Recently, The international authoritative journal Diabetes Care online published the latest research results of Professor LIU Gang 's team entitled " Associations of Habitual Calcium Supplementation With Risk of Cardiovascular Disease and Mortality in Individuals With and Without Diabetes " in the School of Public Health, Tongji Medical College, Huazhong University of Science and Technology. The study found that long-term use of calcium supplements was associated with a significant increase in the risk of cardiovascular and cerebrovascular diseases and premature death in diabetic patients, but not in non-diabetic populations. At the same time, food-derived calcium intake had no effect on the risk of cardiovascular disease and death in diabetic patients.

Calcium is the most abundant mineral in the human body and is very important for the health of the body. It is common to take calcium supplements to prevent osteoporotic fractures. Therefore, it is of great public health significance to study the beneficial or adverse effects of calcium supplements on health. However, the current evidence on the association between calcium supplements and the risk of cardiovascular and cerebrovascular diseases is inconsistent. Experimental studies have shown that unlike calcium in food, calcium in the form of supplements may cause an acute increase in blood calcium levels in a short period of time, and long-term supplementation may cause vascular calcification. Most cohort studies have shown that calcium supplements are not associated with cardiovascular and cerebrovascular diseases in the general population, but some studies in some special populations suggest that calcium supplements may be associated with an increased risk of cardiovascular and cerebrovascular diseases. Compared with the general population, the risk of cardiovascular and cerebrovascular diseases and premature death in diabetic patients is significantly increased by 1-2 times, and abnormal calcium homeostasis is more likely to occur. However, it is not clear whether long-term use of calcium supplements will affect the risk of cardiovascular and cerebrovascular diseases and premature death in diabetic patients.

A total of 434,374 subjects were included in this study, including 21,676 patients with diabetes. After an average follow-up of about 8.1 years and 11.2 years, there were 26,374 cardiovascular events and 20,526 deaths, respectively. Through the control and stratification analysis of a variety of confounding factors ( age, gender, dietary factors, lifestyle, medication, taking other supplements, glomerular filtration rate, serum vitamin D, etc. ), it was found that :

·In the non-diabetic population, long-term use of calcium supplements is not associated with cardiovascular and cerebrovascular diseases and mortality risk. However, in diabetic patients, long-term use of calcium supplements is associated with a significant increase in the risk of cardiovascular and cerebrovascular diseases and death.

·Compared with diabetic patients without long-term calcium supplementation, diabetic patients with long-term calcium supplementation had a 34 % increased risk of cardiovascular and cerebrovascular diseases ( HR : 1.34, 95 % CI : 1.14-1.57 ), a 67 % increased risk of cardiovascular and cerebrovascular disease death ( HR : 1.67, 95 % CI : 1.19-2.33 ), and a 44 % increased risk of all-cause death ( HR : 1.20, 95 % CI : 1.30-1.72 ).

·There was a significant multiplicative and additive interaction between long-term calcium supplementation and diabetes (P _interaction< 0.05). It was estimated that 26-39% of the risk of cardiovascular events and all-cause mortality in diabetic patients taking calcium supplements was attributable to the interaction. However, there was no significant interaction between dietary or serum calcium and diabetes (P _interaction > 0.05).

Figure 1. Prospective association between long-term calcium supplementation

and cardiovascular disease and mortality risk

The above studies suggest that long-term use of calcium supplements is associated with a significant increase in the risk of cardiovascular and cerebrovascular complications and death in diabetic patients, but not in non-diabetic populations. It is worth noting that food-derived calcium intake has no effect on the risk of cardiovascular and cerebrovascular diseases and death in diabetic patients. The above results show that the source of calcium is very important, and it is preferred to supplement calcium with food. Diabetic patients may need to take calcium supplements cautiously for a long time. In the future, more studies are needed to comprehensively evaluate the potential benefits and possible side effects of calcium supplements, especially for diabetic patients.

The above research is based on the previous research results of the team on the relationship between dietary nutritional factors such as serum vitamin D, carotenoids, selenium, folic acid and vitamin B12, different dietary patterns and the risk of complications and premature death in diabetic patients ( Diabetes Care 2021 ; pLoS Medicine 2022 ; diabetes Care 2022 ; jAMA Network Open 2022 ; aJCN 2022 ; diabetes Care 2023 ). The series of research results provide an important scientific basis for the health management of diabetic patients.

QIU Zixin, a doctoral student in the School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, was the first author, and Professor LIU Gang was the communication author. The research work was guided by Professor PAN An of Huazhong University of Science and Technology and Professor JoAnn E Manson of Harvard University. The research was supported by the National Natural Science Foundation of China and Hubei Outstanding Youth Fund.

Paper link：https://doi.org/10.2337/dc23-0109