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

AIMS/HYPOTHESIS: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers. METHODS: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m2) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts. RESULTS: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts. CONCLUSIONS/INTERPRETATION: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification.

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

OBJECTIVE: In this study we aim to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications. RESEARCH DESIGN AND METHODS: We performed a two-stage genome-wide association study for CHD in Chinese patients with T2D (3,596 case and 8,898 control subjects), followed by replications in European patients with T2D (764 case and 4,276 control subjects) and general populations (n = 51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes and its interactions with glycemic, blood pressure (BP), and lipid controls in incident cardiovascular diseases. RESULTS: We identified a novel variant (rs10171703) for CHD (odds ratio 1.21 [95% CI 1.13-1.30]; P = 2.4 × 10-8) and BP (ß ± SE 0.130 ± 0.017; P = 4.1 × 10-14) at PDE1A in Chinese T2D patients but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (Pinteraction = 0.0155) and myocardial infarction (MI) (Pinteraction = 5.1 × 10-4). Patients with CC genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9 × 10-8 < P < 3.6 × 10-5), those with CT genotype had no difference (0.0726 < P < 0.2614), and those with TT genotype had a threefold increase in MI risk (P = 6.7 × 10-3). CONCLUSIONS: We discovered a novel CHD- and BP-related variant at PDE1A that interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes, only when our findings are validated.

High-density lipoprotein subclasses and cardiovascular disease and mortality in type 2 diabetes: analysis from the Hong Kong Diabetes Biobank.

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 < 0.05). Very large HDL-P were positively associated with all-cause mortality [1.75 (1.19, 2.58)]. Small HDL-P improved prediction of mortality [C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851)] and CVD [IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486)] over the RECODe model. CONCLUSION: Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D.

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

RATIONALE & OBJECTIVE: Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes. STUDY DESIGN: Multicenter prospective cohort study. SETTINGS & PARTICIPANTS: 19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank. EXPOSURES: DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR. OUTCOMES: All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%). ANALYTICAL APPROACH: Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates. RESULTS: Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR <30 mL/min/1.73 m2 yielded similar findings. LIMITATIONS: Potential misclassification because of drug use. CONCLUSIONS: Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR.

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

We aim to assess the long-term impact of acute kidney injury (AKI) on progression of diabetic kidney disease (DKD) and all-cause mortality and investigate determinants of AKI in Chinese patients with type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register was followed for 12 years (mean ± SD age 57 ± 13.2 years; 46.9% men; median duration of diabetes 5 years). AKI was defined based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 single nucleotide polymorphisms (SNPs) known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD, and ESRD. Validation was sought in an independent cohort including 6,007 patients (age 61.2 ± 10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (hazard ratio 14.3 [95% CI 12.69-16.11]), for developing ESRD (12.1 [10.74-13.62]), and for all-cause death (7.99 [7.31-8.74]) compared with those without AKI. Incidence rate for ESRD among patients with no episodes of AKI and one, two, and three or more episodes of AKI was 7.1, 24.4, 32.4, and 37.3 per 1,000 person-years, respectively. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts but not ESRD. Elevated SUA may increase the risk of DKD through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a nonmodifiable risk factor may facilitate the identification of individuals at high risk to prevent AKI and its long-term impact in T2D.

Development and validation of the CHIME simulation model to assess lifetime health outcomes of prediabetes and type 2 diabetes in Chinese populations: A modeling study.

BACKGROUND: Existing 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 FINDINGS: We 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. CONCLUSIONS: Our 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.

Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.

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 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10- 103 < P < 1.3 × 10- 75) and 3-year lipid changes (1.4 × 10- 6 < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (ß ± SE = 0.052 ± 0.002), 11.7% in TG (ß ± SE = 0.111 ± 0.006), 5.8% in HDL-C (ß ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (ß ± 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 < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10- 3 < P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10- 10 < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (ß ± 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 < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association. CONCLUSIONS: The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank.

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.

Risk Prediction Scores for Mortality, Cerebrovascular, and Heart Disease Among Chinese People With Type 2 Diabetes.

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.

Five-year effectiveness of short messaging service (SMS) for pre-diabetes.

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. Trail registration ClinicalTrials.gov Identifier NCT01556880, retrospectively registered on March 16, 2012.

Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2 Diabetes: The Hong Kong Diabetes Database.

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.

Cost-Effectiveness of a Short Message Service Intervention to Prevent Type 2 Diabetes from Impaired Glucose Tolerance.

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.

Simple non-laboratory- and laboratory-based risk assessment algorithms and nomogram for detecting undiagnosed diabetes mellitus.

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.

The impact of work nature, lifestyle, and obesity on health-related quality of life in Chinese professional drivers.

OBJECTIVE: To assess the association of work nature, lifestyle and obesity with health-related quality of life (HRQOL) in professional drivers. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A pharmacist care program: positive impact on cardiac risk in patients with type 2 diabetes.

OBJECTIVE: To investigate the effect of a pharmacist care program on cardiovascular risks in type 2 diabetic patients. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Oral health status of low-income, middle-aged to elderly Hong Kong Chinese with type 2 diabetes mellitus.

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.

Health behaviour, metabolic control and periodontal status in medically treated Chinese with type 2 diabetes mellitus.

OBJECTIVE: Relationships between demographic, health behaviour and diabetes mellitus (DM) parameters and periodontal status were assessed among a group of nonsmoking, low-income, middle-aged to elderly medically treated Hong Kong Chinese subjects with type 2 diabetes mellitus (DM). MATERIALS AND METHODS: 193 Chinese, dentate, type 2 DM patients (56.5 +/- 9.0 years; recorded DM duration 7.0 +/- 5.2 years) attending a charity hospital specialist clinic were surveyed. Subject demography, periodontal status, Body Mass Index (BMI), DM control, serum TNF-alpha level and general health behaviour (GHB) were recorded. RESULTS: Periodontitis was prevalent (80.3% of subjects with PPD > or = 5 mm and 65.8% subjects with full-mouth mean PAL > 3.0 mm). Mean HbA1c, fasting plasma glucose and BMI were 7.6 +/- 1.6%, 8.2 +/- 2.9 mmol/L and 25.4 +/- 3.7 kg/m2 respectively. Serum TNF-alpha level was similar to the reported Chinese population norm. Full-mouth mean clinical attachment level was associated with DM duration while full-mouth mean probing pocket depth was associated with GHB (p < 0.05). The Gingival Index, was greater in men, and associated with higher HbA1c% and lower education attainment (p < 0.03). CONCLUSION: In this group of non-smoking, predominantly low-education background, overweight, Chinese subjects with fairly well-controlled type 2 DM, periodontal attachment loss and periodontal disease appeared to be associated with DM duration and health behaviour. Health care providers should consider paying more attention to improving the GHB of their type 2 DM patients with long DM duration. DM subjects with a low educational background, having higher HbA1c% and males are more likely to experience gingival inflammation.

Genetic and clinical characteristics of maturity-onset diabetes of the young in Chinese 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<0.02), higher insulin resistance index (P=0.001) and triglyceride level (P<0.02), lower HDL level (P=0.001) and more hypertension (P<0.05), but no significant difference in the prevalence of diabetic complications. In conclusion, MODY3 and MODY2 account for only 9 and 1%, respectively, of Chinese MODY. A majority of Chinese MODY patients are due to defects in unknown genes and appear to be characterized by insulin resistance.

Acarbose improves glycemic control in insulin-treated Asian type 2 diabetic patients: results from a multinational, placebo-controlled study.

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.