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 1.6mM Na⁺ per 100mg% glucose (0.29mM/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 800mg%, 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.