Type 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes.

Aims/hypothesis: Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes.

Methods: We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong.

NT-proBNP improves prediction of cardiorenal complications in type 2 diabetes: the Hong Kong Diabetes Biobank.

Aims/hypothesis: N-terminal pro B-type natriuretic peptide (NT-proBNP) is a natriuretic peptide that is strongly associated with congestive heart failure (CHF). The utility of NT-proBNP for prediction of cardiovascular events and renal endpoints, compared with clinical risk factors, has not been evaluated in detail. We hypothesise that NT-proBNP can improve risk stratification and prediction of cardiorenal events in type 2 diabetes, beyond that provided by clinical risk factors.

Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank.

Aims/hypothesis: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers.

Methods: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up.

1-year weight change after diabetes diagnosis and long-term incidence and sustainability of remission of type 2 diabetes in real-world settings in Hong Kong: An observational cohort study.

Background: Clinical trials have demonstrated that remission of type 2 diabetes can be achieved following sustained weight loss. However, the feasibility of achieving diabetes remission through weight management in real-world settings remains unclear. In this study, we aimed to examine the association of weight change at 1 year after diabetes diagnosis with long-term incidence and sustainability of type 2 diabetes remission in real-world settings in Hong Kong.

Age- and sex-specific hospital bed-day rates in people with and without type 2 diabetes: A territory-wide population-based cohort study of 1.5 million people in Hong Kong.

Background: Type 2 diabetes affects multiple systems. We aimed to compare age- and sex-specific rates of all-cause and cause-specific hospital bed-days between people with and without type 2 diabetes.

Methods And Findings: Data were provided by the Hong Kong Hospital Authority.

Identification of a Common Variant for Coronary Heart Disease at PDE1A Contributes to Individualized Treatment Goals and Risk Stratification of Cardiovascular Complications in Chinese Patients With Type 2 Diabetes.

Objective: In this study we aim 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 study for CHD in Chinese patients with T2D (3,596 case and 8,898 control subjects), followed by replications in European patients with T2D (764 case and 4,276 control subjects) 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 glycemic, blood pressure (BP), and lipid controls in incident cardiovascular diseases.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

Age-specific population attributable risk factors for all-cause and cause-specific mortality in type 2 diabetes: An analysis of a 6-year prospective cohort study of over 360,000 people in Hong Kong.

Background: The prevalence of type 2 diabetes has increased in both young and old people. We examined age-specific associations and population attributable fractions (PAFs) of risk factors for all-cause and cause-specific mortality in people with type 2 diabetes.

Methods And Findings: We analysed data from 360,202 Chinese with type 2 diabetes who participated in a territory-wide diabetes complication screening programme in Hong Kong between January 2000 and December 2019.

Real world evidence of clinical predictors of glycaemic response to glucose-lowering drugs among Chinese with type 2 diabetes.

Aims: To examine whether simple clinical features can predict the 1-year glycaemic response to glucose-lowering drugs (GLDs) among Chinese with type 2 diabetes.

Materials And Methods: We used data from a diabetes risk assessment and complication screening programme and electronic medical records. We used linear regression models to examine the association between clinical features and 1-year glycaemic response to GLDs.

Attenuated Risk Association of End-Stage Kidney Disease with Metformin in Type 2 Diabetes with eGFR Categories 1-4.

Type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) is a global burden, while the renoprotective effects of metformin remain controversial. In a population-based cohort (2002-2018) including 96,643 patients with T2D observed for 0.7 million person-years, we estimated the risk association of metformin and its dose-relationship with ESKD in a propensity-score overlap-weighting (PS-OW) cohort by eGFR categories.

Incidence of long-term diabetes complications and mortality in youth-onset type 2 diabetes: A systematic review.

Aims: This systematic review aims to assess the incidence of chronic kidney disease (CKD), cardiovascular disease (CVD) and mortality in people with type 2 diabetes diagnosed <20 years.

Methods: We searched MEDLINE, Embase and Cochrane Library for longitudinal studies published between 1 January 2000 and 31 November 2021.

Results: Seventeen studies (15 reporting CKD, 3 reporting CVD, 5 reporting mortality) from seven countries of sample size ranging between 96 and 4,141 were eligible.

A randomized clinical trial of genetic testing and personalized risk counselling in patients with type 2 diabetes receiving integrated care -The genetic testing and patient empowerment (GEM) trial.

Aims: We evaluated the effect of personalized risk counseling incorporating clinical and genetic risk factors on patient empowerment and risk factor control in diabetes.

Methods: Patients with type 2 diabetes (T2D) with suboptimal glycaemic control (HbA1c ≥ 7.5%) were randomized to a genetic counselling (GC) or control group.

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10), which were delineated to 338 distinct association signals.

Clinical Predictors and Long-term Impact of Acute Kidney Injury on Progression of Diabetic Kidney Disease in Chinese Patients With Type 2 Diabetes.

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.

Nonalbuminuric Diabetic Kidney Disease and Risk of All-Cause Mortality and Cardiovascular and Kidney Outcomes in Type 2 Diabetes: Findings From the Hong Kong Diabetes Biobank.

Rationale & Objective: 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.

Study Design: Multicenter prospective cohort study.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

Skin autofluorescence is associated with progression of kidney disease in type 2 diabetes: A prospective cohort study from the Hong Kong diabetes biobank.

Background And Aims: Skin autofluorescence (SAF) can non-invasively assess the accumulation of tissue AGEs. We investigated the association between SAF and kidney dysfunction in participants with T2D.

Methods: Of 4030 participants consecutively measured SAF at baseline, 3725 participants free of end-stage kidney disease (ESKD) were included in the analyses.

Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes: analysis from the Hong Kong Diabetes Register.

Aims/hypothesis: Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes.

Methods: We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data.