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Abstract Objective High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility. Research design and methods HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value. Results Over median (IQR) 5.2 (5.0–5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD [hazard ratio (HR) 0.65 (95% CI 0.52, 0.81)] and all-cause mortality [0.47 (0.38, 0.59)] (false discovery rate

Abstract Background The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear. Methods We used data from Biobank Japan (n = 70,657–128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We 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

BackgroundExisting predictive outcomes models for type 2 diabetes developed and validated in historical European populations may not be applicable for East Asian populations due to differences in the epidemiology and complications. Despite the continuum of risk across the spectrum of risk factor values, existing models are typically limited to diabetes alone and ignore the progression from prediabetes to diabetes. The objective of this study is to develop and externally validate a patient-level simulation model for prediabetes and type 2 diabetes in the East Asian population for predicting lifetime health outcomes.Methods and findingsWe developed a health outcomes model from a population-based cohort of individuals with prediabetes or type 2 diabetes: Hong Kong Clinical Management System (CMS, 97,628 participants) from 2006 to 2017. The Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model comprises of 13 risk equations to predict mortality, micro- and macrovascular complications, and development of diabetes. Risk equations were derived using parametric proportional hazard models. External validation of the CHIME model was assessed in the China Health and Retirement Longitudinal Study (CHARLS, 4,567 participants) from 2011 to 2018 for mortality, ischemic heart disease, cerebrovascular disease, renal failure, cataract, and development of diabetes; and against 80 observed endpoints from 9 published trials using 100,000 simulated individuals per trial. The CHIME model was compared to United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS-OM2) and Risk Equations for Complications Of type 2 Diabetes (RECODe) by assessing model discrimination (C-statistics), calibration slope/intercept, root mean square percentage error (RMSPE), and R2. CHIME risk equations had C-statistics for discrimination from 0.636 to 0.813 internally and 0.702 to 0.770 externally for diabetes participants. Calibration slopes between deciles of expected and observed risk in CMS ranged from 0.680 to 1.333 for mortality, myocardial infarction, ischemic heart disease, retinopathy, neuropathy, ulcer of the skin, cataract, renal failure, and heart failure; 0.591 for peripheral vascular disease; 1.599 for cerebrovascular disease; and 2.247 for amputation; and in CHARLS outcomes from 0.709 to 1.035. CHIME had better discrimination and calibration than UKPDS-OM2 in CMS (C-statistics 0.548 to 0.772, slopes 0.130 to 3.846) and CHARLS (C-statistics 0.514 to 0.750, slopes -0.589 to 11.411); and small improvements in discrimination and better calibration than RECODe in CMS (C-statistics 0.615 to 0.793, slopes 0.138 to 1.514). Predictive error was smaller for CHIME in CMS (RSMPE 3.53% versus 10.82% for UKPDS-OM2 and 11.16% for RECODe) and CHARLS (RSMPE 4.49% versus 14.80% for UKPDS-OM2). Calibration performance of CHIME was generally better for trials with Asian participants (RMSPE 0.48% to 3.66%) than for non-Asian trials (RMPSE 0.81% to 8.50%). Main limitations include the limited number of outcomes recorded in the CHARLS cohort, and the generalizability of simulated cohorts derived from trial participants.ConclusionsOur study shows that the CHIME model is a new validated tool for predicting progression of diabetes and its outcomes, particularly among Chinese and East Asian populations that has been lacking thus far. The CHIME model can be used by health service planners and policy makers to develop population-level strategies, for example, setting HbA1c and lipid targets, to optimize health outcomes.

BackgroundType 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 findingsIn 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.ConclusionsOur 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.

Abstract 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

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.

Purpose: To study oral health conditions, diabetic medical complications and their association in type 2 diabetes mellitus (DM).Materials and Methods: Cross-sectional survey of 364 type 2 DM patients (63.6 +/- 10.1 years, 54% female) and 161 controls (64.1 +/- 10.6 years, 53% female) with or without essential hypertension, predominantly low-income, attending a hospital were recruited. Periodontal disease (Community Periodontal Index [CPI]) and dental status (decayed, missing and filled teeth [DMFT]) were recorded. Fasting plasma glucose and, for DM patients, HbA1C and DM complications were recorded on enrolment and follow up, respectively.Results: Many DM subjects had fair diabetic control. Both groups (control/DM) had poor oral health: DMFT = 14.5/16.8, CPI 4 = 36%/50%, (P < 0.02) while DM subjects had less DT(adjusted) = 2.1/1.4 (P < 0.01). Of the follow-up DM individuals, 294 (81%) had medical complication(s). Regression analyses showed association between advanced periodontal attachment loss (ALoss) and age, male gender, smoking and DM; MT and DMFT were associated with age, female gender, smoking, DM and hypertension. ALoss and DMFT were not associated with DM complications.Conclusions: The oral health of the surveyed Chinese subjects was poor. Type 2 DM subjects were affected more by ALoss and MT but less DT. Subjects with hypertension had higher odds for MT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong.Research Design and Methods: Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time.Results: Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%.Conclusions: From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period. [ABSTRACT FROM AUTHOR]