Several recent high-profile reports have linked high calcium intake, and particularly calcium-supplement use, with increased risk of cardiovascular disease. Since many of the same risk factors associated with cardiovascular disease are shared with diabetes, calcium in turn has been linked with lower insulin sensitivity, impaired glucose tolerance (IGT), and the metabolic syndrome.
IRAS enrolled 863 non-diabetic subjects (age 40-69) at four centers. Insulin sensitivity and acute insulin response were measured at baseline and at regular intervals over a five-year follow-up period. Diabetes and IGT were defined by current fasting and two-hour plasma glucose criteria and/or use of glucose lowering medications.
Lorenzo and colleagues found that the relationship between calcium concentration and incident diabetes was statistically significant but did not follow a linear relationship. Only subjects with the highest concentration of calcium (≥2.38 mmol/L) had a significantly increased risk of developing diabetes. After controlling for age, sex, race/ethnicity, family history of diabetes, body-mass index (BMI), plasma glucose levels, insulin-sensitivity index, acute insulin response, estimated glomerular filtration rate (eGFR), and diuretic drugs, researchers found that only patients at the highest levels of serum calcium (≥2.5 mmol/L) showed a statistically significant increase in incident diabetes. A similar non-linear relationship was seen between the highest categories of serum calcium and impaired fasting glucose.
Of note, in models that looked at albumin-adjusted calcium concentration as well as total calcium intake, no statistically significant relationship with 5-year diabetes risk was seen.
Lorenzo stated that in the past researchers have speculated that the link between calcium and diabetes is related to insulin resistance or insulin secretion. The IRAS shows that people with serum calcium that is pretty much in the normal range, but in the upper-normal range, are those at higher risk for diabetes; and that, most probably, is not related to their metabolic status defined by their obesity, their insulin resistance, or their insulin secretion.
The study’s findings on calcium intake are also important, since it shows that high calcium intake, per se, is not the problem; rather, it is the body’s ability to regulate calcium that seems to be the issue. The study did not address vitamin D or parathyroid hormone levels, both of which are also involved in calcium regulation. In response to a question from the audience, Lorenzo also acknowledged that the study was not able to address physical activity levels, which are also known to have an impact on serum calcium.
However, whether serum calcium plays a causative role in the development of diabetes or is a marker for other adverse processes remains unclear. Lorenzo states that though a relationship does exist, why it does cannot yet be determined.