Hypophosphatemia and Glucose Intolerance: Evidence for Tissue Insensitivity to Insulin

Abstract

Although hypophosphatemia is commonly present in diabetics, little is known about its isolated effects on glucose and insulin metabolism. We therefore investigated glucose metabolism in six nondiabetic subjects with chronic hypophosphatemia. When glucose was infused to maintain a constant hyperglycemic level (125 mg per deciliter [6.9 mmol per liter] above basal levels), the glucose infusion rate was 36 per cent less in the hypophosphatemic group than in controls (4.90 +/- 0.34 mg per kilogram of body weight per minute vs. 7.64 +/- 0.37, P < 0.001), although responses to endogenous insulin were similar. When exogenous insulin was infused at a constant rate to maintain an insulin level about 100 microU per milliliter (718 pmol per liter) above basal levels and glucose was infused as necessary to maintain fasting glucose levels, the infusion rate of glucose was 43 per cent lower in the hypophosphatemic group than in controls (3.80 +/- 0.58 mg per kilogram per minute vs. 6.70 +/- 0.33, P < 0.001), although the clearance rate of insulin was similar in both groups. These results indicate that hypophosphatemia is associated with impaired glucose metabolism in both the hyperglycemic and euglycemic states, and that this associated primarily reflects decreased tissue sensitivity to insulin. (N Engl J Med. 1980; 303; 1259-63.).

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

“…There was a significant association of low serum phosphate concentrations with high 2-h blood glucose levels independent of anthropometric parameters like percent body fat, age and gender. These findings are in line with several other studies which demonstrated a significant correlation between serum phosphate, glucose tolerance (DeFronzo and Lang, 1980;Campillo et al, 1982) and adiposity (Lindgarde and Trell, 1977;Haglin et al, 2001). Especially the inverse correlation between BMI and low serum phosphate concentrations has been described earlier (Lind et al, 1993).…”

“…This finding could be confirmed in a smaller group of subjects using the gold standard for measurement of IS, the hyperinsulinemic euglycemic clamp. Moreover, these results are in line with findings in patients with hypophospatemia caused by pHPT (DeFronzo and Lang, 1980;Sowers and Draznin, 1998).…”

“…pHPT is also associated with impaired glucose tolerance (IGT) and reduced insulin sensitivity (IS) (Ljunghall et al, 1983). The hypophosphatemia present in pHPT and other conditions of various pathogenic origin is thought to be the cause of altered glucose metabolism and impaired responsiveness to insulin (DeFronzo and Lang, 1980). However, there is also evidence, that phosphate supplementation in glucose intolerant hypophosphatemic patients improves glucose tolerance significantly (Wittmann and Nagy, 1997).…”

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

“…that the observed association is confounded by other causal factors related to the serum levels of calcium and insulin sensitivity, such as BMI, physical activity, intake of coffee or alcohol, or excess of oral intake of calcium. Hypophos-phataemia and hypercalcaemia are in part associated, and in some previous studies low serum levels of phosphate have also been related to decreased insulin sensitivity [35]. However, our results remained robust even after adjustment for serum phosphate concentration (model C).…”

Hyperparathyroidism and New Onset Diabetes After Renal Transplantation

“…39,40 In peripheral tissue this increase in intracellular calcium inhibits insulin stimulated glucose uptake and causes insulin resistance. 41,42 There is evidence that hypophosphatemia decreases insulin sensitivity 43 and that phosphate supplementation improves glucose tolerance. Phosphate is involved in the energy balance and ATP generation.…”