Shelley Wood

September 24, 2013

BARCELONA, SPAIN - High concentrations of serum calcium—but not necessarily calcium intake—are associated with an increased risk of developing type 2 diabetes, results from the Insulin Resistance Atherosclerosis Study (IRAS) show. Moreover, calcium concentration appears to act independently of glucose, insulin secretion, and insulin resistance, according to Dr Carlos Lorenzo (University of Texas Health Science Center, San Antonio).

Lorenzo presented the IRAS results here at the European Association for the Study of Diabetes (EASD) 2013 Meeting .

Several recent high-profile reports have linked high calcium intake, and particularly calcium-supplement use, with increased risk of cardiovascular disease. Speaking with heartwire , Lorenzo noted that cardiovascular disease and diabetes share many of the same risk factors and that calcium has also been linked with lower insulin sensitivity, impaired glucose tolerance (IGT), and the metabolic syndrome.

"Our hypothesis was that serum calcium may also play some role in the development of diabetes," he said.

Calcium and Diabetes

IRAS enrolled 863 nondiabetic 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.

Dr Carlos Lorenzo

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 concentrations 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, nonlinear relationship was seen between the highest category 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 five-year diabetes risk was seen.

In the past, explained Lorenzo, researchers have speculated that the link between calcium and diabetes is related to insulin resistance or insulin secretion. "Our study shows that people with serum calcium that is pretty much in the normal range, but in the upper-normal range—those people are at higher risk for diabetes. And that, most probably, is not related to their metabolic status defined by their obesity or their insulin resistance or their insulin secretion."

Calcium Intake Not Linked With Diabetes Incidence

The findings on calcium intake are also important, he noted, since it shows that high calcium intake, per se, is not problematic; rather, it is the body's ability to regulate calcium that seems to be at 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.

Whether serum calcium plays a causative role in the development of diabetes or is a marker for other adverse processes remains unclear; "we can't answer that question," he told heartwire . "There is a relationship, but we can't yet determine why this is happening."

He and his colleagues have not yet looked at whether the addition of serum calcium to existing risk-prediction algorithms could help streamline diabetes-risk forecasts. He also pointed out that the number of people in IRAS who fell into this high-calcium group was relatively small—about 15% to 17% of the study population.

"I suspect [serum calcium levels] won't add much to our prediction equations, but if you have someone in the clinic who has those levels of calcium, that person is going to be at higher risk for diabetes," he concluded.

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