Hypophosphatemia and Glucose Intolerance: Evidence for Tissue Insensitivity to Insulin

Ralph A. Defronzo, Robert Lang

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143 Scopus citations


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 non-diabetic 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 μU 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 association primarily reflects decreased tissue sensitivity to insulin. (N Engl J Med. 1980; 303:1259–63.) HYPOPHOSPHATEMIA has been reported to result in various metabolic disturbances, including erythrocyte, leukocyte, and platelet dys-function, Central-nervous-system abnormalities, and rhabdomyolysis.1 2 One of the most common clinical situations in which hypophosphatemia has been found is poorly controlled diabetes.1 2 3 On initial presentation, total body phosphate stores are usually markedly depleted, but the plasma phosphate concentration may only be mildly to moderately reduced because of a shift in phosphate from the intracellular to extracellular compartment.1 2 3 The negative phosphate balance is the result of many factors, including decreased dietary intake, but more important is a large increase in urinary phosphate excretion caused by the.

Original languageEnglish (US)
Pages (from-to)1259-1263
Number of pages5
JournalNew England Journal of Medicine
Issue number22
StatePublished - Nov 27 1980
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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