Ronald Ching Wan Ma

The Chinese University of Hong Kong | CUHK · Department of Medicine and Therapeutics

Purpose: Robust, affordable plasma proteomic biomarker workflows are needed for large-scale clinical studies. We evaluated aspects of sample preparation to allow LC-MS analysis of more than 1500 samples from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial of adults with type 2 diabetes. Methods: Using LC-MS with data-in...

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 wh...

Aims: To examine whether simple clinical features can predict 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 with linkage to electronic medical records. We used linear regression models to exami...

Background: Renin-angiotensin-system inhibitors (RASi), that include angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) reduce proteinuria, delay chronic kidney disease (CKD) progression, protect against cardiovascular events and heart failure hospitalizations. We examined the associations of discontinuation o...

Objective High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility. Re...

Background Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on c...

Background In Asia, diabetes-associated death due to cardiorenal diseases were 2–3 times higher in women than men which might be due to gender disparity in quality of care and health habits. Methods Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007–2015). We compared treatment target attain...

Objective To evaluate the effect of a team-based multi-component intervention care (MIC) program on obese T2D with poor glycemic control. Methods T2D with HbA1c≥8% and body mass index (BMI)≥27 kg/m² and/or waist circumference≥80cm in women and ≥90cm in men were recruited. The intervention in Diabetes Centre included 1) nurse-led, group-based works...

Human islets are widely used in research for understanding pathophysiological mechanisms leading to diabetes. Sex, age, and body mass index (BMI) are key donor traits influencing insulin secretion. Islet function is also regulated by an intricate network of microRNAs. Here, we profiled 754 microRNAs and 58,190 transcripts in up to 131 different hum...

Aims: Glucokinase (GCK) and glucokinase regulatory protein (GKRP) regulate glucose and lipid metabolism. We investigated the associations of GCKR and GCK polymorphisms with kidney outcomes. Methods: Analyses were performed in a prospective cohort who were enrolled in the Hong Kong Diabetes Register between 1995 and 2017. The associations of GCKR...

Background Interactions between genetic, metabolic, and environmental factors lead to gestational diabetes mellitus (GDM). We aimed to examine interactive effects of cyclin-dependent kinase 5 regulatory subunit-associated protein1-like 1( CDKAL1) rs7747752 polymorphism with low serum levels of L-carnitine, choline, and betaine for GDM. Methods A n...

Background Glucokinase activators (GKAs) are an emerging class of glucose lowering drugs that activate the glucose-sensing enzyme glucokinase (GK). Pending formal cardiovascular outcome trials, we applied two-sample Mendelian randomisation (MR) to investigate the impact of GK activation on risk of cardiovascular diseases. Methods We used independe...

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...

Background Intensive lifestyle modification showed variable success in the prevention of major clinical events and mortality among people with prediabetes. We propose that age may partly explain the heterogeneity and that health hazards related to prediabetes are age-specific. Methods We conducted a retrospective analysis of a territory-wide diabe...

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 studi...

Background Little is known about the lifetime risk of progression to diabetes in the Asian population. We determined remaining lifetime risk of diabetes and life years spent with diabetes in Chinese people with normoglycemia and prediabetes. Methods and findings Using territory-wide diabetes surveillance data curated from electronic medical record...

Abstract Background Family history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control. Methods In a cross-sectional analysis of the prospective Joint Asia Diabetes Evalu...

The cover image is based on the Research Article Associations of the HOMA2‐%B and HOMA2‐IR with progression to diabetes and glycaemic deterioration in young and middle‐aged Chinese by Baoqi Fan et al., https://doi.org/10.1002/dmrr.3525. Image Credit: Liting Hu, Xinge Zhang, Hongjiang Wu, and Baoqi Fan.

Obesity, type 2 diabetes (T2D), and severe coronavirus disease 2019 (COVID-19) are closely associated. The aim of this study was to elucidate the casual and mediating relationships of human serum metabolites on the pathways from obesity/T2D to COVID-19 using Mendelian randomization (MR) techniques. We performed two-sample MR to study the causal eff...

Background: Improvements in glycemic outcomes have stalled since 2010 in several international surveys. We previously reported improvements in glycemic control in 2007-2014 in Hong Kong coinciding with primary care reforms, use of dipeptidyl-peptidase 4 inhibitors (DPP-4is) and metformin. The aim of this study was to estimate more recent trends in...

CONTEXT Leukocyte telomere length (LTL) is a biomarker of biological aging and is associated with metabolic diseases such as type 2 diabetes. Insufficient maternal vitamin D was associated with increased risk for many diseases and adverse later life outcomes. OBJECTIVE This study investigates the relationship between vitamin D levels and offspring...

BACKGROUND The epidemiology of adult-onset type 1 diabetes (T1D) incidence is not well-characterized due to the historic focus on T1D as a childhood-onset disease. PURPOSE We assess the incidence of adult-onset (≥20 years) T1D, by country, from available data. DATA SOURCES A systematic review of MEDLINE, Embase, and the gray literature, through 1...

Aims The study aimed to explore additive interactions of CDKAL1 rs7747752 and GUDCA/DCA for GDM risk and whether the interactive effects on the risk of GDM was mediated via increasing lysophosphatidylcholines (LPC) 18:0 and/or saturated fatty acid (SFA) 16:0. Methods A 1:1 age-matched study nested in a prospective cohort of pregnant women (207 pai...

Aims: Insulin deficiency (ID) and resistance (IR) contribute to progression from normal glucose tolerance to diabetes to insulin requirement although their relative contributions in young-onset diabetes is unknown. Methods: We examined the associations of HOMA2 using fasting plasma glucose and C-peptide in Chinese aged 20-50 years with 1) progre...

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...

OBJECTIVE Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this cohort study, consecutive Chinese pat...

Liver is a major site for glucose metabolism. Patients with type 2 diabetes (T2D) and obesity have increased risk of liver cancer. We explored the association of glycemic burden (GB) and obesity with liver cancer in T2D in the prospective Hong Kong Diabetes Register (1995-2019). We calculated GB using the area under the curve above hemoglobin A1c (...

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%...

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 to other DKD phenotypes. Study Design Multicenter prospective cohort study. Settings & Participants 19,025 Chinese adults with type 2 diabetes enrolled in...

Data resource basics Diabetes has become one of the most challenging health problems, which affects around 1 in 10 adults worldwide.¹,² The last three decades have witnessed a significant change in the global epidemiological patterns of diabetes.³,⁴ However, the existing large epidemiological studies are mainly from North America and Europe. Popula...

MicroRNAs (miRNAs) are elements of the gene regulatory network and manipulating their abundance is essential toward elucidating their role in patho-physiological conditions. We present a detailed workflow that identifies important miRNAs using a machine learning algorithm. We then provide optimized techniques to validate the identified miRNAs throu...

Background To our knowledge, no previous study has examined the inter-relationship between frailty, dysglycaemia, and mortality in frail older adults with type 2 diabetes who are on insulin therapy. We used continuous glucose monitors (CGMs) to profile this patient population and determine the prognostic value of CGM metrics. We hypothesised that i...

Background Obesity, cancer and diabetes frequently coexist. The association of glycaemic variability (GV) and obesity with cancer events had not been explored in diabetes. Methods In the prospective Hong Kong Diabetes Register cohort (1995-2019), we used cox proportional hazards models to examine the risk associations of GV with all-site cancer (p...

Background: Plasma phospholipid fatty acids (FAs) in early and mid-pregnancy have been prospectively related to gestational diabetes mellitus (GDM) risk. Yet, changes of FAs following GDM diagnosis and treatment and their implications for glucose metabolism and control remain understudied. Methods: From the Eunice Kennedy Shriver National Instit...

Aims/hypothesisWe postulated that the increased lifetime risk of chronic kidney disease (CKD) in young-onset diabetes is attributable to both long disease duration and more aggressive disease. We examined whether age at diabetes diagnosis modifies the effect of diabetes duration on risk of CKD.Methods We included 436,744 people with incident type 2...

Aims To investigate the associations and predictive values of serum metabolites in early pregnancy for later development of gestational diabetes mellitus (GDM), and further explore their metabolic pathways to GDM. Methods We conducted a 1:1 nested case-control study including 486 pregnant women from Tianjin, China, and collected blood samples at t...

Aims To investigate association between skin autofluorescence (SAF) and cardiovascular events (CVE) and assess its predictive value in Chinese adults with type 2 diabetes (T2D). Materials and methods SAF was measured non-invasively in 3806 Chinese adults with T2D between 2016 and 2019 with CVE as primary endpoint and individual components as secon...

Aims Using data from a large multi-centre cohort, we aimed to create a risk prediction model for large-for-gestational age (LGA) infants, using both logistic regression and naïve Bayes approaches, and compare the utility of these two approaches. Methods We have compared the two techniques underpinning machine learning: logistic regression (LR) and...

Background The clinical predictors and prognosis of heart failure (HF) by categories of left ventricular ejection fraction (LVEF) have not been well studied in people with diabetes. In a retrospective cohort of Chinese with type 2 diabetes, we examined 1) clinical factors associated with incident decompensated HF, and 2) mortality post-HF, stratifi...

Background Interactions between genetic and nutritional factors can contribute to the risk of gestational diabetes mellitus (GDM). Objectives We aimed to explore the associations of cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) single-nucleotide polymorphism (SNP) rs7747752 and serum concentrations of SFAs with...

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult indi...

Background There are limited population-wide trend data on kidney failure and kidney replacement therapy (KRT) in people with diabetes. We conducted a retrospective cohort study to report incidence trends of kidney failure and KRT and related mortality in people with diabetes in Hong Kong between 2002 and 2015. Methods We used territory-wide elect...

Background: Previous studies have shown that phospholipids fatty acid (FA) levels in early and mid-pregnancy were associated with incident gestational diabetes mellitus (GDM). However, the subsequent changes of such FAs profile following GDM diagnosis/treatment are understudied. Methods: Within the National Institute of Child Health and Human Devel...

Importance: Many health care systems lack the efficiency, preparedness, or resources needed to address the increasing number of patients with type 2 diabetes, especially in low- and middle-income countries. Objective: To examine the effects of a quality improvement intervention comprising information and communications technology and contact wit...

Aims/hypothesis: The long-term effects of metformin in individuals with type 2 diabetes who are at increased risk of severe respiratory infections are unknown. This study aimed to evaluate the effects of metformin use on the risk of first pneumonia hospitalisation and pneumonia-related death in a cohort of Chinese individuals with type 2 diabetes....

Objective The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM). Design In this double-blind, r...

IntroductionTo compare glycemic variability (GV) and time in range (TIR) in Chinese patients with type 2 diabetes (T2D) initiated on once-daily bedtime insulin glargine 300U/ml (Gla-300) versus neutral protamine Hagedorn (NPH) insulin using continuous glucose monitoring (CGM).Methods This was a 24-week, open-label exploratory study with 1:1 randomi...

One potential mechanism by which maternal obesity impacts fetal growth is through hyperglycemia below the threshold for gestational diabetes. Data regarding which measures of maternal glucose metabolism mediate this association is sparse. The objectives of this study were to (i) quantify the associations of maternal pre-pregnancy body mass index (B...

Diabetic cardiomyopathy (DCM) is a common diabetic complication characterized by diastolic relaxation abnormalities, myocardial fibrosis and chronic heart failure. Although TGF‐β/Smad3 signalling has been shown to play a critical role in chronic heart disease, the role and mechanisms of Smad3 in DCM remain unclear. We reported here the potential ro...

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and ma...

Dicer knockout mouse models demonstrated a key role for microRNAs in pancreatic β-cell function. Studies to identify specific microRNA(s) associated with human (pro-)endocrine gene expression are needed. We profiled microRNAs and key pancreatic genes in 353 human tissue samples. Machine-learning workflows identified microRNAs associated with (pro-)...

Abstract 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 v...

Aims/hypothesis Gestational diabetes mellitus (GDM) is generally defined based on glycaemia during an OGTT, but aetiologically includes women with defects in insulin secretion, insulin sensitivity or a combination of both. In this observational study, we aimed to determine if underlying pathophysiological defects evaluated as continuous variables p...

Aims/Introduction β‐cell dysfunction is a hallmark of type 2 diabetes. In a previous pilot study, we identified an association between genetic variants within the human DACH1 gene and young‐onset type 2 diabetes. Here, we characterized the function of dachb, the only dach homologue to be expressed in the pancreas, in developing zebrafish embryos....

We performed two meta-analyses to estimate the effects of lifestyle intervention during pregnancy and after delivery on the risk of postpartum diabetes among women with gestational diabetes mellitus (GDM). We searched the major databases to retrieve articles published in English or Chinese before 15 December 2019. The inclusion criteria were random...

Aims/hypothesis: Infection is an under-recognised but important complication in people with diabetes. Studies on temporal trends in incidence of infection in this population are limited. We report the trends in infection-related hospitalisation in people with diabetes and compared hospitalisation rates between people with and without diabetes in H...