EDWARD S. HORTON, M.D.; CHARLES JOHNSON, M.D.; HAROLD E. LEBOVITZ, M.D.
To define more clearly the factors involved in carbohydrate metabolism in uremia, we studied blood glucose, plasma insulin, and plasma growth hormone responses after the intravenous injections of 25 g of glucose in 17 uremic patients and compared the results with those in 14 normal subjects and 16 patients with maturity-onset diabetes mellitus. The plasma glucose response and the insulin disappearance rate after the intravenous injection of beef insulin, 0.1 unit/kg, were measured in five normal subjects and in five uremic patients with abnormal glucose tolerance. The effect of urea on glucose oxidation by adipose tissue in vitro was also studied.
All but one of the uremic patients had an abnormal response to intravenous glucose (glucose decay constant (Kg) < 1.0). This was associated with a slight decrease in initial insulin secretion, continued elevation of plasma insulin levels, and decreased sensitivity of the tissues to insulin action. The persistent elevation of plasma insulin after intravenous glucose was the result of both a prolonged insulin half-life and continued stimulation of insulin secretion. By comparing the insulin/glucose ratios during the first 10 min after intravenous glucose, we could distinguish 78% of the normal and 70% of the uremic subjects from patients with maturity-onset diabetes mellitus. Insulin resistance in the uremic patients was manifested by elevated fasting plasma insulin in the presence of normal fasting blood glucose levels, high insulin/glucose ratios after intravenous glucose, and decreased blood glucose responsiveness to intravenous beef insulin.
The exact mechanism of the insulin resistance in uremia remains speculative. Elevated plasma growth hormone levels were present in some, but not all, of the uremic patients, and no correlation could be made between increased growth hormone levels and impaired glucose tolerance in individual patients. It is unlikely that urea per se is the cause of the abnormal glucose tolerance in uremia, as no effect of urea on insulin-stimulated glucose oxidation by adipose tissue could be demonstrated in vitro.
HORTON ES, JOHNSON C, LEBOVITZ HE. Carbohydrate Metabolism in Uremia. Ann Intern Med. ;68:63–74. doi: 10.7326/0003-4819-68-1-63
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Published: Ann Intern Med. 1968;68(1):63-74.
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