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BACKGROUND: DNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design. METHODS: The participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively. RESULTS: In the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation. CONCLUSIONS: In this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/genética , Metilación de ADN , Estudios de Cohortes , Estudios LongitudinalesRESUMEN
OBJECTIVE: To understand the prevalence of hypertension and hyperlipidaemia as well as the current status of glycaemic control and its influencing factors among type 2 diabetes mellitus patients in the community in South China, and to provide recommendations for the prevention and control of diabetes. METHODS: Questionnaires, physical examinations and laboratory tests were conducted on patients with type 2 diabetes mellitus who participated in the National Basic Public Health Service Programme in Guangzhou in 2020. The chi-square test, t-test and multi-factor unconditional logistic regression analysis were performed using R 4.1.2 software. RESULT: Among 127,423 type 2 diabetic patients in Guangzhou, 57,695 achieved glycemic control standards, with a glycemic control rate of 45.28%.In this study, the proportion of T2DM patients with hypertension and hyperlipidaemia together was 27.79%, The percentage of T2DM patients with hypertension alone and hyperlipidaemia alone was 28.34% and 20.53% respectively, and the rate of no complications was 23.34%. There was a statistically significant difference in the rate of glycaemic control between the different disease combination states (P < 0.05). The glycaemic control rate was 47.67% in diabetic patients without hypertension and hyperlipidaemia, 52.54% and 37.24% in those with combined hypertension alone and hyperlipidaemia alone respectively, compared to 41.80% in diabetic patients with hypertension and hyperlipidaemia. After adjusting for all covariates, multivariate analysis showed that combined hypertension alone was associated with good glycaemic control (OR 0.817, 95% CI 0.791, 0.843, P < 0.001),when using comorbid T2DM as a control group, combined hyperlipidaemia alone, combined hypertension and hyperlipidaemia were associated with poor glycaemic control (OR 1.521, 95% CI 1.470,1.574, P < 0.001 and OR 1.250, 95% CI 1.211,1.291, P < 0.001), Subgroup analyses as well as multifactorial unconditional logistic regression analyses showed that patients with type 2 diabetes who were overweight and obese, smoked, drank alcohol, had a diagnosis of diabetes for ≥ 6 years, had fair or poor adherence and had a family history of diabetes had lower rates of glycaemic control. CONCLUSION: The results of this study showed that the co-morbidity of hypertension and hyperlipidaemia was high and prevalent among diabetic patients in Guangzhou. Moreover, glycaemic control of T2DM patients with hyperlipidaemia was lower than other diabetic patients. Obesity and overweight, poor lifestyle and dietary habits are also major factors affecting the treatment and control of T2D patients in this region. Therefore, comprehensive measures should be actively taken to control blood glucose levels in type 2 diabetic patients by also incorporating lipid management into the community and strictly controlling lipid levels.
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AIMS: This study investigated the association between serum calcium levels and the prevalence of T2D using a cross-sectional study and Mendelian randomization analysis. METHODS: Cross-sectional data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Serum calcium levels were divided into three groups (low, medium and high groups) according to the tertiles. Logistic regression was used to estimate the association between serum calcium levels and T2D prevalence. Instrumental variables for serum calcium levels were obtained from the UK Biobank and a two-sample MR analysis was performed to examine the causal relationship between genetically predicted serum calcium levels and the risk of T2D. RESULTS: A total of 39,645 participants were available for cross-sectional analysis. After adjusting for covariates, participants in the high serum calcium group had significantly higher odds of T2D (OR = 1.18, 95% CI = 1.07, 1.30, p = 0.001) than those in the moderate group. Restricted cubic spline plots showed a J-shaped curve relationship between serum calcium level and prevalence of T2D. Consistently, Mendelian randomization analysis showed that higher genetically predicted serum calcium levels were causally associated with a higher risk of T2D (OR = 1.16, 95% CI: 1.01, 1.33, p = 0.031). CONCLUSIONS: The results of this study suggest that higher serum calcium levels are causally associated with a higher risk of T2D. Further studies are needed to clarify whether intervening in high serum calcium could reduce the risk of T2D.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Estudios Transversales , Calcio , Encuestas Nutricionales , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma CompletoRESUMEN
BACKGROUND: Evidence indicates that the burden of sleep disorders is increasing, yet recent trends have not been examined. OBJECTIVE: To examine the prevalence of and trends in sleep patterns and medications commonly used for insomnia (MCUFI) in US adults from 2005 through 2018. METHODS: A total of 39,749 participants aged 20 years or older from 7 consecutive National Health and Nutrition Examination Survey cycles during 2005-2018 were included. RESULTS: The age-standardized prevalence of trouble sleeping and using MCUFI was higher in women than men, but men tended to sleep less (sleep duration <7 hours) and were more likely to have sleep disorders. The temporal trends in sleep disorders and MCUFI were similar in men and women, except that trouble sleeping increased more in men (P = 0.024). The prevalence of insufficient sleep decreased from 33.6% in women and 38.1% in men in 2005-2006 to 20.5% in women and 28.6% in men in 2017-2018. The prevalence of MCUFI use was 13.3% in women and 8.9% in men in 2005-2006, peaked at 15.2% for men and 17.0% for women in 2013-2014, and decreased slightly in 2015-2018. CONCLUSION: The prevalence of trouble sleeping and MCUFI use was higher in women, while the prevalence of short sleep duration and sleep disorders was higher in men. Sleep disorders, abnormal sleep duration, and MCUFI use increased at a broadly similar pace in men and women, except that trouble sleeping increased more in men.