Circulating calcium levels and the risk of type 2 diabetes: a systematic review and meta-analysis

Abstract

Abnormal Ca homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating Ca levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase and Google Scholar) and related references with de novo results from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RR) and 95 % CI for the associations. The search yielded twenty eligible publications with eight cohort studies identified for the meta-analysis, which included a total of 89 165 participants. Comparing the highest with the lowest category of albumin-adjusted serum Ca, the pooled RR was 1·14 (95 % CI 1·05, 1·24) for T2DM (n 51 489). Similarly, serum total Ca was associated with incident T2DM (RR 1·25; 95 % CI 1·10, 1·42) (n 64 502). Additionally, the adjusted RR for 1 mg/dl increments in albumin-adjusted serum Ca or serum total Ca levels was 1·16 (95 % CI 1·07, 1·27) and 1·19 (95 % CI 1·11, 1·28), respectively. The observed associations remained with the inclusion of a cohort study with ionised Ca as the exposure. However, data pooled from neither case–control (n 4) nor cross-sectional (n 8) studies manifested a significant correlation between circulating Ca and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating Ca levels are associated with an augmented risk of T2DM.

A Higher Serum Calcium Level is an Independent Risk Factor for Vision-Threatening Diabetic Retinopathy in Patients with Type 2 Diabetes: Cross-Sectional and Longitudinal Analyses

“…Although higher serum calcium levels have been well established as a risk factor for T2D (9)(10)(11), few studies have explored its potential association with diabetic microvascular J o u r n a l P r e -p r o o f complications. Our results suggest that higher serum calcium levels are independently associated with an increased risk of VTDR.…”

“…As the most abundant mineral in the human body, calcium is also involved in biological processes such as insulin release and retinal function (5)(6)(7)(8). Several large cohort studies have associated higher serum calcium levels with a higher risk of type 2 diabetes (T2D) (9)(10)(11). Furthermore, a recent single-cell RNA sequencing study reported that calcium and other metal ion pathways are activated in proliferative DR in the J o u r n a l P r e -p r o o f mouse retina (12).…”

Beneficial Effects of Apple Vinegar on Hyperglycemia and Hyperlipidemia in Hypercaloric-Fed Rats

“…Furthermore, the present study revealed a significant increase in plasma calcium concentrations in nontreated diabetic rats as compared to the control group. In fact, numerous studies have been reported that the high plasma calcium level was directly associated with T2D risk [ 47 , 48 ]. However, the daily coadministration of apple vinegar (2 mL/kg) was not able to ameliorate the calcium plasma level.…”

Longitudinal Observation of Muscle Mass over 10 Years According to Serum Calcium Levels and Calcium Intake among Korean Adults Aged 50 and Older: The Korean Genome and Epidemiology Study

“…Several studies have warned of the adverse effects of a high calcium load. Higher circulating calcium levels have been associated with an increased risk of type 2 diabetes [ 38 ], while calcium supplements have been associated with an increased risk of myocardial infarction [ 39 ]. Nonetheless, given the much lower calcium intake in our population relative to most of the referred studies and the negative effects of lower serum calcium levels on muscle preservation, it may be reasonable to encourage increased calcium intake.…”