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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. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results In this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p 1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p p = 0.024). Conclusions/interpretation rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract

We 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. We included 436,744 people with incident type 2 diabetes in the Hong Kong Diabetes Surveillance Database (HKDSD) and 16,979 people with prevalent type 2 diabetes in the Hong Kong Diabetes Register (HKDR). We used Poisson models to describe joint effects of age at diabetes diagnosis, diabetes duration and attained age on incidence of CKD in HKDSD. We used Cox proportional hazards models to examine interaction effect of age at diabetes diagnosis and diabetes duration on risk of CKD with adjustment for confounders in HKDR. During a median follow-up of 5.3 years, 134,043 cases of CKD were recorded in the HKDSD. The incidence rate ratio for CKD comparing people of the same attained age but diagnosed with diabetes at ages 5 years apart was higher for people with a younger age at diabetes diagnosis, but decreased with increasing age at diabetes diagnosis. During a median follow-up of 6.3 years, 6500 people developed CKD in the HKDR. The increased risk of CKD with longer diabetes duration decreased with older age at diabetes diagnosis. The adjusted HR for CKD associated with 5 year increase in diabetes duration was 1.37 (95% CI 1.13, 1.65) in people with diabetes diagnosed at 20–29 years and 1.01 (95% CI 0.87, 1.18) in those diagnosed at ≥70 years. Young age at diabetes diagnosis amplified the effect of increasing diabetes duration on increased risk of CKD.

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. We performed a retrospective analysis of a consecutive cohort of 22,638 individuals with type 2 diabetes in the Hong Kong Diabetes Register enrolled between 2001 and 2018, with follow-up until 31 December 2019. Overlap propensity-score weighting was performed to balance baseline characteristics. Of 22,638 individuals with type 2 diabetes, after excluding those who had not been prescribed any glucose-lowering drugs (GLDs) and/or with eGFR ≤30 ml min−1 [1.73 m]−2 or treated by dialysis and/or treated with insulin at baseline, we identified 15,784 either prevalent or incident metformin users and 917 users of other GLDs during a mean follow-up period of 7.5 years. Overlap-weighted analysis showed an HR of 0.63 (95% CI 0.52, 0.77) for first pneumonia hospitalisation and 0.49 (95% CI 0.33, 0.73) for pneumonia-related death in metformin users vs users of other GLDs; similar observations resulted following stratification by sex and kidney function. There was also a negative association between metformin exposure over time (proportion of duration of metformin prescriptions during the total follow-up time) and pneumonia events using the penalised spline analysis. Metformin users had a lower neutrophil/lymphocyte ratio at first pneumonia hospitalisation vs non-metformin users (mean [95% CI]: 12.8 [12.1, 13.5] vs 14.8 [12.3, 17.3], p = 0.032). The rate of metformin-associated lactic acidosis was 2.5 per 100,000 person-years. The lower risk of pneumonia events was also observed among incident metformin users vs other GLD users. Long-term use of metformin was associated with reduced risk of pneumonia and pneumonia-related death among Chinese individuals with diabetes. The relevance of these results to other respiratory infections merits further investigation.

Introduction Diabetes and bone health are closely related. We examined the incidence and risk factors of hip fractures in Chinese patients with type 2 diabetes (T2D). Materials and Methods In this prospective cohort, we consecutively enrolled 22,325 adults with T2D above the age of 40 years in the Hong Kong Diabetes Register between 1994 and 2015 with crude hip fracture incidence rate censored in 2017. Results At baseline, the mean age of this cohort was 60.9 ± 10.5 years (mean duration of diabetes 6 years, 52.4% male). During a mean ± standard deviation (SD) follow‐up period of 8.7 ± 5.2 years with 193,553 person‐years, 603 patients were hospitalized due to hip fractures with an incidence (95% confidence interval, CI) of 315.1 (290.4–341.3) per 100,000 person‐years. On multivariable analysis with competing death risk adjusted, the independent hazard ratios (95% CI) for hip fractures in T2D were 2.01 (1.61–2.51) for female sex, 1.08 (1.07–1.09) for age, 0.93 (0.90–0.95) for body mass index, 1.52 (1.25–1.85) for albuminuria and 1.12 (1.02–1.23) for low density lipoprotein‐cholesterol. In men, the 30‐day, 1‐year and 5‐year post‐hip fracture mortality rate (95% CI) were 5.8 (2.4–9.1) %, 29.2 (22.3–35.5) % and 65.9 (57.3–72.8) % respectively. The corresponding rates in women were 3.4 (1.6–5.1) %, 18.6 (14.7–22.4) %, and 46.8 (40.9–52.1) %. Conclusions Southern Chinese patients with T2D have a high risk of hip fracture associated with suboptimal cardiometabolic‐renal risk factors and a high post‐fracture mortality rate. The effects of improving modifiable risk factors on bone health warrants further evaluation., With prospective follow up of nearly 9 years, we identified several risk factors associated with increase hip fracture incidence in Southern Chinese patients with type 2 diabetes in the Hong Kong Diabetes Register. These include female sex, age, body mass index, albuminuria and low density lipoprotein.

We aimed to describe trends in rates of hospitalisation for lower extremity amputation (LEA) and 1 year mortality rates after LEA in people with diabetes in Hong Kong between 2001 and 2016.The Hong Kong Diabetes Surveillance Database is a territory-wide population-based diabetes cohort (N = 770,078) identified from the Hong Kong Hospital Authority electronic medical system. We identified LEA events using ICD-9 procedure codes and 1 year mortality after LEA from linkage to the Hong Kong Death Registry. Joinpoint regression models were used to describe the trends.Between 2001 and 2016, 6113 hospitalisations for LEAs in men and 4149 in women were recorded in the Hong Kong Diabetes Surveillance Database. The rates of minor LEAs declined by 48.6% (average annual per cent change [AAPC]: -3.8; 95% CI -5.7, -1.9) in men and by 59.5% (AAPC: -6.3; 95% CI -10.6, -1.8) in women. The rates of major LEAs declined by 77.9% (AAPC: -8.0; 95% CI -9.6, -6.5) in men and by 79.3% (AAPC: -10.4; 95% CI -13.1, -7.6) in women. The cumulative 1 year mortality rates after minor and major LEAs were 18.5% and 41.8% in men, and 21.3% and 42.0% in women, respectively, for the whole period. No change was detected in 1 year mortality rates during the surveillance in both sexes.Although hospitalisation rates for LEAs have declined overall in people with diabetes, there were no improvements in 1 year mortality rates after LEA. Continuous efforts are needed to further prevent LEAs and improve the survival rate of people undergoing LEAs. Graphical abstract.

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 Hong Kong. Methods Hospital admissions with infection, including pneumonia, influenza, tuberculosis, kidney infection, urinary tract infection, cellulitis, osteomyelitis, foot infection and sepsis, listed as principal diagnosis occurring between 2001 and 2016 were identified from people with diabetes in the electronic medical record system of the Hong Kong Hospital Authority. Data on hospitalisation for a subset of these infections in the general population between 2007 and 2016 were obtained from the Department of Health. The number of people with diabetes ranged between 117,322 in 2001 and 570,929 in 2016, and the number without diabetes ranged between 5,242,614 in 2007 and 5,593,153 in 2016. Joinpoint regression was used to describe the trends. Results In people with diabetes, over a period of 16 years, the age-standardised annual rates of hospitalisation decreased for tuberculosis but increased for influenza; rates of hospitalisation for pneumonia increased up until 2004/2005 and declined in men and stabilised in women. The rates of hospitalisation for most infection types were unchanged or increased in the 20–44 year and 45–64 year age groups and decreased in those aged 65 years or above. Trends for most of the infections were similar when comparing sexes. Between 2007 and 2016, the rate ratios of hospitalisation for most infection types between people with and without diabetes were stable, and the rate ratios remained higher in people with diabetes, ranging from 1.3–1.4 for pneumonia to 3.2–4.9 for kidney infections in 2016 compared with non-diabetic individuals. Conclusions/interpretation Despite advances in medical care, hospitalisation due to infections remains a major healthcare burden in people with diabetes. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s00125-020-05286-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Background Nationwide studies on contemporary trends in incidence of diabetes-related complications in Asia are lacking. We describe trends in incident coronary heart disease (CHD), stroke, heart failure, hyperglycaemic crisis, and lower-extremity amputation (LEA) in people with diabetes in Hong Kong between 2001 and 2016. Methods The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide diabetes cohort identified from Hong Kong Hospital Authority electronic medical record system. We identified events of CHD, stroke, heart failure and hyperglycaemic crisis using hospital principal diagnosis codes at discharge and that of LEA using inpatient procedure codes. We used Joinpoint regression analysis to describe incidence trends by age and sex. Results Between 2001 and 2016, a total of 390,071 men and 380,007 women aged 20 years or older with diabetes were included in the HKDSD. Event rates of CHD, stroke, heart failure, hyperglycaemic crisis and LEA declined by 69.4% (average annual percent change: − 7.6, 95% CI − 10.2, − 5.0), 70.3% (− 8.7, 95% CI − 9.8, − 7.5), 63.6% (− 6.4, 95% CI − 8.0, − 4.7), 59.1% (− 6.6, 95% CI − 12.4, − 0.44), and 67.5% (− 5.8, 95% CI − 7.2, − 4.4), in men and by 77.5% (− 9.9, 95% CI − 11.8, − 7.9), 74.5% (− 9.0, 95% CI − 9.6, − 8.4), 65.8% (− 7.0, 95% CI − 8.0, − 6.0), 81.7% (− 8.5, 95% CI − 10.5, − 6.5), and 72.7% (− 9.1. 95% CI − 12.2, − 5.8) in women, respectively, over a 16-year period in people with diabetes in Hong Kong. Joinpoint analysis identified greater declines in event rates of the five diabetes-related complications in the earlier one-third of study period and slowed down but remained significant until 2016. Event rates decreased for all age groups above 45 years for both sexes. There was no significant change in event rates in the group aged 20–44 years except for decline in hyperglycaemic crisis. Conclusions The event rates of diabetes-related complications have declined substantially with no evidence of stabilization or increase in Hong Kong up to 2016. Improvements in outcome were observed for all age subgroups but not in young people with diabetes, calling for urgent action to improve quality of care to prevent complications in young people at risk.

Aims To explore the pattern of insulin use and glycaemic control in Asian people with type 2 diabetes, stratified by gender, young‐onset diabetes (YOD; diagnosed before age 40 years), and diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR]

AIMS/HYPOTHESIS: The aim of the study was to describe trends in all-cause and cause-specific mortality rates in Hong Kong Chinese people with diabetes from 2001 to 2016.METHODS: The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide diabetes cohort identified from the Hong Kong Hospital Authority electronic medical record system. Deaths between 2001 and 2016 were identified from linkage to the Hong Kong Death Registry. We used Joinpoint regression analysis to describe mortality patterns among people with diabetes by age and sex, and standardised mortality ratios (SMRs) to compare all-cause mortality rates in people with and without diabetes.RESULTS: Between 2001 and 2016, a total of 390,071 men and 380,007 women aged 20 years or older with diabetes were included in the HKDSD. There were 96,645 deaths among men and 88,437 deaths among women. Mortality rates for all-cause, cardiovascular disease and cancer among people with diabetes declined by 52.3%, 72.2% and 65.1% in men, respectively, and by 53.5%, 78.5% and 59.6% in women, respectively. Pneumonia mortality rates remained stable. The leading cause of death in people with diabetes has shifted from cardiovascular disease to pneumonia in the oldest age group, with cancer remaining the most common cause of death in people aged 45-74 years. The all-cause SMRs for men declined from 2.82 (95% CI 2.72, 2.94) to 1.50 (95% CI 1.46, 1.54), and for women, they declined from 3.28 (95% CI 3.15, 3.41) to 1.67 (95% CI 1.62, 1.72). However, among people aged 20-44 years, the declines in all-cause mortality rates over the study period were not statistically significant for both men (average annual per cent change [AAPC]: -3.2% [95% CI -7.3%, 1.0%]) and women (AAPC: -1.2% [95% CI -6.5%, 4.4%]). The SMRs in people aged 20-44 years fluctuated over time, between 7.86 (95% CI 5.74, 10.5) in men and 6.10 (95% CI 3.68, 9.45) in women in 2001, and 4.95 (95% CI 3.72, 6.45) in men and 4.92 (95% CI 3.25, 7.12) in women in 2016.CONCLUSIONS/INTERPRETATION: Absolute and relative mortality has declined overall in people with diabetes in Hong Kong, with less marked improvements in people under 45 years of age, calling for urgent action to improve care in young people with diabetes.

BackgroundThe 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, stratified by LVEF.MethodsWe conducted a retrospective analysis of the Hong Kong Diabetes Register comprising 23,348 people with type 2 diabetes without history of HF enrolled between 1993–2015, followed for incident decompensated HF until 2017. Heart failure subtypes were defined according to LVEF on echocardiography. Multivariate Cox proportional hazards models were used to identify clinical factors associated with incident HF versus no HF, stratified by HF subtypes. All-cause mortality rates were compared by HF subtypes.ResultsOver median follow-up of 7.1 years from enrolment, 1,195 (5.1%) people developed decompensated HF. Among 611 (51.1%) people with echocardiography, 24.1% had HF with reduced LVEF (HFrEF) (LVEF vs 26.9%,p = 0.034) and HFrEF (vs 31.3%,p vs 71.0%,p = 0.38), but similar to HFrEF group (vs 55.8%,p = 0.651).ConclusionsIn Chinese with type 2 diabetes, HFpEF was the predominant HF subtype. One-year mortality following decompensated HF was lowest in HFpEF group but 10-year mortality was similar between HFpEF and HFrEF.

Sulfonylureas (SUs) are predominantly metabolized by cytochrome p450 2C9 (CYP2C9) and cytochrome p450 2C19 (CYP2C19) enzymes. CYP2C9 polymorphisms are associated with greater treatment response and hypoglycemic risk in SU users. However, there are no large scale pharmacogenetic studies investigating the effect of loss-of-function alleles CYP2C19*2 and CYP2C19*3, which occur frequently in East Asians. Retrospective pharmacogenetic analysis was performed in 11,495 genotyped patients who were enrolled in the Hong Kong Diabetes Register between 1995 and 2017, with follow-up to December 31, 2019. The associations of CYP2C19 polymorphisms with SU treatment failure, early HbA1c response, and severe hypoglycemia were analyzed by Cox regression or logistic regression assuming an additive genetic model. There were 2341 incident SU users that were identified (mean age 59 years, median diabetes duration 9 years), of which 324 were CYP2C19 poor metabolizers (CYP2C19 *2/*2 or *2/*3 or *3/*3). CYP2C19 poor metabolizers had lower risk of SU treatment failure (hazard ratio 0.83, 95% confidence interval (CI) 0.72-0.97, P = 0.018) and were more likely to reach the HbA1c treatment target

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 secondary endpoints. Cox proportional hazard models were used to examine associations between SAF and endpoints with adjustment for conventional risk factors. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were performed to evaluate SAF's predictive value. Results During a median 1.8 (interquartile range, 1.2–3.1) years of follow-up, 172 individuals experienced CVE. Multivariate Cox model showed that SAF was independently associated with CVE (HR 1.18 per SD, 95% CI [1.02, 1.37]), coronary heart disease (HR 1.29 per SD, 95% CI [1.02, 1.63]), and congestive heart failure (HR 1.53 per SD, 95% CI [1.14, 2.05]). SAF yielded additional value on CVE risk stratification with enhanced IDI (95% CI) (0.023 [0.001, 0.057]) and continuous NRI (0.377 [0.002, 0.558]) over traditional risk factors. Conclusions Higher SAF was independently associated with CVE in Chinese adults with T2D and yielded incremental predictive information for CVE. SAF has potential as a prognostic maker for CVE.

Skin autofluorescence (SAF), a non-invasive measure of the accumulation of advanced glycation end products (AGEs) in skin collagen, is associated with baseline estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). We aimed to investigate whether SAF can identify individuals with type 2 diabetes (T2D) at high-risk of renal function decline. A total of 3,806 Chinese with T2D had SAF measured between 2016 to 2019. The primary endpoint was incident end-stage kidney disease (ESKD) or ≥40% decline in eGFR relative to baseline. The secondary endpoint was the annual change in eGFR during follow-up. A Cox proportional hazard model was used for the primary endpoint, and linear mixed-effects model with random intercept and slope for eGFR slope and the association between SAF and rate of eGFR change. People with prevalent ESKD were excluded. Mean ± SD age was 60.4 ± 10.4 years, with mean ± SD eGFR 81.5 ± 22.9 ml/min/1.73 m2; median (interquartile range [IQR]) UACR was 2.2 (0.8-9.6) mg/mmol; and median eGFR slope was -2.18 ml/min/1.73 m2/year. During a median (IQR) 1.76 (1.13-3.13) years of follow-up, 219 experienced the primary endpoint. SAF was associated with increased risk of progression of kidney disease (adjusted hazard ratio 1.16 per SD, 95% CI [1.01, 1.33]), even after adjustment for established risk factors including eGFR and UACR. SAF was identified as an independent determinant of rate of eGFR decline (adjusted Beta coefficient -2.85 per SD, 95% CI [-3.82, -1.87]). Using the median eGFR slope as the cut-off, higher SAF was associated with faster eGFR decline (adjusted odds ratio 1.12 per SD, 95% CI [1.03, 1.22]) on multivariate logistic regression. This study demonstrates for the first time in a prospective setting that higher SAF is independently associated with increased risk of progression of kidney disease in individuals with T2D. Disclosure Q. Jin: None. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. A. Jenkins: Advisory Panel; Self; Abbott Diabetes, Sanofi-Aventis, Other Relationship; Self; Amgen Inc., Research Support; Self; Abbott, International Diabetes Federation, JDRF, Medtronic, Mylan N. V. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. E. S. Lau: None. A. Luk: None. R. Ozaki: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. T. So: None. H. Yeung: None. K. Loo: n/a. C. K. Lim: Stock/Shareholder; Self; GemVCare Ltd. Funding Research Grants Council of Hong Kong (R4012-18)

The incidence of liver cancer and related mortality is increasing globally. Liver is a major site for glucose metabolism. People with type 2 diabetes (T2D) had increased risk of liver cancer. However, the association of glycemic burden (GB) with liver cancer in T2D remains unclear. We calculated GB using area under the curve above 5.7% of HbA1c (AUC_A1c) in patients with T2D enrolled in the prospective Hong Kong Diabetes Register established since 1995. Structured baseline data were linked to laboratory and hospitalization records in a territory-wide electronic medical record system with data censored in 2019. We performed Cox regression analysis to investigate the association of GB with incident liver cancer defined as first hospitalization with ICD9 code (155). We included 18,173 patients (50.93% male, age: 58.43±12.48 years, HbA1c: 7.58±1.66%, BMI: 25.51±4.06 kg/m2, disease duration: 20.68 ±7.63 years), who had ≥ 10 years of disease duration, > 3 years of observation, and ≥ 5 HbA1c measurements (21.98±12.33). During a median (IQR) follow up period of 10.62 (8.09, 15.88) years (218,381patient-years), 160 patients developed liver cancer with an incidence of 7.33 per 10,000 patient-years. We excluded 3 years of HbA1c values prior to incident liver cancer to avoid reverse causality. After adjusting for confounders, every 1 unit increase in AUC_A1c increased the hazard ratio (HR) of liver cancer by 1.22 (95% CI: 1.01-1.47), while AUC_A1c top quantile group had a HR of 1.78 (1.01-3.13) versus the lowest quantile group. In subgroup analysis, obese patients (BMI>25 kg/m2) had a HR of 1.34 (1.05-1.70) for liver cancer versus non-obese subjects. Amongst patients who developed liver cancer (n=1420) within 3 years of enrolment, one unit increase of AUC_A1c was associated with a HR of 1.49 (1.07-2.07) for liver cancer. GB and obesity independently increased the risk of liver cancer in T2D, emphasizing the importance of metabolic control for cancer risk reduction. Disclosure D. Mao: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. E. S. H. Lau: None. A. Yang: None. H. Wu: None. M. Shi: None. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. A. Luk: None.

Introduction: The overall evidence for the long-term exposure of metformin on cardiovascular-renal (CV) outcomes in patients with type 2 diabetes (T2D) at different stages of chronic kidney disease (CKD) remains controversial. Methods: We conducted a prospective analysis of 14,766 Chinese patients with T2D enrolled between 2000 and 2016 observed until 31 December 2019. We compared all-cause mortality and incidence of major adverse CV events (MACE) and end-stage kidney disease (ESKD) in prevalent and new metformin users versus other glucose lowering drugs (GLDs) users stratified by CKD stage. Results: During a mean follow-up of 9.6 years (141,310 person-years), we identified 1,798 deaths in metformin users (n=13,967) and 352 deaths in other-GLDs users (n=799). The mean daily dosage of metformin was 1,450 mg and duration of exposure was 7.8 years in CKD stage 1-2 (n=12,375). The respective figures were 1000 mg and 5.7 years in CKD stage 3-4 (n=1,592). Compared with other-GLDs, metformin exposure was associated with reduced risk of all-cause mortality (All: HR=0.48, 95% CI: 0.43-0.54; CKD stage 1-2: HR=0.38, 0.33-0.44; stage 3A: HR=0.53, 0.41-0.69); MACE (All: HR=0.85, 0.72-0.99; stage 1-2: HR=0.80, 0.65-0.99; stage 3-4: HR=0.97, 0.74-1.27) and ESKD (All: HR=0.65, 0.54-0.80; stage 1-2: HR=0.53, 0.33-0.85; stage 3-4: HR=0.80, 0.63-1.02). New users of metformin (n=4,013) had reduced risk of all-cause mortality across all CKD stages; MACE in stage 1-2 and ESKD in stage 1, 2 and 3 compared with users of other oral-GLDs (n=536). Increasing duration and dosage of metformin (up to 1500 mg/day) was associated with reduced or neutral risk of MACE, ESKD and all-cause mortality. The rate of metformin-associated lactic acidosis (MALA) was 5.39 per 100,000 patient-years in CKD stage 3-4. Conclusion: Long-term metformin use was associated with reduced or neutral risk of all-cause mortality, MACE and ESKD among Chinese patients with T2D at CKD stage 1-3 with low risk of MALA. Disclosure A. Yang: None. E. S. H. Lau: None. H. Wu: None. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. A. Luk: None. A. W. Fu: Research Support; Self; Merck KGaA. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. Funding Asia Diabetes Foundation; Merck Pharmaceutical (HK) Limited; Chinese University of Hong Kong (to A.Y.)

Background: The roles of insulin deficiency (ID) and resistance (IR) in young patients with type 2 diabetes (T2D) are uncertain. We explored the associations of HOMA2 IR and HOMA2 %B using fasting C peptide and plasma glucose (FPG) with incident T2D and insulin use in Chinese aged 18-50 years. Methods: Cohort 1 included subjects without T2D in 1998-2002 with glycemic status ascertained in 2012-2013. Cohort 2 included patients with T2D (1995-2014) with documentation of glycemic deterioration (continuous insulin use or failure of 2 oral drugs). Results: In cohort 1, 62 subjects developed (T2D-progressors) and 285 did not develop T2D (T2D-non-progressors) during 10-year follow-up. In cohort 2 (n=737), 293 (39.8%) required insulin after a median follow-up period of 8.6 years. At baseline, T2D-non-progressors had lower HOMA2 IR [median (IQR) 0.77 (0.60, 1.06)] vs. 1.06 (0.81, 1.38)] and similar HOMA2 %B [84.3 (72, 111.5) vs. 85.1 (75.6, 100.7)] compared with T2D-progressors. Non-insulin-requiring T2D patients had lower HOMA2 IR [1.47 (1.02, 2.11) vs. 1.76 (1.19, 2.42)] and higher HOMA2 %B [62.4 (39.4, 87.4) vs. 45.4 (25.8, 71.8)] than insulin-requiring patients. When stratified by median values and using low HOMA2 %B plus low HOMA2 IR as referent, subjects with high HOMA2 %B plus high HOMA2 IR had age and sex-adjusted odds ratio (95% CI) of 2.47 (1.28, 4.93) and those with low HOMA2% B plus high HOMA2 IR had 5.27 (2.27, 12.84) of incident T2D. In the T2D cohort, using high HOMA2 %B plus low HOMA2 IR as referent, the hazard ratio (95% CI) for insulin use increased with low HOMA2 %B [2.18 (1.47, 3.23)], high HOMA2 IR [2.45 (1.64, 3.64)] and low HOMA2 %B plus high HOMA2 IR [4.25 (2.82, 6.41)] adjusted for age, sex and disease duration. These associations were attenuated after adjusting for obesity, FPG, HbA1c and TG/HDL-C. Conclusions: In young to middle-aged Chinese, progressive worsening in IR and ID contribute to onset of T2D and insulin requirement, which can be attenuated by early control of metabolic factors. Disclosure B. Fan: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. A. Luk: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. H. Wu: None. M. Shi: None. A. Yang: None. C. H. Tam: None. E. S. H. Lau: None. D. Mao: None. C. K. P. Lim: Stock/Shareholder; Self; GemVCare Ltd. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum.

Background: Diabetes predisposes to heart failure (HF). In a prospective cohort of Chinese with type 2 diabetes, we examined 1) clinical factors associated with incident HF, and 2) mortality post-HF, stratified by ejection fraction (EF). Methods: Between 1 Jun 1993 and 30 Jun 2015, 23348 patients with type 2 diabetes without history of HF were enrolled in the Hong Kong Diabetes Register, and followed for incident HF until 30 Jun 2017. HF subtypes were defined according to EF on echocardiogram: HF with reduced EF (HFrEF), EF =50%. Multivariate Cox regression was used to identify clinical factors associated with incident HF vs. no HF, by HF subtypes. 1-year and 5-year mortality rates were compared by HF subtypes. Results: Over a follow-up of 7.1 years from enrolment, 1195 patients developed HF, of whom 611 (51.1%) had an echocardiogram within 2 years of HF episode. Distribution of HF subtypes as follows: HFrEF 24.1%, HFmrEF 15.2%, HFpEF 60.7%. Old age, low GFR, albuminuria and history of coronary artery disease were associated with increased hazards for all HF subtypes. In addition, female sex, high BMI and history of neuropathy were associated with HFpEF, and low HDL cholesterol was associated with HFmrEF. Over a follow-up of 2.1 years post-HF, 760 patients (63.6%) died with a mortality rate of 189.4 per 1000 person-year. 1-year mortality rate was lower in HFpEF group (16.2%) than those with HFmrEF (vs. 26.9%, p=0.034) and HFrEF (vs. 31.3%, p Conclusions: HFpEF was the predominant HF subtype in Chinese with diabetes. Clinical factors predicting incident HF differed according to subtypes. 1-year mortality was lower in HFpEF group but mortality at 5 years were similar between HFpEF and HFrEF with a trend of higher mortality in HFmrEF group. Disclosure A. Luk: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. X. Zhang: None. E. Fung: None. H. Wu: None. E. S. Lau: None. A. Yang: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc.

Introduction: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are renin angiotensin system inhibitors (RASi) which can reduce the proinflammatory-vasoconstricting activity of ACE/angiotensin II and enhance the anti-inflammatory-vasodilatory activity of ACE2/angiotensin 1-7. These drugs may be protective across a range of respiratory infections including bacterial and viral pneumonias. We examined long-term use of ACEi/ARBs on the risk of first pneumonia hospitalization and pneumonia-related death in Chinese patients with type 2 diabetes (T2D). Methods: Prospective analysis of 16,285 Chinese T2D patients with new RASi use observed between 2001 and 2019. Overlap weighting was performed to balance baseline characteristics. We used time-dependent Cox model to estimate the hazard ratio (HR) of outcomes while adjusting for the time-varying covariates. Results: There were 6,379 (39.2%) ACEi-users only, 4,065 (25.0%) ARBs-users and 5,841 (35.9%) non RASi-users. During a median observation of 7.6 years, 6.1% had first pneumonia hospitalization, 1.3% died during or within one month of pneumonia hospitalization and 17.6% died from other causes. No association was observed between RASi use and first pneumonia hospitalization. However, RASi-users had lower risk for pneumonia-related death (HR 0.51, 95% CI 0.35-0.76) than non-users [ACEi-users only: HR 0.53 (0.34-0.81); ARBs-users: HR 0.58 (0.32-1.04)]. We also noted reduced risk for all-cause death in RASi-users (HR 0.60, 95% CI 0.54-0.67) [ACEi-users only: HR 0.61 (0.54-0.69); ARBs-users: HR 0.67 (0.57-0.79)]. Conclusions: Long-term use of RASi was associated with reduced risk of pneumonia-related death and all-cause death, but not first pneumonia hospitalization, in Chinese patients with T2D. Relevance to other respiratory infections such as coronavirus-disease 2019 (COVID-19) merits further investigation. Disclosure M. Shi: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. A. Yang: None. E. S. H. Lau: None. H. Wu: None. B. Fan: None. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. A. Luk: None. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA.

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 electronic medical records including laboratory, diagnostic and procedural data to identify people with kidney failure and KRT. We used Joinpoint regression models to estimate the average annual percent change (AAPC) of kidney failure and KRT incidence for entire study period, and annual percent change (APC) for each linear trend segment, along with 1-year and 5-year mortality rates. Findings During 4.9 million person-years of follow-up of 712,222 people with diabetes, 31,425 developed kidney failure, among whom 23.0% (n=7,233) received KRT. The incidence of kidney failure declined by 46.8% from 2002 to 2007 (APC: -11.6, 95% CI: -16.3, -6.7), then flattened from 2007 to 2015 (APC: -0.9, 95% CI: -3.1, 1.3). The incidence of KRT remained constant (AAPC: -1.6, 95% CI: -4.4, 1.2). The 1-year mortality rates declined statistically significantly after both kidney failure and KRT. The 5-year mortality rates declined after kidney failure but the decline was not statistically significant after KRT. Interpretation The findings of our study highlight the importance of developing new strategies to prevent a looming epidemic of kidney failure in people with diabetes in Hong Kong. Funding Asia Diabetes Foundation

Few studies have investigated the relationship between rLTL and mortality in patients with type 2 diabetes in a large prospective study, particularly in the Asian population. This study investigates the relationship between rLTL and the risk of death in Chinese patients with type 2 diabetes.Consecutive Chinese patients with type 2 diabetes (N = 5349) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using a quantitative polymerase chain reaction. Mortality and clinical outcomes were obtained based on ICD-9 codes.The mean (SD) age of the subjects was 57.5 (13.3) years and mean (SD) follow-up duration was 13.4 (5.5) years. Baseline rLTL was significantly shorter in the 1925 subjects who subsequently died compared with the remaining subjects (4.3 ± 1.2 vs. 4.7 ± 1.2, P 0.001). Shorter rLTL was associated with a higher risk of mortality (HR: 1.19 (1.14-1.23), P 0.001), which remained significant after adjusting for traditional risk factors.Shorter rLTL was significantly associated with an increased risk of all-cause and CVD mortality in patients with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for mortality risk in patients with type 2 diabetes.

Background Lifetime glycemic exposure and its relationship with age at diagnosis in type 2 diabetes (T2D) are unknown. Pharmacologic glycemic management strategies for young-onset T2D (age at diagnosis 3 times higher for young-onset versus usual-onset T2D (41.0 [95% confidence interval 39.1–42.8] versus 12.1 [11.8–12.3] A1C-years [1 A1C-year = 1 year with 8% average A1C]). Younger age at diagnosis was associated with faster glycemic deterioration (A1C slope over time +0.08% [0.078–0.084%] per year for age at diagnosis 20 years versus +0.02% [0.016–0.018%] per year for age at diagnosis 50 years; p-value for interaction, In a population-based cohort, Calvin Ke and colleagues investigate age at diagnosis and glycemic trajectories in Type 2 diabetes patients., Author summary Why was this study done? Young-onset type 2 diabetes (diagnosed before age 40 years) is an aggressive disease, associated with higher risks of mortality and other complications compared with usual-onset type 2 diabetes (diagnosed at age 40 years or after). Although exposure to hyperglycemia is a key risk factor for type 2 diabetes complications, the magnitude of this exposure over a lifetime has never been quantified. Because young people were excluded from randomized control trials of oral glucose-lowering drugs, it is unknown whether these drugs are effective for treating young-onset type 2 diabetes. What did the researchers do and find? Young-onset type 2 diabetes was associated with over triple the exposure to hyperglycemia from diagnosis until age 75 years compared with usual-onset type 2 diabetes. Diabetes progressed much faster in young-onset type 2 diabetes compared with usual-onset type 2 diabetes. Compared with usual-onset type 2 diabetes, people with young-onset type 2 diabetes had smaller responses to most metformin-based drug combinations and greater responses to other combinations containing sulfonylureas. What do these findings mean? Excess exposure to hyperglycemia and rapid disease progression in young-onset T2D call for better treatment strategies. The differential responses to oral glucose-lowering drugs between young- and usual-onset T2D suggest that better disease classification could guide personalized therapy.

OBJECTIVE Several studies support potential links between relative leukocyte telomere length (rLTL), a biomarker of biological aging, and type 2 diabetes. This study investigates relationships between rLTL and incident cardiovascular disease (CVD) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Consecutive Chinese patients with type 2 diabetes (N = 5,349) from the Hong Kong Diabetes Register for whom DNA obtained at baseline was stored and follow-up data were available were studied. rLTL was measured by using quantitative PCR. CVD was diagnosed on the basis of ICD-9 code. RESULTS Mean follow-up was 13.4 years (SD 5.5 years). rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA1c, and urine albumin-to-creatinine ratio (ACR), and positively with estimated glomerular filtration rate (eGFR) (all P < 0.001). Subjects with CVD at baseline had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than did subjects without CVD (4.6 ± 1.2 ΔΔCt) (P < 0.001). Of the 4,541 CVD-free subjects at baseline, the 1,140 who developed CVD during follow-up had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than those who remained CVD-free after adjusting for age, sex, smoking, and albuminuria status (4.7 ± 1.2 ΔΔCt) (P < 0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (for each unit decrease, hazard ratio 1.252 [95% CI 1.195–1.311], P < 0.001), which remained significant after adjusting for age, sex, BMI, systolic blood pressure, LDL cholesterol, HbA1c, eGFR, and ACR (hazard ratio 1.141 [95% CI 1.084–1.200], P < 0.001). CONCLUSIONS rLTL is significantly shorter in patients with type 2 diabetes and CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in patients with type 2 diabetes.

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.

Objective: Diabetes is a leading cause of nontraumatic lower extremity amputation (LEA). We describe the secular trends in incidence rates of LEA and one-year mortality rates after LEA in people with diabetes in Hong Kong between 2001 and 2016. Methods: The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide population-based diabetes cohort identified from the Hong Kong Hospital Authority electronic medical system. We identified LEA events using ICD-9 procedure codes and that of one-year mortality after LEAs from the linkage to the Hong Kong Death Registry. We used Joinpoint regression models to describe the trends in incidence of LEAs from 2001 to 2016 and one-year mortality rates after LEAs from 2001 to 2015. Results: Between 2001 and 2016, a total of 390,071 men and 380,007 women with diabetes aged 20 years or older were included in the HKDSD, among whom 6,113 LEAs in men and 4,149 LEAs in women were recorded. The event rates of minor LEAs declined by 48.6% (average annual percent change [AAPC]: -3.8, 95% CI -5.7, -1.9) from 14.0 to 7.2 per 10,000 in men and by 59.5% (AAPC: -6.3, 95% CI -10.6, -1.8) from 7.9 to 3.2 per 10,000 in women. The rates of major LEAs declined by 77.9% (AAPC: -8.0, 95% CI -9.6, -6.5) from 19.5 to 4.3 per 10,000 in men and by 79.3% (AAPC: -10.4, 95% CI -13.1, -7.6) from 11.6 to 2.4 per 10,000 in women. The one-year mortality rates after both minor and major LEAs remained constant during the surveillance period in both sexes. The AAPC for one-year mortality rates was 1.5 (95% CI -3.0, 6.1) in men and 0.6 (95% CI -4.7, 6.1) in women after minor LEAs, and was -2.1 (95% CI -4.8, 0.6) in men and 2.6 (-1.4, 6.7) in women after major LEAs. Conclusions: Although the event rates of LEAs have declined overall in people with diabetes in Hong Kong, there was no improvement in one-year mortality rates after LEAs. Urgent action to improve the quality of care and ongoing surveillance after LEAs in people with diabetes is needed. Disclosure H. Wu: None. A. Yang: None. E.S. Lau: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. A.P. Kong: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Sanofi. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. E. Chow: None. W. So: None. J.C. Chan: None. A. Luk: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Roche Pharma. Other Relationship; Self; Merck Sharp & Dohme Corp.

Background: There is a resurgence of interest in the role of 1-hour post-load plasma glucose (PG) in risk stratification for type 2 diabetes and a cut-off of 8.6 mmol/L has been proposed to define dysglycaemia in addition to other existing criteria of prediabetes. We examined the efficacy of 1-hour PG level in predicting future type 2 diabetes in a longitudinal community-based cohort of Hong Kong Chinese. Methods: Between 2001-2003, 489 adults without diabetes underwent 75-gram oral glucose tolerance test (OGTT). Blood samples were collected at 0, 15, 30, 60 and 120 minutes for measurement of plasma glucose and insulin levels. Between 2012-2014, progression to diabetes was ascertained either by reviewing medical records or by repeating OGTT and HbA1c. Area under the receiver-operating characteristic (ROC) curve was calculated to assess the discrimination of each parameter (fasting PG, 1-hour PG, 2-hour PG, disposition index) for development of diabetes. High 1-hour PG was defined using threshold of 8.6 mmol/L. Results: Over 12-year follow-up, 46 people (9.4%) developed diabetes. The area under ROC curve were 0.79 (95% CI 0.71, 0.86) for fasting PG, 0.84 (95% CI 0.78, 0.89) for 1-hour PG, 0.79 (95% CI 0.72, 0.86) for 2-hour PG, and 0.78 (95% CI 0.71, 0.85) for disposition index with no difference between each parameter. In multivariate logistic regression, high 1-hour PG was associated with new-onset diabetes with odds ratio (OR) 4.87 (95% CI 1.91, 14.1, p=0.002), independent of impaired fasting glucose (OR 2.19 [95% CI 0.87, 5.32, p=NA), impaired glucose tolerance (OR 3.69 [95% CI 1.67, 8.27, p=0.001]) and other clinical variables including age, sex, smoking, family history of diabetes, history of gestational diabetes, waist and blood pressure. Conclusions: One-hour PG is similar to fasting and 2-hour PG in prediction of type 2 diabetes. High 1-hour PG identifies people with high risk of diabetes independent of other criteria of prediabetes and clinical risk factors. Disclosure A. Luk: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Roche Pharma. Other Relationship; Self; Merck Sharp & Dohme Corp. E.S. Lau: None. A.P. Kong: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Sanofi. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. E. Chow: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. J.C. Chan: None.

Background Validated algorithms to classify type 1 and 2 diabetes (T1D, T2D) are mostly limited to white pediatric populations. We conducted a large study in Hong Kong among children and adults with diabetes to develop and validate algorithms using electronic health records (EHRs) to classify diabetes type against clinical assessment as the reference standard, and to evaluate performance by age at diagnosis. Methods We included all people with diabetes (age at diagnosis 1.5–100 years during 2002–15) in the Hong Kong Diabetes Register and randomized them to derivation and validation cohorts. We developed candidate algorithms to identify diabetes types using encounter codes, prescriptions, and combinations of these criteria (“combination algorithms”). We identified 3 algorithms with the highest sensitivity, positive predictive value (PPV), and kappa coefficient, and evaluated performance by age at diagnosis in the validation cohort. Results There were 10,196 (T1D n = 60, T2D n = 10,136) and 5101 (T1D n = 43, T2D n = 5058) people in the derivation and validation cohorts (mean age at diagnosis 22.7, 55.9 years; 53.3, 43.9% female; for T1D and T2D respectively). Algorithms using codes or prescriptions classified T1D well for age at diagnosis Conclusions Our validated set of algorithms accurately classifies T1D and T2D using EHRs for Hong Kong residents enrolled in a diabetes register. The choice of algorithm should be tailored to the unique requirements of each study question.

OBJECTIVE There has been a shift toward new classes of glucose-lowering drugs (GLDs) in the past decade but no improvements in glycemic control or hospitalization rates due to severe hypoglycemia (SH) in previous surveys. We examined trends in GLDs use, glycemic control, and SH rate among patients with diabetes in Hong Kong, which introduced a territory-wide, team-based diabetes care model since 2000. RESEARCH DESIGN AND METHODS Using population-based data from the Hong Kong Diabetes Surveillance Database, we estimated age- and sex-standardized proportion of GLD classes, mean hemoglobin A1c (HbA1c) levels, and SH rates in 763,809 patients with diabetes aged ≥20 years between 2002 and 2016. RESULTS Between 2002 and 2016, use declined for sulfonylureas (62.9% to 35.3%) but increased for metformin (48.4% to 61.4%) and dipeptidyl peptidase 4 inhibitors (DPP-4is) (0.01% in 2007 to 8.3%). The proportion of patients with HbA1c of 6.0–7.0% (42–53 mmol/mol) increased from 28.6% to 43.4%, while the SH rate declined from 4.2/100 person-years to 1.3/100 person-years. The main improvement in HbA1c occurred between 2007 and 2014, decreasing from mean (SD) 7.6% (1.6) (59.5 [19.0] mmol/mol) to 7.2% (1.7) (54.8 [18.9] mmol/mol) (P < 0.001). The 20–44 years age-group had the highest proportion of HbA1c ≥9% (75 mmol/mol) and rising proportions not on GLDs (from 2.0% to 7.7%). CONCLUSIONS In this 15-year survey, the modest but important improvement in HbA1c since 2007 coincided with diabetes service reforms, increase in metformin, decrease in sulfonylureas, and modest rise in DPP-4i use. Persistently poor glycemic control and underuse of GLDs in the youngest group calls for targeted action.

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

OBJECTIVE The implementation of the Chronic Care Model (CCM) improves health care quality. We examined the sustained effectiveness of multicomponent integrated care in type 2 diabetes. RESEARCH DESIGN AND METHODS We searched PubMed and Ovid MEDLINE (January 2000–August 2016) and identified randomized controlled trials comprising two or more quality improvement strategies from two or more domains (health system, health care providers, or patients) lasting ≥12 months with one or more clinical outcomes. Two reviewers extracted data and appraised the reporting quality. RESULTS In a meta-analysis of 181 trials (N = 135,112), random-effects modeling revealed pooled mean differences in HbA1c of −0.28% (95% CI −0.35 to −0.21) (−3.1 mmol/mol [−3.9 to −2.3]), in systolic blood pressure (SBP) of −2.3 mmHg (−3.1 to −1.4), in diastolic blood pressure (DBP) of −1.1 mmHg (−1.5 to −0.6), and in LDL cholesterol (LDL-C) of −0.14 mmol/L (−0.21 to −0.07), with greater effects in patients with LDL-C ≥3.4 mmol/L (−0.31 vs. −0.10 mmol/L for 12 months (SBP −3.4 vs. −1.4 mmHg, Pdifference = 0.034; DBP −1.7 vs. −0.7 mmHg, Pdifference = 0.047; LDL-C −0.21 vs. −0.07 mmol/L for 12-month studies, Pdifference = 0.049). Patients with median age CONCLUSIONS Despite the small effect size of multicomponent integrated care (in part attenuated by good background care), team-based care with better information flow may improve patient-provider communication and self-management in patients who are young, with suboptimal control, and in low-resource settings.

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 (primary outcome) and cause-specific death (secondary outcome). We also explored the joint association of obesity and GV with these outcomes and site-specific cancer. We expressed GV using HbA1c variability score (HVS) defined as percentage of HbA1c values varying by 0.5% compared with values in preceding visit. Findings We included 15,286 patients (type 2 diabetes: n=15,054, type 1 diabetes: n=232) with ≥10 years of diabetes and ≥3 years of observation (51.7% men, age (mean±SD): 61.04±10.73 years, HbA1c: 7.54±1.63%, body mass index [BMI]: 25.65±3.92 kg/m2, all-site cancer events: n=928, cancer death events: n=404). There were non-linear relationships between HVS and outcomes but there was linearity within the high and low HVS groups stratified by the median (IQR) value of HVS (42.31 [27.27, 56.28]). In the high HVS group, the adjusted hazard ratios (aHR) of each SD of HVS was 1.15 (95% CI: 1.04, 1.26) for all-site cancer (n=874). The respective aHRs for breast (n=77), liver (n=117) and colorectal (n=184) cancer were 1.44 (1.07, 1.94), 1.37 (1.08, 1.74), and 1.09 (0.90, 1.32). In the high GV group, the respective aHRs were 1.21 (1.06, 1.39), 1.27 (1.15, 1.40), and 1.15 (1.09, 1.22) for cancer, vascular, and noncancer nonvascular death. When stratified by obesity (BMI ≥25 kg/m2), the high HVS & obese group had the highest aHRs of 1.42 (1.16, 1.73), 2.44 (1.24, 4.82), and 2.63 (1.45, 4.74) respectively for all-site, breast, and liver cancer versus the low GV & non-obese group. The respective aHRs were 1.45 (1.07, 1.96), 1.47 (1.12, 1.93), and 1.35 (1.16, 1.57) for cancer, vascular, and noncancer nonvascular death. Interpretation Obesity and high GV were associated with increased risk of all-site, breast, liver cancer, and cancer-specific death in T2D. Funding The Chinese University of Hong Kong Diabetes Research Fund

Background & Aims Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for chronic kidney disease (CKD). Given the high prevalence of NAFLD among patients with diabetes who are also at risk of CKD, we aimed to investigate the association between NAFLD and albuminuria, a marker commonly found in diabetic nephropathy. Methods This study included a cohort of Chinese patients with type 2 diabetes from the Hong Kong Diabetes Registry recruited between March 2013 and May 2014. Liver stiffness measurement (LSM), with probe-specific cut-offs, was used to detect advanced liver fibrosis. While controlled attenuation parameter (CAP) was used to assess liver steatosis using transient elastography. Results A total of 1,763 Chinese patients with type 2 diabetes were recruited in this analysis. The mean (standard deviation) age and duration of diabetes were 60.7 (11.5) years and 10.8 (8.5) years, respectively. The prevalence of albuminuria was higher in diabetic patients with liver steatosis and those with advanced fibrosis (no NAFLD vs. liver steatosis vs. advanced fibrosis: 41.4% vs. 46.2% vs. 64.2%, p p = 0.039) in patients with eGFR ≥60 ml/min/1.73 m 2 . The odds of albuminuria increased with greater severity of liver fibrosis in a dose dependent manner, with the highest odds observed in patients with LSM scores ≥11.5 kPa assessed by M probe or ≥11.0 kPa assessed by XL probe (adjusted OR 1.53; 95% CI 1.07–2.20; p = 0.021). Conclusions Advanced liver fibrosis, but not steatosis, is independently associated with albuminuria in Chinese patients with type 2 diabetes. Attention should be paid to liver fibrosis in patients with obesity and type 2 diabetes complicated with albuminuria. Lay summary In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis.

AIM Levels of branched-chain amino acids (BCAAs, namely, isoleucine, leucine, and valine) are modulated by dietary intake and metabolic/genetic factors. BCAAs are associated with insulin resistance and increased risk of type 2 diabetes (T2D). Although insulin resistance predicts heart failure (HF), the relationship between BCAAs and HF in T2D remains unknown. METHODS In this prospective observational study, we measured BCAAs in fasting serum samples collected at inception from 2139 T2D patients free of cardiovascular-renal diseases. The study outcome was the first hospitalization for HF. RESULTS During 29 103 person-years of follow-up, 115 primary events occurred (age: 54.8 ± 11.2 years, 48.2% men, median [interquartile range] diabetes duration: 5 years [1-10]). Patients with incident HF had 5.6% higher serum BCAAs than those without HF (median 639.3 [561.3-756.3] vs 605.2 [524.8-708.7] μmol/L; P = .01). Serum BCAAs had a positive linear association with incident HF (per-SD increase in logarithmically transformed BCAAs: hazard ratio [HR] 1.22 [95% CI 1.07-1.39]), adjusting for age, sex, and diabetes duration. The HR remained significant after sequential adjustment of risk factors including incident coronary heart disease (1.24, 1.09-1.41); blood pressure, low-density lipoprotein cholesterol, and baseline use of related medications (1.31, 1.14-1.50); HbA1c , waist circumference, triglyceride, and baseline use of related medications (1.28, 1.11-1.48); albuminuria and estimated glomerular filtration rate (1.28, 1.11-1.48). The competing risk of death analyses showed similar results. CONCLUSIONS Circulating levels of BCAAs are independently associated with incident HF in patients with T2D. Prospective cohort analysis and randomized trials are needed to evaluate the long-term safety and efficacy of using different interventions to optimize BCAAs levels in these patients.

DKD causes co-morbidities made preventable by attaining multiple targets. Patient empowerment, regular feedback and team-based care assisted by JADE Technology with risk stratification and decision support may improve targets attainment and clinical outcomes. In 2014-2018, 2435 patients1 with DKD2 (age:67.6±9.9 years, DM duration:16.5±9.7 years; BMI:26.9±4.7 kg/m2; A1c:7.9±1.6%; SBP:139±18 mmHg; LDL-C:2.35±1.05 mmol/L; TG:1.92±1.29 mmol/L; RASi:70.0%; statin:74.8%; CVD:32.0%, cancer:5.0%, heart failure:3.9%, ≥3 targets3:33.6%), were randomized to usual care (UC=809), empowered care (EC=819) and team-based empowered care (TEC=807) for 1 year with endpoints defined at year 1 and when study ends. After structured assessment, EC and TEC received JADE report, with EC receiving 3-monthly phone calls by nurses and TEC, additional 3-monthly review by a doctor-nurse team with JADE follow-up reports. Amongst 1837 returnees at 1 year, TEC had the lowest HbA1c and LDL-C and highest proportion with ≥3 targets (TMT)4. Non-returnees had worse risk profiles and were less likely to have familial DM and received prior DM education. At study end (2019)5, TMT group (27/408) had fewer CV-renal-cancer endpoints than non-TMT group (66/676) with RR of 0.678 (95% CI: 0.668-0.687). Empowerment, information support and continuing team-based care improve risk factor control and clinical outcomes in DKD. Disclosure J.C.N. Chan: Board Member; Self; Asia Diabetes Foundation. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Merck Sharp & Dohme Corp., Sanofi-Aventis. Research Support; Self; Amgen Inc., AstraZeneca, Lee Powder, Lilly Diabetes, Pfizer Inc., Sanofi-Aventis. Speaker’s Bureau; Self; Ascensia Diabetes Care. Stock/Shareholder; Self; GemVCare. K.T. Nguyen: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker’s Bureau; Self; Abbott. Other Relationship; Self; AstraZeneca, Novo Nordisk A/S, Sanofi-Aventis. A. Tan: None. Y.C. Chia: None. C. Hwu: None. E. Hong: None. Y. Thewjitcharoen: None. J. Du: None. S. Yoo: None. R.C. Mirasol: None. E.S. Lau: None. V. Lau: None. A.W.C. Fu: None. M. Mohamed: None. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. Speaker’s Bureau; Self; Takeda Pharmaceutical Company Limited. C. Tsang: None. A. Luk: None. Funding Asia Diabetes Foundation

Background: There are recent claims that high dietary BCAA may improve insulin resistance although this conflicts with the recommendation that low protein/BCAA diet may confer renoprotection in patients with chronic kidney disease (CKD) stages 3-5. Type 2 diabetes (T2D) has dysregulated energy metabolism where excessive BCAA intake can be harmful. We examined the risk association of BCAA and rate of estimated glomerular filtration rate (eGFR) decline in a prospective T2D cohort. Method: We measured serum BCAA in 2340 adults with CKD stages 1-2 at baseline with available stored sera. By using linear regression analysis, we examined the association of serum BCAA with annual change in eGFR, which was estimated from a linear mixed model using at least three eGFR measurements from baseline until the onset of CKD or data censored on June 2017. Results: In this study cohort with mean±SD follow-up of 10.0±5.3 years (age 55.2±11.2 years, BMI 25.4±4.3 kg/m2, HbA1c 7.6±1.7%, annual change in eGFR -1.37±1.28 ml/min/1.73m2), patients with incident CKD had higher serum BCAA (median [IQR]: 622.7 [540.3-730] vs. 595.8 [518.3-680.3] µM; P Conclusions: In Chinese T2D patients with CKD stages 1-2, high serum BCAA was independently associated with a modest decline in eGFR, suggesting the renoprotective effect of a low BCAA diet may be extended to early CKD with careful monitoring. Disclosure L. Lim: Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. E.S. Lau: None. H. Lee: None. C.H. Tam: None. C.K. Lim: None. A. Luk: None. E. Chow: Research Support; Self; Powder Pharmaceuticals Inc., Sanofi-Aventis. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. J.C. Chan: Board Member; Self; Asia Diabetes Foundation. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Merck Sharp & Dohme Corp., Sanofi-Aventis. Research Support; Self; Amgen Inc., AstraZeneca, Lee Powder, Lilly Diabetes, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; Ascensia Diabetes Care. Stock/Shareholder; Self; GemVCare. A.P. Kong: Advisory Panel; Self; Lilly Diabetes. Research Support; Self; AstraZeneca, Lilly Diabetes. Speaker's Bureau; Self; Abbott. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. Funding Hong Kong Society of Endocrinology, Metabolism and Reproduction; Hong Kong Association for the Study of Obesity

Objective: Over two thirds of the world’s population with diabetes reside in Asia but data on time trends of diabetes incidence in this region is limited. Using population-wide data, we report trends in the incidence of type 1 and type 2 diabetes (T2D) in Hong Kong over a 14-year period. Methods: The Hong Kong Diabetes Surveillance Database (HKDSD) hosts clinical information of people with diabetes under the care of the Hong Kong Hospital Authority, a statutory body governing all public hospitals and out-patient clinics locally. Diabetes type was determined using a validated algorithm that considers both encounter codes and prescription data. Gender-specific incidence rates (per 100,000 person-year) separated by age categories were standardized to age structure of the World Health Organization population. Average annual percentage change (AAPC) was calculated using joinpoint regression analysis to describe incidence trends over time. Results: The HKDSD included 2426 cases of type 1 diabetes (T1D) and 535490 cases of T2D newly detected between 2002-2015. Among youth (age Conclusions: We observed an increase in incidence of T2D in youth and young adults and stabilization in older adults. Incidence of T1D continued to climb in youth but remained constant in adults. This study highlights the emerging problem of young-onset diabetes and calls for effective strategy for diabetes prevention in young people. Disclosure A. Luk: None. C. Ke: None. E.S. Lau: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. E. Chow: Research Support; Self; Powder Pharmaceuticals Inc., Sanofi-Aventis. A.P. Kong: Advisory Panel; Self; Lilly Diabetes. Research Support; Self; AstraZeneca, Lilly Diabetes. Speaker's Bureau; Self; Abbott. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. J.C. Chan: Board Member; Self; Asia Diabetes Foundation. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Merck Sharp & Dohme Corp., Sanofi-Aventis. Research Support; Self; Amgen Inc., AstraZeneca, Lee Powder, Lilly Diabetes, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; Ascensia Diabetes Care. Stock/Shareholder; Self; GemVCare. W. So: None.

Objective: To examine how T2D onset age affects A1C trajectory and A1C lowering with insulin and other drugs. Methods: We conducted a cohort study (2000-16) in adults aged 18-75 years (y) with young-onset T2D (YOD; onset age Results: Glycemic burden was tripled in YOD versus UOD (38.8 versus 11.8 A1C-y). After accounting for drugs, YOD was associated with a higher baseline A1C (7.6%) and slope (0.05%/y) versus UOD (7.4%, 0.00%/y). Non-insulin drugs lowered A1C similarly across onset ages. The post-insulin A1C remained elevated for YOD, regardless of time to insulin start, but improved significantly for UOD. Conclusions: YOD is associated with an aggressive A1C rise and excess glycemic burden despite insulin and other drugs. More effective strategies are needed to lower A1C in people with YOD. Disclosure C. Ke: None. A. Luk: None. B.R. Shah: None. T. Stukel: None. E.S. Lau: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. A.P. Kong: Advisory Panel; Self; Lilly Diabetes. Research Support; Self; AstraZeneca, Lilly Diabetes. Speaker's Bureau; Self; Abbott. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. E. Chow: Research Support; Self; Powder Pharmaceuticals Inc., Sanofi-Aventis. J.C. Chan: Board Member; Self; Asia Diabetes Foundation. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Merck Sharp & Dohme Corp., Sanofi-Aventis. Research Support; Self; Amgen Inc., AstraZeneca, Lee Powder, Lilly Diabetes, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; Ascensia Diabetes Care. Stock/Shareholder; Self; GemVCare. Funding University of Toronto; Royal College of Physicians and Surgeons of Canada; Canadian Society of Endocrinology and Metabolism; Chinese University of Hong Kong; Asia Diabetes Foundation

Background: Hyperglycemia and obesity are major risk factors of many types of cancer. Branched-chain amino acids (BCAA including leucine, isoleucine and valine) are essential amino acids that regulate energy homeostasis. Serum BCAA levels are determined by dietary intake and tissue metabolism. Contrary to claims that BCAA-rich diet/supplements may improve weight and insulin resistance, recent data suggest that BCAA may contribute to tumorigenesis. We examined the association of serum BCAA with cancer risk in a prospective Chinese cohort with type 2 diabetes (T2D). Methods: Between 1995 and 2007, after written consents, all patients had structured assessment including eye/feet examination and blood/urine tests. We measured serum total BCAA in 2607 patients who were cancer-free at baseline and with available stored serum samples, who subsequently developed cancer after one year of enrolment into the HKDR. We performed Cox proportional hazards models with serum BCAA as the predictor variable, adjusting for age, sex, duration of T2D, cardiovascular risk factors (HbA1c, systolic blood pressure, LDL-cholesterol, triglyceride and body mass index) and drug usage. The primary outcome was the first occurrence of any cancer with data censored on 30 June 2017. Results: After a mean±SD follow-up of 13.4±4.2 years, 289 (11.1%) patients developed cancer, mainly from the digestive tract (n=138 including 54 colorectal, 35 liver and 14 pancreatic), genitourinary tract (n=47), lung (n=45) and breast (n=21). The median (interquartile range) serum BCAA at baseline was not statistically different between patients with incident cancer and those without (612.3 [528.5-716.3] vs. 603.7 [522.7-706.3] µmol/L; P=0.48). In the unadjusted model of the total cohort, every doubling of serum BCAA was not associated with any increased risk of primary outcome (hazard ratio [HR] 0.86, 95% confidence interval 0.68-1.07). In subgroup analysis, the corresponding HR for genitourinary cancer was 1.38 (0.92-2.06), which was accentuated to 1.65 (1.08-2.54; P=0.022) after adjustment for aforementioned covariates. By contrast, the associations were not significant for digestive tract (0.9, 0.65-1.24), colorectal (0.92, 0.57-1.48), liver (1.14, 0.62-2.09), pancreatic (0.67, 0.21-2.15), lung (0.69, 0.37-1.31) and breast (0.62, 0.25-1.53) cancer, adjusting for age, sex and duration of T2D. There were no significant BCAA-sex interactions in all analyses. Conclusions: In Chinese T2D patients, high serum BCAA level was independently associated with an excess risk of incident genitourinary cancer, whereby validation in a larger cohort is needed. Although the directions of the associations with different cancer types were mixed, these were consistent with current evidence which shows that the BCAA metabolism reprogramming in cancer is complex and likely dependent on the tissue of origin. Funding: HKASO, HKSEMR

Background Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. Methods and findings One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%–38.1%) to 47.2% (95% CI 40.3%–54.2%), 16.1% (95% CI 11.0%–21.2%) to 34.7% (95% CI 28.1%–41.3%), and 52.3% (95% CI 45.3%–59.2%) to 64.3% (95% CI 57.7%–71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%–32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86–33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72–8.80) and 10.09 per 1,000 person-years (95% CI 4.92–15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30–39 years was 20.56 per 1,000 person-years (95% CI 12.57–31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85–1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92–17.72] versus 4.86 per 1,000 person-years [95% CI 2.13–9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55–40.60] versus 14.1 per 1,000 person-years [95% CI 8.20–22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08–2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23–35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. Conclusions High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS., Ronald Ching Wan Ma and colleagues reveal the higher incidence of diabetes and CVD in Chinese women with polycystic ovary syndrome., Author summary Why was this study done? Besides reproductive abnormality, it is known that women with polycystic ovary syndrome (PCOS) are at high risk of metabolic complications, such as insulin resistance (IR), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). The majority of the accessible longitudinal studies regarding the progression of T2DM in women with PCOS are from the United States, Australia, and Europe. Previous studies have mainly relied on self-report of diabetes status or linkage through national patient registries, which might underestimate the prevalence and incident rate of T2DM in women with PCOS. What did the researchers do and find? During 2016–2017, we prospectively investigated the progression of glycaemic status among 199 Chinese women with PCOS and compared the data with those of 242 women without PCOS by using oral glucose tolerance test (OGTT) for comprehensive glycaemic status screening. We found that the age-standardised incidence rate of T2DM among women with PCOS was around 2.5-fold higher compared with the local female population incidence rate. We noted that the incidence rate of T2DM of both normal-weight and overweight women with PCOS was around double that of respective control groups. This is a key controversial area in international literature and differs from data on individuals of European descent. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS. Chinese women with PCOS were at 6-fold higher risk of developing T2DM compared with those without PCOS. High waist-to-hip ratio (WHR), elevated triglyceride, and presence of hyperandrogenism are associated with the progression to T2DM in PCOS. What do these findings mean? This study highlighted the risk of diabetes and metabolic abnormalities in women with PCOS. The study has shed some light on the potential burden of young-onset diabetes associated with PCOS. This work has already been considered in the recent international guidelines, suggesting the clinical relevance of this work. Our data provide useful insights that universal screening should be considered in all Chinese adult women with PCOS. Our data suggested WHR, elevated triglyceride, and hyperandrogenism are associated with the progression to T2DM in PCOS, although we were unable to explore relationships with IR. Therefore, further research is clearly warranted.

Key Points Question What are the effects of a quality improvement intervention on the care and cardiometabolic risk factors of patients with type 2 diabetes in low- and middle-income countries in the Asia-Pacific region? Findings In this randomized clinical trial of 20 834 patients with type 2 diabetes in 8 Asia-Pacific countries, the intervention group received a technology-guided structured evaluation, automated personalized reports to encourage patient empowerment, and nurse reminders to increase patient engagement over a 12-month period. Clinical events were similar between the control and intervention groups at 12 months; however, the intervention group was more likely to experience reductions in multiple risk factors and increases in the attainment of diabetes-associated targets. Meaning The study’s findings indicate that the use of information and communications technology and nurses to empower and engage patients did not change the number of clinical events but did reduce cardiometabolic risk factors among patients with type 2 diabetes in low- and middle-income countries., 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 with nonphysician personnel on the care and cardiometabolic risk factors of patients with type 2 diabetes in 8 Asia-Pacific countries. Design, Setting, and Participants This 12-month multinational open-label randomized clinical trial was conducted from June 28, 2012, to April 28, 2016, at 50 primary care or hospital-based diabetes centers in 8 Asia-Pacific countries (India, Indonesia, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam). Six countries were low and middle income, and 2 countries were high income. The study was conducted in 2 phases; phase 1 enrolled 7537 participants, and phase 2 enrolled 13 297 participants. Participants in both phases were randomized on a 1:1 ratio to intervention or control groups. Data were analyzed by intention to treat and per protocol from July 3, 2019, to July 21, 2020. Interventions In both phases, the intervention group received 3 care components: a nurse-led Joint Asia Diabetes Evaluation (JADE) technology-guided structured evaluation, automated personalized reports to encourage patient empowerment, and 2 or more telephone or face-to-face contacts by nurses to increase patient engagement. In phase 1, the control group received the JADE technology–guided structured evaluation and automated personalized reports. In phase 2, the control group received the JADE technology–guided structured evaluation only. Main Outcomes and Measures The primary outcome was the incidence of a composite of diabetes-associated end points, including cardiovascular disease, chronic kidney disease, visual impairment or eye surgery, lower extremity amputation or foot ulcers requiring hospitalization, all-site cancers, and death. The secondary outcomes were the attainment of 2 or more primary diabetes-associated targets (glycated hemoglobin A1c, This randomized clinical trial examines the effects of a quality improvement intervention comprising information and communications technology and increased contact with nurses on the clinical care and cardiometabolic risk factors of patients with type 2 diabetes in Asia-Pacific countries.

Type 2 diabetes and chronic kidney disease (CKD) may share common risk factors. Here we used a 3-stage procedure to discover novel predictors of CKD by repeatedly applying a stepwise selection based on the Akaike information criterion to subsamples of a prospective complete-case cohort of 2755 patients. This cohort encompassed 25 clinical variables and 36 genetic variants associated with type 2 diabetes, obesity, or fasting plasma glucose. We compared the performance of the clinical, genetic, and clinico-genomic models and used net reclassification improvement to evaluate the impact of top selected genetic variants to the clinico-genomic model. Associations of selected genetic variants with CKD were validated in 2 independent cohorts followed by meta-analyses. Among the top 6 single-nucleotide polymorphisms selected from clinico-genomic data, three (rs478333 of G6PC2 , rs7754840 and rs7756992 of CDKAL1 ) contributed toward the improvement of prediction performance. The variant rs478333 was associated with rapid decline (over 4% per year) in estimated glomerular filtration rate. In a meta-analysis of 2 replication cohorts, the variants rs478333 and rs7754840 showed significant associations with CKD after adjustment for conventional risk factors. Thus, this novel 3-stage approach to a clinico-genomic data set identified 3 novel genetic predictors of CKD in type 2 diabetes. This method can be applied to similar data sets containing clinical and genetic variables to select predictors for clinical outcomes.

Background Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings. Methods and findings The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1–4, low–high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007–2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007–2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35–140.18]), the non-JADE group had higher (145.32 [95% CI 138.68–152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12–74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15–1.30) and 0.70 (95% CI 0.66–0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score–matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias. Conclusions ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings., Lee-Ling Lim and colleagues reveal how personalised medical guidance can reduce clinical outcomes for diabetes patients in Hong Kong., Author summary Why was this study done? The public healthcare systems are overburdened with manpower shortage, long waiting time, infrequent structured evaluation, and insufficient patient engagement, while structured patient assessment and education is often not provided in the private sector due to high costs and/or lack of capacity. In 2007, we developed the web-based Joint Asia Diabetes Evaluation (JADE) Program, a multicomponent data-driven integrated care program, to close care gaps in both private and public sectors in Hong Kong. It combines the use of nonphysician personnel (e.g., nurses), information and communications technology (ICT), and structured evaluation with issue of personalized JADE reports to empower patients and promote shared decision-making. In 2007, we also established a community-based, nurse-led diabetes center to complement public and private care in Hong Kong by increasing community access to JADE-assisted evaluation for personalized empowerment and engagement. What did the researchers do and find? This retrospective analysis involved 16,624 patients with type 2 diabetes enrolled from the public and private sector in Hong Kong between 2007 and 2015. We categorized these patients into 3 groups, namely non-JADE, JADE, and JADE-Personalized (JADE-P), and compared their risk for clinical events after 6 years of follow-up. Compared with the JADE group (publicly funded evaluation with JADE reports and group education), the non-JADE group (publicly funded evaluation only) had 19%–34% higher risk of clinical events, including hospitalization. Compared with the JADE group, the JADE-P group (self-paid evaluation with JADE reports, personalized empowerment, and annual telephone reminder for engagement) had 23%–36% lower risk of clinical events, including hospitalization and death. What do these findings mean? Multicomponent, data-driven integrated care, assisted by nonphysician personnel and ICT, is associated with a reduction in clinical events and death in patients with type 2 diabetes. Its implementation in the private sector is an affordable option for patients who opt for a more user-friendly and personalized care and may reduce the burden of hospitalization in the public sector.

Background There is very limited data on the time trend of diabetes incidence in Asia. Using population-level data, we report the secular trend of the incidence of type 1 and type 2 diabetes in Hong Kong between 2002 and 2015. Methods and findings The Hong Kong Diabetes Surveillance Database hosts clinical information on people with diabetes receiving care under the Hong Kong Hospital Authority, a statutory body that governs all public hospitals and clinics. Sex-specific incidence rates were standardised to the age structure of the World Health Organization population. Joinpoint regression analysis was used to describe incidence trends. A total of 562,022 cases of incident diabetes (type 1 diabetes [n = 2,426]: mean age at diagnosis is 32.5 years, 48.4% men; type 2 diabetes [n = 559,596]: mean age at diagnosis is 61.8 years, 51.9% men) were included. Among people aged, Andrw Oy Luk et al report the increasing incidence of Type 1 and 2 diabetes in Hong Kong., Author summary Why was this study done? Diabetes affects over 400 million people worldwide, and over half of the diabetes population comes from Asian countries. Most studies on the burden of diabetes in Asia reported the diabetes prevalence, i.e., the proportion of the population with disease, but few have considered diabetes incidence, i.e., the rate at which new cases have developed in the population. Knowledge of disease incidence informs how population exposure to risk factors has changed over time and is useful for projection of future prevalence. What did the researchers do and find? We identified 562,022 people with new-onset type 1 or type 2 diabetes occurring between 2002 and 2015 in the electronic medical record system of the Hong Kong Hospital Authority. We calculated the incidence rates of diabetes according to age categories and gender and analysed incidence trends over time. We found that the incidence of both type 1 and type 2 diabetes increased in children and adolescents (aged

OBJECTIVE Young-onset diabetes is heterogeneous in etiology and disease progression. We compared the incidence of diabetes-related complications and mortality in patients with young-onset type 2 diabetes with or without anti-GAD antibodies and patients with type 1 diabetes. We determined changes in glycemic control before and after commencement of insulin therapy stratified by antibody status. RESEARCH DESIGN AND METHODS Between 1994 and 2012, 1,504 consecutively enrolled patients with type 2 diabetes who had received a diagnosis at RESULTS Anti-GAD antibodies were positive in 8.1% of patients with type 2 diabetes (GAD+). By multivariate Cox regression, patients with GAD+ had a lower hazard of CVD (hazard ratio [HR] 0.43, P = 0.048), a higher hazard of severe hypoglycemia (HR 1.63, P = 0.032), and a similar hazard of ESRD and mortality compared with counterparts without anti-GAD antibodies (GAD−). Compared with patients with type 1 diabetes, ESRD was more likely to develop (HR 2.91, P = 0.043) in patients with GAD+, but no differences were detected in the hazards of severe hypoglycemia, CVD, and mortality. Among new insulin users (n = 304), patients with GAD+ had larger reductions in HbA1c than patients with GAD−after 12 months of insulin use (−2.30 ± 3.80% [25 ± 42 mmol/mol] vs −0.72 ± 1.86% [8 ± 20 mmol/mol], P = 0.05). CONCLUSIONS Anti-GAD positivity identifies a group of patients with a different prognosis compared with patients without antibodies and those with type 1 diabetes. Patients with GAD+ responded differently to insulin compared with patients with GAD−.

Background Diet quality has been linked to obesity, but this relationship remains unclear in individuals with type 2 diabetes (T2D). The aim of this study is to examine the association between diet quality and obesity in Chinese adults with T2D. Methods Between April and November 2016, a total of 211 Chinese T2D adults who underwent assessment of diabetes-related treatment goals and metabolic control were recruited into two groups based on their body mass index (BMI): obese group (BMI ≥30 kg/m2) and non-obese group (BMI = 18.5–24.9 kg/m2). Diet quality indices including Alternate Healthy Eating Index-2010 (AHEI-2010), Diet Quality Index-International (DQI-I), and Dietary Approach to Stop Hypertension (DASH) score, were derived from a validated food frequency questionnaire. Results Obese T2D patients had significantly lower AHEI-2010 (P

Objective: Young-onset type 2 diabetes (YOD, defined as age Methods: We conducted a prospective cohort study measuring all-cause hospitalization in YOD and usual-onset type 2 diabetes (T2D) among adults aged 20-75 years using the Hong Kong Diabetes Register (2000-2015, n=21,779). We estimated the impacts of YOD and risk factor control on hospitalization rate after T2D diagnosis using negative binomial regression. Results: YOD hospitalization had a bimodal distribution, with a disproportionate burden of mental illness < age 40 years (35.9% of bed-days; Figure. 1). YOD was associated with a 3-fold increase in hospitalization rate vs. usual-onset T2D (adjusted rate ratio 2.8, 95% confidence interval 2.5-3.2). Intensified risk factor control (A1C Conclusions: YOD is associated with substantial excess hospitalization across the adult lifespan. Urgent efforts are required to develop aggressive management strategies, and to address the unrecognized burden of mental illness in YOD. Disclosure C. Ke: None. E.S.H. Lau: None. A. Luk: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Sanofi. R.C. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd. A.P. Kong: Research Support; Self; AstraZeneca. E. Chow: Research Support; Self; Sanofi. P.M. Clarke: None. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck & Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company.

Background: Obesity predicts cardiovascular(CV)-renal disease. Contrary to claims that branched-chain amino acids (BCAA)-rich diet/supplements may improve weight and insulin resistance, recent data suggest impaired oxidation of BCAA (leucine, isoleucine and valine) may contribute to CV-renal disease. We examined the associations of serum BCAA, obesity and CV-renal events in a prospective Chinese T2D cohort (1994-2007). Method: We measured serum total BCAA in 579 and 566 patients (top and lowest BMI quintiles respectively) using the colorimetric ELISA kit. Patients were monitored for clinical outcomes with data censored on May 2015. We analysed the effect of serum BCAA on incident CV-renal events using multivariate Cox regression. Results: At baseline, obese group had shorter T2D duration, worse clinical profile and higher serum BCAA than lean group. After 11 years of follow-up, obese group had higher incidence of heart failure (HF), chronic kidney and any CV disease than the lean group. In all patients, every unit increase in Ln (BCAA) elevated the risk of incident HF by 64% (hazard ratio [HR] 1.64, 95% CI 1.01-2.66). Conclusions: Serum BCAA independently predicted incident HF in T2D population even after adjustment for obesity. The associations of this biomarker with dietary patterns and clinical outcomes will provide new insights regarding the health impacts of nutrition. Model 1Model 2EventHR (95% CI)P-valueEventHR (95% CI)P-valueAny CV disease181 (21.5%)1.37 (1.01-1.85)0.044167 (21.0%)1.26 (0.88-1.79)0.206Heart failure91 (9.4%)1.59 (1.06-2.39)0.02585 (9.3%)1.64 (1.01-2.66)0.045Coronary heart disease103 (11.4%)1.19 (0.78-1.81)0.42897 (11.4%)1.05 (0.65-1.71)0.836Stroke100 (10.2%)1.42 (0.96-2.10)0.08390 (9.8%)1.35 (0.86-2.10)0.191Chronic kidney disease401 (52.0%)1.15 (0.89-1.49)0.271379 (51.6%)0.89 (0.65-1.22)0.463Model 1: adjusted for age, sex, T2D duration Model 2: Model 1 + A1c, systolic BP, LDL-cholesterol, log(triglyceride), BMI top and lowest quintiles (0,1), log(ACR), baseline eGFR, use of insulin, RAS inhibitors, oral blood glucose/lipid lowering agents, smoking status Disclosure L. Lim: Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Sanofi-Aventis. E.S.H. Lau: None. A. Luk: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Sanofi. E. Chow: Research Support; Self; Sanofi. H. Lee: None. R.C. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck & Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company. A.P. Kong: Research Support; Self; AstraZeneca.

Aims/Introduction Biosimilar insulin can reduce treatment costs, although the extent of its use is largely unknown. We examined biosimilar insulin use and its associations with the quality of glycemic control using the Joint Asia Diabetes Evaluation register. Materials and Methods We carried out a cross‐sectional analysis in 81,531 patients with type 1 and type 2 diabetes enrolled into the Joint Asia Diabetes Evaluation Program from 2007 to 2014. All insulin related terms are extracted from the Joint Asia Diabetes Evaluation portal, and compared clinical profiles between biosimilar and originator insulin users. Multivariate analysis was performed to assess the association of biosimilar insulin compared with originator insulin with dosage, glycated hemoglobin and hypoglycemia events. Results Amongst 81,531 patients, 20.5% (n = 16,738) were insulin‐treated. In four countries with high use of biosimilar insulin, 4.7% (n = 719) of insulin users (n = 10,197) were treated with biosimilar insulin (India n = 507, 70.3%; the Philippines n = 90, 12.5%; China n = 62, 8.6%; Vietnam n = 60, 8.3%). Biosimilar insulin users were younger and had higher body mass index, glycated hemoglobin, insulin dosage and more frequent hypoglycemia than originator insulin users. These associations were non‐significant after adjustment for confounders. Only age, college education, diabetes education, lipid control, physical activity and history of cardiovascular complications were independently associated with these quality measures. Conclusions Biosimilar insulin use is not uncommon in Asia. Data exclusion due to incomplete capturing of brand names suggests possibly higher use. The multiple determinants of the quality of glycemic control call for establishment of prospective cohorts and diabetes registers to monitor the safety and efficacy of different brands of biosimilar insulin and their impacts on clinical outcomes.