Association of short-term and long-term weight loss with the risk of major adverse cardiovascular disease: Community-based cohort study.

BACKGROUND: This study evaluated temporal association of changes in BMI over time with major adverse cardiovascular event (MACE) in Korean middle-aged adults. METHODS: Between 2001 and 2002, 6855 individuals from the Korean Genome and Epidemiology Study were included and followed up until 2014. The main predictor was the change in BMI determined using group-based trajectory modelling (decreasing, stable, and increasing) from the baseline to 4-, 6-, and 8-years of follow-up. The primary outcome was the occurrence of MACE. RESULTS: During the mean 10.2 years follow-up, MACEs occurred in 350 (5.1 %) individuals. The median (interquartile rage) age of study population was 50 (44-59) years. In primary analysis with 4-year trajectory model, decreasing BMI trajectory was associated with a 1.41-fold higher risk of the MACEs (hazard ratio [HR], 1.41; 95 % confidence interval [CI], 1.06-1.91) compared with stable BMI trajectory. In secondary analyses with 6- and 8-year trajectory models, this association disappeared, and the corresponding HRs (95 % CIs) were 1.14 (0.81-1.61) and 0.98 (0.65-1.49), respectively. There were concomitant improvements in cardiometabolic risk factors in decreasing BMI group, but unfavorable risk burden remained up to 4 to 6 years. CONCLUSIONS: The initial 4-year weight loss was paradoxically associated with a higher risk of MACEs, probably due to residual cardiovascular burden. However, this association became null in participants with sustained weight loss ≥ 6 years, suggesting a possible lag effect of weight loss on MACEs.

Excess mortality among patients on dialysis: Comparison with the general population in Korea.

BACKGROUND: Although patients with end-stage renal disease (ESRD) experience excess mortality compared with the general population, the standardized mortality ratio (SMR) for Korean patients on dialysis has not yet been investigated. In this study, we evaluated the SMR among all Korean ESRD patients on maintenance dialysis in 2009 and 2010, and compared it according to age categories, sex, and dialysis modality. METHODS: We used data from all patients on maintenance dialysis between January 1, 2009 and December 31, 2010 in Korea using the database of the Korean Health Insurance Review and Assessment Service, and the SMR was determined by calculating of the ratio between the number of actual deaths and expected deaths. RESULTS: A total of 45,568 patients in 2009 and 48,170 patients in 2010 were included in the analysis. The overall age- and sex-adjusted SMR was 10.3 [95% confidence interval (CI), 10.0-10.6] in 2009 and 10.9 (95% CI, 10.7-11.2) in 2010. The SMR for females was much higher than for males. The SMR gradually decreased with increasing age groups. The overall SMR for maintenance hemodialysis patients was lower than that of peritoneal dialysis patients. CONCLUSION: The SMR among Korean ESRD patients is likely to be higher than in other countries. Further evaluation is needed to attempt to improve the outcomes.

Epigenetic modifications in the pathogenesis of diabetic nephropathy.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Diabetic vascular complications such as DN can progress despite subsequent glycemic control, suggesting a metabolic memory of previous exposure to hyperglycemia. Diabetes profoundly impacts transcription programs in target cells through activation of multiple signaling pathways and key transcription factors leading to aberrant expression of pathologic genes. Emerging evidence suggests that these factors associated with the pathophysiology of diabetic complications and metabolic memory also might be influenced by epigenetic mechanisms in chromatin such as DNA methylation, histone lysine acetylation, and methylation. Key histone modifications and the related histone methyltransferases and acetyltransferases have been implicated in the regulation of inflammatory and profibrotic genes in renal and vascular cells under diabetic conditions. Advances in epigenome profiling approaches have provided novel insights into the chromatin states and functional outcomes in target cells affected by diabetes. Because epigenetic changes are potentially reversible, they can provide a window of opportunity for the development of much-needed new therapies for DN in the future. In this review, we discuss recent developments in the field of epigenetics and their relevance to diabetic vascular complications and DN pathogenesis.