A 4-h hyperglycaemic excursion induces rapid and slow changes in major electrolytes in blood in healthy human subjects

Hyperglycaemia is well known to cause reductions in plasma Na⁺ levels or even hyponatraemia due to an osmotically induced dilution of the interstitium and blood. It is, however, unclear whether this dilution is significantly counteracted by ion regulatory homeostatic mechanism(s) or not. Furthermore, the effects of moderate hyperglycaemia on other major ions are less well known. To further clarify these questions, we measured the changes in blood osmolarity and concentrations of Na⁺, K⁺, Cl⁻, Mg²⁺ and Ca²⁺ during a 4-h-long experimental hyperglycaemia in healthy subjects rendered temporarily insulin deficient using the hyperglycaemic clamp. Hyperglycaemia, 16.8 mM, was rapidly imposed from a baseline of 4.4 mM by intravenous somatostatin and glucose infusions in 19 healthy subjects (10 m, 9 f; age 36 ± 5 years (mean ± SD); BMI 22.7 ± 2.9 kg/m²). Subsequently, glycaemia was returned to basal and measurements continued until all dynamic changes had stopped (at ~8 h). Osmolarity increased from 281.8 ± 0.7 to 287.9 ± 0.7, while Na⁺ decreased from 143.9 ± 0.3 to 138.7 ± 0.2, Cl⁻ from 101.7 ± 0.2 to 99.5 ± 0.1, Ca²⁺ from 1.98 ± 0.04 to 1.89 ± 0.02 and Mg²⁺ from 0.84 ± 0.01 to 0.80 ± 0.00 mM. All these changes were rapidly reaching stable levels. K⁺ increased from 4.02 ± 0.02 to 4.59 ± 0.02 mM (P < 0.0001) also reaching stable levels but with some delay. Na⁺, Cl⁻, Mg²⁺ and Ca²⁺ are essentially determined by blood dilution, and their values will remain diminished as long as the hyperglycaemia lasts. Partial suppression of insulin-stimulated Na⁺/K⁺ pumping lead to increased K⁺ levels. The combination of elevated K⁺ and decreased Mg²⁺ and Ca²⁺ levels may lead to an altered excitability, which is particularly relevant for diabetic patients with heart disease.