Publications by authors named "Kam Piu Lau"

6 Publications

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Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.

Genome Med 2021 02 19;13(1):29. Epub 2021 Feb 19.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

Background: The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear.

Methods: We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients.

Results: Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10 < P < 1.3 × 10) and 3-year lipid changes (1.4 × 10 < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (β ± SE = 0.052 ± 0.002), 11.7% in TG (β ± SE = 0.111 ± 0.006), 5.8% in HDL-C (β ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (β ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10 < P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10 < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (β ± SE = 0.011 ± 0.005, P = 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI) = 1.07 (1.03-1.11)], TG [OR (95% CI) = 1.05 (1.01-1.09)], and LDL-C [OR (95% CI) = 1.05 (1.01-1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8 × 10 < P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association.

Conclusions: The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.
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http://dx.doi.org/10.1186/s13073-021-00831-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893928PMC
February 2021

Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank.

PLoS Med 2020 07 28;17(7):e1003209. Epub 2020 Jul 28.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

Background: Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D.

Methods And Findings: In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1-9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03-1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06-1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10-8) but not glycemic progression (HR: 1.01 [95% CI 0.96-1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort.

Conclusions: Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.
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http://dx.doi.org/10.1371/journal.pmed.1003209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386560PMC
July 2020

A Hong Kong Chinese kindred with familial hypocalciuric hypercalcaemia caused by mutation.

F1000Res 2019 9;8:1612. Epub 2019 Sep 9.

Department of Chemical Pathology, Prince of Wales Hospital, Shatin, Hong Kong.

Familial hypocalciuric hypercalcaemia (FHH) is a genetic disorder of altered calcium homeostasis. Mutations in the , and genes have been reported to cause FHH. We report a Hong Kong Chinese kindred with FHH type 3 (FHH3) caused by mutations in . The proband, a 51-year-old woman with hypercalcaemia, was initially diagnosed to have primary hyperparathyroidism but repeated parathyroidectomy failed to normalize her plasma calcium concentrations. Later, FHH was suspected and yet no mutations were identified in the gene which causes FHH type 1 (FHH1), the most common form of FHH. Genetic testing of revealed a heterozygous c.43C>T (p.Arg15Cys) mutation, confirming the diagnosis of FHH3. The elder brother and niece of the proband, who both have hypercalcaemia, were found to harbour the same mutation. To our knowledge, this is the first Chinese kindred of FHH3 reported in the English literature.
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http://dx.doi.org/10.12688/f1000research.20344.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826774PMC
June 2020

Association between educational level and cardiovascular disease and all-cause mortality in patients with type 2 diabetes: a prospective study in the Joint Asia Diabetes Evaluation Program.

Clin Epidemiol 2018 25;10:1561-1571. Epub 2018 Oct 25.

Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China,

Purpose: The aim of this study was to describe the association between educational level and incident cardiovascular disease (CVD) and all-cause mortality in Hong Kong Chinese patients with type 2 diabetes.

Patients And Methods: We included 12,634 patients with type 2 diabetes who were enrolled into the Joint Asia Diabetes Evaluation Program between June 1, 2007, and June 30, 2017. We classified patients' educational level into the following three groups: ≤6 years, 6-13 years, and >13 years. Incident CVD events were identified using hospital discharge diagnoses. Death was identified from Hong Kong Death Register. We estimated HRs for incident CVD and all-cause mortality using Cox regression models.

Results: Patients with the highest educational level were younger and had shorter diabetes duration and better glycemic control at enrollment than those with the lowest educational level. During the median follow-up of 6.2 years for CVD and 6.4 years for all-cause mortality, 954 CVD events and 833 deaths were recorded. HRs for CVD and all-cause mortality were 0.73 (95% CI: 0.57, 0.94) and 0.71 (95% CI: 0.54, 0.94) for the highest educational level compared to the lowest educational level, after adjustment for age, sex, diabetes duration, and family history of diabetes.

Conclusion: Educational level is inversely associated with the risk of CVD and all-cause mortality among Hong Kong Chinese patients with type 2 diabetes. Hong Kong Chinese patients with type 2 diabetes and low educational level should be given special attention for the prevention of key complications of diabetes.
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http://dx.doi.org/10.2147/CLEP.S177437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208565PMC
October 2018

Borderline ankle-brachial index is associated with increased prevalence of micro- and macrovascular complications in type 2 diabetes: A cross-sectional analysis of 12,772 patients from the Joint Asia Diabetes Evaluation Program.

Diab Vasc Dis Res 2015 Sep 3;12(5):334-41. Epub 2015 Jul 3.

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China Asia Diabetes Foundation, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

Borderline ankle-brachial index is increasingly recognised as a marker of cardiovascular risk. We evaluated the impact of borderline ankle-brachial index in 12,772 Chinese type 2 diabetes patients from the Joint Asia Diabetes Evaluation Program between 2007 and 2012. Cardiovascular risk factors, complications and health-related quality of life were compared between patients with normal ankle-brachial index (1.0-1.4), borderline ankle-brachial index (0.90-0.99) and peripheral arterial disease (ankle-brachial index < 0.9). The prevalence of peripheral arterial disease and borderline ankle-brachial index was 4.6% and 9.6%, respectively. Borderline ankle-brachial index patients were older, more likely to be smokers and hypertensive, had longer duration of diabetes, poorer kidney function and poorer health-related quality of life than patients with normal ankle-brachial index. After adjustment for traditional cardiovascular risk factors, borderline ankle-brachial index was an independent predictor of diabetes-related micro- and macrovascular complications including retinopathy (odd ratios: 1.19 (95% confidence interval: 1.04-1.37)), macroalbuminuria (1.31 (1.10-1.56)), chronic kidney disease (1.22 (1.00-1.50)) and stroke (1.31 (1.05-1.64)). These findings suggest that patients with diabetes and borderline ankle-brachial index are at increased cardiovascular risk and may benefit from more intensive management.
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http://dx.doi.org/10.1177/1479164115590559DOI Listing
September 2015

Effects of structured versus usual care on renal endpoint in type 2 diabetes: the SURE study: a randomized multicenter translational study.

Diabetes Care 2009 Jun;32(6):977-82

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.

Objective: Multifaceted care has been shown to reduce mortality and complications in type 2 diabetes. We hypothesized that structured care would reduce renal complications in type 2 diabetes.

Research Design And Methods: A total of 205 Chinese type 2 diabetic patients from nine public hospitals who had plasma creatinine levels of 150-350 micromol/l were randomly assigned to receive structured care (n = 104) or usual care (n = 101) for 2 years. The structured care group was managed according to a prespecified protocol with the following treatment goals: blood pressure <130/80 mmHg, A1C <7%, LDL cholesterol <2.6 mmol/l, triglyceride <2 mmol/l, and persistent treatment with renin-angiotensin blockers. The primary end point was death and/or renal end point (creatinine >500 micromol/l or dialysis).

Results: Of these 205 patients (mean +/- SD age 65 +/- 7.2 years; disease duration 14 +/- 7.9 years), the structured care group achieved better control than the usual care group (diastolic blood pressure 68 +/- 12 vs. 71 +/- 12 mmHg, respectively, P = 0.02; A1C 7.3 +/- 1.3 vs. 8.0 +/- 1.6%, P < 0.01). After adjustment for age, sex, and study sites, the structured care (23.1%, n = 24) and usual care (23.8%, n = 24; NS) groups had similar end points, but more patients in the structured care group attained >or=3 treatment goals (61%, n = 63, vs. 28%, n = 28; P < 0.001). Patients who attained >or=3 treatment targets (n = 91) had reduced risk of the primary end point (14 vs. 34; relative risk 0.43 [95% CI 0.21-0.86] compared with that of those who attained
Conclusions: Attainment of multiple treatment targets reduced the renal end point and death in type 2 diabetes. In addition to protocol, audits and feedback are needed to improve outcomes.
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http://dx.doi.org/10.2337/dc08-1908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681013PMC
June 2009
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