Recently, Professor Liu Gang's research group from the school of Public Health has made some new progress in the associations of vitamin D with microvascular and macrovascular complications among patients with type 2 diabetes (T2D), the relevant results were published in the international authoritative journals Diabetes Care and American Journal of Clinical Nutrition, respectively.
On September 28th, the latest results of Professor Liu Gang's research group were published online in Diabetes Care, an authoritative journal in the field of diabetes, which entitled Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study. This study suggested that higher concentrations of serum 25 hydroxyvitamin D [25(OH)D] were significantly associated with decreased risk of microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. In addition, vitamin D receptor (VDR) gene polymorphisms showed effect modification of the risk of microvascular complications. Chen Xue, a master’s degree candidate from the School of Public Health, is the first author, while Professor Liu Gang is the corresponding author.
On June 30th, the study with a title of Vitamin D Status, Genetic Factors, and Risk of Cardiovascular Disease Among Individuals With Type 2 Diabetes: A Prospective Study published online in the American Journal of Clinical Nutrition, which is a top journal in the field of clinical nutrition. The study showed that higher concentrations of serum 25(OH)D were significantly associated with lower risk of cardiovascular diseases (CVD) in patients with T2D, and the risk tended to plateau at levels around 50 nmol/L. In addition, the associations were independent of genetic susceptibility and genetic variants in VDR. Wan Zhenzhen, a doctoral student of the School of Public Health, is the first author, and Professor Liu Gang is the corresponding author.
These were additional important research findings based on the group's early findings on dietary nutrition (serum carotenoids, vitamin D, selenium, folic acid and vitamin B12, nuts, low carbon and low-fat diet mode), lifestyle factors and risk of diabetes complications as well as premature death (JACC2018; Circle Res2019; Lancet Diabetes Endocrinol2020; Diabetes Care20212022a, b; PLoS Med2022; JAMA NetworkOpen2022; Diabetologia2022; Engineering2022; Am J Clin Nutr2022a, b). These series of results provided important scientific evidence for the health management of diabetic patients.
The first study included 14709 patients with T2D and the median follow-up period was 11.2 years. Multivariable-adjusted analyses (adjusted for age, gender, ethnic, lifestyle factors, dietary factors, physical activity, append outdoor in summer, body mass index, estimated glomerular filtration rate, history of hypertension or hypercholesterolemia, season of blood draw and blood glucose control status, etc.) and stratified analyses both suggested that:
Higher serum 25(OH)D concentrations were significantly associated with lower
risk of composite diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a 33% lower risk for composite diabetic microvascular complications (HR: 0.65, 95% Cl: 0.51-0.84), a 38% lower risk for diabetic retinopathy (HR: 0.62, 95% CI: 0.40-0.95), a 44% lower risk for diabetic neuropathy (HR: 0.56, 95% CI: 0.40-0.79), and a 52% lower risk for diabetic neuropathy (HR: 0.48, 95% CI: 0.26-0.89).
Dose-response analysis showed linear relationships between serum 25(OH)D (range from 10 to 106 nmol/L) and composite diabetic microvascular complications, diabetic retinopathy and diabetic nephropathy.
In genetic analysis, participants carried TT alleles of rs1544410 (BsmI) or GG alleles of rs731236 (TaqI) had significantly increased risk of composite diabetic complications. Moreover, compared with the reference group, participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC of rs1544410 and AA of rs731236) had 46% and 45% decreased risk of composite diabetic microvascular complications, respectively, although no significant interaction was observed.
In addition, some previous epidemiological studies conducted in general population found that higher serum vitamin D concentrations were significantly associated with lower risk of CVD, which is a major cause of mortality and disability of patients with T2D. However, recent large-scale randomized controlled trials did not find significant cardiovascular or other health effects of vitamin D supplementations. The presence of threshold effect has been proposed, suggesting that the beneficial effects from vitamin D supplementation may only be present when the vitamin D concentration is below a particular threshold (e.g., 50 nmol/L). However, in patients with T2D, vitamin D deficiency or insufficiency is particularly common, the associations of vitamin D status with risk of CVD complications remains unclear.
The second study conducted among 15,103 participants with T2D. During a median of 11.2 years of follow-up, 3534 incident CVD events were documented. After adjusting for a multitude of potential confounding factors, including age, sex, ethnicity, healthy diet, lifestyle factors, the blood draw season, time spent outdoors in the summer, diabetic controlling status and stratified analyses showed that:
Higher serum 25(OH)D concentrations were significantly associated with lower risk of CVD among patients with T2D. Compared with individuals with 25(OH)D concentrations <25 nmol/L, participants with 25(OH)D concentrations ≥75 nmol/L had a 25% lower risk for CVD (HR: 0.75, 95% CI: .64-0.88) and a 31% lower risk for ischemic heart disease (HR: 0.69, 95% CI: 0.56-0.84).
Dose-response analyses demonstrated that serum 25(OH)D concentrations were nonlinearly associated with decreased risk of CVD risk, which levelled off at around 50 nmol/L.
A genetic risk score (GRS) was constructed based on 73 single nucleotide polymorphisms (SNPs) related to ischemic heart disease, and the joint analyses with serum 25(OH)D showed that compared with participants with 25(OH)D <25 nmol/L and high genetic risk, participants 25(OH)D ≥50 nmol/L and low genetic risk had a 50% decreased risk of ischemic heart disease (HR: 0.50, 95% CI: 0.39-0.65).
The above findings suggested that as a modifiable dietary nutritional factor, vitamin D might be applied to the prevention of microvascular and macrovascular complications in patients with diabetes. This series of research results provided important population data for the health management of vitamin D and T2D.
The collaborators of these studies included Professor JoAnn E.Manson, a member of the National Academy of Medical Sciences and Harvard University, and Professor Pan An, Professor Liu Liegang, Professor Shan Zhilei, Associate Professor Guo Yanjun, lecturer Chen Liangkai, all from the School of Public Health. These studies were funded by grants from the Hubei Province Science Fund for Distinguished Young Scholars, the National Nature Science Foundation of China, ect.
Related article link:
https://doi.org/10.2337/dc22-0513
https://doi.org/10.1093/ajcn/nqac183
