(See https://diabetesjournals.org/care/article-abstract/45/6/1453/146867/Associations-of-Serum-Carotenoids-With-Risk-of?redirectedFrom=fulltext for details).
On May 3, 2022, Diabetes Care, an authoritative journal in diabetes, published online the latest research results of Professor Liu Gang's team from the School of Public Health entitled "Associations of Serum Carotenoids With Risk of Cardiovascular Mortality Among Individuals With Type 2 Diabetes". The study suggested that high concentrations of serum β-carotenoids were associated with an increased risk of cardiovascular disease (CVD) mortality in patients with diabetes. Zixin Qiu and Xue Chen, graduate students from the School of Public Health, were the co-first authors, and Prof. Gang Liu was the corresponding author.
The paper shows another important finding of the team based on the previous research on serum vitamin D, selenium, folic acid, and vitamin B12, low carbon and low-fat diet and other dietary factors, and the risk of cardiovascular disease, dementia, and premature death in patients with type 2 diabetes (T2D). This series of research results provide an essential scientific basis for dietary nutrition and health management of T2D patients.
T2D has become a public health problem worldwide. CVD is the primary cause of mortality among patients with diabetes. Therefore, it is crucial to explore the prevention strategies of CVD mortality in patients with T2D. Accumulating evidence has suggested that dietary factors play an essential role in preventing CVD mortality among patients with diabetes. Carotenoids, known as common natural antioxidants, are produced by plants and some microorganisms. However, the health effect of carotenoids, especially β-carotene, on CVD risk has been controversial, with some observational studies showing inverse associations between carotenoids and CVD, but several large randomized controlled trials (RCTs) raised concerns about the cardiovascular safety of high β-carotene supplements, especially in smokers. Some experimental studies also suggest that β-carotenoids may promote oxidation under certain conditions. However, among patients with diabetes who have elevated oxidative stress status and a higher risk of developing CVD, whether carotenoids status, especially β-carotene, would influence the cardiovascular outcomes of this particular population remains unclear.
This analysis included 3,107 individuals with T2D. During an average of 14 years of follow-up, 441 cardiovascular deaths occurred. After adjustment for or stratification by multiple confounding factors (i.e., lifestyles, dietary factors, glucose control, and blood lipids), higher concentrations of serum β-carotene, but not other individual carotenoids, were significantly associated with an increased risk of cardiovascular mortality among individuals with T2D.
When extreme quartiles of β-carotene were compared, the multivariable-adjusted HR was 2.47 (95% CI 1.62, 3.76) for cardiovascular mortality (P trend=0.002). According to the restricted cubic spline model, higher serum β-carotene concentrations were significantly associated with an elevated risk of cardiovascular mortality in a dose-response manner in the range of 65 nmol/L-950 nmol/L (P=0.001). After further adjustment of dietary β-carotene intakes, the association between serum β-carotene concentrations and CVD mortality remained largely unchanged, suggesting that the observed association seems unlikely to be dietary in origin but may be mainly attributed to β-carotene in supplements. This finding, if replicated, underscores the need to estimate the optimal serum β-carotene concentrations in individuals with T2D.
Folate (vitamin B9) and cobalamin (vitamin B12), involved in 1-carbon metabolism, are essential nutrients for nucleotide and amino acid biosynthesis. Folate and vitamin B12 deficiency has been associated with anemia and cardiovascular diseases (CVD) in general populations. Meanwhile, compared with healthy individuals, vitamin B12 deficiency is more common in patients with type 2 diabetes (T2D), owing to medication interactions (e.g., metformin) or malnutrition. However, the dose-response associations between serum folate and vitamin B12 levels with CVD mortality among patients with T2D remain unclear. To address these research gaps, this research group carried out relevant research.
The relevant results were published in JAMA Network Open on January 31, 2022, with the title "Associations of Serum Folate and Vitamin B12 Levels With Cardiovascular Disease Mortality Among Patients With Type 2 Diabetes". Yujie Liu (MBBS) and Tingting Geng (Ph.D.) were the co-first authors, and Professor Gang Liu was the corresponding author.
This cohort study enrolled 7700 patients with T2D for serum folate analysis and 4860 patients with T2D for serum vitamin B12 analysis. After an average follow-up of 9.2 years, through multivariable Cox proportional hazards regression models and stratified analysis (confounding factors controlling include age, gender, dietary factors, lifestyle, medication, blood glucose control status, etc.), we found that low levels of serum folate were associated with a higher risk of CVD mortality, and both low and high levels of serum vitamin B12 were associated with a higher risk of CVD mortality among T2D patients.
Nonlinear associations were observed for serum levels of folate and vitamin B12 with the risk of CVD mortality among patients with T2D through dose-response analysis. Compared with participants in the second quartile of serum folate levels (7.1-12.1 ng/mL), the risk for CVD mortality increased by 43% (HR: 1.43, 95%CI: 1.04-1.98) for participants in the lowest serum folate level quartile (<7.1 ng/mL). Compared with participants in the second quartile of serum vitamin B12 levels (369.1-506.0 pg/mL), the risk for CVD mortality increased by 74% (HR: 1.74, 95%CI: 1.20-1.52) for participants in the lowest quartile (<369.1 pg/mL), and 132% (HR: 2.32, 95% CI, 1.60-3.35) for participants in the highest quartile (≥703.5 pg/mL). In addition, serum folate was found to be more strongly associated with the risk of CVD mortality in T2D patients with poor glycemic control (HbA1c≥7.0%). These findings indicate that folate and vitamin B12, as modifiable dietary nutritional factors, may be used to prevent CVD mortality in T2D patients.
