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Objective: This study aims to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications. Research Design and Methods: We performed a two-stage genome-wide association studies for CHD in Chinese patients with T2D (3,596 cases and 8,898 controls), followed by replications in European patients with T2D (764 cases and 4,276 controls) and general populations (n=51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes, and its interactions with glycaemic, blood pressure (BP) and lipid controls on incident cardiovascular diseases. Results: We identified a novel variant (rs10171703) for CHD (OR [95% CI] = 1.21 [1.13–1.30]; P=2.4×10-8) and BP (β±SE = 0.130±0.017; P = 4.1×10-14) at PDE1A in Chinese T2D patients, but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (Pinteraction = 0.0155) and myocardial infarction (MI) (Pinteraction = 5.1×10-4). Patients with CC-genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9×10-8 < P < 3.6×10-5), those with CT-genotype had no difference (0.0726 < P < 0.2614), and those with TT-genotype had a threefold increase in MI risk (P = 6.7×10-3). Conclusions: We discovered a novel CHD- and BP-related variant at PDE1A which interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes only when our findings are validated.

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.

We aim to assess the long-term impact of AKI on progression of diabetic kidney disease and all-cause mortality, and investigate determinants of AKI in Chinese patients with type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register were followed for 12 years (mean[SD] age 57±13.2 years; 46.9% men; duration of diabetes 5 years). AKI was defined based on the KDIGO criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 SNPs known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD and ESRD. Validation was sought in an independent cohort including 6,007 patients (mean age 61.2±10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (HR [95% CI]: 14.3[12.69-16.11]), ESRD (12.1[10.74-13.62]) and all-cause death (7.99[7.31-8.74]), compared with those without AKI. Incidence rate for ESRD among patients with 0, 1, 2, ³ 3 episodes of AKI were 7.1, 24.4, 32.4, 37.3 per 1000 person-years. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts, but not ESRD. Elevated SUA may increase the risk of diabetic kidney disease through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a non-modifiable risk factor may facilitate the identification of high-risk individuals to prevent AKI and its long-term impact in T2D.

We aim to assess the long-term impact of acute kidney injury (AKI) on progression of diabetic kidney disease (DKD) and all-cause mortality and investigate determinants of AKI in Chinese patients with type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register was followed for 12 years (mean ± SD age 57 ± 13.2 years; 46.9% men; median duration of diabetes 5 years). AKI was defined based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 single nucleotide polymorphisms (SNPs) known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD, and ESRD. Validation was sought in an independent cohort including 6,007 patients (age 61.2 ± 10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (hazard ratio 14.3 [95% CI 12.69–16.11]), for developing ESRD (12.1 [10.74–13.62]), and for all-cause death (7.99 [7.31–8.74]) compared with those without AKI. Incidence rate for ESRD among patients with no episodes of AKI and one, two, and three or more episodes of AKI was 7.1, 24.4, 32.4, and 37.3 per 1,000 person-years, respectively. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts but not ESRD. Elevated SUA may increase the risk of DKD through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a nonmodifiable risk factor may facilitate the identification of individuals at high risk to prevent AKI and its long-term impact in T2D.

Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes.Multicenter prospective cohort study.19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank.DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR.All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%).Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates.Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR 30 mL/min/1.73 mPotential misclassification because of drug use.Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR.

Additional file 1: Supplementary methods: 1) Hong Kong Diabetes Register TRS Study Group Members; 2) Hong Kong Diabetes Biobank Study Group Members; and 3) Cohort descriptions. Figure S1. Principal component analysis (PCA). Figure S2. Pooled correlations of each candidate polygenic risk scores with measured lipid traits. Figure S3. Proportion of phenotypic variance in lipid traits explained by each candidate polygenic risk scores. Figure S4. Geometric means of measured lipid traits stratified by the quintile of polygenic risk score with the best performance. Figure S5. Geometric means of measured lipid traits at baseline and follow-up, and three-year changes in lipid traits stratified by quintile of polygenic risk scores in adolescents.

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 r) r − 103 P − 75) and 3-year lipid changes (1.4 × 10− 6 P 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 − 3 P − 10 P β ± SE = 0.011 ± 0.005, Ptrend = 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− 4 P Conclusions The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

Hongjiang Wu,1,2 Eric SH Lau,3 Alice PS Kong,2,4 Ronald CW Ma,2,4 Risa Ozaki,4 Kitty KT Cheung,4 Elaine Chow,4 Chiu Chi Tsang,5 Kam Piu Lau,6 Eric MT Hui,7 Wing Yee So,8 Danijela Gasevic,1,9 Sarah H Wild,1 Juliana CN Chan,2–4 Andrea Luk2–4 1Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK; 2Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; 3Asia Diabetes Foundation, Prince of Wales Hospital, Hong Kong SAR, China; 4Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; 5Alice Ho Miu Ling Nethersole Hospital, Tai Po, Hong Kong SAR, China; 6Northern District Hospital, Fanling, Hong Kong SAR, China; 7Department of Family Medicine, Prince of Wales Hospital, Hong Kong SAR, China; 8Hospital Authority Head Office, Hong Kong SAR, China; 9School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia 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 >13years. 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 6.2years for CVD and 6.4years 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. Keywords: socioeconomic status, educational level, diabetes, cardiovascular disease, all-cause mortality

Background In a randomized controlled trial of 628 Chinese patients with type 2 diabetes receiving multidisciplinary care in the Joint Asia Diabetes Evaluation (JADE) Progam, 372 were randomized to receive additional telephone-based peer support (Peer Empowerment And Remote communication Linked by information technology, PEARL) intervention. After 12 months, all-cause hospitalization was reduced by half in the PEARL group especially in those with high Depression Anxiety and Stress Scale (DASS) scores. Methods We used stratified analyses, negative binomial regression, and structural equation modelling (SEM) to examine the inter-relationships between emotions, self-management, cardiometabolic risk factors, and hospitalization. Results Hospitalized patients were older, more likely to have heart or kidney disease, and negative emotions than those without hospitalization. Patients with high DASS score who did not receive peer support had the highest hospitalization rates. After adjustment for confounders, peer support reduced the frequency of hospitalizations by 48% with a relative risk of 0.52 (95% CI 0·35–0·79;p = 0·0018). Using SEM, improvement of negative emotions reduced treatment nonadherence (Est = 0.240, p = 0.034) and hospitalizations (Est=−0.218, p = 0.001). The latter was also reduced by an interactive term of peer support and chronic kidney disease (Est = 0.833, p =

PURPOSE We examined the effects of participating in a "train-the-trainer" pro- gram and being a peer supporter on metabolic and cognitive/psychological/ behavioral parameters in Chinese patients with type 2 diabetes. METHODS In response to our invitation, 79 patients with fair glycemic control (HbA1c

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

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 μmol/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 500 μmol/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 ≥3 treatment goals (61%, n = 63, vs. 28%, n = 28; P < 0.001). Patients who attained ≥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 ≤2 targets (n = 114). 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.