Hyperglycemia-induced hyponatremia: Reevaluation of the Na+ correction factor

This study addresses the clinically important relationship between the decreases in plasma Na+ and the increases in plasma glucose concentrations seen in diabetes and other hyperglycemic syndromes. This plasma 'Na+ correction factor', is generally accepted as 1.6 mM Na+ per 100 mg% glucose (0.29 mM/mM in SI units) assuming osmotic equilibrium, although much larger numbers have been measured in experiments on normal humans. To resolve this controversy, a mathematical model of whole-body fluid-electrolyte balance was used to perform the experiment wherein plasma glucose concentration was increased to diabetic levels and the plasma Na+ concentration changes assessed, without the complications seen in human experiments. The findings, based on osmotic grounds, were that the factor 1) was significantly < 1.6, approaching 1 in some cases, 2) depended upon the anthropometry of the subject; it was inversely proportional to the ratio of extracellular to total body water, which increases with higher fat content and 3) was approximately linear up to glucose concentrations of about 800 mg%, but decreased up to 10% for higher glucose concentrations. To explain the experimental data, a hypothesis of Na+ sequestration in cells was incorporated in the model, resulting in close prediction of measured transient Na+ changes.