Effects of acute insulin deficiency on glucose and ketone body turnover in man. Evidence for the primacy of overproduction of glucose and ketone bodies in the genesis of diabetic ketoacidosis

J. M. Miles, R. A. Rizza, M. W. Haymond, J. E. Gerich

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Abstract

To assess the relative contribution of overproduction and underutilization of glucose and ketone bodies to the development of diabetic ketoacidosis in man, the effects of acute insulin deficiency on glucose and ketone body turnovers were determined in seven ketosis-prone (type I) diabetic subjects. After termination of prolonged intravenous infusions of insulin, which had been maintaining the subjects euglycemic, plasma free insulin decreased from 18 ± 4 μU/ml to 7 ± 1 μU/ml, P < 0.01; plasma glucagon increased from 67 ± 6 pg/ml to 259 ± 67 pg/ml, P < 0.05, but plasma growth hormone and cortisol did not increase. Plasma glucose increased from 5.4 ± 0.3 mM to 15.6 ± 1.0 mM, P < 0.01; plasma ketone bodies (β-hydroxybutyrate plus acetoacetate) increased from 1.4 ± 0.4 mM to 7.2 ± 1.5 mM, P < 0.01. Glucose production increased abruptly from 13.2 ± 1.1 μmol/kg-min to a maximum of 26.1 ± 2.9 μmol/kg-min at 2 h but then decreased toward baseline rates; glucose utilization also increased transiently. In contrast, both ketone body production and utilization increased progressively throughout the study from 5.4 ± 1.4 and 5.5 ± 1.1 to 18.3 ± 3.9 and 14.7 ± 2.1 μmol/kg-min, respectively, P < 0.01. Clearance of both glucose and ketone bodies decreased more than 50%, P < 0.01. These results indicate that overproduction of glucose and ketone bodies is the primary process involved in the initiation of diabetic ketoacidosis in man. However, persistent overproduction of glucose and ketone bodies may not be necessary for the maintenance of hyperglycemia and hyperketonemia, since clearance of both substrates is impaired. Finally, since, of all counter-insulin hormones measured, only plasma glucagon increased coincident with increases in glucose and ketone body production, these results provide further evidence that glucagon may be the most important counter-insulin hormone involved in the genesis of ketoacidosis.

Original languageEnglish (US)
Pages (from-to)926-930
Number of pages5
JournalDiabetes
Volume29
Issue number11
StatePublished - 1980

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Ketone Bodies
Diabetic Ketoacidosis
Insulin
Glucose
Glucagon
Ketosis
Hormones
Hydroxybutyrates
Intravenous Infusions
Hyperglycemia
Growth Hormone
Hydrocortisone
Maintenance

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Effects of acute insulin deficiency on glucose and ketone body turnover in man. Evidence for the primacy of overproduction of glucose and ketone bodies in the genesis of diabetic ketoacidosis. / Miles, J. M.; Rizza, R. A.; Haymond, M. W.; Gerich, J. E.

In: Diabetes, Vol. 29, No. 11, 1980, p. 926-930.

Research output: Contribution to journalArticle

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abstract = "To assess the relative contribution of overproduction and underutilization of glucose and ketone bodies to the development of diabetic ketoacidosis in man, the effects of acute insulin deficiency on glucose and ketone body turnovers were determined in seven ketosis-prone (type I) diabetic subjects. After termination of prolonged intravenous infusions of insulin, which had been maintaining the subjects euglycemic, plasma free insulin decreased from 18 ± 4 μU/ml to 7 ± 1 μU/ml, P < 0.01; plasma glucagon increased from 67 ± 6 pg/ml to 259 ± 67 pg/ml, P < 0.05, but plasma growth hormone and cortisol did not increase. Plasma glucose increased from 5.4 ± 0.3 mM to 15.6 ± 1.0 mM, P < 0.01; plasma ketone bodies (β-hydroxybutyrate plus acetoacetate) increased from 1.4 ± 0.4 mM to 7.2 ± 1.5 mM, P < 0.01. Glucose production increased abruptly from 13.2 ± 1.1 μmol/kg-min to a maximum of 26.1 ± 2.9 μmol/kg-min at 2 h but then decreased toward baseline rates; glucose utilization also increased transiently. In contrast, both ketone body production and utilization increased progressively throughout the study from 5.4 ± 1.4 and 5.5 ± 1.1 to 18.3 ± 3.9 and 14.7 ± 2.1 μmol/kg-min, respectively, P < 0.01. Clearance of both glucose and ketone bodies decreased more than 50{\%}, P < 0.01. These results indicate that overproduction of glucose and ketone bodies is the primary process involved in the initiation of diabetic ketoacidosis in man. However, persistent overproduction of glucose and ketone bodies may not be necessary for the maintenance of hyperglycemia and hyperketonemia, since clearance of both substrates is impaired. Finally, since, of all counter-insulin hormones measured, only plasma glucagon increased coincident with increases in glucose and ketone body production, these results provide further evidence that glucagon may be the most important counter-insulin hormone involved in the genesis of ketoacidosis.",
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