Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects

Background: Hypophosphatemia is associated with impaired glucose tolerance and insulin resistance in primary hyperparathyroidism. However, little is known about the association between serum phosphate and glucose metabolism in healthy subjects. Methods: We measured fasting serum phosphate levels ( SP, normal range 2.6 - 4.5 mg/dl) and serum calcium ( S-Ca, normal range 2.1 - 2.6 mmol/l) in 881 non-diabetic subjects ( 341 male/540 female, age: 38 +/- 1 years, body mass index 25.9 +/- 0.2 kg/m(2) ( mean +/- standard error of the mean). An oral glucose tolerance test ( OGTT) with determination of glucose and insulin every 30 min was performed in all subjects. Insulin secretion and insulin sensitivity ( IS) were estimated from the OGTT using validated indices. Furthermore, we tested whether serum phosphate predicts glucose tolerance in 115 subjects during a lifestyle intervention program ( LIP). Results: Serum phosphate was negatively correlated with 2-h blood glucose levels independent of age, gender and percent body fat ( r = -0.13, P < 0.0001). This association remained significant after additional adjustment for S-Ca, creatinine and parathyroid hormone. Serum phosphate was positively correlated with IS ( r = 0.10, P = 0.0006), but not with insulin secretion. This was independent of age, gender, percent body fat, S-Ca and serum creatinine. In the subjects taking part in the LIP low serum phosphate levels at baseline were associated with higher postprandial glucose levels. Conclusions: In non-diabetic subjects, low serum phosphate levels are associated with high 2-h blood glucose levels and reduced IS. Whether low serum phosphate levels are a cause or a consequence of low IS and impairment of glucose tolerance needs to be tested in further studies.