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).

Diabetes in older people: position statement of The Hong Kong Geriatrics Society and the Hong Kong Society of Endocrinology, Metabolism and Reproduction.

Following a survey on the clinical practice of geriatricians in the management of older people with diabetes and a study of hypoglycaemia in diabetic patients, a round-table discussion with geriatricians and endocrinologists was held in January 2015. Consensus was reached for six domains specifically related to older diabetic people: (1) the considerations when setting an individualised diabetic management; (2) inclusion of geriatric syndrome screening in assessment; (3) glycaemic and blood pressure targets; (4) pharmacotherapy; (5) restrictive diabetic diet; and (6) management goals for nursing home residents.

Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. RESULTS: In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). CONCLUSIONS: The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia.

Natural history and outcome in Chinese patients with gastroenteropancreatic neuroendocrine tumours: - a 17-year retrospective analysis.

BACKGROUND: There is rising incidence of gastroenteropancreatic neuroendocrine tumours (GEP- NETs) in many parts of the world, but epidemiological data from Asian populations is rare. METHODS: We conducted a retrospective study in a tertiary medical centre in Hong Kong, using updated diagnostic criteria. The presentation, clinical features, and disease outcome were reviewed for all patients with GEP-NETs confirmed histopathologically at the Prince of Wales Hospital, the Chinese University of Hong Kong, between 1996 and 2013, according to the latest 2010 World Health Organization Classification. RESULTS: Among 126 patients, GEP- NETs were found in pancreas (34.9 %), rectum (33.3 %), and stomach (8.7 %), and most of them were non- functional GEP- NETs (91.3 %), mostly of grade 1 (G1) (87.3 %), and about 20 % had metastases on presentation. Age under 55 years, G1 tumours and absence of metastases were significant favourable predictors for survival in univariate analysis; whereas G2/3 tumours, size ≥2 cm, and metastases were significant predictors for disease progression (p < 0.05). In multivariate analysis, age and metastases on presentation were significant predictors of mortality (respective hazard ratios [HR] 1.05 [95 % confidence interval {CI} 1.02-1.08] and 6.52 [95 % CI 3.22-13.2]) and disease progression (respective HRs 1.05 [95 % CI 1.02-1.07] and 4.12 [95 % CI 1.96-8.68]), while higher tumour grade also independently predicted disease progression (HR 5.17 [95 % CI 2.05-13.05]) (all p < 0.05). CONCLUSION: Non-functional tumours with non-specific symptoms account for the vast majority of GEP-NETs in this Chinese series. Multidisciplinary approach in the management of patients with GEP-NETs may help improve the treatment efficacy and outcome.

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.

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.

An uncommon cause of Cushing's syndrome in a 70-year-old man.

Cushing's syndrome due to exogenous steroids is common, as about 1% of the general populations use exogenous steroids for various indications. Although endogenous Cushing's syndrome due to ectopic adrenocorticotropic hormone from a pancreatic neuroendocrine tumour is rare, a correct and early diagnosis is important. The diagnosis and management require high clinical acumen and collaboration between different specialists. We report a case of ectopic adrenocorticotropic hormone Cushing's syndrome due to pancreatic neuroendocrine tumour with liver metastasis. Early recognition by endocrinologists with timely surgical resection followed by referral to oncologists led to a favourable outcome for the patient up to 12 months after initial presentation.

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.

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.

Use of laparoscopic sleeve gastrectomy and adjustable gastric banding for suboptimally controlled diabetes in Hong Kong.

Bariatric surgery has recently been considered as an option for treatment of type 2 diabetes mellitus (T2DM). We assessed the effect of laparoscopic gastric banding and laparoscopic sleeve gastrectomy in a cohort of 39 T2DM Chinese patients with body mass index (BMI) over 30 kg/m(2) . Their mean body weights and BMI before surgery were 108 kg and 40 kg/m(2) , respectively, and 18 patients (46%) had suboptimal diabetic control (HbA1c >7%). After a mean follow-up of 27 months, 4 of 11 insulin-dependent patients (36%) were able to stop their insulin therapy, and 18 patients (46%) achieved remission of T2DM (HbA1c <6.5% without the use of medication). Glycaemic control remained poor in only nine other patients (27%). Logistic regression analysis showed that a short history of T2DM and high BMI could predict remission of diabetes after restrictive procedures. Our results suggest that restrictive surgery can significantly improve glycaemic control in obese T2DM patients.

Association of genetic variants of NOS1AP with type 2 diabetes in a Chinese population.

AIMS/HYPOTHESIS: Chromosome 1q21-q24 has been shown to be linked to type 2 diabetes. The International Type 2 Diabetes 1q Consortium showed that one of the nominal associations was located in the NOS1AP gene. Although this association was not replicated in additional samples of European descent, it remains unknown whether NOS1AP plays a role in Chinese individuals. METHODS: In stage 1 analyses, 79 single nucleotide polymorphisms (SNPs) of the NOS1AP gene were successfully genotyped in a group of Shanghai Chinese individuals, comprising 1,691 type 2 diabetes patients and 1,720 control participants. In stage 2 analyses, the SNP showing the strongest association was genotyped in additional Chinese individuals, including 1,663 type 2 diabetes patients and 1,408 control participants. RESULTS: In stage 1 analyses, 20 SNPs were nominally associated with type 2 diabetes (p < 0.05), with SNP rs12742393 showing the strongest association (OR 1.24 [95% CI 1.11-1.38]; p = 0.0002, empirical p = 0.019). Haplotype analysis also confirmed the association between rs12742393 and type 2 diabetes. In stage 2 analyses, the difference in allele frequency distribution of rs12742393 did not reach statistical significance (p = 0.254). However, the meta-analysis showed a significant association between rs12742393 and type 2 diabetes with an OR of 1.17 (95% CI 1.07-1.26; p = 0.0005). CONCLUSIONS/INTERPRETATION: Our data suggest that NOS1AP variants may not play a dominant role in susceptibility to type 2 diabetes, but a minor effect cannot be excluded.

Development and validation of equations estimating glomerular filtration rates in Chinese patients with type 2 diabetes.

Existing equations to calculate the estimated glomerular filtration rate (eGFR) were derived from nondiabetic Caucasian patients with chronic kidney disease. Here, we developed formulas to more accurately predict the eGFR in Chinese patients with type 2 diabetes and validated their performance in 202 type 2 diabetic and 46 nondiabetic individuals. Within the diabetic cohort, 135 were randomly assigned to a training group, whereas the remaining 67 diabetic and all of the nondiabetic patients were assigned to a validation group. Reference GFR was measured by (51)Cr-EDTA plasma clearance. The new eGFR-estimating formulas, derived using a stepwise regression model, were compared with existing prediction equations in the validation group. The formulas are: 313 x (Age)-0.494 (years) x [SCr]-1.059 (mg/dl) x [Alb]+0.485 (g/dl) for men, and 783 x (Age)-0.489 (years) x [SCr]-0.877 (mg/dl) x [SUN]-0.150 (mg/dl) for women. Compared with existing equations, the new formulas were more accurate and precise in calculating eGFR in diabetic patients, but, similar to other equations, were less accurate in the nondiabetic cohort. Our newly developed equations are simple to use and can be applied in routine clinical practice to calculate eGFR in Chinese patients with type 2 diabetes.

Independent predictive roles of eotaxin Ala23Thr, paraoxonase 2 Ser311Cys and beta-adrenergic receptor Trp64Arg polymorphisms on cardiac disease in Type 2 Diabetes--an 8-year prospective cohort analysis of 1297 patients.

AIMS: To examine the independent and joint effects of multiple genetic variants on a cardiac end-point in an 8-year prospective study of a Chinese diabetic cohort. METHODS: Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for inflammation, thrombosis, vascular tone regulation and lipid metabolism were genotyped in 1297 Chinese patients with no prior history of coronary heart disease (CHD) or heart failure at baseline. Cardiac end-point was defined by the occurrence of CHD and/or heart failure. RESULTS: In Cox regression model, after adjustment for baseline confounding variables including age, sex, smoking status, duration of diabetes, glycaemic control, lipid levels, waist circumference, blood pressure, albuminuria and estimated glomerular filtration rate, genetic variants, including Ala/Ala of SCYA11 (eotaxin) Ala23Thr, Cys/Cys or Cys/Ser of PON2 (paraoxonase 2) Ser311Cys and Arg/Arg of ADRB3 (beta3-adrenergic receptor) Trp64Arg, were independently associated with incident cardiac end-point, with respective hazard ratios (95% confidence interval) of 1.70 (1.10-2.61, P=0.037), 1.42 (1.08-1.88, P=0.013) and 3.84 (1.18-12.50, P=0.025). Analysis of the joint effect of the risk alleles showed significant increased risk of the cardiac end-point with increasing number of risk alleles (P<0.001). The adjusted risk for the cardiac end-point was 4.11 (P=0.002) for patients carrying four risk alleles compared with those carrying one or no risk allele. CONCLUSIONS: The independent risk conferred by genetic variants encoding pathways such as inflammation and lipid metabolism, not adequately reflected by conventional biomarkers, may identify high-risk individuals for intensified control of modifiable risk factors.

Association of the POU class 2 homeobox 1 gene (POU2F1) with susceptibility to Type 2 diabetes in Chinese populations.

AIMS: POU class 2 homeobox 1 (POU2F1), also known as octamer-binding transcription factor-1 (OCT-1), is a ubiquitous transcription factor that plays a key role in the regulation of genes related to inflammation and cell cycles. POU2F1 is located on chromosome 1q24, a region with linkage for Type 2 diabetes in Chinese and other populations. We examined the association of POU2F1 genetic variants with Type 2 diabetes in Hong Kong Chinese using two independent cohorts. METHODS: We genotyped five haplotype-tagging single nucleotide polymorphisms at POU2F1 in 1378 clinic-based patients with Type 2 diabetes and 601 control subjects, as well as 707 members from 179 families with diabetes. RESULTS: We found significant associations of rs4657652, rs7532692, rs10918682 and rs3767434 (OR = 1.26-1.59, 0.0003 < P(unadjusted) < 0.035) with Type 2 diabetes in the clinic-based case-control cohorts. Rs3767434 was also associated with Type 2 diabetes (OR = 1.55, P(unadjusted) = 0.013) in the family-based cohort. Meta-analysis revealed similar associations. In addition, the risk G allele of rs10918682 showed increased usage of insulin treatment during a mean follow-up period of 7 years [hazard ratio = 1.50 (1.05-2.14), P = 0.025]. CONCLUSIONS: Using separate cohorts, we observed consistent results showing the contribution of multiple variants at POU2F1 to the risk of Type 2 diabetes.

Evaluation of erectile dysfunction and associated cardiovascular risk using structured questionnaires in Chinese type 2 diabetic men.

Erectile dysfunction (ED) is not uncommon, but frequently underdiagnosed in type 2 diabetic men. In this study, we aimed to explore the frequency and severity of ED in Chinese type 2 diabetic men using a structured questionnaire. We furthermore sought to investigate the associations of ED with diabetes-related complications and metabolic indices. A consecutive cohort of 313 Chinese type 2 diabetic men aged between 25 and 76 years attending a diabetic centre were recruited between October 2006 and June 2007. Of the study population, the frequency of ED was 39.3% according to the National Institutes of Health (NIH) Consensus Conference criteria, compared with 84.3% (41.7% of them having moderate to severe ED) as diagnosed by International Index of Erectile Function (IIEF-5) questionnaire. After adjusting for potential confounding factors by multivariable logistic regression, ED defined by NIH criterion was associated with advanced age [OR = 1.05 (95% CI 1.01-1.09), p = 0.012], the presence of diabetic retinopathy [OR = 2.43 (95% CI 1.27-4.66), p = 0.008] and coronary heart disease [OR = 2.63 (95% CI 1.21-5.70), p = 0.015]. ED defined by IIEF-5 was associated with advanced age [OR = 1.12 (95% CI 1.06-1.17), p < 0.0001], use of insulin therapy [OR = 2.94 (95% CI 1.12-7.73), p = 0.029] and urinary albumin-creatinine ratio [OR = 2.29 (95% CI 1.05-5.01), p = 0.037]. In conclusion, ED was highly prevalent in Chinese type 2 diabetic men and was associated with multiple cardiovascular risk factors and complications. Advanced age, use of insulin therapy, the existence of microvascular complications such as retinopathy, albuminuria and coronary heart disease were associated with ED. NIH criteria diagnosed a much lower rate of ED compared with IIEF-5. Overall, structured questionnaires are useful and objective tools to detect ED, which should prompt a comprehensive risk assessment in these subjects.

Phenotype-genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling.

AIMS/HYPOTHESIS: Cardiovascular and renal diseases share common risk factors. We used structural equation modelling (SEM) to evaluate the independent and combined effects of phenotypes and genotypes implicated in cardiovascular diseases on renal function in type 2 diabetes. METHODS: 1,188 type 2 diabetic patients were stratified into high-risk and low-risk groups according to bimodal distributions of the logarithmically transformed (log(e)) urinary albumin:creatinine ratio and plasma creatinine levels. Models for these groups, comprising continuous and non-ranking categorical data, were developed separately to evaluate the inter-relationships among measured variables and latent factors using non-linear SEMs, Bayesian estimation and model selection as assessed by a goodness-of-fit statistic. RESULTS: Inter-correlated measured variables (obesity, glycaemia, lipid, blood pressure) and variants of the genes encoding endothelial nitric oxide synthase (NOS), beta-adrenergic receptor (ADRB), components of the renin-angiotensin system (RAS) and lipid metabolism were loaded onto their respective latent factors of phenotypes and genotypes. In addition to direct and indirect effects, latent factors of obesity, lipid and BP interacted with latent factors of ADRB and RAS genotypes to influence renal function. Together with variants of the genes encoding peroxisome proliferator-activated receptor gamma, atrial natriuretic peptide, adducin, G protein beta(3) subunit, epithelial sodium channel alpha subunit and matrix metallopeptidase 3, these parameters explained 39-80% of the variance in renal function in the high-risk and low-risk models. CONCLUSIONS/INTERPRETATION: SEM is a useful tool for confirming and quantifying multiple interactions of biological pathways with genetic determinants. The combined and interactive effects of blood pressure, lipid and obesity on renal function may have therapeutic implications, especially in type 2 diabetic individuals with genetic risk factors.