Glycemia varies widely in patients with
diabetic ketoacidosis (DKA), with plasma
glucose concentrations between 10 to 50 mmol/L commonly encountered. The mechanism of this glycemic variability is uncertain. Our study examined the differential effects of fasting and
dehydration on
hyperglycemia induced by withdrawal of
insulin in
type 1 diabetes. To evaluate the respective roles of
dehydration and fasting in the pathogenesis of DKA, 25 subjects with
type 1 diabetes were studied during 5 hours of
insulin withdrawal before (control) and after either 32 hours of fasting (n = 10) or
dehydration of 4.1% +/- 2.0% of baseline
body weight (n = 15). Samples were obtained every 30 minutes during
insulin withdrawal for substrate and counterregulatory
hormone levels and rates of
glucose production and disposal. Fasting resulted in reduced plasma
glucose concentrations compared with the control study, while
dehydration resulted in increased plasma
glucose concentrations compared with the control study (P < .001).
Glucose production and disposal were decreased during the fasting study and increased during the
dehydration study compared with the control study.
Glucagon concentrations and rates of development of
ketosis and
metabolic acidosis were increased during both fasting and
dehydration compared with control. These data suggest that fasting and
dehydration have differential effects on glycemia during
insulin deficiency, with
dehydration favoring the development of
hyperglycemia and fasting resulting in reduced
glucose concentrations. This finding is probably attributable to the differing effect of these conditions on endogenous
glucose production, as well as to differences in substrate availability and counterregulatory
hormone concentrations. The severity of pre-existing fasting and
dehydration likely explains much of the variability in plasma
glucose concentrations observed in DKA.