Effects of hypophosphatemia on glucose tolerance and insulin secretion

Phosphate is an active participant in energy metabolism, and its deficiency has been associated with changes in insulin sensitivity and glucose tolerance. In the present study, we have investigated insulin secretion and glucose tolerance in individuals with moderate and acute phosphate deprivation and in patients with chronic hypophosphatemia. The individuals with dietary phosphate deprivation, evidenced by a significant reduction in phosphaturia from 232.3 +/- 37.1 to 56.8 +/- 23.9 mmol/24 hours, but with normal serum levels of inorganic phosphorus, presented circulating glucose and insulin levels similar to those of the pre-dietary period during the oral and intravenous glucose tolerance tests. In contrast, patients with chronic hypophosphatemia (inorganic phosphorus < 0.65 mmol/l) presented in hyperinsulinemia during the postabsorptive state and during the early and late phases of insulin secretion after the oral and intravenous glucose stimulus. The physiological response of a fall in serum phosphate after glucose administration observed in individuals with chronic hypophosphatemia was similar to that of normal individuals. The presence of hyperinsulinemia both basally and after glucose stimulation, with normal glycemia, in phosphate-depleted individuals suggests that this condition is associated with reduced insulin sensitivity. However, severe phosphate deprivation is necessary for the manifestation of this undesirable association. The deviation of phosphate to the intracellular medium occurring after glucose administration in hypophosphatemic individuals is similar to that of normal individuals and explains the occurrence of severe hypophosphatemia in malnourished hypophosphatemic individuals when submitted to parenteral refeeding.