P. C. Y. Tong

Erectile Dysfunction Predicts Coronary Heart Disease in Type 2 Diabetes

OBJECTIVES We examined the predictive power of erectile dysfunction (ED) on coronary heart disease (CHD) events in Chinese men with type 2 diabetes. BACKGROUND Subjects with diabetes are prone to develop cardiovascular complications. Erectile dysfunction is strongly associated with CHD in cross-sectional studies, but prospective data are lacking. METHODS A consecutive cohort of men with no clinical evidence of cardiovascular disease underwent comprehensive assessments for diabetic complications. Erectile dysfunction was defined according to the definition of the National Institutes of Health Consensus Conference 1992. Coronary heart disease events were censored with centralized territory-wide hospital databases in 2005. RESULTS Of 2,306 subjects (age: 54.2 +/- 12.7 years; follow-up: 4.0 [range 1.7 to 7.1] years), 26.7% had ED at baseline. The incidence of CHD events was higher in men with ED than those without (19.7/1,000 person-years, 95% confidence interval [CI] 14.3 to 25.2 person-years vs. 9.5/1,000 person-years, 95% CI 7.4 to 11.7 person-years). Men who developed CHD events were older; had a higher frequency of ED and microvascular complications; had longer duration of diabetes; and had higher blood pressure, total cholesterol, low-density lipoprotein cholesterol, and urinary albumin/creatinine ratio but lower high-density lipoprotein cholesterol and estimated glomerular filtration rate than those without CHD events. Erectile dysfunction remained an independent predictor for CHD events (hazard ratio 1.58, 95% CI 1.08 to 2.30, p = 0.018) after adjustment for other covariates along with age, duration of disease, and use of antihypertensive agents and albuminuria. CONCLUSIONS In type 2 diabetic men without clinically overt cardiovascular disease, the presence of ED predicts a new onset of CHD events. Symptoms of ED should be independently sought to identify high-risk subjects for comprehensive cardiovascular assessments.

The central roles of obesity-associated dyslipidaemia, endothelial activation and cytokines in the Metabolic Syndrome--an analysis by structural equation modelling.

Hypothesis: The multi-faceted components of the metabolic syndrome now include markers of inflammation and endothelial activation. Despite this growing body of epidemiological data, standard statistical methods fail to evaluate the nature of these associations adequately. In this pilot study, we hypothesize that obesity may lead to endothelial activation which is in part mediated by dyslipidaemia and proinflammatory cytokines. These factors interact to give rise to hyperinsulinaemia, hypertension and an anti-fibrinolytic state. To test this hypothesis, we used confirmatory factor analysis and structural equation modelling to fit these data to a model designed on theoretical grounds.Methods: Metabolic syndrome variables, cytokines (IL6 and TNFα), markers of inflammation and endothelial activation were measured in 107 Caucasian non-diabetic subjects aged 40–75 y. Using confirmatory factor analysis, we identified six factors to represent composite measurements of blood pressure, obesity, dyslipidaemia, hyperinsulinaemia, endothelial activation and the anti-fibrinolytic state. We fitted these variables to two separate models, one using IL-6 and the other TNFα as the cytokine, and examined the inter-relationships (path analysis) amongst these variables, based on the above hypothesis.Results: Men were centrally more obese and had increased markers of endothelial activation, inflammation and the anti-fibrinolytic state as well as hyperinsulinaemia and dyslipidaemia, compared with women. Obesity indexes (both body mass index and waist–hip ratio) were strongly associated with multiple cardiovascular risk factors. Both IL6 and TNFα were correlated with age, male gender, obesity indexes and markers of endothelial activation. Only IL-6 was associated with smoking while TNFα was correlated with hyperinsulinaemia. In the TNFα model, 61% of the obesity variance was explained by male gender, 36% of TNFα variance by age and dyslipidaemia, 43% of dyslipidaemia variance by age and obesity, 33% of hyperinsulinaemia variance by dyslipidaemia and a non-smoking state, 29% of anti-fibrinolytic state variance by hyperinsulinaemia, 65% of endothelial activation variance by TNFα, dyslipidaemia and hyperinsulinaemia, 34% of blood pressure variance by hyperinsulinaemia and endothelial activation. In the IL-6 model, we observed similar relationships except that 23% of IL6 variance was explained by smoking and age.Conclusions: Using confirmatory factor analysis and structural equation modelling, we found that obesity, dyslipidemia and cytokines were the principal explanatory variables for the various components of the metabolic syndrome, with IL6 and TNFα having different explanatory variables and effects. These complex inter-relationships were in part mediated by hyperinsulinaemia and endothelial activation. While this hypothetical model was based on scientific evidence, supported by rigorous analysis, it requires further confirmation in large-scale prospective studies. Given the complexity of the biological system and its interactions with exogenous factors, structural equation modelling provides a useful scientific tool for hypothesis testing, complementary to the more traditional experimental and cohort studies.

Glucose Intolerance and Cardiometabolic Risk in Children Exposed to Maternal Gestational Diabetes Mellitus in Utero

OBJECTIVE. The goal was to examine the carbohydrate tolerance and cardiometabolic risk among children exposed to maternal gestational diabetes mellitus in utero. METHODS. In this study, 164 Chinese children whose mothers had participated in a previous study on the screening and diagnosis of gestational diabetes mellitus (63 had gestational diabetes mellitus and 101 had normal glucose tolerance during the index pregnancies) underwent follow-up evaluations at a median age of 8 years (range: 7–10 years). Childrens weight, height, hip and waist circumferences, and blood pressure were measured, and weight-adjusted oral glucose tolerance tests were performed. RESULTS. Six children (3.7%) demonstrated impaired glucose regulation or diabetes mellitus at the follow-up evaluation. Children exposed to maternal gestational diabetes mellitus had significantly higher systolic (94 ± 1.2 vs 88 ± 0.9 mmHg) and diastolic (62 ± 0.8 vs 57 ± 0.6 mmHg) blood pressure values and lower high-density lipoprotein cholesterol (1.58 ± 0.04 vs 1.71 ± 0.03 mmol/L) levels, after adjustment for age and gender. A high (≥90th percentile) umbilical cord insulin level at birth was associated with abnormal glucose tolerance in the offspring. CONCLUSIONS. Maternal gestational diabetes mellitus increases the offsprings cardiometabolic risk, and in utero hyperinsulinemia is an independent predictor of abnormal glucose tolerance in childhood.

Phenotypic and genetic clustering of diabetes and metabolic syndrome in Chinese families with type 2 diabetes mellitus

The aim of this study was to investigate the familiality and clustering of type 2 diabetes (T2DM) and metabolic syndrome (MES) predominantly in families with young‐onset diabetes from the Hong Kong Family Diabetes Study.

Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with nephropathy

Cytokine‐induced inflammation is involved in the pathogenesis of type 2 diabetes mellitus (DM). We investigated plasma concentrations and ex vivo production of cytokines and chemokines, and intracellular signalling molecules, mitogen‐activated protein kinases (MAPK) in T helper (Th) cells and monocytes in 94 type 2 diabetic patients with or without nephropathy and 20 healthy controls. Plasma concentrations of inflammatory cytokines tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, IL‐18 and chemokine CCL2 in patients with diabetic nephropathy (DN) were significantly higher than control subjects, while IL‐10, CXCL8, CXCL9, CXCL10 and adiponectin concentrations of DN were significantly higher than patients without diabetic nephropathy (NDN) and control subjects (all P < 0·05). Plasma concentrations of TNF‐α, IL‐6, IL‐10, IL‐18, CCL2, CXCL8, CXCL9, CXCL10 and adiponectin exhibited significant positive correlation with urine albumin : creatinine ratio in DN patients. The percentage increases of ex vivo production of IL‐6, CXCL8, CXCL10, CCL2 and CCL5 upon TNF‐α activation were significantly higher in both NDN and DN patients than controls (all P < 0·05). The percentage increases in IL‐18‐induced phosphorylation of extracellular signal‐regulated kinase (ERK) in Th cells of NDN and DN were significantly higher than controls (P < 0·05), while the percentage increase in TNF‐α‐induced phosphorylation of p38 MAPK in monocytes and IL‐18‐induced phosphorylation of p38 MAPK in Th cells and monocytes were significantly higher in NDN patients than controls. These results confirmed that the aberrant production of inflammatory cytokines and chemokines and differential activation of MAPK in different leucocytes are the underlying immunopathological mechanisms of type 2 DM patients with DN.

Cardiovascular risks and metabolic syndrome in Hong Kong Chinese women with polycystic ovary syndrome

BACKGROUND Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidaemia and hypertension which are characteristic features of the metabolic syndrome (MetS). METHODS A total of 295 premenopausal Chinese women with PCOS diagnosed by the Rotterdam criteria (mean age: 30.2 +/- 6.4 years) and 98 control subjects without PCOS were evaluated for prevalence of MetS and cardiovascular risk factors, including dyslipidaemia and dysglycaemia. RESULTS Using the 2005 modified Adult Treatment Panel III criteria, MetS (presence of three or more risk factors) was found in 24.9% of PCOS women compared to 3.1% of controls. The prevalence of MetS in PCOS women increased from 16.7% at under 30 years of age to 53.3% at over 40 years. MetS was also more prevalent in overweight and obese (41.3%) than normal-weight PCOS women (0.9%). However, multivariate regression analysis showed that women with PCOS had a 5-fold increase in risk of MetS (odds ratio 4.90; 95% confidence interval: 1.35-17.84) compared with women without PCOS even after controlling for age and BMI, suggesting PCOS alone is an independent risk factor for MetS. CONCLUSIONS There is high prevalence of MetS in Hong Kong Chinese women with PCOS despite their relatively young age. Recognition of these cardiometabolic risk factors requires a high level of awareness in conjunction with early and regular screening.

The associations of body mass index, C-peptide and metabolic status in Chinese Type 2 diabetic patients.

Background  Chinese Type 2 diabetic subjects are generally less obese than their Caucasian counterparts. We hypothesized that lean and obese Chinese Type 2 diabetic subjects have different metabolic and insulin secretory profiles. We compared the clinical features, C peptide and metabolic status between lean/normal weight and obese diabetic subjects.

Chronic hepatitis B viral infection independently predicts renal outcome in type 2 diabetic patients.

Aims/hypothesisWe examined the association between chronic hepatitis B virus (HBV) infection and clinical outcomes in a consecutive cohort of Chinese patients with type 2 diabetes.Subjects, materials and methodsBetween 1995 and 1999, 2,838 type 2 diabetes patients underwent comprehensive assessments and blood screening for hepatitis B surface antigen (HBsAg). The risk of occurrence of cardiovascular events and end-stage renal disease (defined as need for dialysis, doubling of serum creatinine or serum creatinine ≥500 μmol/l) was compared between HBsAg-positive and HBsAg-negative groups.ResultsAt baseline, HBV-infected patients (n=286, 10.1%) were younger (51.0±11.5 vs 53.7±12.7 years, p=0.004), had earlier onset of diabetes (51.0±11.5 vs 53.7±12.7 years, p=0.001) and a higher frequency of retinopathy (28 vs 22%, p=0.03) than non-HBV-infected patients. After a median follow-up of 3.5 years (interquartile range: 1.7–5.9 years) and adjustment of age, glycaemic control and other potential confounding factors, HBV-infected patients were more likely to develop end-stage renal disease than non-HBV infected patients (8.7 vs 6.4%) with a hazard ratio of 4.5 (95% CI 1.1–18.6). The difference in the frequency of cardiovascular endpoints was not statistically significant.ConclusionsIn Chinese type 2 diabetes patients, chronic HBV infection was associated with increased risk of end-stage renal disease, and this was independent of other potential confounding factors. Early identification of HBV status and close surveillance of renal function are important in patients with type 2 diabetes who are living in areas where HBV is endemic or who are at risk of chronic HBV infection.

Triglyceride predicts cardiovascular mortality and its relationship with glycaemia and obesity in Chinese type 2 diabetic patients.

To examine the lipid profile in Chinese type 2 diabetic patients and their relationship with anthropometric parameters, glycaemic control and cardiovascular mortality.

The Joint Asia Diabetes Evaluation (JADE) Program: a web-based program to translate evidence to clinical practice in Type 2 diabetes

Aims  The Joint Asia Diabetes Evaluation (JADE) Program is the first web‐based program incorporating a comprehensive risk engine, care protocols, clinical decision and self‐management support to improve ambulatory diabetes care. The aim was to validate the risk stratification system of the JADE Program using a large prospective cohort.