Insulin glargine compared to neutral protamine Hagedorn (NPH) insulin in patients with type-2 diabetes uncontrolled with oral anti-diabetic agents alone in Hong Kong: a cost-effectiveness analysis.

BACKGROUND: International guidelines recommend using basal insulin in patients with type-2 diabetes mellitus if glycaemic target cannot be attained on non-insulin anti-diabetic drugs. Available choices of basal insulin include intermediate-acting neutral protamine Hagedorn (NPH) insulin and long-acting insulin analogues like insulin glargine U100. Despite clear advantages of glargine U100, the existing practice in Hong Kong still favours NPH insulin due to lower immediate drug costs. OBJECTIVES: The objective of this study was to assess the cost-effectiveness of insulin glargine U100 compared to NPH insulin in patients with type-2 diabetes uncontrolled with non-insulin anti-diabetic agents alone in Hong Kong. METHODS: The IQVIA™ Core Diabetes Model (CDM) v9.0 was used to conduct the cost-effectiveness analysis of glargine U100 versus NPH. Baseline characteristics were collected from the Hong Kong Diabetes Registry. Efficacy rates were extracted from a published study comparing glargine U100 and NPH in Asia, utilities from published literature, and costs constructed using the Hong Kong Hospital Authority (HA) Gazette (public healthcare setting). The primary outcome was an incremental cost-effectiveness ratio (ICER). RESULTS: Insulin glargine U100 resulted in an ICER of HKD 98,663 per Quality Adjusted Life Year (QALY) gained. The incremental gains in QALY and costs were 0.217 years and HKD 21,360 respectively. Results from scenario and probabilistic sensitivity analyses were consistent with that from base case analysis. CONCLUSION: Insulin glargine U100 is a cost-effective treatment for patients with type 2 diabetes compared to NPH insulin in setting in Hong Kong. This was mainly driven by the significantly lower rates of hypoglycaemia of insulin glargine U100 than NPH insulin.

High risk of conversion to diabetes in first-degree relatives of individuals with young-onset type 2 diabetes: a 12-year follow-up analysis.

AIM: Family history of diabetes is an established risk factor for Type 2 diabetes, but the impact of a family history of young-onset diabetes (onset < 40 years) on future risk of diabetes among first-degree relatives is unclear. In this prospective study, we examined the influence of family history of late- versus young-onset diabetes on the development of diabetes in a young to middle-aged Chinese population. METHODS: Some 365 siblings identified through probands with Type 2 diabetes and 452 participants from a community-based health awareness project (aged 18-55 years) who underwent metabolic assessment during the period 1998-2002 were followed to 2012-2013 to determine their glycaemic status. Multivariate logistic regression was performed to investigate the association of family history of diabetes presented at different age categories with development of diabetes. RESULTS: In this cohort, 53.4% (n = 167) of participants with a family history of young-onset diabetes, 30.1% (n = 68) of those with a family history of late-onset diabetes and 14.4% (n = 40) of those without a family history developed diabetes. Using logistic regression, family history of diabetes presented at ages ≥ 50, 40-49, 30-39 and < 30 years, increased conversion to diabetes with respective odds ratios of 2.4, 5.8, 9.4 and 7.0 (P < 0.001 for all), after adjustment for socio-economic status, smoking, obesity, hypertension and dyslipidaemia. Among participants without diabetes at baseline, risk association of family history of late-onset diabetes with incident diabetes was not sustained, whereas that of family history of young-onset diabetes remained robust on further adjustment for baseline glycaemic measurements. CONCLUSIONS: First-degree relatives of people with Type 2 diabetes, especially relatives of those with young-onset diabetes, are at high risk for diabetes.

A multicentre demonstration project to evaluate the effectiveness and acceptability of the web-based Joint Asia Diabetes Evaluation (JADE) programme with or without nurse support in Chinese patients with Type 2 diabetes.

AIMS: To test the hypothesis that delivery of integrated care augmented by a web-based disease management programme and nurse coordinator would improve treatment target attainment and health-related behaviour. METHODS: The web-based Joint Asia Diabetes Evaluation (JADE) and Diabetes Monitoring Database (DIAMOND) portals contain identical built-in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow-up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND (n = 1728) or JADE, plus nurse-coordinated follow-up visits (n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving ≥ 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l). RESULTS: Of 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow-up of 12.5 (4.6) months. The proportion of participants attaining ≥ 2 treatment targets increased in both groups (JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [DIAMOND -8 mmol/mol vs JADE -7 mmol/mol (-0.69 vs -0.62%)] and LDL cholesterol (DIAMOND -0.32 mmol/l vs JADE -0.28 mmol/l), with no between-group difference. The JADE group was more likely to self-monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001). CONCLUSIONS: Integrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self-care. (Clinical trials registry no.: NCT01274364).

Early gene-diet interaction between glucokinase regulatory protein (GCKR) polymorphism, vegetable and fish intakes in modulating triglyceride levels in healthy adolescents.

BACKGROUND AND AIMS: The benefits of dietary vegetable and fish consumptions on improving glucose and lipid metabolism have been well established. Recently, the T-allele of a common genetic variant rs780094 at glucokinase regulatory protein (GCKR) was reported to be associated with elevated triglyceride (TG) levels but reduced fasting plasma glucose (FPG) and type 2 diabetes risk. However, the dietary modulation on genetic risk is not clearly understood. METHODS AND RESULTS: A cohort of 2095 Chinese adolescents (mean age 15.6 ± 2.0 years, 45.3% male) recruited from a population-based school survey for cardiovascular risk factor assessment, with dietary data including weekly vegetable and fish consumptions as well as clinical data were genotyped for the GCKR rs780094 polymorphism. In the linear regression analysis with adjustment for sex, age, body mass index, and socioeconomic status (school banding, paternal and maternal education levels), the frequency of vegetable intake per week was inversely associated with FPG (P = 0.044). Individuals with low fish intake generally had elevated TG levels but reduced TC, HDL-C and LDL-C (0.006 < P < 0.029). We also observed significant associations of the minor T-allele of GCKR rs780094 with decreased FPG (P = 0.013) and increased TG levels (P = 2.7 × 10(-8)). There were significant gene-diet interactions between rs780094 and vegetable consumption (P(interaction) = 0.009), and between rs780094 and fish consumption (P(interaction) = 0.031) in modulating TG levels. The T-allele of GCKR locus was associated with higher TG levels amongst individuals with ≥7 vegetable meals per week (P = 6.4 × 10(-9)), and among individuals with <7 fish meals per week (P = 0.020 and 7.0 × 10(-7) for 4-6 and ≤3 meals per week, respectively). High intake of vegetable exerted a reduction in TG levels only among CC genotype carriers (Ptrend = 0.020), while high intake of fish was associated with reduced TG levels only among TT genotype carriers (Ptrend = 0.026). CONCLUSIONS: In summary, our data indicated that the favorable associations of higher vegetable and fish intakes on TG levels are dependent on the genetic background of an individual. In particular, at-risk TT- genotype carriers of the GCKR variant may derive more benefits from a high fish intake, while the CC-genotype carriers may find further benefits from a high consumption of vegetable.

Non-linear relationship between birthweight and cardiometabolic risk factors in Chinese adolescents and adults.

AIM: To investigate the relationship between birthweight and cardiometabolic traits in two cohorts: one of Chinese adolescents and one of Chinese adults. METHODS: Birthweight and clinical data, including anthropometric traits, fasting plasma glucose and fasting plasma insulin levels, blood pressure and lipid profiles were collected from 2035 adolescents and 456 adults. A subset of 735 subjects underwent an oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min. RESULTS: Among adolescents, birthweight showed U-shaped relationships with larger body size, obesity, abdominal obesity in girls, insulin resistance and worse lipid profiles (0.0013 < P(quadratic) < 0.0499), as well as an inverse association with fasting plasma glucose (P(linear) = 0.0368). After further adjustment for adiposity, decreasing birthweight was associated with elevated fasting plasma glucose levels, greater insulin resistance and worse lipid profiles (3.1 × 10⁻5 < P(linear) < 0.0058). Among adults, high birthweight was associated with larger body size and abdominal obesity in men, while low birthweight was associated with elevated glucose levels at 15, 30, 60 and 120 min and a greater area under the curve at 0-120 min, as well as with ß-cell dysfunction (6.5 × 10⁻5 < P(linear) < 0.0437). Adjustment for adult adiposity did not substantially change the relationships. There was significant interaction between birthweight and abdominal obesity in elevating fasting plasma insulin and homeostasis model assessment of insulin resistance (P > 0.05), with abdominally obese adolescents in the lowest birthweight category (≤ 2.5 kg) having the highest risk of insulin resistance. CONCLUSIONS: Both high and low birthweights are associated with an increased risk of cardiometabolic abnormalities including obesity, abdominal obesity, hyperglycaemia, dyslipidaemia and insulin resistance, as well as with ß-cell dysfunction.

Eczema phenotypes are associated with multiple vitamin D pathway genes in Chinese children.

BACKGROUND: Vitamin D is increasingly recognized to play crucial roles in cutaneous immunity, and vitamin D treatment improved eczema control in small clinical trials. Several vitamin D-related genes were associated with asthma, but there are no data for eczema. METHODS: Twenty-three single-nucleotide polymorphisms (SNPs) of five vitamin D-related genes (CYP27A1, CYP2R1, CYP27B1, GC and VDR) were genotyped in 1442 Chinese children with eczema and 1231 non-allergic controls. SNPs that followed Hardy-Weinberg equilibrium and yielded ≥ 95% genotyping call-rate were included. Haplotypic associations and SNP-SNP interactions for eczema diagnosis and subphenotypes were analysed. RESULTS: Atopic eczema was associated with rs4674343 of CYP27A1 (odds ratio 0.66, 95% confidence interval 0.53-0.83, P = 0.0004). Increased eosinophil percentage was associated with CYP2R1 rs2060793A (P = 0.001) and rs1933064A (P = 0.001). Two CYP2R1 haplotypes increased eczema risk whereas one VDR haplotype lowered eczema risk. GC rs7041 and CYP2R1 rs7935792 interacted to modulate total IgE (cross-validation consistency 10/10, P = 0.047). Specifically, high-risk eczema patients had higher log-transformed total IgE than low-risk patients (2.76 ± 0.76 vs 2.60 ± 0.80, P = 0.002). CONCLUSION: A vitamin D-related SNP rs4674343 on CYP27A1 was found to be protective against atopic eczema. CYP2R1 and VDR haplotypes altered eczema susceptibility and eosinophil percentage, and GC and CYP2R1 interacted to determine total IgE among eczema patients.

Maternal history of diabetes is associated with increased cardiometabolic risk in Chinese.

OBJECTIVE: Positive family history is associated with increased type 2 diabetes (T2D) risk, and reflects both genetic and environmental risks. Several studies have suggested an excess maternal transmission of T2D, although the underlying mechanism is unknown. We aimed to examine the association between maternal diabetes and cardiometabolic risk in the offspring. METHODS: Parental history of diabetes and clinical data including anthropometric traits, fasting plasma glucose and insulin (FPG, FPI), blood pressure and lipid profile were collected from 2581 unrelated Chinese offspring (2026 adolescents from a population-based school survey and 555 adults from a community-based health screening programme). A subset of subjects (n=834) underwent oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min for evaluation of the areas under the curve (AUC) of glucose and insulin at 0-120 min, homoeostasis model assessment of insulin resistance (HOMA-IR) and bell-cell function, insulinogenic index, insulin sensitivity index (ISI) and oral disposition index (DI). RESULTS: A positive parental history of diabetes was associated with increased risk of obesity (odd ratios (OR) (95% confidence interval (CI))=1.48 (1.10-2.00)), central obesity (OR (95% CI)=1.67 (1.21-2.32)), higher FPI, HOMA-IR, 2-h insulin, AUC of glucose at 0-120 min, triglycerides, reduced ISI and DI. Compared with individuals without parental diabetes, offspring with diabetic mother had significantly increased risk of obesity (OR (95% CI)=1.59 (1.07-2.35)), central obesity (OR (95% CI)=1.88 (1.23-2.88)), higher glucose levels and BP, were more insulin resistant but also had impaired first-phase insulin response and worse lipid profile. However, paternal history of diabetes had no effect on any of the studied traits, except higher body mass index, waist circumference in females and FPG. CONCLUSIONS: Our findings suggested that maternal history of diabetes conferred increased risk of cardiometabolic abnormalities, and was associated with both insulin resistance and impaired first-phase insulin secretion. Further investigation into the mechanism of transgenerational diabetes is warranted.

Diabetes and pregnancy: perspectives from Asia.

There has been a marked increase in the prevalence of diabetes in Asia over recent years. Diabetes complicating pregnancy, in particular gestational diabetes, has also increased markedly in the region. Multi-ethnic studies have highlighted the increased risk of gestational diabetes mellitus among the different Asian populations. Prevalence of gestational diabetes in Asian countries varies substantially according to the screening strategy and diagnostic criteria applied, and ranges from 1% to 20%, with evidence of an increasing trend over recent years. The International Association for Diabetes in Pregnancy Study group criteria have been adopted by some Asian countries, although they present significant challenges in implementation, especially in low-resource settings. Studies on offspring of mothers with gestational diabetes have reported adverse cardiometabolic profiles and increased risk of diabetes and obesity. Gestational diabetes is likely to be a significant factor contributing to the epidemic of diabetes and other non-communicable diseases in the Asian region. In recognition of this, several large-scale prevention and intervention programmes are currently being implemented in different Asian countries in order to improve glucose control during pregnancy, as well as overall maternal health. Lessons emerging from gestational diabetes studies in Asia may help inform and provide insights on the overall burden and treatment strategies to target gestational diabetes, with the ultimate aim to reduce its adverse short- and long-term consequences.

Pharmacological reduction of NEFA restores the efficacy of incretin-based therapies through GLP-1 receptor signalling in the beta cell in mouse models of diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is associated with reduced incretin effects. Although previous studies have shown that hyperglycaemia contributes to impaired incretin responses in beta cells, it is largely unknown how hyperlipidaemia, another feature of type 2 diabetes, contributes to impaired glucagon-like peptide 1 (GLP-1) response. Here, we investigated the effects of NEFA on incretin receptor signalling and examined the glucose-lowering efficacy of incretin-based drugs in combination with the lipid-lowering agent bezafibrate. METHODS: We used db/db mice to examine the in vivo efficacy of the treatment. Beta cell lines and mouse islets were used to examine GLP-1 and glucose-dependent insulinotropic peptide receptor signalling. RESULTS: Palmitate treatment decreased Glp1r expression in rodent insulinoma cell lines and isolated islets. This was associated with impairment of the following: GLP-1-stimulated cAMP production, phosphorylation of cAMP-responsive elements binding protein (CREB) and insulin secretion. In insulinoma cell lines, the expression of exogenous Glp1r restored cAMP production and the phosphorylation of CREB. Treatment with bezafibrate in combination with des-fluoro-sitagliptin or exendin-4 led to more robust glycaemic control, associated with improved islet morphology and beta cell mass in db/db mice. CONCLUSIONS/INTERPRETATION: Elevated NEFA contributes to impaired responsiveness to GLP-1, partially through downregulation of GLP-1 receptor signalling. Improvements in lipid control in mouse models of obesity and diabetes increase the efficacy of incretin-based therapy.

Associations of uric acid and gamma-glutamyltransferase (GGT) with obesity and components of metabolic syndrome in children and adolescents.

BACKGROUND: The combined effect of uric acid, gamma-glutamyltransferase (GGT) and cardiovascular risk factors clustering in the youth remains under-explored. OBJECTIVE: The objective of this study was to examine the association between uric acid, GGT, obesity and the individual components of metabolic syndrome in children and adolescents. METHODS: We performed a cross-sectional observational study of 2067 children and adolescents (875 boys and 1192 girls) aged 6-20 years who were healthy volunteers and were recruited from primary and secondary schools in Hong Kong between 2007 and 2008. Subjects were divided into two strata (75th percentile as cut-off) for comparison between odds of cardiovascular risk factors. RESULTS: After adjustment by multivariable logistic regression, subjects in upper stratum, i.e., >75th percentile, of either serum uric acid or GGT levels were associated with obesity, low high-density lipoprotein cholesterol (HDL-C) level and high blood pressure (adjusted odds ratios [AOR] ranged from 1.63 to 5.82, all P < 0.005) compared with those in the lower stratum. There were combined effect for upper stratum of both uric acid and GGT in the association with obesity, low HDL-C and high blood pressure (AOR ranged from 2.60 to 10.69, all P < 0.05) after adjustment for age, sex and body mass index z-score (except for obesity status) as well as body height (for high blood pressure). CONCLUSION: Uric acid and GGT have combined effect in association with obesity and other cardiovascular risk factors in children and adolescents.

Association between KCNQ1 genetic variants and obesity in Chinese patients with type 2 diabetes.

AIMS/HYPOTHESIS: There is evidence of overlap between susceptibility loci for type 2 diabetes and obesity. The aim of this study is to explore the association between the established type 2 diabetes locus KCNQ1 and obesity in Han Chinese. METHODS: We recruited 6,667 and 6,606 diabetic case-control samples from Shanghai and Hong Kong, respectively. Of the samples, 7.5% and 6.3% were excluded because of genotyping failure or data missing in the association analyses of rs2237892 and rs2237895 with obesity/BMI, respectively. RESULTS: We found that rs2237892 was associated with lower BMI and lower incidence of overweight/obesity in diabetic patients from Hong Kong (BMI, ß = -0.0060 per diabetes risk C allele for log(10)BMI [95% CI -0.0088, -0.0032; p = 2.83 × 10(-5)]; overweight/obesity, OR 0.880 for C allele [95% CI 0.807, 0.960; p = 0.004]) and in the meta-analysis of cases from the two regions (BMI, combined ß = -0.0048 per C allele for log(10)BMI [95% CI -0.0070, -0.0026; p = 2.20 × 10(-5)]; overweight/obesity, combined OR 0.890 for C allele [95% CI 0.830, 0.955; p = 0.001]). rs2237895 was also related to decreased BMI (combined ß = -0.0042 per diabetes risk C allele for log(10)BMI [95% CI -0.0062, -0.0022; p = 4.30 × 10(-5)]). A significant association with waist circumference was detected for rs2237892 in the pooled analyses (ß = -0.0026 per C allele for log(10)[waist circumference] [95% CI -0.0045, -0.0007; p = 0.007]). However, neither an association with the risk of being overweight or obese nor associations with quantitive traits were detected for rs2237892 or rs2237895 in controls. CONCLUSION: Our findings indicate that KCNQ1 is associated with obesity in Chinese patients with type 2 diabetes.

Self-reported waist circumference: a screening tool for classifying children with overweight/obesity and cardiometabolic risk factor clustering.

OBJECTIVES: The objectives of this study were twofold - (i) to assess the agreement between self-reported waist circumference (SRWC) and assessor measured waist circumference (MWC) and (ii) to evaluate the diagnostic ability of SRWC for classifying (i) a clustering of cardiometabolic risk factors (CMRFs) and (ii) overweight/obese status in Hong Kong Chinese children aged 6-18 years. METHODS: A cross-sectional study with cluster random sampling was conducted. A self-administrated questionnaire, which included demographic data, body weight, body height and waist circumference, was given to children to bring home for completion. Children were asked to return the questionnaire and fast themselves for at least 8 h on the day of the survey. Anthropometric measurements and blood pressure were taken by trained research staff and fasting blood samples were collected for measurements of fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. RESULTS: A total of 515 boys and 711 girls were included in the data analysis. Agreement between SRWC and MWC was assessed by intra-class correlation coefficient and it ranged from 0.77 to 0.87. The ability of sex-specific SRWC values to classify children with a clustering of CMRFs and overweight/obesity exhibited moderately high to high sensitivity and specificity, and the area under the receiver operating characteristics ranged from acceptable to excellent (from 0.76 to 0.84). CONCLUSIONS: SRWC has good agreement with MWC and could be used as a screening tool to classify children with a clustering of CMRFs and overweight/obesity status in Hong Kong Chinese children.

A systematic review on use of Chinese medicine and acupuncture for treatment of obesity.

Obesity is a major health hazard and despite lifestyle modification, many patients frequently regain any lost body weight. The use of western anti-obesity drugs has been limited by side effects including mood changes, suicidal thoughts, and gastrointestinal or cardiovascular complications. The effectiveness and safety of traditional Chinese medicine including Chinese herbal medicine (CHM) and acupuncture provide an alternative established therapy for this medical challenge. In this systematic review, we used standard methodologies to search, review, analyse and synthesize published data on the efficacy, safety and relapse of weight regain associated with use of CHM and acupuncture. We also examined the rationale, mechanisms and potential utility of these therapies. A total of 12 electronic databases, including Chinese, English, Korean and Japanese, were searched up to 28 February 2010. Randomized controlled trials (RCTs) for CHM and/or acupuncture with comparative controls were considered. We used the Jadad scale to assess methodological qualities, the random effect model in the pooled analysis of therapeutic efficacy to adjust for heterogeneity and funnel plots to explore publication bias. After screening 2,545 potential articles from the electronic databases, we identified 96 RCTs; comprising of 49 trials on CHM treatment, 44 trials on acupuncture treatment and 3 trials on combined therapy for appraisal. There were 4,861 subjects in the treatment groups and 3,821 in the control groups, with treatment duration ranging from 2 weeks to 4 months. Of the 77 publications written in Chinese, 75 had a Jadad score <3, while 16 of the 19 English publications had a Jadad score of >3. Efficacy was defined as body weight reduction ≥ 2 kg or body mass index (BMI) reduction ≥ 0.5 kg/m(2) . Compared with placebo or lifestyle modification, CHM and acupuncture exhibited respective 'risk ratio' (RR) of 1.84 (95% CI: 1.37-2.46) and 2.14 (95% CI: 1.58-2.90) in favour of body weight reduction, with a mean difference in body weight reduction of 4.03 kg (95% CI: 2.22-5.85) and 2.76 kg (95% CI: 1.61-3.83) and a mean difference in BMI reduction of 1.32 kg m(-2) (95% CI: 0.78-1.85) and 2.02 kg m(-2) (95% CI: 0.94-3.10), respectively. Compared with the pharmacological treatments of sibutramine, fenfluramine or orlistat, CHM and acupuncture exhibited an RR of 1.11 (95% CI: 0.96-1.28) and 1.14 (95% CI: 1.03-1.25) in body weight reduction, mean difference in body weight reduction of 0.08 kg (95% CI: -0.58 to 0.74) and 0.65 kg (95% CI: -0.61 to 1.91), and mean difference in BMI reduction of 0.18 kg m(-2) (95% CI: -0.39 to 0.75) and 0.83 kg m(-2) (95% CI: 0.29-1.37), respectively. There were fewer reports of adverse effects and relapses of weight regain in CHM intervention studies conducted in China than studies conducted outside China. CHM and acupuncture were more effective than placebo or lifestyle modification in reducing body weight. They had a similar efficacy as the Western anti-obesity drugs but with fewer reported adverse effects. However, these conclusions were limited by small sample size and low quality of methodologies.

Circulating LL-37 is a biomarker for eczema severity in children.

BACKGROUND: Eczema lesions are characterized by impaired expression of antimicrobial peptides such as cathelicidin, which play crucial roles in the innate immune defence against cutaneous infections. LL-37 corresponds to amino acids 134-170 of human cathelicidin and is a multifunctional host defence molecule essential for normal immune responses to infection and tissue injury. OBJECTIVES: The aim of this study was to investigate the relationship between childhood eczema and circulating LL-37 levels. METHODS: One hundred and forty-four eczema children and 36 controls were recruited. Eczema severity was assessed by SCORing Atopic Dermatitis (SCORAD) and serum LL-37 concentration measured using enzyme immunoassay. Patients' skin hydration and transepidermal water loss at forearms were measured using Corneometer and Tewameter. RESULTS: Patients' mean SCORAD was 49.2 and their disease was classified as mild (n=28; 12.8%), moderate (n=95; 43.6%) and severe (n=95; 43.6%). Serum LL-37 concentrations did not differ between eczema patients and controls (mean: 832 pg/mL vs. 952 pg/mL, P=0.471). However, serum LL-37 concentrations increased with increasing eczema severity among the patients (P=0.005 for trend). This biomarker shows weakly positive correlation with patients' objective SCORAD (r=0.207, P=0.013) and age (r=0.170, P=0.041), but not skin hydration or transepidermal water loss (P>0.09). Linear regression confirmed significant association between objective SCORAD and serum LL-37 when adjusted for age and gender as covariates (ß=0.171, P=0.038). On the other hand, serum LL-37 did not differ between patients with and without heavy growth of staphylococci (P=0.151). CONCLUSIONS: Circulating LL-37 may be a biomarker for severity of childhood eczema, which supports the importance of innate immunity in eczema pathogenesis.

Addressing different biases in analysing drug use on cancer risk in diabetes in non-clinical trial settings--what, why and how?

Motivated by recent reports on associations between diabetes and cancer, many researchers have used administrative databases to examine risk association of cancer with drug use in patients with diabetes. Many of these studies suffered from major biases in study design and data analysis, which can lead to erroneous conclusions if these biases are not adjusted. This article discusses the sources and impacts of these biases and methods for correction of these biases. To avoid erroneous results, this article suggests performing sensitivity and specificity analysis as well as using a drug with a known effect on an outcome to ascertain the validity of the proposed methods. Using the Hong Kong Diabetes Registry, we illustrated the impacts of biases of drug use indication and prevalent user by examining the effects of statins on cardiovascular disease. We further showed that 'immortal time bias' may have a neutral impact on the estimated drug effect if the hazard is assumed to be constant over time. On the contrary, adjustment for 'immortal time bias' using time-dependent models may lead to misleading results biased towards against the treatment. However, artificial inclusion of immortal time in non-drug users to correct for immortal time bias may bias the result in favour of the therapy. In conclusion, drug use indication bias and prevalent user bias but not immortal time bias are major biases in the design and analysis of drug use effects among patients with diabetes in non-clinical trial settings.

PP103. Arterial stiffness in women with previous GDM - A follow up of Chinese HAPO study cohort.

INTRODUCTION: It is well known that women with history of gestational diabetes (GDM) are at risk of future DM. Whether they are at a higher risk of hypertension and cardiovascular risk remained to be determined. OBJECTIVES: To determine whether Chinese women who have been diagnosed GDM according to the new IADPSG criteria have a higher risk of hypertension & arterial stiffness than women with normal glucose tolerance (NGT) during pregnancy. METHODS: Chinese women who had participated in the HAPO study between 2001 and 2006 in Hong Kong were followed up at a median of 6years postpartum. All underwent anthropometric & BP measurements. Central systolic and diastolic blood pressures (SBP & DBP), augmentation index (AI) and pulse wave velocity (PWV) were assessed by using SphygmoCor(®) PVx.A total of 608 women (494 NGT, 114 GDM) were followed up till early 2012. RESULTS: Although there was no significant difference in the rate of hypertension, the central SBP (106±12 vs 102±13mmHg, p=0.03), AI (22.1±8.3 vs 18.9±8.5%, p<0.001) and PWV (6.8±1.0 vs 6.6±0.8, p=0.03) were all higher in women with history of GDM. CONCLUSION: The findings suggest a higher risk of subclinical atherosclerosis amongst women with GDM despite the blood pressure may appear normal at the time of follow up.