmol/L, 7.2 mmol/L and 7.7 mmol/L, respectively; all are lower than the current cut-off thresholds for the screening and diagnosis of GDM. Conclusions:  Women who had a glycemic level below the criteria for a positive screening test and below the diagnostic threshold for GDM still have a significant cardiometabolic risk.
    Journal of Obstetrics and Gynaecology Research 08/2012; · 0.84 Impact Factor
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    ABSTRACT: Purpose: To examine the sensitivity of ultrasonography (US) compared with conventional radiography in detection of lower limb (thigh) medial arterial calcification (MAC) in type 2 diabetic patients and evaluate its association with diabetes-related complications. Materials and Methods: The study was approved by the local research ethics committee, and informed written consent was obtained. US was performed in 289 patients with type 2 diabetes mellitus, and MAC severity was assigned a score from 0 to 8. Among the patients, 263 underwent radiographic examinations. All subjects underwent clinical evaluation to detect the presence of diabetes-related complications. Results: US helped detect MAC in more subjects compared with radiography (65.8% vs 12.2%). US helped detect MAC from mild (scores 1-4) to severe (scores 5-8) degrees, while mild degree of MAC was poorly demonstrated with radiography. The incidence of nephropathy, retinopathy, sensory neuropathy, and macrovascular complications increased with the severity of MAC (based on US scoring). With univariate analysis, the presence of MAC was associated with nephropathy (P < .001), retinopathy (P < .001), sensory neuropathy (P = .004), and macrovascular complications (P < .001). After adjustment for potential confounders, the presence of severe MAC was associated with nephropathy, retinopathy, and macrovascular complications, with the odds ratios of 3.4 (95% confidence interval [CI]: 1.53, 7.43; P = .003), 2.6 (95% CI: 1.22, 5.32; P = .013), and 3.8 (95% CI: 1.37, 10.6; P = .01), respectively. Conclusion: In type 2 diabetic Chinese patients, US was more sensitive than conventional radiography in the detection of MAC, particularly when the MAC was mild. The presence of severe MAC was associated with diabetic nephropathy, retinopathy, and macrovascular complications. US detection of MAC was a potential early marker to identify diabetes-related complications. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112440/-/DC1.
    Radiology 07/2012; 265(1):294-302. · 6.34 Impact Factor
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    ABSTRACT: To determine the relationship between in utero hyperinsulinemia and children's arterial stiffness at adolescence. Indices of arterial stiffness were measured using the SphygmoCor apparatus in 129 adolescents (42 offsprings of mother with gestational diabetes and 87 offsprings of mother with normal glucose tolerance during pregnancy) at 15 years of age. Adolescent of mothers with gestational diabetes had similar central aortic blood pressure, augmentation pressure (AP), augmentation index (AI), and carotid-femoral pulse wave velocity (PWV) as that of controls. However, both umbilical cord C-peptide and insulin levels correlated positively AI (R=0.28 and 0.24; p=0.011 and 0.035, respectively), and umbilical insulin level correlated positively with AP (R=0.25; p=0.025). The correlations were significant between umbilical cord C-peptide and AP (R=0.24; p=0.035) and AI (R=0.29; p=0.011) after adjustment for subjects' age, sex, body weight and height. Adolescents who had umbilical cord C-peptide levels at highest quartile (n=25), based on the reference ranges of the original cohort, had a significant greater PWV (5.26±0.12 m/s vs 4.98±0.12 m/s; p=0.0049) than those with C-peptide levels at the lower 3 quartiles (n=57) after adjustment for age, sex, body weight and height. In utero hyperinsulinemia appears to increase the offspring's arterial stiffness at early adolescence.
    Diabetes research and clinical practice 11/2011; 95(1):169-75. · 2.74 Impact Factor
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    ABSTRACT: To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS). Randomized controlled double-blind trial. A tertiary referral center, Hong Kong. Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70). Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months. Menstrual status as well as clinical and biochemical hyperandrogenism. There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms. We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population. ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry).
    Fertility and sterility 06/2011; 96(2):445-451.e1. · 3.97 Impact Factor
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    ABSTRACT: Adolescent offspring of women with a history of gestational diabetes (GD) were evaluated for their cardiometabolic risks at a mean age of 15 years. One hundred and twenty-nine adolescents who were assessed for their cardiometabolic risks at 8 years of age were reassessed at 15 years of age. Adolescent offspring of mothers with GD had similar blood pressure, plasma lipid profile, and a rate of abnormal glucose tolerance as control subjects. In utero hyperinsulinemia was associated with a 17-fold increase in metabolic syndrome and a 10-fold increase in overweight at adolescence, independent of birth weight, Tanner stage, maternal GD status, and mother's BMI. In utero environment of hyperinsulinemia, irrespective of the degree of maternal GD, was associated with increased risk of overweight and metabolic syndrome during early adolescence in the offspring.
    Diabetes care 03/2010; 33(6):1382-4. · 7.74 Impact Factor
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    ABSTRACT: Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts. Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG. Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals.
    PLoS ONE 01/2010; 5(7):e11428. · 3.53 Impact Factor
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    ABSTRACT: Elevated blood pressure (BP) is an important risk factor for the development of coronary heart disease (CHD), although the threshold above which the risk increases has not been clearly defined. The aim of the present study was to examine the full-range association between BP and CHD. A prospective cohort of 3861 Chinese women with Type 2 diabetes mellitus (T2DM) was followed for a median of 5.61 years. Restricted cubic spline analysis was used to examine the relationship between BP and CHD. Subjects who developed CHD were older, more likely to be smokers, had a significantly longer duration of diabetes, higher systolic BP (SBP), glycated hemoglobin, albuminuria, low-density lipoprotein-cholesterol, and triglycerides, and lower estimated glomerular filtration rate and high-density lipoprotein-cholesterol. Mortality was higher in those who developed CHD compared with those who did not, with all-cause death in 30.2% and 7.8% of patients, respectively. Over 21,641 and 22 049 person-years follow up, 4.4% of patients (n = 169) developed CHD and 8.8% (n = 340) died, respectively. The relative risk of SBP for CHD was constant up to 120 mmHg, after which it started to rise: from 130 mmHg, each 10-mmHg increase in SBP was associated with a 1.13-fold increased risk of CHD. We identified 130 mmHg as the threshold of SBP for increased risk of CHD in Chinese female patients with T2DM. It appears that 67-77 mmHg is the optimal range for diastolic BP, within which the risk of CHD is lowest.
    Journal of Diabetes 06/2009; 1(2):90-8. · 2.94 Impact Factor
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    ABSTRACT: The goal was to examine the carbohydrate tolerance and cardiometabolic risk among children exposed to maternal gestational diabetes mellitus in utero. In this study, 164 Chinese children whose mothers had participated in a previous study on the screening and diagnosis of gestational diabetes mellitus (63 had gestational diabetes mellitus and 101 had normal glucose tolerance during the index pregnancies) underwent follow-up evaluations at a median age of 8 years (range: 7-10 years). Children's weight, height, hip and waist circumferences, and blood pressure were measured, and weight-adjusted oral glucose tolerance tests were performed. Six children (3.7%) demonstrated impaired glucose regulation or diabetes mellitus at the follow-up evaluation. Children exposed to maternal gestational diabetes mellitus had significantly higher systolic (94+/-1.2 vs 88+/-0.9 mmHg) and diastolic (62+/-0.8 vs 57+/-0.6 mmHg) blood pressure values and lower high-density lipoprotein cholesterol (1.58+/-0.04 vs 1.71+/-0.03 mmol/L) levels, after adjustment for age and gender. A high (>or=90th percentile) umbilical cord insulin level at birth was associated with abnormal glucose tolerance in the offspring. Maternal gestational diabetes mellitus increases the offspring's cardiometabolic risk, and in utero hyperinsulinemia is an independent predictor of abnormal glucose tolerance in childhood.
    PEDIATRICS 01/2009; 122(6):1229-34. · 4.47 Impact Factor
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    ABSTRACT: Mesenteric fat, a reflection of visceral adiposity, may play an important role in the pathogenesis of metabolic syndrome and cardiovascular diseases (CVD). In this study, we examined the independent relationship between mesenteric fat thickness and metabolic syndrome and defined its optimal cutoff value to identify high-risk subjects for metabolic syndrome and CVD. A total of 290 Chinese subjects had an ultrasound examination for measurements of thickness of mesenteric, preperitoneal, and subcutaneous fat as well as carotid intima-media thickness (IMT). Anthropometric measurements and metabolic risk profile were assessed by physical examination and blood taking. Twenty (6.9%) subjects had metabolic syndrome according to the National Cholesterol Education Panel Adult Treatment Panel III criteria with Asian definitions for central obesity (waist circumference >80 cm in women and >90 cm in men). Mesenteric fat thickness had significant correlations (P < 0.05) with various metabolic variables. On multivariate regression, mesenteric fat thickness was an independent determinant of all components of metabolic syndrome after adjustment for age, sex, homeostasis model assessment of insulin resistance, and other fat deposits. The odds ratio of metabolic syndrome was increased by 1.35 (95% CI 1.10-1.66)-fold for every 1-mm increase in mesenteric fat thickness. On receiver-operating characteristic curve analysis, mesenteric fat thickness of > or =10 mm was the optimal cutoff value to identify metabolic syndrome, with sensitivity of 70% and specificity of 75%. Subjects with mesenteric fat thickness > or =10 mm had higher carotid IMT than those with thickness <10 mm (0.73 +/- 0.19 vs. 0.64 +/- 0.16 mm, P = 0.001). Mesenteric fat thickness was an independent determinant of metabolic syndrome and identified subjects with increased carotid IMT.
    Diabetes Care 02/2006; 29(2):379-84. · 7.74 Impact Factor
  • Chinese medical journal 10/2004; 117(9):1404-7. · 0.90 Impact Factor