A 74-year-old woman is admitted to the hospital in an obtunded condition. Her temperature is 37deg C, pulse is 95/ min, respirations are 22/min, and blood pressure is 90/60 mm Hg. She appears dehydrated and has poor skin turgor. Her serum glucose level is 872 mg/dL. Urinalysis shows 4+ glucosuria, but no ketones, protein, or blood. Which of the following factors is most important in the pathogenesis of this patient's condition?