Biomedical subjects

Kathryn C B Tan

Publications and source records attributed to Kathryn C B Tan.

13 recordsLinked to original sources

PubMed2026

Handgrip strength and risk of common infections and sepsis: Two prospective cohorts with proteomic mediation analysis.

BACKGROUND: Recent evidence links adiposity with the risk of severe infections, but whether muscle strength may also be an independent risk factor is less studied. We investigated the association between handgrip strength and risk of common infections and sepsis and explored potential mediation by plasma proteomic biomarkers. METHODS: We analyzed data from 405,451 UK Biobank participants and replicated the main findings in 4474 Chinese adults from the Hong Kong Osteoporosis Study (HKOS). Baseline handgrip strength was measured by a dynamometer. Cox models were used to estimate its association with incidence of pneumonia, urinary tract infection (UTI), skin infection, and sepsis, adjusting for sociodemographic, lifestyle, and health-related factors. Mediation analyses were performed using 2912 plasma proteins in a UK Biobank subsample (n = 42,414) to identify biological pathways. RESULTS: In UK Biobank (median follow-up 13.6-15.3 years), lower handgrip strength was associated with significantly increased risk of pneumonia (hazard ratio per 5-kg decrement=1.10; 95% CI=1.09-1.11), UTI (1.10; 1.09-1.11), skin infection (1.05; 1.04-1.05), and sepsis (1.08; 1.07-1.10). Associations were largely consistent in HKOS, and the relative risks associated with low grip strength were generally most pronounced in underweight individuals. GDF15 and PLAUR were identified as the most important proteins which mediated 12-14% of these associations. CONCLUSION: Low handgrip strength is associated with increased risks of common infections and sepsis, particularly in underweight individuals, with partial mediation by proteins related to inflammation and immune-related pathways. Handgrip strength assessment may provide prognostic value beyond body mass index for clinical risk stratification.

Humans↗

PubMed2006

Endothelial nitric oxide synthase G894T (Glu298Asp) polymorphism was predictive of glycemic status in a 5-year prospective study of Chinese subjects with impaired glucose tolerance.

Subjects with impaired glucose tolerance (IGT) have a high risk of developing type 2 diabetes mellitus (DM) and its related complications. However, both environmental and genetic factors may influence the progression or regression of hyperglycemia. Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene have been associated with DM in cross-sectional studies, but their predictive values in glycemic progression are not known. We examined the relationship of the eNOS promoter -T786C (-T786C), intron 4 variable tandem repeat (in4a/b), and exon 7 G894T (G894T) polymorphisms, and their haplotypes, with the long-term glycemic outcome in a Chinese cohort with IGT. Two hundred fifty-six Chinese subjects with IGT at baseline participated in a 5-year follow-up study to assess their glycemic outcome. Each individual was genotyped for the above-mentioned polymorphisms. At 5 years, 40.2% of the subjects had reverted to normal glucose tolerance; 39.9% remained in IGT/impaired fasting glucose and 19.9% had developed DM. A significant gene effect of exon 7 G894T polymorphism on glycemic status at 5 years was demonstrated, with carriers of T(894) being more likely to have persistent hyperglycemia compared with GG subjects (P = .003). On stepwise logistic regression analysis, the presence of the T allele remained a significant risk factor for persistent hyperglycemia (odds ratio, 2.72; 95% confidence interval, 1.36-5.99; T+ vs GG; P = .013), together with male sex, high body mass index, and high 2-hour glucose at baseline. No significant effect of -T786C or in4a/b polymorphism on fifth-year glycemic status was observed. The eNOS G894T polymorphism appears to be predictive of persistent hyperglycemia in Chinese subjects with IGT.

Adult↗

PubMed2006

Advanced glycation endproducts in nondiabetic patients with obstructive sleep apnea.

SUBJECT OBJECTIVE: The formation and accumulation of advanced glycation endproducts (AGEs) has been implicated in the progression of age-related diseases such as diabetes mellitus and atherosclerosis. We hypothesize that AGE concentrations may be increased in subjects with obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: One hundred nineteen nondiabetic patients with OSA and 234 age-matched healthy controls and 134 patients with type 2 diabetes were recruited for participation in the study. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit antisera raised against AGE-RNase. RESULTS: Serum AGEs were increased in OSA subjects, as compared with controls, but were less increased than the AGEs of patients with type 2 diabetes (control: 3.22 +/- 0.54 unit per mL; OSA: 3.68 +/- 0.39; diabetes mellitus: 4.11 +/- 0.99; analysis of variance p < .01). In the subjects with OSA, serum AGEs correlated with the duration of nocturnal desaturation (r = 0.21, p = .025) and plasma total 8-isoprostane concentration, a biochemical marker of oxidative stress (r = 0.22, p = .015), but not with fasting glucose level. On general linear model univariate analysis, the association between serum AGEs and 8-isoprostane was independent of age, sex, body mass index, smoking status, and glucose. CONCLUSION: Serum levels of AGEs were increased in nondiabetic subjects with OSA and were associated with the severity of OSA. Whether increased AGE formation contributes significantly to the high cardiovascular risk associated with OSA remains to be determined.

Diabetes Mellitus, Type 2↗

PubMed2005

HDL dysfunction in obstructive sleep apnea.

OBJECTIVE: HDL is anti-atherogenic and has antioxidant property. HDL dysfunction has been reported in patients with coronary heart disease and we hypothesize that HDL may also be dysfunctional in obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: 128 OSA patients and 82 controls were recruited. HDL dysfunction was determined by evaluating the ability of HDL to inhibit LDL oxidation ex vivo. Plasma HDL was incubated with native LDL in the presence of dichlorofluorescein which fluoresced upon interaction with lipid oxidation products. Plasma levels of oxidized LDL and 8-isoprostane were measured by ELISA and a specific enzyme immunoassay, respectively. RESULTS: Plasma total 8-isoprostane levels were elevated in OSA subjects (p<0.01). Despite having similar concentrations of plasma lipids and apolipoproteins as controls, OSA subjects had greater degree of HDL dysfunction (p<0.01) and increased oxidized LDL levels (p<0.05). The apnea-hypopnea index was the main determinant of HDL dysfunction in OSA, accounting for 30% of its variance, with oxidized LDL and apolipoprotein AI contributing to 8% and 5% of its variance respectively (p<0.001). CONCLUSION: HDL is dysfunctional in preventing the formation and inactivation of oxidized lipids in OSA subjects and may partly contribute to their increased cardiovascular risk.

Adult↗

PubMed2005

Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes.

The antidiabetic hormone adiponectin circulates in blood as several oligomeric complexes, and the ratios between them are critical in determining insulin sensitivity. In this study we investigated the role of testosterone in regulating the oligomeric complex distribution of adiponectin. Gel filtration analysis revealed that circulating adiponectin existed as the forms of high molecular weight (HMW), middle molecular weight, and low molecular weight complexes in both human and mice. The concentration of HMW adiponectin in female was significantly higher than that in male, whereas there were no gender differences for the other two forms. Castration induced a dramatic elevation of the HMW form but had no effect on either the middle molecular weight or the low molecular weight form in mice. Testosterone treatment, on the other hand, caused a specific reduction of HMW adiponectin in the circulation. Pulse-chase labeling experiments in rat adipocytes revealed that the three oligomeric forms of adiponectin were secreted into the culture medium at different rates and that testosterone selectively impeded the secretion of HMW adiponectin but not the other two forms. The inhibitory effect of testosterone on secretion of HMW adiponectin was largely restored by the transcription inhibitor actinomycin D, suggesting the involvement of a transcriptional event in this process. The selective inhibition of HMW adiponectin by testosterone might contribute to the sex dimorphism of adiponectin in terms of its oligomeric complex distribution and could partly explain why men have higher risk to insulin resistance and atherosclerosis than women.

Adipocytes↗

PubMed2004

Glycoxidized low-density lipoprotein regulates the expression of scavenger receptors in THP-1 macrophages.

Low-density lipoprotein (LDL) in patients with diabetes is subject to modification by both oxidation and glycation. In contrast to oxidized LDL, the biological effects of glycoxidized LDL have not been well characterised. In this study, the effects of oxidized, glycated, glycoxidized and oxidized LDL on scavenger receptor gene expressions, and the induction of oxidized LDL uptake and cholesteryl ester accumulation in THP-1 macrophages were compared. Modified LDL was incubated with THP-1 macrophages. Gene expression of scavenger receptor class A (SR-A), CD36 and scavenger receptor class B type I (SR-BI) was determined by quantitative reverse transcriptase PCR (RT-PCR). Glycoxidized LDL was able to significantly induce SR-A and CD36 expression by 3- and 4.5-fold, respectively, in macrophages whereas SR-BI expression was suppressed by glycoxidized LDL, glycated LDL and oxidized LDL. Incubation with glycoxidized LDL enhanced the uptake of DiI-labeled oxidized LDL by macrophages to a greater extent than that of glycated LDL or oxidized LDL. Glycoxidized LDL also induced a significant degree of intracellular cholesteryl ester accumulation. Taken together, our results would suggest that glycoxidized LDL might be an important candidate in the initiation of foam cell formation and might play a significant role in the pathogenesis of atherosclerosis in diabetes mellitus.

CD36 Antigens↗

PubMed2004

Cerebrotendinous xanthomatosis in a Hong Kong Chinese kinship with a novel splicing site mutation IVS6-1G>T in the sterol 27-hydroxylase gene.

We reported a Hong Kong Chinese proband with Cerebrotendinous Xanthomatosis in which a novel acceptor splicing site mutation (IVS6-1G>T) was identified. Family screening revealed the same mutation in his elder brother and the youngest sister. All the three affected siblings were compound heterozygous for IVS6-1G>T and a known missense mutation R372Q (GenBank Accession No. M62401). Significant phenotypic variation was noted among them that the youngest sister was still symptom-free at the time of writing.

Asian People↗

PubMed2004

Association between acute-phase reactants and advanced glycation end products in type 2 diabetes.

OBJECTIVE: Type 2 diabetes is associated with chronic low-grade inflammation, but the underlying mechanism(s) is not well understood. Because in vitro studies have shown that advanced glycation end products (AGEs) can trigger inflammatory responses, the present study has investigated whether serum concentration of AGEs is an important determinant of circulating levels of inflammatory markers, like C-reactive protein (CRP), in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Diabetic patients (n = 210) and healthy control subjects (n = 110) of similar BMI were recruited. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit anti-sera raised against AGE-RNase. Plasma high-sensitivity CRP was measured by an immunoturbidimetric assay and interleukin (IL)-6 by enzyme-linked immunosorbent assay. RESULTS: Serum AGEs were increased in diabetic patients compared with control subjects (4.24 +/- 0.88 vs. 3.15 +/- 0.81 unit/ml, respectively, P < 0.01). Both plasma CRP (1.55 [0.81-2.95] vs. 0.88 mg/dl [0.51-1.89], respectively, P < 0.01; median [interquartile range]) and IL-6 (0.80 [0.68-0.97] vs. 0.69 pg/ml [0.48-0.84], respectively, P < 0.01) were also higher in diabetic patients than in control subjects. In the diabetic patients, log(CRP) correlated with AGEs (r = 0.22, P = 0.002) and with log(IL-6) (r = 0.29, P < 0.001). Forward stepwise linear regression analysis showed that BMI, log(IL-6), and AGEs were significant independent determinants of log(CRP) in the diabetic patients, accounting for 17, 12, and 10% of the variation in log(CRP), respectively. CONCLUSIONS: Serum concentration of AGEs is increased in patients with diabetes and is an independent determinant of plasma CRP levels. Subclinical inflammation in these patients may therefore be partly due to activation of the inflammatory response by AGEs.

Acute-Phase Proteins↗

PubMed2003

Effect of the microsomal triglyceride transfer protein -493 G/T polymorphism and type 2 diabetes mellitus on LDL subfractions.

Genetic variation in the microsomal triglyceride transfer protein (MTP) affects the secretion pattern and plasma concentration of apolipoprotein (aopB)-containing lipoproteins and a common functional -493 G/T polymorphism has been reported to influence plasma lipids levels. Recent data suggest that carriers of the T allele might be more sensitive to detrimental factors such as features of the insulin resistance syndrome. Since type 2 diabetes is associated with obesity and insulin resistance, the present study investigated the effect of this polymorphism on plasma lipids, apoB and LDL subfractions in 281 Chinese type 2 diabetic subjects and 364 non-diabetic controls. The frequency of the rare T allele was 0.162 and 0.126 in subjects with and without diabetes respectively. There were no differences in the effect of the polymorphism on plasma lipids and apoB in the two groups. However, the TT genotype was associated with a higher concentration of small dense LDL-III than the GT or GG variants in the diabetic subjects (P=0.01) whereas no such effect was observed in the controls. In the diabetic patients, age, plasma triglyceride and the MTP genotype were independent determinants of LDL-III concentrations in linear regression analysis (R(2)=10%, P=0.04) whereas in the controls, only plasma triglyceride and age were important determinants (R(2)=15%, P=0.01). In conclusion, the -493 G/T polymorphism only has a minor effect on LDL subfraction pattern in Chinese and the effect is only apparent in the presence of type 2 diabetes.

Adult↗

PubMed2003

C-reactive protein predicts the deterioration of glycemia in chinese subjects with impaired glucose tolerance.

OBJECTIVE: Recent studies have shown that C-reactive protein (CRP) predicts future risk of diabetes in healthy Caucasians. We determined whether plasma CRP level was elevated in Chinese subjects with impaired glucose tolerance (IGT) and whether CRP level could be used to predict progression to type 2 diabetes or reversion to normal glucose tolerance (NGT) in these high-risk individuals. RESEARCH DESIGN AND METHODS: A total of 228 subjects with IGT at baseline from the Hong Kong Cardiovascular Risk Factors Prevalence Study underwent repeat oral glucose tolerance testing after 2 years. Plasma high-sensitivity CRP was measured from their stored baseline samples and from 228 subjects with NGT matched for age and BMI by an immunoturbidimetric assay. RESULTS: Subjects with IGT at baseline had higher plasma CRP levels than subjects with NGT: 1.18 mg/l (0.52-2.52) vs. 0.87 mg/l (0.37-1.84), median (interquartile range), P = 0.01. At 2 years, 117 subjects with IGT reverted to NGT, 84 remained in IGT, and 21 progressed to diabetes. Individuals who progressed to diabetes had the highest plasma CRP levels at baseline (P < 0.0001). Those with baseline CRP levels in the third and top quartile had a relative risk of remaining in IGT or progressing to diabetes of 2.87 (95% CI 1.06-7.82) and 2.76 (1.06-7.31), respectively, after adjusting for anthropometric measure and lifestyle factors. CONCLUSIONS: CRP independently predicts the risk of remaining in IGT or progressing to diabetes in Chinese subjects with IGT. CRP might provide an adjunctive measure for identifying subjects with the highest risk of progression to diabetes who would derive the greatest benefits from preventive interventions.

Adult↗

PubMed2003

Consensus statement on iodine deficiency disorders in Hong Kong.

This article reviews the available data on the study of iodine deficiency disorders in Hong Kong and to discuss the approach towards preventing such disorders in Hong Kong. The importance of iodine and iodine deficiency disorders is described, and the available data on the dietary iodine intake and urinary iodine concentration in different populations of Hong Kong are summarised and discussed. Dietary iodine insufficiency among pregnant women in Hong Kong is associated with maternal goitrogenesis and hypothyroxinaemia as well as neonatal hypothyroidism. Borderline iodine deficiency exists in the expectant mothers in Hong Kong. Women of reproductive age, and pregnant and lactating women should be made aware and educated to have an adequate iodine intake, such as iodised salt, as an interim measure. A steering group involving all stakeholders should be formed to advise on the strategy of ensuring adequate iodine intake, including universal iodisation of salt in Hong Kong. Continuous surveillance of iodine status in the Hong Kong population is necessary.

Deficiency Diseases↗

PubMed2002

Advanced glycation end products and endothelial dysfunction in type 2 diabetes.

OBJECTIVE: Data from experimental studies have suggested that the increased formation of advanced glycation end products (AGEs) is one of the causes of endothelial dysfunction in diabetes. This study was performed to investigate whether changes in endothelium-dependent vasodilation, a marker of endothelial function, were related to serum AGEs concentrations in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: For this study, 170 patients with type 2 diabetes and 83 healthy nondiabetic control subjects of similar age were recruited. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay. Endothelium-dependent and -independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound. RESULTS: Serum AGEs were increased in diabetic patients compared with control subjects (4.6 +/- 0.7 vs. 3.1 +/- 0.8 unit/ml; P < 0.01), and both endothelium-dependent (5.1 +/- 2.5 vs. 9.1 +/- 4.1%; P < 0.01) and endothelium-independent vasodilation (13.2 +/- 4.6 vs. 16.4 +/- 5.5%; P < 0.01) were impaired. On univariate analysis of all subjects, serum AGEs correlated with endothelium-dependent vasodilation (r = -0.51, P < 0.01); a weaker association was found with endothelium-independent vasodilation (r = -0.24, P < 0.01). On multiple regression analyses including age, sex, smoking status, and plasma lipids, only serum AGEs remained a significant independent determinant of endothelium-dependent vasodilation (r(2) = 0.34, P < 0.01). CONCLUSIONS: Increased serum concentrations of AGEs in patients with type 2 diabetes is associated with endothelial dysfunction, independent of other cardiovascular risk factors. Further studies to determine whether treatment targeting AGEs will lead to an amelioration of endothelial dysfunction are warranted.

Age of Onset↗

PubMedDate not supplied

Effects of angiotensin II receptor antagonist on endothelial vasomotor function and urinary albumin excretion in type 2 diabetic patients with microalbuminuria.

BACKGROUND: Microalbuminuria is associated with dysfunction of the vascular endothelium in patients with diabetes mellitus. The objective of the present study was to determine whether treatment with losartan at a dose sufficient to lower urinary albumin excretion was accompanied by an improvement in endothelial function in type 2 diabetic patients with microalbuminuria. METHODS: Endothelial function was measured in 80 type 2 diabetic patients with microalbuminuria and 68 non-diabetic controls using high-resolution vascular ultrasound. The diabetic patients were randomised to receive either losartan 50 mg daily or placebo in a 6-month double-blind study. Urinary albumin excretion and endothelial function were assessed at baseline, 3 and 6 months. RESULTS: Both endothelium-dependent (p<0.01) and -independent vasodilation (p<0.01) were significantly impaired in diabetic patients with or without history of hypertension compared to the non-diabetic controls. At baseline, the losartan- and placebo-treated groups were comparable in their clinical characteristics. Blood pressure did not change significantly in either group throughout the study. Urinary mean albumin excretion rate (MAER) decreased in the losartan-treated group (p<0.01) whereas an increase was observed in the placebo group (p<0.05). At 6 months, the losartan-treated group had significantly lower MAER than the placebo-treated group [54.5 (58.3) vs 78.5 (100.5) microg/min, p<0.05; median (interquartile range)]. No significant differences were found in endothelium-dependent or -independent vasodilation. CONCLUSIONS: Type 2 diabetic patients with microalbuminuria have impaired endothelium-dependent and -independent vasodilation. Treatment with low-dose losartan is sufficient to reduce microalbuminuria in these patients without alteration in endothelial function and systemic blood pressure.

Adult↗