Association of Serum Homocysteine with Cardiovascular and All-Cause Mortality in Adults with Diabetes: A Prospective Cohort Study

Abstract

Background. Homocysteine (Hcy) was implicated in oxidative stress and diabetes biologically. However, the clinical evidence on the link between Hcy level and diabetes is limited and controversial. This study is aimed at investigating the association of serum Hcy with all-cause and cardiovascular mortality in diabetic patients. Methods. Serum Hcy was measured among 2,286 adults with type 2 diabetes in NHANES 1999-2006. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CIs for the association of Hcy with all-cause and cause-specific mortality. Results. Over a median follow-up of 11.0 (interquartile range, 8.9-13.4) years, 952 of the 2286 patients with diabetes died, covering 269 (28.3%) cardiovascular deaths and 144 (15.2%) cancer deaths. Restricted cubic spline showed the linear relationship between Hcy and all-cause mortality risk. After multivariate adjustment, higher serum Hcy levels were independently associated with increased risk of all-cause and cardiovascular mortality. Compared with participants in the bottom tertile of Hcy, the multivariate-adjusted HRs and 95% CI for participants in the top quartile were 2.33 (1.64-3.30) for all-cause mortality ( p trend < 0.001 ), 2.24 (1.22-4.10) for CVD mortality ( p trend = 0.017 ), and 2.05 (0.90-4.69) for cancer mortality ( p trend = 0.096 ). The association with total mortality was especially stronger among patients with albuminuria. Serum Hcy significantly improved reclassification for 10-year mortality in diabetic patients (net reclassification index = 0.253 and integrated discrimination improvement = 0.011 ). Conclusions. Serum Hcy was associated with risks of all-cause and cardiovascular mortality in diabetic adults. Our results suggested that Hcy was a promising biomarker in risk stratification among diabetic patients.

Associations between homocysteine, vitamin B12, and folate and the risk of all-cause mortality in American adults with stroke

“…Every 1 μmol/L increase in Hcy concentration increased mortality in these patients by 5.3%. Data specific to the stroke population are unavailable; however, previous studies of the general, non-stroke population have reported a higher all-cause mortality risk with high plasma Hcy levels ( 24 , 25 ). Many previous studies have reported the effect of Hcy levels on stroke prognosis and the results have been controversial ( 7 , 9 , 20 , 26 , 27 ).…”

SAH is a major metabolic sensor mediating worsening metabolic crosstalk in metabolic syndrome

“…During recent decades, HHcy has emerged as a critical metabolic component that worsens other metabolic risk factors, including hyperglycemia and hyperlipidemia (HL) [ 7 , 13 ] and was associated with increased risk of CVD and all-cause mortality [ 20 , 21 ].…”

“…Recent studies showed that HHcy is considered as a risk factor for cerebral infarction and is positively correlated with total cholesterol (TC), TG, low-density lipoprotein cholesterol LDL-C and fasting blood glucose levels in cerebral infarction patients [ 22 ]. Furthermore, HHcy has been recognized as a promising biomarker in risk stratification in diabetes [ 21 ] and a predictor of death in non-insulin-dependent diabetic patients [ 23 ].…”

Navigating the future of diabetes: innovative nomogram models for predicting all-cause mortality risk in diabetic nephropathy

“…Participants included adult patients with diabetes, excluding those who were pregnant. Diabetes was defined as a diagnosis of diabetes and the use of insulin or oral hypoglycemic agents, with fasting blood glucose levels greater than 7.0 mmol/L (126 mg/dL) or glycated hemoglobin A1c (HbA1c) levels exceeding 6.5% [ 15 ]. The diagnosis of diabetic nephropathy was established in diabetic patients with an albumin-to-creatinine ratio (ACR) ≥ 300 mg/g or an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m 2 [ 16 ].…”