FTO-rs9939609 Polymorphism is a Predictor of Future Type 2 Diabetes: A Population-Based Prospective Study.

The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective study included 1443 nondiabetic subjects at baseline, and they were examined for developing T2D after 5-year follow-up. Cox proportional hazards model was used to evaluate the hazard ratio (HR) of rs9939609 to the future T2D in the models adjusted for the confounding factors including socio-economic status, lifestyle factors (smoking and drinking history, sporting habits, and leisure time), and clinical patterns (obese status, blood pressures, and dyslipidemia) at baseline. The area under receiver operating characteristic curve (AUC) was used to measure the power to predict individuals with T2D. The FTO-rs9939609 polymorphism was a significant predictor of future T2D in the model unadjusted, and it remained significant in the final model after adjustment for the confounding factors, showing an additive effect of the A-allele (HR = 1.35, 95% CI = 1.02-1.78, P = 0.036, AUC = 0.676). For normoglycemic subjects at baseline, the similar final adjusted model reported the increased HR per A-allele (HR = 1.50, 95% CI = 1.09-2.07, P = 0.012, AUC = 0.697). Five-year changes in BMI, waist circumference, and systolic blood pressure did not remove the contribution of rs9939609 to increased HR of T2D. The population attributable risk for risk genotype was 13.6%. In conclusion, the study indicates that the FTO-rs9939609 polymorphism is an important genetic predictor for future T2D in Vietnamese population.

Protease-Activated Receptor-2 Plays a Critical Role in Vascular Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice.

BACKGROUND: The coagulation system is closely linked with vascular inflammation, although the underlying mechanisms are still obscure. Recent studies show that protease-activated receptor (PAR)-2, a major receptor of activated factor X, is expressed in both vascular cells and leukocytes, suggesting that PAR-2 may contribute to the pathogenesis of inflammatory diseases. Here we investigated the role of PAR-2 in vascular inflammation and atherogenesis. METHODS: We generated apolipoprotein E-deficient ( ApoE-/-) mice lacking systemic PAR-2 expression ( PAR-2-/- ApoE-/-). ApoE-/- mice, which lack or express PAR-2 only in bone marrow (BM) cells, were also generated by BM transplantation. Atherosclerotic lesions were investigated after 20 weeks on a Western-type diet by histological analyses, quantitative reverse transcription polymerase chain reaction, and Western blotting. In vitro experiments using BM-derived macrophages were performed to confirm the proinflammatory roles of PAR-2. The association between plasma activated factor X level and the severity of coronary atherosclerosis was also examined in humans who underwent coronary intervention. RESULTS: PAR-2-/- ApoE-/- mice showed reduced atherosclerotic lesions in the aortic arch ( P<0.05) along with features of stabilized atherosclerotic plaques, such as less lipid deposition ( P<0.05), collagen loss ( P<0.01), macrophage accumulation ( P<0.05), and inflammatory molecule expression ( P<0.05) compared with ApoE-/- mice. Systemic PAR2 deletion in ApoE-/-mice significantly decreased the expression of inflammatory molecules in the aorta. The results of BM transplantation experiments demonstrated that PAR-2 in hematopoietic cells contributed to atherogenesis in ApoE-/- mice. PAR-2 deletion did not alter metabolic parameters. In vitro experiments demonstrated that activated factor X or a specific peptide agonist of PAR-2 significantly increased the expression of inflammatory molecules and lipid uptake in BM-derived macrophages from wild-type mice compared with those from PAR-2-deficient mice. Activation of nuclear factor-κB signaling was involved in PAR-2-associated vascular inflammation and macrophage activation. In humans who underwent coronary intervention, plasma activated factor X level independently correlated with the severity of coronary atherosclerosis as determined by Gensini score ( P<0.05) and plaque volume ( P<0.01). CONCLUSIONS: PAR-2 signaling activates macrophages and promotes vascular inflammation, increasing atherosclerosis in ApoE-/- mice. This signaling pathway may also participate in atherogenesis in humans.

CDKN2A-rs10811661 polymorphism, waist-hip ratio, systolic blood pressure, and dyslipidemia are the independent risk factors for prediabetes in a Vietnamese population.

BACKGROUND: People with prediabetes are at greater risk for heart attack, stroke, kidney disease, vision problems, nerve damage and high blood pressure, compared to those without the disease. Prediabetes is a complex disorder involving both genetic and environmental factors in its pathogenesis. This cross-sectional study aimed to investigate the independent risk factors for prediabetes, considering the contribution of genetic factors (TCF7L2-rs7903146, IRS1-rs1801278, INSR-rs3745551, CDKN2A-rs10811661, and FTO-rs9939609), socio-economic status, and lifestyle factors. RESULTS: Among the candidate genes studied, the CDKN2A-rs10811661 polymorphism was found to be the most significant factor associated with prediabetes in the model unadjusted and adjusted for age, sex, obesity-related traits, systolic blood pressure, dyslipidemia, socio-economic status, and lifestyle factors. In the final model, the CDKN2A-rs10811661 polymorphism (OR per T allele = 1.22, 95 % CI = 1.04-1.44, P = 0.017), systolic blood pressure (OR per 10 mmHg = 1.14, 95 % CI = 1.08-1.20, P < 0.0001), waist-hip ratio (OR = 1.25, 95 % CI = 1.10-1.42, P < 0.0001), dyslipidemia (OR = 1.57, 95 % CI = 1.15-2.14, P = 0.004), and residence (OR = 1.93, 95 % CI = 2.82-4.14, P < 0.0001) were the most significant independent predictors of prediabetes, in which the power of the adjusted prediction model was 0.646. CONCLUSIONS: The study suggested that the CDKN2A-rs10811661 polymorphism, waist-hip ratio, systolic blood pressure, and dyslipidemia were significantly associated with the increased risk of prediabetes in a Vietnamese population. The studied genetic variant had a small effect on prediabetes.

Knowledge and associated factors towards type 2 diabetes among a rural population in the Red River Delta region, Vietnam.

INTRODUCTION: Knowledge about type 2 diabetes (T2D) and attitude towards the condition are known to affect compliance and play an important role in diabetes management. T2D knowledge is a prerequisite for individuals and communities to take action on control of the disease. METHODS: A cross-sectional study was designed to identify knowledge and related factors towards T2D, risk factors, complications, prevention and treatment of the disease. A total of 2580 subjects representative of the general population aged 40-64 years was recruited from a typical province of Red River Delta region, Vietnam. The trained surveyors interviewed subjects directly to collect data, using a structured questionnaire. To evaluate the overall knowledge of T2D, 14 questions were used to calculate the 100 points. Total knowledge score was classified into the following four categories: highly insufficient (≤25 points), insufficient (26-50 points), satisfactory (51-75 points), and highly satisfactory (>75 points). Association between inadequate knowledge (<50 points) and variables was evaluated using multivariate logistic regression. RESULTS: The highly insufficient, insufficient, satisfactory, and highly satisfactory levels of the overall knowledge were 75, 17.9, 6.8, and 0.3%, respectively. Of the total population, more than 65% thought that there is no cure for diabetes, and more than 90% did not know the essential combination of drugs, diet, and physical activity in T2D treatment. Less than 10% of the population understood the concept of T2D, its risk factors, complications, approaches to prevention and treatment. The rural-urban difference of T2D knowledge was found in rates of understanding at least one risk factor (34.8% vs 63%), all the three methods for T2D prevention (1.7% vs 10.3%), and three combined approaches for T2D treatment (8.9% vs 16.4%). Age, residence, educational level, and occupation were the most significant factors associated with inadequate knowledge. CONCLUSIONS: The study shows a low level of diabetes knowledge among the general population aged 40-64 years in the Red River Delta, and significantly lower awareness in rural areas compared with urban areas. The limited awareness has indicated the urgent need for communication and education to improve the T2D knowledge of the Vietnamese population on risk factors, serious level, complications, prevention and treatment, taking into account the age, residence, educational level, and occupation of the subjects.

Metabolic syndrome among a middle-aged population in the Red River Delta region of Vietnam.

BACKGROUND: Metabolic syndrome (MetS) is a clustering of metabolic risk factors for cardiovascular diseases and type 2 diabetes. The study aimed to estimate the prevalence of MetS, its components, and their associations among rural middle-aged population in Vietnam. METHODS: A cross-sectional study with a representative sample (n = 2443) was conducted to collect data on demographic, socioeconomic, anthropometric, lifestyles, plasma glucose, and lipid profile. The age- and sex-adjusted prevalences of MetS and its components were calculated using the direct standardization. Associations of risk factors with MetS were evaluated using logistic regression, taken into account the confounding factors. RESULTS: The total age- and sex-adjusted prevalence (95% CI) of MetS was 16.3% (14.0 - 18.6). The most frequent component of MetS was high triglycerides (43.2%), followed by low HDL-C (42.0%), elevated blood pressure (29.2%), high plasma glucose (14.3%), and central obesity (12.3%). Of the total population, only 17.6% did not have any component of MetS and more than 40% had at least two MetS components. The association of MetS with residence, age, body mass index, marital status, and siesta time per day was statistically significant in univariate analysis and replicated in multivariate analysis. CONCLUSION: The MetS prevalence and its components are common and major public health burden in the middle-aged adults in Vietnam. Habitants living in urban, being never-married, having an increase in age, BMI, and siesta time per day are significantly associated with MetS, and they should be paid much more attention for screening and implementing preventive activities.

Incidence and prediction nomogram for metabolic syndrome in a middle-aged Vietnamese population: a 5-year follow-up study.

PURPOSE: We aimed to determine the incidence and prediction nomogram for new-onset metabolic syndrome (MetS) in a middle-aged Vietnamese population. METHODS: A population-based prospective study was conducted in 1150 participants aged 40-64 years without MetS at baseline and followed-up for 5 years. Data on lifestyle factors, socioeconomic status, family diabetes history, and anthropometric measures were collected. MetS incidence was estimated in general population and subgroup of age, gender, and MetS components. A Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for MetS. A prediction nomogram was developed and checked for discrimination and calibration. RESULTS: During median follow-up of 5.14 years, the accumulate MetS incidence rate was 23.4% (95% CI: 22.2-24.7). The annual incidence rate (95% CI) was 52.9 (46.7-60.1) per 1000 person-years in general population and higher in women [56.6 (48.7-65.9)] than men [46.5 (36.9-59.3)]. The HRs (95% CI) for developing MetS were gender [females vs males: 2.04 (1.26-3.29)], advanced age [1.02 (1.01-1.04) per one year], waist circumference [1.08 (1.06-1.10) per one cm] and other obesity-related traits, and systolic blood pressure [1.02 (1.01-1.03) per one mmHg]. The prediction nomogram for MetS had a good discrimination (C-statistics = 0.742) and fit calibration (mean absolute error = 0.009) with a positive net benefit in the predicted probability thresholds between 0.13 and 0.70. CONCLUSIONS: The study is the first to indicate an alarmingly high incidence of MetS in a middle-aged population in Vietnam. The nomogram with simply applicable variables would be useful to qualify individual risk of developing MetS.

Association of the common FTO-rs9939609 polymorphism with type 2 diabetes, independent of obesity-related traits in a Vietnamese population.

Type 2 diabetes (T2D) is a complex disorder resulting from both genetic and environmental factors in its pathogenesis. A case-control study was designed with subjects recruited from a general population to investigate whether the association between T2D and the common T>A polymorphism (rs9939609) in fat mass and obesity associated (FTO) gene is mediated by obesity-related measurements, considering the contribution of socio-economic status and lifestyle factors. The significant association between the FTO rs9939609 polymorphism and T2D was first observed in the model unadjusted (OR per A allele=1.61, 95% CI=1.06-2.44, P=0.024). It remained consistently replicated in the final model after adjustments for sex, age, systolic blood pressure, socio-economic status, lifestyle factors, and obesity-related measurements (body mass index, waist-hip ratio, body fat percentage, and body adiposity index), showing an increased T2D risk with an additive effect of the alleles (ORs per A allele=1.80-1.92, 95% CI=1.09-3.19, P<0.05). The FTO-rs9939609 polymorphism, systolic blood pressure, and waist-hip ratio were the most significant independent predictors for T2D, in which the power of the adjusted prediction model was 0.769. In conclusion, the study suggested that the FTO-rs9939609 polymorphism was significantly associated with the increased risk of T2D, independent of obesity-related measurements in a Vietnamese population.