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.

Practical considerations for the use of sodium-glucose co-transporter type 2 inhibitors in treating hyperglycemia in type 2 diabetes.

Sodium-glucose co-transporter type 2 (SGLT2) inhibitors are a new class of oral anti-diabetic agents with a unique, insulin-independent mode of action. In patients with diabetes who have adequate renal function, SGLT2 inhibitors reduce hyperglycemia by blocking renal glucose reabsorption and increasing urinary glucose excretion. These agents are indicated for the treatment of hyperglycemia in type 2 diabetes mellitus (T2DM), as an adjunct to diet and exercise. In terms of efficacy, they are comparable to most other oral agents, and carry a low risk of hypoglycemia unless combined with sulfonylureas or insulin. They may be used in combination regimens with metformin, sulfonylureas, or insulin. Beyond glucose lowering, SGLT2 inhibitors are associated with modest weight loss and mild anti-hypertensive effects. Emerging cardiovascular and renal outcomes data suggest other potentially beneficial non-glycemic effects, although these findings await confirmation from further studies. The main adverse effects are increased risk of volume depletion and of genitourinary infections, although these can be managed with standard interventions. Rare cases of euglycemic ketoacidosis have been reported in a subset of patients treated with these agents, an issue currently under investigation. SGLT2 inhibitors represent a promising alternative treatment option for T2DM patients in whom the effectiveness of oral anti-hyperglycemic therapy is limited by the risk of hypoglycemia, weight gain, or other adverse effects. Safety and efficacy (up to 4 years) have been demonstrated in a range of T2DM patient populations, although more studies will be needed to determine whether treatment with SGLT2 inhibitors improves patient-important outcomes in the longer term.

Progression to treatment failure among Chinese patients with type 2 diabetes initiated on metformin versus sulphonylurea monotherapy--The Hong Kong Diabetes Registry.

AIMS: To assess the development of treatment failure in Chinese patients with type 2 diabetes mellitus (T2DM) initiated on metformin or sulphonylurea (SU) monotherapy, with consideration of various potential sources of biases. METHODS: A 1:1-matched new metformin and SU user cohort on immortal time and mean propensity score after multiple imputation was selected from a cohort of 5889 Chinese patients with T2DM. Treatment failure was defined as progression to (i) combination oral anti-hyperglycemia drug therapy, (ii) insulin use, or (iii) a treatment haemoglobin A1c (HbA1c) >7.5% (58 mmol/mol). Stratified Cox regression analysis on the matched pairs was employed to examine the associations between initial monotherapy and onset of treatment failure. RESULTS: Of 554 new metformin and 840 new SU users, 380 were matched. During a median follow-up duration of 3 years, 173 (45.6%) metformin users and 220 (57.9%) SU users experienced treatment failure (annual failure rates of 15% and 19%, respectively). The median time from monotherapy starting to treatment failure was 3.0 [inter-quartile range (IQR): 1.8-5.4] years for metformin users, versus 1.8 (IQR: 0.9-4.1) years for SU users (p<0.001). Stratified Cox regression analysis showed significantly lower risk of treatment failure for metformin users (HR [95% CI], 0.62[0.47-0.81]; p<0.001). Consistent results were found in analyses based on traditional adjustment schemes with or without imputation. CONCLUSIONS: By systematically incorporating new-user design, multiple imputation and matching methods, we found that Chinese patients with T2DM initiated on metformin monotherapy were associated with a significant delay in the onset of treatment failure compared to SU monotherapy.

Borderline ankle-brachial index is associated with increased prevalence of micro- and macrovascular complications in type 2 diabetes: A cross-sectional analysis of 12,772 patients from the Joint Asia Diabetes Evaluation Program.

Borderline ankle-brachial index is increasingly recognised as a marker of cardiovascular risk. We evaluated the impact of borderline ankle-brachial index in 12,772 Chinese type 2 diabetes patients from the Joint Asia Diabetes Evaluation Program between 2007 and 2012. Cardiovascular risk factors, complications and health-related quality of life were compared between patients with normal ankle-brachial index (1.0-1.4), borderline ankle-brachial index (0.90-0.99) and peripheral arterial disease (ankle-brachial index < 0.9). The prevalence of peripheral arterial disease and borderline ankle-brachial index was 4.6% and 9.6%, respectively. Borderline ankle-brachial index patients were older, more likely to be smokers and hypertensive, had longer duration of diabetes, poorer kidney function and poorer health-related quality of life than patients with normal ankle-brachial index. After adjustment for traditional cardiovascular risk factors, borderline ankle-brachial index was an independent predictor of diabetes-related micro- and macrovascular complications including retinopathy (odd ratios: 1.19 (95% confidence interval: 1.04-1.37)), macroalbuminuria (1.31 (1.10-1.56)), chronic kidney disease (1.22 (1.00-1.50)) and stroke (1.31 (1.05-1.64)). These findings suggest that patients with diabetes and borderline ankle-brachial index are at increased cardiovascular risk and may benefit from more intensive management.

Metabolic profiles and treatment gaps in young-onset type 2 diabetes in Asia (the JADE programme): a cross-sectional study of a prospective cohort.

BACKGROUND: The prevalence of diabetes is increasing in young adults in Asia, but little is known about metabolic control or the burden of associated complications in this population. We assessed the prevalence of young-onset versus late-onset type 2 diabetes, and associated risk factors and complication burdens, in the Joint Asia Diabetes Evaluation (JADE) cohort. METHODS: JADE is an ongoing prospective cohort study. We enrolled adults with type 2 diabetes from 245 outpatient clinics in nine Asian countries or regions. We classified patients as having young-onset diabetes if they were diagnosed before the age of 40 years, and as having late-onset diabetes if they were diagnosed at 40 years or older. Data for participants' first JADE assessment was extracted for cross-sectional analysis. We compared clinical characteristics, metabolic risk factors, and the prevalence of complications between participants with young-onset diabetes and late-onset diabetes. FINDINGS: Between Nov 1, 2007, and Dec 21, 2012, we enrolled 41,029 patients (15,341 from Hong Kong, 9107 from India, 7712 from Philippines, 5646 from China, 1751 from South Korea, 705 from Vietnam, 385 from Singapore, 275 from Thailand, 107 from Taiwan). 7481 patients (18%) had young-onset diabetes, with age at diagnosis of mean 32·9 years [SD 5·7] versus 53·9 years [9·0] with late-onset diabetes (n=33,548). Those with young-onset diabetes had longer disease duration (median 10 years [IQR 3-18]) than those with late-onset diabetes (5 years [2-11]). Fewer patients with young-onset diabetes achieved HbA1c concentrations lower than 7% compared to those with late-onset diabetes (27% vs 42%; p<0·0001) Patients with young-onset diabetes had higher mean concentrations of HbA1c (mean 8·32% [SD 2·03] vs 7·69% [1·82]; p<0·0001), LDL cholesterol (2·78 mmol/L [0·96] vs 2·74 [0·93]; p=0·009), and a higher prevalence of retinopathy (1363 [20%] vs 5714 (18%); p=0·011) than those with late-onset diabetes, but were less likely to receive statins (2347 [31%] vs 12,441 [37%]; p<0·0001) and renin-angiotensin-system inhibitors (1868 [25%] vs 9665 [29%]; p=0·006). INTERPRETATION: In clinic-based settings across Asia, one in five adult patients had young-onset diabetes. Compared with patients with late-onset diabetes, metabolic control in those with young-onset diabetes was poor, and fewer received organ-protective drugs. Given the risk conferred by long-term suboptimum metabolic control, our findings suggest an impending epidemic of young-onset diabetic complications. FUNDING: The Asia Diabetes Foundation (ADF) and Merck.

Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies.

BACKGROUND: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. OBJECTIVES: We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. DATA SOURCES: Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. METHODS: We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied. RESULTS: Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension. CONCLUSIONS: Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.

Delivery of integrated diabetes care using logistics and information technology--the Joint Asia Diabetes Evaluation (JADE) program.

Diabetes is a global epidemic, and many affected individuals are undiagnosed, untreated, or uncontrolled. The silent and multi-system nature of diabetes and its complications, with complex care protocols, are often associated with omission of periodic assessments, clinical inertia, poor treatment compliance, and care fragmentation. These barriers at the system, patient, and care-provider levels have resulted in poor control of risk factors and under-usage of potentially life-saving medications such as statins and renin-angiotensin system inhibitors. However, in the clinical trial setting, use of nurses and protocol with frequent contact and regular monitoring have resulted in marked differences in event rates compared to epidemiological data collected in the real-world setting. The phenotypic heterogeneity and cognitive-psychological-behavioral needs of people with diabetes call for regular risk stratification to personalize care. Quality improvement initiatives targeted at patient education, task delegation, case management, and self-care promotion had the largest effect size in improving cardio-metabolic risk factors. The Joint Asia Diabetes Evaluation (JADE) program is an innovative care prototype that advocates a change in clinic setting and workflow, coordinated by a doctor-nurse team and augmented by a web-based portal, which incorporates care protocols and a validated risk engine to provide decision support and regular feedback. By using logistics and information technology, supported by a network of health-care professionals to provide integrated, holistic, and evidence-based care, the JADE Program aims to establish a high-quality regional diabetes database to reflect the status of diabetes care in real-world practice, confirm efficacy data, and identify unmet needs. Through collaborative efforts, we shall evaluate the feasibility, acceptability, and cost-effectiveness of this "high tech, soft touch" model to make diabetes and chronic disease care more accessible, affordable, and sustainable.

Inhibition of human MCF-7 breast cancer cells and HT-29 colon cancer cells by rice-produced recombinant human insulin-like growth binding protein-3 (rhIGFBP-3).

BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3) in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL) were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively) and HT-29 colon cancer cells (65.14 ± 3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively) when compared with wild type rice. CONCLUSION/SIGNIFICANCE: These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future.

Histopathological correlations of islet amyloidosis with apolipoprotein E polymorphisms in type 2 diabetic Chinese patients.

OBJECTIVE: Islet amyloidosis and arteriosclerosis are histopathological hallmarks in type 2 diabetes. Apolipoprotein E (ApoE) is a common component of amyloidosis. ApoE [Latin Small Letter Open E]4 allele is associated with arteriosclerosis and cerebral amyloidosis in Alzheimer disease. We examined the correlations of ApoE polymorphisms with islet amyloidosis in type 2 diabetes. METHODS: Genomic DNA samples were obtained from 117 autopsy cases with type 2 diabetes and 209 nondiabetic cases. ApoE genotypes and amylin gene mutations were determined by polymerase chain reaction-ligase detection reaction analysis. Islet amyloidosis and arteriosclerosis were evaluated by staining of thioflavin T, amylin, ApoE, and amyloid P component. RESULTS: In the diabetic group, 33.3% in group [Latin Small Letter Open E]2 ([Latin Small Letter Open E]2[Latin Small Letter Open E]2, [Latin Small Letter Open E]2[Latin Small Letter Open E]3), 23.6% in group [Latin Small Letter Open E]3 ([Latin Small Letter Open E]3[Latin Small Letter Open E]3), and 62.5% in group [Latin Small Letter Open E]4 ([Latin Small Letter Open E]4[Latin Small Letter Open E]4, [Latin Small Letter Open E]3[Latin Small Letter Open E]4) had islet amyloidosis. After adjustment for confounders, group [Latin Small Letter Open E]4 had an odds ratio of 7.0 (95% confidence interval, 1.3-38.0; P = 0.023) in having islet amyloidosis compared to group [Latin Small Letter Open E]3. Diabetic cases with islet amyloidosis had more severe arteriosclerosis (P = 0.0111), arteriolar hyalinosis (P = 0.0369), and interstitial fibrosis (P = 0.0188) than those without amyloidosis. Immunoreactivity of both ApoE and amyloid P component was detected in islet amyloid deposits and arteriosclerotic lesions. CONCLUSIONS: In type 2 diabetes, islet amyloidosis and arteriosclerosis share common pathophysiological features with ApoE [Latin Small Letter Open E]4 as a probable linking factor.

Microtubule network is required for insulin-induced signal transduction and actin remodeling.

Both microtubule and actin are required for insulin-induced glucose uptake. However, the roles of these two cytoskeletons and their relationship in insulin action still remain unclear. In this work, we examined the morphological change of microtubule/actin and their involvement in insulin signal transduction using rat skeletal muscle cells. Insulin rapidly led to microtubule clustering from ventral to dorsal surface of the cell. Microtubule filaments were rearranged to create space where new actin structures formed. Disruption of microtubule prevented insulin-induced actin remodeling and distal insulin signal transduction, with reduction in surface glucose transporter isoform 4 (GLUT4) and glucose uptake. Though microtubule mediated actin remodeling through PKCζ, reorganization of microtubule depended on tyrosine phosphorylation of insulin receptor, the mechanism is different from insulin-induced actin remodeling, which relied on the activity of PI3-kinase and PKCζ. We propose that microtubule network is required for insulin-induced signal transduction and actin remodeling in skeletal muscle cells.

Sustained antidiabetic effects of a berberine-containing Chinese herbal medicine through regulation of hepatic gene expression.

Diabetes and obesity are complex diseases associated with insulin resistance and fatty liver. The latter is characterized by dysregulation of the Akt, AMP-activated protein kinase (AMPK), and IGF-I pathways and expression of microRNAs (miRNAs). In China, multicomponent traditional Chinese medicine (TCM) has been used to treat diabetes for centuries. In this study, we used a three-herb, berberine-containing TCM to treat male Zucker diabetic fatty rats. TCM showed sustained glucose-lowering effects for 1 week after a single-dose treatment. Two-week treatment attenuated insulin resistance and fatty degeneration, with hepatocyte regeneration lasting for 1 month posttreatment. These beneficial effects persisted for 1 year after 1-month treatment. Two-week treatment with TCM was associated with activation of AMPK, Akt, and insulin-like growth factor-binding protein (IGFBP)1 pathways, with downregulation of miR29-b and expression of a gene network implicated in cell cycle, intermediary, and NADPH metabolism with normalization of CYP7a1 and IGFBP1 expression. These concerted changes in mRNA, miRNA, and proteins may explain the sustained effects of TCM in favor of cell survival, increased glucose uptake, and lipid oxidation/catabolism with improved insulin sensitivity and liver regeneration. These novel findings suggest that multicomponent TCM may be a useful tool to unravel genome regulation and expression in complex diseases.

White rice vinegar improves pancreatic beta-cell function and fatty liver in streptozotocin-induced diabetic rats.

Vinegar is a traditional remedy for ailments including diabetes. This study was conducted to investigate the beneficial effects of vinegar in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were orally administered with white rice vinegar (WRV, 2 ml/kg body weight per day, n = 6) or with an equal volume of drinking water (n = 6) for 1 month. Fasting and random blood glucose was measured from tail vein samples. Body weight, 24-h food and water intake were monitored 1 week and 1 month after STZ injection. Fasting serum insulin concentrations were assayed using ELISA. Pancreatic beta- and alpha-cell proportions were measured using immunofluorescence microscopy. Periodic acid Schiff staining was performed to access glycogen contents and histological changes in liver tissues. Compared with control animals, the WRV-treated rats had less weight loss, lower fasting and random blood glucose, higher fasting serum insulin and higher beta-cell proportion. The WRV treatment also improved fatty changes and glycogen storages in the liver of STZ rats. Oral intake of WRV improved fasting hyperglycemia and body weight loss through attenuating insulin deficiency, pancreatic beta-cell deficit, and hepatic glycogen depletion and fatty changes in STZ-induced diabetic rats.

Predictive role of multilocus genetic polymorphisms in cardiovascular disease and inflammation-related genes on chronic kidney disease in Type 2 diabetes--an 8-year prospective cohort analysis of 1163 patients.

BACKGROUND: Chinese diabetic patients are at greater risk of developing chronic kidney disease (CKD) than Caucasian counterparts. In this hypothesis-generating study, we examined the independent and joint effects of multiple genetic variants on CKD in a prospective Chinese cohort of Type 2 diabetic patients. METHODS: Seventy-seven single-nucleotide polymorphisms (SNPs) of 54 candidate genes for cardiorenal diseases and inflammation were genotyped in 1163 patients with no past history of CKD at baseline. CKD was defined as the first estimated glomerular filtration rate <60 mL/min/1.73 m(2) or the first hospitalization with a diagnosis of renal disease. RESULTS: In Cox-regression analysis, 15 SNPs of 13 genes were associated with incident CKD. After correction for multiple comparisons, 6 SNPs including PON1 55Met, PON2 311Cys CETP-629C, ITGA2 873A, LTA 26Asn and LTA 252Gly remained independently associated with CKD, with respective hazard ratios (95% confidence interval):2.6 (1.4-4.8, P = 0.002), 1.5 (1.2-1.9, P = 0.003), 1.4 (1.1-1.7, P = 0.001), 2.2 (1.3-3.7, P = 0.002), 1.6 (1.1-2.2, P = 0.008) and 1.5 (1.1-2.1, P = 0.019). Analysis of joint effect of the six SNPs showed stepwise increase in risk of CKD with the accumulation of risk alleles and weighted genetic risk score (P(trend) = 8.9 × 10(-7) and 4.0 × 10(-5), respectively). CONCLUSIONS: In Type 2 diabetes, there are independent and joint effects of multiple genetic variants on risk of CKD. Risk associations with PON1, PON2, CETP, ITGA2 and LTA genetic polymorphisms underline the importance of lipid metabolism, haemostasis and inflammation in the development of CKD in patients with Type 2 diabetes.

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.

Associations of sleep duration with obesity and serum lipid profile in children and adolescents.

INTRODUCTION: The association between sleep duration, obesity, and serum lipid profile in the youth population is under-explored. OBJECTIVE: To evaluate the association between sleep duration, obesity and serum lipid profile in the youth population. METHODS: We conducted a cross-sectional population-based study with students recruited from primary and secondary schools in Hong Kong. Anthropometric measurements, fasting lipid profiles and validated questionnaires on sleep duration were performed. A subgroup (n=138) was randomly selected for both questionnaires and actigraphy to assess the agreement between subjective and objective measurements of sleep duration. RESULTS: We studied 2053 healthy children and adolescents aged 6-20 years. Their mean ages were 13.0±3.3 (boys) and 13.6±3.3 (girls) years. The average sleep duration during schooldays, weekends, and long holidays was 8.0±1.1, 9.6±1.2, and 9.8±1.2h in boys and 7.7±1.1, 9.9±1.2, and 10.1±1.2h in girls, respectively. Using logistic regression, age, and pubertal stage were associated with obesity in secondary school students, whereas male gender and short sleep duration were associated with obesity in primary school children. In secondary school children, those with long sleep duration, as compared to those with short sleep duration, were significantly associated with reduced risk to have high TC and LDL-C levels after adjustment for age, gender, BMI, and pubertal stage. There was no significant association between sleep duration and lipid levels in primary school children. CONCLUSION: Reduced sleep duration was associated with obesity and atherogenic dyslipidemia in young school children in Hong Kong.

Associations of intra-renal arterial resistance index with chronic kidney disease and carotid intima-media thickness in type 2 diabetes mellitus.

Renal dysfunction can be evaluated by increased intra-renal arterial resistance index (RI). We evaluated 113 Chinese men with type 2 diabetes on their RI. Results suggest that RI is associated with chronic kidney disease and subclinical arteriosclerosis. RI may help monitoring the deterioration of intra-renal hemodynamics.

Predictive role of polymorphisms in interleukin-5 receptor alpha-subunit, lipoprotein lipase, integrin A2 and nitric oxide synthase genes on ischemic stroke in type 2 diabetes--an 8-year prospective cohort analysis of 1327 Chinese patients.

OBJECTIVE: Ischemic stroke is prevalent in type 2 diabetes and may be due to metabolic, vascular and inflammatory factors. Genetic variants implicated in these pathways may have joint effects on stroke risk. In this proof-of-concept study, we examined gene-gene interactions on risk of incident ischemic stroke in an 8-year prospective cohort of Chinese type 2 diabetic patients. METHODS: Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for cardiovascular disease and inflammation were genotyped in 1327 patients with no past history of ischemic stroke. The association of SNPs with stroke was tested using Cox proportional hazard regression analysis. Permutation procedure was performed to control for multiple statistical comparisons. RESULTS: Genetic variants including A/A of IL5RA (interleukin-5 alpha subunit) -5091G>A, X/X of LPL (lipoprotein lipase) S447X, A/A of ITGA2 (integrin A2) G873A and T/T or G/T of NOS3 (endothelial nitric oxide synthase) G894T showed significant correlations with incident ischemic stroke. The hazard ratios (HR) increased with number of genetic risk factors reaching an adjusted HR (confidence interval) of 3.68 (1.78-7.62, P=4.4×10(-4)) in those with ≥2 genetic risk factors compared to those without. CONCLUSION: Polymorphisms in IL5RA, LPL, ITGA2 and NOS3 genes were independently associated with ischemic stroke in Chinese diabetic population.

Low triglyceride and nonuse of statins is associated with cancer in type 2 diabetes mellitus: the Hong Kong Diabetes Registry.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have increased cancer risks. The authors reported nonlinear associations of cancer with triglyceride and other lipids in T2DM. Crosstalk between lipid metabolism and the renin-angiotensin system may increase cancer risk via activation of insulin-like growth factor-1 pathway in T2DM. In this analysis, the authors explored associations of cancer risk with high/low triglyceride in T2DM and possible modifying effects of statins on this risk association, if any. METHODS: A consecutive cohort of 5166 Chinese patients with T2DM, free of cancer at enrollment and not using statins at or before enrollment, was analyzed using Cox models. Biological interactions were estimated using relative excess risk because of interaction, attributable proportion because of interaction, and synergy index. Relative excess risk because of interaction > 0, attributable proportion because of interaction > 0, or synergy index > 1 indicates biological interaction. RESULTS: During 5.25 years of follow-up (median), 4.7% (n = 243) patients developed cancer. Triglyceride < 1.70 mmol/L was associated with increased cancer risk in the entire cohort and in statin nonusers, but not in statin users. Patients with triglyceride < 1.70 mmol/L plus nonuse of statins during follow-up had 2.74-fold increased cancer risk compared with their counterparts with either triglyceride ≥ 1.70 mmol/L or use of statins or both. There was significant interaction between triglyceride < 1.70 mmol/L and nonuse of statins (relative excess risk because of interaction, 0.99; 95% confidence interval [CI], 0.07-1.90 and attributable proportion because of interaction, 0.36; 95% CI, 0.02-0.70). CONCLUSIONS: In Chinese T2DM patients, triglyceride < 1.70 mmol/L might be associated with increased cancer risk, which was attenuated in the presence of use of statins.

Lipid control and use of lipid-regulating drugs for prevention of cardiovascular events in Chinese type 2 diabetic patients: a prospective cohort study.

BACKGROUND: Dyslipidaemia is an important but modifiable risk factor of cardiovascular disease (CVD) in type 2 diabetes. Yet, the effectiveness of lipid regulating drugs in Asians is lacking. We examined the effects of lipid control and treatment with lipid regulating drugs on new onset of CVD in Chinese type 2 diabetic patients. METHODS: In this prospective cohort consisting of 4521 type 2 diabetic patients without history of CVD and naïve for lipid regulating treatment recruited consecutively from 1996 to 2005, 371 developed CVD after a median follow-up of 4.9 years. We used Cox proportional hazard regression to obtain the hazard ratios (HR) of lipids and use of lipid regulating drugs for risk of CVD. RESULTS: The multivariate-adjusted HR (95% confidence interval) of CVD in patients with high LDL-cholesterol (≥ 3.0 mmol/L) was 1.36 (1.08 - 1.71), compared with lower values. Using the whole range value of HDL-cholesterol, the risk of CVD was reduced by 41% with every 1 mmol/L increase in HDL-cholesterol. Plasma triglyceride did not predict CVD. Statins use was associated with lower CVD risk [HR = 0.66 (0.50 - 0.88)]. In sub-cohort analysis, statins use was associated with a HR of 0.60 (0.44 - 0.82) in patients with high LDL-cholesterol (≥ 3.0 mmol/L) and 0.49 (0.28 - 0.88) in patients with low HDL-cholesterol. In patients with LDL-cholesterol < 3.0 mmol/L, use of fibrate was associated with HR of 0.34 (0.12 - 1.00). Only statins were effective in reducing incident CVD in patients with metabolic syndrome [(HR = 0.58(0.42 - 0.80)]. CONCLUSIONS: In Chinese type 2 diabetic patients, high LDL-cholesterol and low HDL-cholesterol predicted incident CVD. Overall, patients treated with statins had 40-50% risk reduction in CVD compared to non-users.