Impairment of insulin-mediated glucose metabolism by hyperosmolality in man

The deterioration of glucose tolerance and insulin resistance observed in states of hypertonic dehydration are commonly ascribed to a concomitant increase in circulating insulin counterregulatory hormones. To examine the effect of hyperosmolality per se on carbohydrate metabolism, tissue sensitivity to insulin was assessed by means of the euglycemic insulin clamp technique and simultaneous 3H-3-glucose kinetic analysis. Eight healthy volunteers participated in three protocols: (1) In the hyperosmolal study, serum osmolality was raised from 280 +/- 1 to 302 +/- 1 mosm/kg by a primed continuous infusion of hypertonic mannitol. Following 2 h of hypertonicity, a euglycemic insulin clamp study was performed. The plasma insulin concentration was acutely raised and maintained at 147 +/- 20 microU/ml, while plasma glucose was maintained at basal levels; (2) In the control insulin clamp study, isotonic sodium chloride was infused instead of mannitol. No significant change in serum osmolality was observed during the control study; (3) To examine the effect of mannitol per se on insulin-mediated glucose metabolism, isotonic mannitol was infused in a third study to raise the plasma mannitol level to a similar extent as observed during the infusion of hypertonic mannitol. The serum tonicity did not change during the isotonic mannitol infusion. Insulin-mediated glucose utilization (M) was 6.69 +/- 0.51 mg/kg X min in the control study and decreased to 5.84 +/- 0.40 mg/kg X min following the exposure to hyperosmolality (P less than 0.05).2+ +/- 0.60 versus 4.30 +/- 0.43 mg/kg X min per microU/ml X 100).(ABSTRACT TRUNCATED AT 250 WORDS)