1-year weight change after diabetes diagnosis and long-term incidence and sustainability of remission of type 2 diabetes in real-world settings in Hong Kong: An observational cohort study.

BACKGROUND: Clinical trials have demonstrated that remission of type 2 diabetes can be achieved following sustained weight loss. However, the feasibility of achieving diabetes remission through weight management in real-world settings remains unclear. In this study, we aimed to examine the association of weight change at 1 year after diabetes diagnosis with long-term incidence and sustainability of type 2 diabetes remission in real-world settings in Hong Kong. METHODS AND FINDINGS: This was a population-based observational cohort study. The territory-wide Risk Assessment and Management Programme for Diabetes Mellitus (RAMP-DM) provides regular comprehensive assessments of metabolic control and complication screening for people with diabetes in Hong Kong. We included 37,326 people with newly diagnosed type 2 diabetes who were enrolled in the RAMP-DM between 2000 and 2017, followed until 2019. Diabetes remission was defined as 2 consecutive HbA1c <6.5% measurements at least 6 months apart in the absence of glucose-lowering drugs (GLDs) and with no record of GLDs at least 3 months before these measurements. During a median follow-up of 7.9 years, 6.1% (2,279) of people achieved diabetes remission, with an incidence rate of 7.8 (95% CI: 7.5, 8.1) per 1,000 person-years. After adjusting for age at diabetes diagnosis, sex, assessment year, body mass index, other metabolic indices, smoking, alcohol drinking, and medication use, the hazard ratio (HR) for diabetes remission was 3.28 (95% CI: 2.75, 3.92; p < 0.001) for people with ≥10% weight loss within 1 year of diagnosis, 2.29 (95% CI: 2.03, 2.59; p < 0.001) for those with 5% to 9.9% weight loss, and 1.34 (95% CI: 1.22, 1.47; p < 0.001) for those with 0% to 4.9% weight loss compared to people with weight gain. During a median follow-up of 3.1 years, 67.2% (1,531) of people who had achieved diabetes remission returned to hyperglycaemia, with an incidence rate of 184.8 (95% CI: 175.5, 194.0) per 1,000 person-years. The adjusted HR for returning to hyperglycaemia was 0.52 (95% CI: 0.41, 0.65; p < 0.001) for people with ≥10% weight loss, 0.78 (95% CI: 0.68, 0.92; p = 0.002) for those with 5% to 9.9% weight loss, and 0.90 (95% CI: 0.80, 1.01; p = 0.073) for those with 0% to 4.9% weight loss compared to people with weight gain. Diabetes remission was associated with a 31% (HR: 0.69, 95% CI: 0.52, 0.93; p = 0.014) decreased risk of all-cause mortality. The main limitation of the study is that the reliability of HbA1c used to define diabetes remission can be affected by other medical conditions. Furthermore, we did not have data on bariatric surgery. CONCLUSIONS: In this study, greater weight loss within the first year of diabetes diagnosis was associated with an increased likelihood of achieving diabetes remission and a decreased risk of returning to hyperglycaemia among those who had achieved diabetes remission. However, both the incidence of diabetes remission and the probability of its long-term sustainability were low with conventional management in real-world settings, in an era when the importance of weight loss was not fully appreciated. Our study provides evidence for policymakers to design and implement early weight management interventions and diabetes remission initiatives.

Age-specific population attributable risk factors for all-cause and cause-specific mortality in type 2 diabetes: An analysis of a 6-year prospective cohort study of over 360,000 people in Hong Kong.

BACKGROUND: The prevalence of type 2 diabetes has increased in both young and old people. We examined age-specific associations and population attributable fractions (PAFs) of risk factors for all-cause and cause-specific mortality in people with type 2 diabetes. METHODS AND FINDINGS: We analysed data from 360,202 Chinese with type 2 diabetes who participated in a territory-wide diabetes complication screening programme in Hong Kong between January 2000 and December 2019. We compared the hazard ratios and PAFs of eight risk factors, including three major comorbidities (cardiovascular disease [CVD], chronic kidney disease [CKD], all-site cancer) and five modifiable risk factors (suboptimal HbA1c, suboptimal blood pressure, suboptimal low-density lipoprotein cholesterol, smoking, and suboptimal weight), for mortality across four age groups (18 to 54, 55 to 64, 65 to 74, and ≥75 years). During a median 6.0 years of follow-up, 44,396 people died, with cancer, CVD, and pneumonia being the leading causes of death. Despite a higher absolute mortality risk in older people (crude all-cause mortality rate: 59.7 versus 596.2 per 10,000 person-years in people aged 18 to 54 years versus those aged ≥75 years), the relative risk of all-cause and cause-specific mortality associated with most risk factors was higher in younger than older people, after mutually adjusting for the eight risk factors and other potential confounders including sex, diabetes duration, lipid profile, and medication use. The eight risk factors explained a larger proportion of mortality events in the youngest (PAF: 51.6%, 95% confidence interval [CI] [39.1%, 64.0%], p < 0.001) than the oldest (PAF: 35.3%, 95% CI [27.2%, 43.4%], p < 0.001) age group. Suboptimal blood pressure (PAF: 16.9%, 95% CI [14.7%, 19.1%], p < 0.001) was the leading attributable risk factor for all-cause mortality in the youngest age group, while CKD (PAF: 15.2%, 95% CI [14.0%, 16.4%], p < 0.001) and CVD (PAF: 9.2%, 95% CI [8.3%, 10.1%], p < 0.001) were the leading attributable risk factors in the oldest age group. The analysis was restricted to Chinese, which might affect the generalisability to the global population with differences in risk profiles. Furthermore, PAFs were estimated under the assumption of a causal relationship between risk factors and mortality. However, reliable causality was difficult to establish in the observational study. CONCLUSIONS: Major comorbidities and modifiable risk factors were associated with a greater relative risk for mortality in younger than older people with type 2 diabetes and their associations with population mortality burden varied substantially by age. These findings highlight the importance of early control of blood pressure, which could reduce premature mortality in young people with type 2 diabetes and prevent the onset of later CKD and related mortality at older ages.

Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

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.

Secular trends in all-cause and cause-specific mortality rates in people with diabetes in Hong Kong, 2001-2016: a retrospective cohort study.

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.

Excess Burden of Mental Illness and Hospitalization in Young-Onset Type 2 Diabetes: A Population-Based Cohort Study.

Background: Type 2 diabetes (T2D) increases hospitalization risk. Young-onset T2D (YOD) (defined as onset before age 40 years) is associated with excess morbidity and mortality, but its effect on hospitalizations is unknown. Objective: To determine hospitalization rates among persons with YOD and to examine the effect of age at onset on hospitalization risk. Design: Prospective cohort study. Setting: Hong Kong. Participants: Adults aged 20 to 75 years in population-based (2002 to 2014; n = 422 908) and registry-based (2000 to 2014; n = 20 886) T2D cohorts. Measurements: All-cause and cause-specific hospitalization rates. Negative binomial regression models estimated effect of age at onset on hospitalization rate and cumulative bed-days from onset to age 75 years for YOD. Results: Patients with YOD had the highest hospitalization rates by attained age. In the registry cohort, 36.8% of YOD bed-days before age 40 years were due to mental illness. The adjusted rate ratios showed increased hospitalization in YOD versus usual-onset T2D (onset at age ≥40 years) (all-cause, 1.8 [95% CI, 1.7 to 2.0]; renal, 6.7 [CI, 4.2 to 10.6]; diabetes, 3.7 [CI, 3.0 to 4.6]; cardiovascular, 2.1 [CI, 1.8 to 2.5]; infection, 1.7 [CI, 1.4 to 2.1]; P < 0.001 for all). Models estimated that intensified risk factor control in YOD (hemoglobin A1c level <6.2%, systolic blood pressure <120 mm Hg, low-density lipoprotein cholesterol level <2.0 mmol/L [<77.3 mg/dL], triglyceride level <1.3 mmol/L [<115.1 mg/dL], waist circumference of 85 cm [men] or 80 cm [women], and smoking cessation) was associated with a one-third reduction in cumulative bed-days from onset to age 75 years (97 to 65 bed-days). Limitation: Possible residual confounding. Conclusion: Adults with YOD have excess hospitalizations across their lifespan compared with persons with usual-onset T2D, including an unexpectedly large burden of mental illness in young adulthood. Efforts to prevent YOD and intensify cardiometabolic risk factor control while focusing on mental health are urgently needed. Primary Funding Source: Asia Diabetes Foundation.

Glycaemia control and the risk of hospitalisation for infection in patients with type 2 diabetes: Hong Kong Diabetes Registry.

BACKGROUND: Infection occurs more commonly in diabetic patients compared with the general population and is an under-recognised but important morbidity in patients with diabetes. We examined the impact of glycaemic control on hospitalisation for infection in a large prospective cohort of Chinese adults with type 2 diabetes. METHODS: Between July 1994 and June 2014, 22 846 patients with type 2 diabetes underwent detailed assessment of metabolic control and diabetes complications. Patients were followed for occurrence of infection requiring hospitalisation as identified using discharge diagnosis codes. RESULTS: Over a median follow-up of 4.8 years, 20.3% of patients were hospitalised for any infection type, with respiratory tract, genitourinary tract, and skin being the most commonly affected sites. In multivariate Cox regression, time-dependent HbA1c was associated with all-site infection (hazard ratio [HR] 1.07 [95% confidence interval {CI}:1.05-1.09, P < 0.001]), genitourinary tract infection (HR 1.09 [95% CI: 1.04-1.14], P < 0.001), and skin infection (HR 1.16 [95% CI 1.12-1.21]. P < 0.001), but not infection of respiratory tract, and was independent of age, gender, disease duration, smoking, body mass index, glomerular filtration rate, haemoglobin, history of stroke, congestive heart failure, coronary heart disease, peripheral artery disease, diabetic neuropathy and cancer, and baseline drug use. Against an arbitrary HbA1c interval of >7.0-8.0% (53-64 mmol/mol), patients with HbA1c ≤6.0% (42 mmol/mol) and >8.0% (64 mmol/mol) had excess risks of infection-related hospitalisation adjusted for other factors. CONCLUSIONS: In patients with type 2 diabetes, burden of serious infection is high. In the diabetic population, a U-shape relationship between glycaemia and infection-related hospitalisation was detected.

Low testosterone and clinical outcomes in Chinese men with type 2 diabetes mellitus - Hong Kong Diabetes Registry.

AIMS: To assess the implications of low testosterone on cardiovascular risk factors, metabolic syndrome (MES) and clinical outcomes in Chinese men with Type 2 Diabetes (T2D). METHODS: A prospective cohort study carried out in a university hospital involving a consecutive cohort of 1239 Chinese men with T2D and a median disease duration of 9years followed up for 4.8years. Clinical characteristics, frequency of MES, serum total testosterone and clinical events were analyzed. Multivariate logistic regression was performed to examine the independent association of low testosterone with MES after adjustment for confounding covariates. Cox proportional hazards regression analysis was used to derive hazard ratio for clinical outcomes. RESULTS: More men with low testosterone had cardiovascular-renal disease and MES than those with normal testosterone. The adjusted odds ratio (OR) of low testosterone for MES was 2.63 (95% Confidence Interval [CI] 1.56-4.61). After a median follow-up of 4.8years, the hazard ratio (HR) of low testosterone was 2.22 (95% CI 1.23-4.01) for incident non-prostate cancer. In a multivariate Cox-regression model, the HRs were attenuated but remained significant with adjustment for MES and renal parameters. CONCLUSIONS: Chinese men with low testosterone had high prevalence of cardiovascular disease and MES with high incidence non-prostate cancer.

Health-Related Quality of Life after Bariatric Surgery and its Correlation with Glycaemic Status in Hong Kong Chinese Adults.

BACKGROUND: To evaluate health-related quality of life (HRQOL) following bariatric surgery and its correlation with different glycaemic status in Hong Kong Chinese adults. MATERIALS AND METHODS: In 2002-2008, obese Chinese adults were recruited for bariatric surgery, undergoing laparoscopic adjustable gastric banding or laparoscopic sleeve gastrectomy. Patients were invited to complete the Chinese Hong Kong Medical Outcomes Study Short-Form Health Survey (SF-36) at baseline and at 1-year post operation. RESULTS: Sixty patients (60 % female) completed baseline and 1-year follow-up HRQOL assessments. Mean age was 38 years and mean BMI was 41.6 kg/m(2). At baseline, 30.0 % of patients had diabetes and 31.7 % prediabetes. Mean absolute weight reduction 1 year after bariatric surgery was 19.8 kg. Statistically significant improvements in SF-36 scores were demonstrated in all physical domains and in three of the four psychological domains. Greater body weight reduction was associated with greater improvements in certain physical domains postoperatively. After adjusting for co-variables, abnormal glucose tolerance was associated with greater improvements in five of the eight HRQOL domains. CONCLUSIONS: Bariatric surgery resulted in significant gains in HRQOL as well as significant reductions in body weight in obese Chinese adults. This study suggests that bariatric surgery offers greater HRQOL improvements in patients with prediabetes and diabetes compared with normoglycaemic individuals.

Effect of weight reduction on the severity of lower urinary tract symptoms in obese male patients with benign prostatic hyperplasia: a randomized controlled trial.

PURPOSE: We assessed whether weight reduction is an effective intervention for the management of lower urinary tract symptoms (LUTS) and investigated the relationship between obesity and LUTS. MATERIALS AND METHODS: This was a prospective randomized controlled trial that enrolled obese men older than 50 years with LUTS. The study period was 52 weeks. All patients received standardized alpha-adrenergic blocker therapy for the treatment of benign prostatic hyperplasia (BPH) during the run-in period. Patients were randomized to receive either a standardized prerecorded video program on the general principle of weight reduction or a comprehensive weight reduction program. Patients were assessed at different time points with symptom assessment, uroflowmetry, transrectal ultrasound, and metabolic assessment. RESULTS: Sixty-five patients were allocated to each study arm. After the study period, no significant difference in weight reduction was found between the two arms. When the pre- and postintervention parameters were compared, none were statistically different between the 2 arms, namely nocturia, International Prostate Symptom Score, quality of life assessment, and uroflowmetry parameters. When the whole study population was taken as a single cohort, these parameters were also not significantly different between the group with a body mass index of 25 to <30 kg/m(2) and the group with a BMI of 30 to 35 kg/m(2). CONCLUSIONS: We found no association between obesity and LUTS. This could have been due to the less marked weight difference in our cohort. Whereas weight reduction may be an effective measure to improve LUTS, the implementation of a successful program remains a challenge.

Additive effects of blood glucose lowering drugs, statins and renin-angiotensin system blockers on all-site cancer risk in patients with type 2 diabetes.

BACKGROUND: Hyperglycemia is associated with increased risk of all-site cancer that may be mediated through activation of the renin-angiotensin-system (RAS) and 3-hydroxy-3-methyl-glutaryl-coenzyme-A-reductase (HMGCR) pathways. We examined the joint associations of optimal glycemic control (HbA1c <7%), RAS inhibitors and HMGCR inhibitors on cancer incidence in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes, with or without a history of cancer or prior exposure to RAS or HMGCR inhibitors at baseline were observed between 1996 and 2005. All patients underwent a comprehensive assessment at baseline and were followed until the censored date at 2005 or their death. RESULTS: After a median follow-up period of 4.91 years (interquartile range, 2.81 to 6.98), 271 out of 6,103 patients developed all-site cancer. At baseline, patients with incident cancers were older, had longer disease duration of diabetes, higher alcohol and tobacco use, and higher systolic blood pressure and albuminuria, but lower triglyceride levels and estimated glomerular filtration rate (P <0.05). Patients who developed cancers during follow-up were less likely to have started using statins (22.5% versus 38.6%, P <0.001), fibrates (5.9% versus 10.2%, P = 0.02), metformin (63.8% versus 74.5%, P <0.001) or thiazolidinedione (0.7% versus 6.8%, P <0.001) than those who remained cancer-free. After adjusting for co-variables, new treatment with metformin (hazard ratio: 0.39; 95% confidence interval: 0.25, 0.61; P <0.001), thiazolidinedione (0.18; 0.04, 0.72; P = 0.015), sulphonylurea (0.44; 0.27, 0.73; P = 0.014), insulin (0.58; 0.38, 0.89; P = 0.01), statins (0.47; 0.31, 0.70; P <0.001) and RAS inhibitors (0.55; 0.39, 0.78; P <0.001) were associated with reduced cancer risk. Patients with all three risk factors of HbA1c ≥7%, non-use of RAS inhibitors and non-use of statins had four-fold adjusted higher risk of cancer than those without any risk factors (incidence per 1,000-person-years for no risk factors: 3.40 (0.07, 6.72); one risk factor: 6.34 (4.19, 8.50); two risk factors: 8.40 (6.60, 10.20); three risk factors: 13.08 (9.82, 16.34); P <0.001). CONCLUSIONS: Hyperglycemia may promote cancer growth that can be attenuated by optimal glycemic control and inhibition of the RAS and HMGCR pathways.

Additive effect of aldose reductase Z-4 microsatellite polymorphism and glycaemic control on cataract development in type 2 diabetes.

AIMS: To examine the additive effect of the z-4 microsatellite polymorphism of aldose reductase gene (ALR2) and glycaemic control on risk of cataract in a prospective cohort of Chinese type 2 diabetic patients. METHODS: The (CA)n microsatellite polymorphism of ALR2 was determined using PCR followed by capillary gel electrophoresis. Cataract was defined by presence of lens opacity on direct ophthalmoscopy or history of cataract surgery. A non-linear curve approach was used to identify the threshold of glycated hemoglobin (HbA1c) at which the odds ratio (OR) for cataract started to increase. The association of z-4 allele with cataract, above and below this threshold, was assessed using multiple logistic regression analysis. RESULTS: Of the 5823 patients analyzed, 28.1% had cataracts. After adjusting for conventional risk factors and using non-z-4 carriers with HbA1c<8.0% as referent group (n = 3173), the OR (95% confidence intervals) for cataract was highest in z-4 carriers with HbA1c ≥ 8.0% [1.43 (1.05-1.96), n = 244], compared to non-z-4 carriers with HbA1c ≥ 8.0 [1.27 (1.10-1.47), n = 1836] and z-4 carriers with HbA1c<8.0%[1.01 (0.77-1.29), n = 420, P(trend) < 0.001]. This additive association remained significant after additional adjustments for drug use (P(trend) = 0.002) and renal function (P(trend) = 0.01). CONCLUSIONS: In type 2 diabetic patients with suboptimal glycaemic control, the z-4 allele of ALR2 (CA)n polymorphism was independently associated with increased susceptibility to cataracts.

Genetic associations of type 2 diabetes with islet amyloid polypeptide processing and degrading pathways in asian populations.

Type 2 diabetes (T2D) is a complex disease characterized by beta cell dysfunctions. Islet amyloid polypeptide (IAPP) is highly conserved and co-secreted with insulin with over 40% of autopsy cases of T2D showing islet amyloid formation due to IAPP aggregation. Dysregulation in IAPP processing, stabilization and degradation can cause excessive oligomerization with beta cell toxicity. Previous studies examining genetic associations of pathways implicated in IAPP metabolism have yielded conflicting results due to small sample size, insufficient interrogation of gene structure and gene-gene interactions. In this multi-staged study, we screened 89 tag single nucleotide polymorphisms (SNPs) in 6 candidate genes implicated in IAPP metabolism and tested for independent and joint associations with T2D and beta cell dysfunctions. Positive signals in the stage-1 were confirmed by de novo and in silico analysis in a multi-centre unrelated case-control cohort. We examined the association of significant SNPs with quantitative traits in a subset of controls and performed bioinformatics and relevant functional analyses. Amongst the tag SNPs, rs1583645 in carboxypeptidase E (CPE) and rs6583813 in insulin degrading enzyme (IDE) were associated with 1.09 to 1.28 fold increased risk of T2D (P Meta = 9.4×10(-3) and 0.02 respectively) in a meta-analysis of East Asians. Using genetic risk scores (GRS) with each risk variant scoring 1, subjects with GRS≥3 (8.2% of the cohort) had 56% higher risk of T2D than those with GRS = 0 (P = 0.01). In a subcohort of control subjects, plasma IAPP increased and beta cell function index declined with GRS (P = 0.008 and 0.03 respectively). Bioinformatics and functional analyses of CPE rs1583645 predicted regulatory elements for chromatin modification and transcription factors, suggesting differential DNA-protein interactions and gene expression. Taken together, these results support the importance of dysregulation of IAPP metabolism in T2D in East Asians.

Diabetes and its comorbidities--where East meets West.

Fetal programming associated with in utero exposure to maternal stress is thought to alter gene expression, resulting in phenotypes that promote survival in a pathogen-rich and nutrient-poor environment but substantially increase the risk of cardiovascular, metabolic and renal disorders (such as diabetes mellitus) in adults with obesity. These (epi)genetic phenomena are modified by environmental and socioeconomic factors, resulting in multiple subphenotypes and clinical consequences. In individuals from areas undergoing rapid economic development, which is associated with a transition from communicable to noncommunicable diseases, an efficient innate immune response can exaggerate obesity-associated inflammation. By contrast, in individuals with a genetic predisposition to autoimmune or monogenic diabetes mellitus, obesity can lead to atypical presentation of diabetes mellitus, termed 'double diabetes mellitus'. The increasingly young age at diagnosis of diabetes mellitus in developing countries results in prolonged exposure to glucolipotoxicity, low-grade inflammation and increased oxidative stress, which put enormous strain on pancreatic ß cells and renal function. These conditions create a metabolic milieu conducive to cancer growth. This Review discusses how rapid changes in technology and human behaviour have brought on the global epidemic of metabolic diseases, and suggests that solutions will be based on using system change, technology and behavioural strategies to combat this societal-turned-medical problem.

Use of thiazolidinedione and cancer risk in Type 2 diabetes: the Hong Kong diabetes registry.

We examined possible anticancer effects of thiazolidinediones (TZDs) in 6074 Chinese with Type 2 diabetes free of cancer at enrolment. During a median follow-up of 4.93 years, 270 patients developed cancer. Use of TZDs was associated with reduced risk of cancer in a dose-response manner in multivariable analysis.

Validity of glycated hemoglobin in screening and diagnosing type 2 diabetes mellitus in Chinese subjects.

BACKGROUND/AIMS: The application of glycated hemoglobin (HbA(1c)) for the diagnosis of diabetes is currently under extensive discussion. In this study, we explored the validity of using HbA(1c) as a screening and diagnostic test in Chinese subjects recruited in Nanjing, China. METHODS: In total, 497 subjects (361 men and 136 women) with fasting plasma glucose (PG) ≥ 5.6 mmol/L were recruited to undergo the oral glucose tolerance test (OGTT) and HbA(1c) test. Plasma lipid, uric acid, and blood pressure were also measured. RESULTS: Using a receiver operating characteristic curve, the optimal cutoff point of HbA(1c) related to diabetes diagnosed by the OGTT was 6.3%, with a sensitivity and specificity of 79.6% and 82.2%, respectively, and the area under the curve was 0.87 (95% confidence interval, 0.83 to 0.92). A HbA(1c) level of 6.5% had a sensitivity and specificity of 62.7% and 93.5%, respectively. When comparing the HbA(1c) ≥ 6.5% or OGTT methods for diagnosing diabetes, the former group had significantly higher HbA(1c) levels and lower levels of fasting and 2-hour PG than the latter group. No significant difference was observed in the other metabolism indexes between the two groups. CONCLUSIONS: Our results suggest that HbA(1c) ≥ 6.5% has reasonably good specificity for diagnosing diabetes in Chinese subjects, which is in concordance with the American Diabetes Association recommendations.

Diabetes and cancer: the mechanistic implications of epidemiological analyses from the Hong Kong Diabetes Registry.

Diabetes is a disorder of energy metabolism associated with increased cancer risk, but the underlying mechanism is poorly understood. In a prospective cohort of patients enrolled in the Hong Kong Diabetes Registry, we explored risk factors for cancer including drug usage in type 2 diabetes. In a series of published papers, we reported a linear risk association of cancer with glycated haemoglobin with a threshold at 6.0%-6.5% and non-linear risk associations of body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride and white blood cell (WBC) count in V-shaped or A-shaped manners. Detailed pharmacoepidemiological analysis revealed markedly attenuated cancer risk in patients treated with insulin and oral anti-diabetic drugs compared with non-users of these drugs. We further observed significant drug-subphenotype interactions with attenuated cancer risk in metformin users with low high-density lipoprotein cholesterol, renin-angiotensin system (RAS) inhibitor users with high WBC count and statin users with co-presence of low low-density lipoprotein cholesterol plus albuminuria or low triglyceride. These novel observations corroborate with experimental findings of possible consequences of hyperglycaemia on dysregulation of cholesterol metabolism, renin-angiotensin system and adenosine 5'-monophosphate-activated protein kinase pathways, all of which may be implicated in carcinogenesis. On the basis of these epidemiological and experimental findings, we argue for the strong need to strengthen the health care system to ensure that type 2 diabetes subjects receive appropriate drugs to optimize internal milieu to reduce all events including cancer. Apart from mechanistic studies, large-scale, randomized clinical trials using medications such as statin, renin-angiotensin system inhibitors and metformin in patients with risk-conferring subphenotypes are needed to confirm their anti-cancer effects.

Cardiovascular disease risk factors are highly prevalent in the office-working population of Nanjing in China.

OBJECTIVE: To establish a profile of the modifiable cardiovascular disease (CVD) risk factors in the office-working population of Nanjing, China. BACKGROUND: With increasing modernization in China, CVD is now common among Chinese. Relevant information on the prevalence of CVD risk factors in China is, however, limited. METHODS: We recruited 2648 office working people aged 23-79 years without history of CVD or diabetes from 7 work units of Nanjing during the years 2003 to 2005. Information from a self-reported questionnaire on lifestyle, physical examination, fasting blood for lipid profiles, and a 75-gram oral glucose tolerance test (OGTT) were obtained from each participant. We analyzed the following 7 CVD risk factors: smoking, inadequate physical activity, unhealthy dietary habit, obesity, hypertension, dyslipidemia, and hyperglycemia. RESULTS: The whole study population had an average of 2.8 risk factors, while 95.6%, 79.4% and 55.6% of them had respectively ≥ 1, ≥ 2 and ≥ 3 of the 7 CVD risk factors. Men had a higher proportion of smoking, hypertension, dyslipidemia, hyperglycemia, but lower in light physical activity compared with women. Number of CVD risk factors increased with age. Although risk factors in men were more common than women, they increased alarmingly in postmenopausal women. CONCLUSIONS: CVD risk factors are common in office-working people in Nanjing, China. Effective interventions and treatment against risk factors should be adopted in the high risk population, which may greatly reduce the future burden of CVD in the Chinese population.

The Complexity of Vascular and Non-Vascular Complications of Diabetes: The Hong Kong Diabetes Registry.

Diabetes is a complex disease characterized by chronic hyperglycemia and multiple phenotypes. In 1995, we used a doctor-nurse-clerk team and structured protocol to establish the Hong Kong Diabetes Registry in a quality improvement program. By 2009, we had accrued 2616 clinical events in 9588 Chinese type 2 diabetic patients with a follow-up duration of 6 years. The detailed phenotypes at enrollment and follow-up medications have allowed us to develop a series of risk equations to predict multiple endpoints with high sensitivity and specificity. In this prospective database, we were able to validate findings from clinical trials in real practice, confirm close links between cardiovascular and renal disease, and demonstrate the emerging importance of cancer as a leading cause of death. In addition to serving as a tool for risk stratification and quality assurance, ongoing data analysis of the registry also reveals secular changes in disease patterns and identifies unmet needs.

Comprehensive risk assessments of diabetic patients from seven Asian countries: The Joint Asia Diabetes Evaluation (JADE) program.

BACKGROUND: The aim of the web-based Joint Asia Diabetes Evaluation (JADE) program is to establish a registry for quality assurance, monitoring, and evaluation. METHODS: The JADE electronic portal provides templates for data collection, supplemented by risk stratification, care protocols, and decision support. Herein, data from 3687 patients with Type 2 diabetes, enrolled over 15 months in 2007-2009 from seven Asian countries, are reported. RESULTS: Of the patients, 46.1% were men, the median (range) age was 58 (15-93 years), and median disease duration was 6.5 (0-71) years; 16.2% had at least one cardiovascular-renal complication (10.0% coronary heart disease, 3.3% stroke, 3.1% peripheral vascular disease, 0.4% end-stage renal disease), 20.4% had diabetic retinopathy, 15.0% had sensory neuropathy, 7.5% had chronic kidney disease, and 20.7% of men had erectile dysfunction. Hypertension, dyslipidemia, and central obesity affected 84.6%, 76.8%, and 53.5% of patients, respectively. Treatment targets were HbA1c <7% in 35.3%, blood pressure <130/80 mmHg in 32.3%, and low-density lipoprotein-cholesterol <2.6 mmol/L in 34.0%. The rate of attaining one, two, and three targets was 38.7%, 23.4%, and 5.4%, respectively. Using the JADE Risk Engine, 60% of patients with clinical complications and 20% of those with multiple risk parameters were predicted to have a major event within 5 years. Older age, short disease duration, adherence to diet, control of other risk factors, and not smoking were independently associated with HbA1c <7% (all P < 0.05). CONCLUSIONS: It is possible to use a web-based protocol to establish a registry for risk stratification and facilitate early intervention.