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Background Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. Methods and findings In 1995–2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1–9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8–13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3–49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03–1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06–1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10−8) but not glycemic progression (HR: 1.01 [95% CI 0.96–1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. Conclusions Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression., Author summary Why was this study done? There is marked heterogeneity in the rate of progression to insulin requirement in patients with type 2 diabetes (T2D). Whereas some patients can maintain optimal glycemic control with oral glucose-lowering drugs for prolonged periods, others experience rapid deterioration in glycemia, requiring early insulin treatment. It is important to gain insight into what factors are associated with glycemic progression. Previous studies identified baseline HbA1c, young age, and weight gain as independent clinical predictors for glycemic progression in White populations, but there is a paucity of data in Asians. Besides environmental and lifestyle factors including obesity, it is well known that genetic factors play a pivotal role in the onset of diabetes. However, it remains unclear whether genetic variants of body mass index (BMI) and T2D predicts glycemic progression once T2D develops. Moreover, genetic variants associated with response to oral glucose-lowering drugs might also predict glycemic progression. What did the researchers do and find? We investigated glycemic progression among 7,091 Chinese patients with T2D from the Hong Kong Diabetes Register enrolled between 1995 and 2007. We explored the associations of clinical variables and different polygenic risk scores (PRSs) of obesity, T2D, and response to oral glucose-lowering drugs with glycemic progression and validated the associations of PRSs in another multicenter prospective cohort of Hong Kong Diabetes Biobank (HKDB). We found that there was an approximately 1.3-year delay of insulin use after oral glucose-lowering drug failure in real-world practice. We observed a U-shape association between BMI and glycemic progression and found that young age of diagnosis, high HbA1c and triglyceride, use of tobacco, and presence of microvascular complications also predicted rapid glycemic progression. We found that the PRS derived from 123 known risk variants for T2D was associated with early age of diagnosis and rapid glycemic progression, with validation in the replication cohort of HKDB, whereas the PRS derived from 63 BMI-related variants was associated with BMI but not glycemic progression. What do these findings mean? This study highlighted the delay in insulin treatment after oral glucose-lowering drug failure, which represents an important treatment gap in clinical practice. This work emphasized the importance of both genetic and modifiable risk factors, notably lipo-glucotoxicity, obesity, and tobacco use on glycemic progression, which enables identification of high-risk patients for optimal control of risk factors to improve glycemic durability. This study provides novel insights toward the underlying pathophysiology underlining glycemic progression, highlighting some overlap with pathogenesis of T2D. Our work highlights the potential utility of incorporating PRSs for drug response to guide clinical management of T2D.

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.

Context Risk scores for cardiovascular and mortality outcomes have not been commonly applied in Chinese populations. Objective To develop and externally validate a set of parsimonious risk scores [University of Hong Kong-Singapore (HKU-SG)] to predict the risk of mortality, cerebrovascular disease, and ischemic heart disease among Chinese people with type 2 diabetes and compare HKU-SG risk scores to other existing ones. Design Retrospective population-based cohorts drawn from Hong Kong Hospital Authority health records from 2006 to 2014 for development and Singapore Ministry of Health records from 2008 to 2016 for validation. Separate five-year risk scores were derived using Cox proportional hazards models for each outcome. Setting Study participants were adults with type 2 diabetes aged 20 years or over, consisting of 678,750 participants from Hong Kong and 386,425 participants from Singapore. Main Outcome Measures Performance was evaluated by discrimination (Harrell C-index), and calibration plots comparing predicted against observed risks. Results All models had fair external discrimination. Among the risk scores for the diabetes population, ethnic-specific risk scores (HKU-SG and Joint Asia Diabetes Evaluation) performed better than UK Prospective Diabetes Study and Risk Equations for Complications Of type 2 Diabetes models. External validation of the HKU-SG risk scores for mortality, cerebrovascular disease, and ischemic heart disease had corresponding C-indices of 0.778, 0.695, and 0.644. The HKU-SG models appeared well calibrated on visual plots, with predicted risks closely matching observed risks. Conclusions The HKU-SG risk scores were developed and externally validated in two large Chinese population-based cohorts. The parsimonious use of clinical predictors compared with previous risk scores could allow wider implementation of risk estimation in diverse Chinese settings.

Objective An observational post-randomized controlled trial (RCT) design was adopted to evaluate the long-term sustainability and maintenance of improved glycemic control, lipid profile, reduced progression to diabetes at 3-year following a 2-year short messaging service (SMS). We performed a naturalistic follow-up to the 104 participants of SMS intervention, a 2-year randomized controlled trial comparing the SMS to non-SMS for pre-diabetes. All participants were arranged screening for diabetes at 5-year assessment. Primary outcome of this post-RCT study was cumulative incidence of diabetes whereas secondary outcomes were the change in biometric data over a 5-year period. Results After a mean 57-month follow-up, 19 (18.3%) were lost to follow-up after the RCT period. Progression to diabetes occurred in 20 and 16 patients among the intervention and control group respectively, with no significant between-group difference (8.06 and 7.31 cases per 100 person years, respectively; Hazard Ratio in the intervention group, 1.184; 95% confidence interval, 0.612 to 2.288; p-value = 0.616). No significant effect of SMS on reduction in diabetes was observed in overall and pre-defined subgroups. The SMS intervention preserved the clinical benefits within the trial period but failed to transform from treatment efficacy to long-term effectiveness beyond 2 years after intervention. Trial registration ClinicalTrials.gov Identifier NCT01556880, retrospectively registered on March 16, 2012

Background The aim of the present study was to develop a simple nomogram that can be used to predict the risk of diabetes mellitus (DM) in the asymptomatic non-diabetic subjects based on non-laboratory- and laboratory-based risk algorithms. Methods Anthropometric data, plasma fasting glucose, full lipid profile, exercise habits, and family history of DM were collected from Chinese non-diabetic subjects aged 18-70 years. Logistic regression analysis was performed on a random sample of 2518 subjects to construct non-laboratory- and laboratory-based risk assessment algorithms for detection of undiagnosed DM; both algorithms were validated on data of the remaining sample (n = 839). The Hosmer-Lemeshow test and area under the receiver operating characteristic (ROC) curve (AUC) were used to assess the calibration and discrimination of the DM risk algorithms. Results Of 3357 subjects recruited, 271 (8.1%) had undiagnosed DM defined by fasting glucose ≥7.0 mmol/L or 2-h post-load plasma glucose ≥11.1 mmol/L after an oral glucose tolerance test. The non-laboratory-based risk algorithm, with scores ranging from 0 to 33, included age, body mass index, family history of DM, regular exercise, and uncontrolled blood pressure; the laboratory-based risk algorithm, with scores ranging from 0 to 37, added triglyceride level to the risk factors. Both algorithms demonstrated acceptable calibration (Hosmer-Lemeshow test: P = 0.229 and P = 0.483) and discrimination (AUC 0.709 and 0.711) for detection of undiagnosed DM. Conclusion A simple-to-use nomogram for detecting undiagnosed DM has been developed using validated non-laboratory-based and laboratory-based risk algorithms.

Aims. To investigate the costs and cost-effectiveness of a short message service (SMS) intervention to prevent the onset of type 2 diabetes mellitus (T2DM) in subjects with impaired glucose tolerance (IGT). Methods. A Markov model was developed to simulate the cost and effectiveness outcomes of the SMS intervention and usual clinical practice from the health provider’s perspective. The direct programme costs and the two-year SMS intervention costs were evaluated in subjects with IGT. All costs were expressed in 2011 US dollars. The incremental cost-effectiveness ratio was calculated as cost per T2DM onset prevented, cost per life year gained, and cost per quality adjusted life year (QALY) gained. Results. Within the two-year trial period, the net intervention cost of the SMS group was $42.03 per subject. The SMS intervention managed to reduce 5.05% onset of diabetes, resulting in saving $118.39 per subject over two years. In the lifetime model, the SMS intervention dominated the control by gaining an additional 0.071 QALY and saving $1020.35 per person. The SMS intervention remained dominant in all sensitivity analyses. Conclusions. The SMS intervention for IGT subjects had the superiority of lower monetary cost and a considerable improvement in preventing or delaying the T2DM onset. This trial is registered with ClinicalTrials.gov NCT01556880., published_or_final_version

Research Poster Presentations - Session 1: Disease-Specific Studies: Diabetes/Endocrine Disorders - Cost Studies

Aim To determine the efficacy of delivering short-message service (SMS) to provide diabetes-related information in reducing the risk of developing diabetes in Chinese professional drivers with pre-diabetes. Methods A pilot single-blinded randomized controlled trial was conducted in Hong Kong between 05/2009 and 04/2012. Professional drivers with impaired glucose tolerance (IGT) were randomly allocated to either a SMS group receiving messages comprising knowledge and lifestyle modification on diabetes or to a control group with usual care. Primary outcomes were the incidence rate of diabetes mellitus over 12 and 24 months period. Results Fifty-four, out of 104 professional drivers recruited, were randomly allocated to intervention group. Fewer subjects developed diabetes at 12 months in intervention group (5.56%) compared to control group (16.00%). Relative risk (RR) of diabetes onset was 0.35 (95%CI: 0.10–1.24) and the number needed to treat (NNT) for preventing one diabetes was 9.57. At 24 months, RR increased to 0.62 (95%CI: 0.24–1.61) with a NNT of 10.58. Logistic regression showed a significant odds ratio of 0.04 ( P =0.021) for intervention group compared to control group at 12-month follow-up for completers and a non-significant odds ratio of 0.34 ( P =0.303) at 24-month follow-up. Conclusions The SMS program proved to have potential to reduce the risk of developing diabetes at 12 months but additional measures should be integrated to prevent or delay disease progression.

To assess the association of work nature, lifestyle and obesity with health-related quality of life (HRQOL) in professional drivers.A total of 3376 Chinese professional drivers aged 18 to 70 years were recruited to assess the HRQOL by SF-12 summary scores (Physical Component Summary [PCS]; Mental Component Summary [MCS]), and collect data for work nature, lifestyle, and body mass index. Factors associated with HRQOL were examined by multiphase regression analyses.Professional drivers reported poorer physical and mental HRQOL than the general population. Shift work and lorry driving had significant negative effect on HRQOL. Obesity was associated with lower PCS but higher MCS.HRQOL of professional drivers tended to be low, especially among lorry drivers and shift drivers. Health intervention programs should promote regular exercise, healthy eating, no smoking, and weight control, which are modifiable factors improving HRQOL.

Aims To investigate the prevalence of undiagnosed diabetes mellitus (DM) and cardiovascular risk factors among professional drivers in Hong Kong. Methods Chinese professional drivers with no history of DM were invited to complete a questionnaire on their health status, followed by taking their body measurements, fasting blood glucose (FG) and lipids. 75 g OGTT were performed when FG ≥ 5.6 to Results Of these 3376 drivers (male 92.6%, mean age 50.9 ± 7.6 years), the prevalence of undiagnosed DM, prediabetes, and metabolic syndrome was 8.1% (272/3376, 95% CI 7.1–9.0%), 10.0% (337/3376, 95% CI 9.0–11.0%) and 26.8% (904/3376, 95% CI 25.3–28.3%) respectively, while the corresponding WHO Standard Population age-standardized prevalence was 7.8%, 9.0% and 24.7% respectively. Many of them were obese (51.2%), had hypertension (57.0%) and high cholesterol (58.7%), and a third had hypertriglyceridaemia (34.9%) and low HDL-cholesterol (29.3%). Their median working hours were 60.0 (IQR 14) h. Majority had exercise Conclusions Hong Kong professional drivers have higher prevalence of undiagnosed DM, cardiovascular risk factors and metabolic syndrome than the general population. Therefore, health care measures targeting against them should be taken to prevent and detect DM and cardiovascular diseases.

To investigate the effect of a pharmacist care program on cardiovascular risks in type 2 diabetic patients.A 9-month, prospective, randomized, controlled study was conducted in a public hospital in Hong Kong. Patients in the intervention group had regular drug-counseling sessions with pharmacists in addition to routine medical care, whereas patients in the control group received only routine medical care. The primary outcome was the change in coronary heart disease (CHD) risk.A total of 105 patients completed the study. Patients in the intervention group had a statistically significant reduction in CHD risk compared to those in the control group (-1.64% ± 3.56%; n = 51 vs -0.01% ± 3.08%; n = 54, P = .013). For stroke, a reduction in risk was noted in the intervention group, while an increased risk was noted in the control group (-1.06% ± 1.82% vs 0.31% ± 2.51%, P = .002). In addition, hemoglobin A1c levels were significantly reduced in the intervention group compared with the control group (-1.57% ± 1.50% vs -0.40% ± 1.19%, P.001); a similar profile was seen with low-density lipoprotein cholesterol (-0.36 ± 0.76 vs -0.03 ± 0.74, P = .026). Furthermore, there were nonsignificant improvements in high-density lipoprotein cholesterol, triglyceride, and blood pressure in the intervention group. The increased level of understanding regarding medications in the intervention group was statistically significant (P.001), yielding a better enhancement in compliance compared with patients in the control group (22.5% ± 13.4% vs 2.0% ± 5.0%, P.001).The pharmacist care program implemented in this study demonstrated a significant cardiovascular risk reduction in type 2 diabetic patients; therefore such a program would be a valuable addition to a multidisciplinary care of diabetic patients.

In Caucasians, maturity-onset diabetes of the young (MODY) is mostly caused by mutations in the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes. Most Japanese MODY patients, however, are not linked to known MODY genes. In this study, we examined the genetic and clinical characteristics of Chinese subjects with MODY. The study included 146 unrelated families fulfilling the minimum criteria for MODY: two consecutive generations of type II diabetes with at least one member diagnosed under the age of 25. We screened for mutations in the HNF-4alpha (MODY1), MODY2 and MODY3 genes by direct sequencing. Antibody to glutamic acid decarboxylase (GAD-Ab) was measured in subjects with MODY of unknown cause (MODYX). Insulin resistance index and other clinical data were compared in sex-, age- and duration-matched MODY3 and MODYX patients. In all, 13 families had MODY3 mutations and two had MODY2 mutations. No MODY1 mutation was found. Four of the 12 different MODY3 mutations were newly identified novel mutations (Q243E, A311D, P379R and P488fsdelC). In subjects with MODYX, 3% were GAD-Ab positive and 60% were overweight. Compared to MODY3 patients, MODYX patients had higher body mass index (P

The purpose of the study was to determine the efficacy and tolerability of acarbose in Asian type 2 diabetic patients insufficiently controlled by insulin. Asian type 2 diabetic patients on stable insulin dosages were enrolled into a multinational, double-blind, placebo-controlled parallel arm study. After a 2-week screening phase, patients were randomly assigned to 50 mg acarbose t.i.d. or matching placebo for 6 weeks, followed by 100 mg acarbose t.i.d. or placebo for 12 weeks. The primary efficacy parameter was change from baseline in HbA 1c ; secondary variables included the changes in fasting and postprandial blood glucose. After 18 weeks of treatment there was a difference in HbA 1c levels between the two treatment groups (−0.69%, 95% CI (−1.18; −0.2), P =0.008) in favour of acarbose. Reductions in 1-h postprandial glucose levels from baseline to endpoint were observed with acarbose treatment ( P =0.029). There were no differences in fasting blood glucose, total triglyceride and cholesterol between the two groups. Safety profiles were similar for both treatment arms except for the higher incidence of flatulence in the acarbose group (28.6% vs. 16.4% for placebo). Adjunctive acarbose therapy offers an efficacious and safe means for improvement of glycemic control in Asian type 2 diabetic patients insufficiently controlled by insulin.