Serum calcium is independently associated with insulin sensitivity measured with euglycaemic–hyperinsulinaemic clamp in a community-based cohort

Abstract

Aims/hypothesis Diabetes mellitus type 2 is associated with altered calcium metabolism. Moreover, in diseases with supranormal serum calcium levels, such as primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively little is known about the relationship between serum calcium concentration and the underlying causes of diabetes-insulin resistance and defective insulin secretionin the normocalcaemic general population. Materials and methods We investigated associations between serum calcium concentration and insulin sensitivity and secretion in a population-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, n=961). Insulin sensitivity index (M/I; glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated from the early insulin response (EIR) during an OGTT.Results In a multivariable linear regression model adjusting for BMI, physical activity, smoking, consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg −1 min −1 (mU/l) −1 × 100 (0.024 mg kg −1 min −1 [pmol/l] −1 ×100) decrease in M/I (p=0.01). The results remained robust in individuals with normal fasting glucose, normal glucose tolerance and serum calcium within the normal range (n=413, regression coefficient for 1 SD increase −0.45, p=0.001). Serum calcium was not associated with EIR. Dietary intake of calcium was not independently associated with insulin sensitivity or EIR. Conclusion/interpretation Our data support the notion that endogenous calcium may be involved early in the development of diabetes and that this effect is mediated mainly through effects on insulin sensitivity rather than defective insulin secretion. Dietary intake of calcium does not seem to influence insulin sensitivity.

Serum calcium level is associated with metabolic syndrome in the general population: FIN-D2D study

“…Increasing intracellular calcium levels have been shown to decrease the effect of insulin in adipocytes due to reduced number of glucose transporters (GLUT4) and decreased insulin receptor activity (5,7). The dietary intake of calcium did not seem to influence insulin sensitivity (4).…”

“…Previous reports have shown that patients with diabetes have elevated serum calcium levels compared with non-diabetic individuals (3), and this has mainly been linked to impaired insulin sensitivity rather than defective insulin secretion (4). In diseases with markedly elevated serum calcium, such as primary hyperparathyroidism, there is a two-to four-fold higher prevalence of type 2 diabetes and glucose intolerance compared with the general population (5).…”

Reduced Expression of Nuclear-Encoded Genes Involved in Mitochondrial Oxidative Metabolism in Skeletal Muscle of Insulin-Resistant Women With Polycystic Ovary Syndrome

“…It is easy to infer that dysregulation of Ca 2ϩ homeostasis could have a pronounced disturbing effect on insulin-stimulated glucose disposal and mitochondrial function. Abnormal Ca 2ϩ homeostasis has been reported in skeletal muscle of patients with type 2 diabetes (47), and more recently, serum calcium was demonstrated to be independently associated with insulin resistance measured with euglycemic-hyperinsulinemic clamp (48). Although similar abnormalities in muscle transcripts of calcium pathway genes were not reported in studies of patients with type 2 diabetes (20 -22), it is too early to conclude that the observed changes should play a unique role for insulin resistance in skeletal muscle of PCOS subjects.…”

Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: A prospective study

“…In T2DM subjects, calcium levels have been shown to be higher (10, 13) and associated with fasting glucose or insulin resistance (8,9,12); conversely, other studies have reported no relationship with markers of glucose control (15), insulin resistance (7), or insulin secretion (7,9).…”

“…Similarly, crosssectional and case-control studies investigating the relationship between calcium homeostasis and glucose metabolism have reported conflicting results (7)(8)(9)(10)(11)(12)(13)(14)(15); however, only a few studies have prospectively evaluated the association between serum calcium and risk of incident T2DM, suggesting that higher levels of serum calcium predict an increased risk of T2DM (16)(17)(18). These studies have relied either on total serum calcium or the indirect, albumincorrected estimate of serum calcium: these measurements, however, only approximate the levels biological-active serum calcium (iCa) (19).…”