Studies on the mass action effect of glucose in NIDDM and IDDM

Evidence for glucose resistance

S. Del Prato, M. Matsuda, D. C. Simonson, L. C. Groop, P. Sheehan, F. Leonetti, R. C. Bonadonna, Ralph A Defronzo

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The ability of hyperglycaemia to enhance glucose uptake was evaluated in 9 non-insulin-dependent (NIDDM), 7 insulin-dependent (IDDM) diabetic subjects, and in 6 young and 9 older normal volunteers. Following overnight insulin-induced euglycaemia, a sequential three-step hyperglycaemic clamp (+ 2.8 + 5.6, and + 11.2 mmol/l above baseline) was performed with somatostatin plus replacing doses of basal insulin and glucagon, 3-3H-glucose infusion and indirect calorimetry. In the control subjects as a whole, glucose disposal increased at each hyperglycaemic step (13.1 ± 0.6, 15.7 ± 0.7, and 26.3 ± 1.1 μmol/kg·min). In NIDDM (10.5 ± 0.2, 12.1 ± 1.0, and 17.5 ± 1.1 μmol/kg·min), and IDDM (11.2 ± 0.8, 12.9 ± 1.0, and 15.6 ± 1.1 μmol/kg·min) glucose disposal was lower during all three steps (p < 0.05- 0.005). Hepatic glucose production declined proportionally to plasma glucose concentration to a similar extent in all four groups of patients. In control subjects, hyperglycaemia stimulated glucose oxidation (+4.4 ± 0.7 μmol/kg·min) only at +11.2 mmol/l (p < 0.05), while non-oxidative glucose metabolism increased at each hyperglycaemic step (+3.1 ± 0.7; +3.5 ± 0.9, and +10.8 ± 1.7 μmol/kg·min; all p < 0.05). In diabetic patients, no increment in glucose oxidation was elicited even at the highest hyperglycaemic plateau (IDDM = + 0.5 ± 1.5; NIDDM = + 0.2 ± 0.6 μmol/kg·min) and non-oxidative glucose metabolism was hampered (IDDM = +1.8 ± 1.5, +3.1 ± 1.7, and +4.3 ± 1.8; NIDDM= +0.7 ± 0.6, 2.1 ± 0.9, and +7.0 ± 0.8 μmol/kg·min; p < 0.05-0.005). Blood lactate concentration increased and plasma non-esterified fatty acid (NEFA) fell in control (p < 0.05) but not in diabetic subjects. The increments in blood lactate were correlated with the increase in non-oxidative glucose disposal and with the decrease in plasma NEFA. In conclusion: 1) the ability of hyperglycaemia to promote glucose disposal is impaired in NIDDM and IDDM; 2) stimulation of glucose oxidation and non-oxidative glucose metabolism accounts for glucose disposal; 3) both pathways of glucose metabolism are impaired in diabetic patients; 4) impaired ability of hyperglycaemia to suppress plasma NEFA is present in these patients. These results suggest that glucose resistance, that is the ability of glucose itself to promote glucose utilization, is impaired in both IDDM and NIDDM patients.

Original languageEnglish (US)
Pages (from-to)687-697
Number of pages11
JournalDiabetologia
Volume40
Issue number6
DOIs
StatePublished - 1997

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Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Glucose
Hyperglycemia
Fatty Acids
Insulin
Lactic Acid
Indirect Calorimetry
Somatostatin
Glucagon

Keywords

  • Glucose oxidation
  • Glucose-mediated glucose metabolism
  • Hyperglycaemia
  • Mass action effect
  • Non-oxidative glucose metabolism

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Del Prato, S., Matsuda, M., Simonson, D. C., Groop, L. C., Sheehan, P., Leonetti, F., ... Defronzo, R. A. (1997). Studies on the mass action effect of glucose in NIDDM and IDDM: Evidence for glucose resistance. Diabetologia, 40(6), 687-697. https://doi.org/10.1007/s001250050735

Studies on the mass action effect of glucose in NIDDM and IDDM : Evidence for glucose resistance. / Del Prato, S.; Matsuda, M.; Simonson, D. C.; Groop, L. C.; Sheehan, P.; Leonetti, F.; Bonadonna, R. C.; Defronzo, Ralph A.

In: Diabetologia, Vol. 40, No. 6, 1997, p. 687-697.

Research output: Contribution to journalArticle

Del Prato, S, Matsuda, M, Simonson, DC, Groop, LC, Sheehan, P, Leonetti, F, Bonadonna, RC & Defronzo, RA 1997, 'Studies on the mass action effect of glucose in NIDDM and IDDM: Evidence for glucose resistance', Diabetologia, vol. 40, no. 6, pp. 687-697. https://doi.org/10.1007/s001250050735
Del Prato S, Matsuda M, Simonson DC, Groop LC, Sheehan P, Leonetti F et al. Studies on the mass action effect of glucose in NIDDM and IDDM: Evidence for glucose resistance. Diabetologia. 1997;40(6):687-697. https://doi.org/10.1007/s001250050735
Del Prato, S. ; Matsuda, M. ; Simonson, D. C. ; Groop, L. C. ; Sheehan, P. ; Leonetti, F. ; Bonadonna, R. C. ; Defronzo, Ralph A. / Studies on the mass action effect of glucose in NIDDM and IDDM : Evidence for glucose resistance. In: Diabetologia. 1997 ; Vol. 40, No. 6. pp. 687-697.
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TY - JOUR

T1 - Studies on the mass action effect of glucose in NIDDM and IDDM

T2 - Evidence for glucose resistance

AU - Del Prato, S.

AU - Matsuda, M.

AU - Simonson, D. C.

AU - Groop, L. C.

AU - Sheehan, P.

AU - Leonetti, F.

AU - Bonadonna, R. C.

AU - Defronzo, Ralph A

PY - 1997

Y1 - 1997

N2 - The ability of hyperglycaemia to enhance glucose uptake was evaluated in 9 non-insulin-dependent (NIDDM), 7 insulin-dependent (IDDM) diabetic subjects, and in 6 young and 9 older normal volunteers. Following overnight insulin-induced euglycaemia, a sequential three-step hyperglycaemic clamp (+ 2.8 + 5.6, and + 11.2 mmol/l above baseline) was performed with somatostatin plus replacing doses of basal insulin and glucagon, 3-3H-glucose infusion and indirect calorimetry. In the control subjects as a whole, glucose disposal increased at each hyperglycaemic step (13.1 ± 0.6, 15.7 ± 0.7, and 26.3 ± 1.1 μmol/kg·min). In NIDDM (10.5 ± 0.2, 12.1 ± 1.0, and 17.5 ± 1.1 μmol/kg·min), and IDDM (11.2 ± 0.8, 12.9 ± 1.0, and 15.6 ± 1.1 μmol/kg·min) glucose disposal was lower during all three steps (p < 0.05- 0.005). Hepatic glucose production declined proportionally to plasma glucose concentration to a similar extent in all four groups of patients. In control subjects, hyperglycaemia stimulated glucose oxidation (+4.4 ± 0.7 μmol/kg·min) only at +11.2 mmol/l (p < 0.05), while non-oxidative glucose metabolism increased at each hyperglycaemic step (+3.1 ± 0.7; +3.5 ± 0.9, and +10.8 ± 1.7 μmol/kg·min; all p < 0.05). In diabetic patients, no increment in glucose oxidation was elicited even at the highest hyperglycaemic plateau (IDDM = + 0.5 ± 1.5; NIDDM = + 0.2 ± 0.6 μmol/kg·min) and non-oxidative glucose metabolism was hampered (IDDM = +1.8 ± 1.5, +3.1 ± 1.7, and +4.3 ± 1.8; NIDDM= +0.7 ± 0.6, 2.1 ± 0.9, and +7.0 ± 0.8 μmol/kg·min; p < 0.05-0.005). Blood lactate concentration increased and plasma non-esterified fatty acid (NEFA) fell in control (p < 0.05) but not in diabetic subjects. The increments in blood lactate were correlated with the increase in non-oxidative glucose disposal and with the decrease in plasma NEFA. In conclusion: 1) the ability of hyperglycaemia to promote glucose disposal is impaired in NIDDM and IDDM; 2) stimulation of glucose oxidation and non-oxidative glucose metabolism accounts for glucose disposal; 3) both pathways of glucose metabolism are impaired in diabetic patients; 4) impaired ability of hyperglycaemia to suppress plasma NEFA is present in these patients. These results suggest that glucose resistance, that is the ability of glucose itself to promote glucose utilization, is impaired in both IDDM and NIDDM patients.

AB - The ability of hyperglycaemia to enhance glucose uptake was evaluated in 9 non-insulin-dependent (NIDDM), 7 insulin-dependent (IDDM) diabetic subjects, and in 6 young and 9 older normal volunteers. Following overnight insulin-induced euglycaemia, a sequential three-step hyperglycaemic clamp (+ 2.8 + 5.6, and + 11.2 mmol/l above baseline) was performed with somatostatin plus replacing doses of basal insulin and glucagon, 3-3H-glucose infusion and indirect calorimetry. In the control subjects as a whole, glucose disposal increased at each hyperglycaemic step (13.1 ± 0.6, 15.7 ± 0.7, and 26.3 ± 1.1 μmol/kg·min). In NIDDM (10.5 ± 0.2, 12.1 ± 1.0, and 17.5 ± 1.1 μmol/kg·min), and IDDM (11.2 ± 0.8, 12.9 ± 1.0, and 15.6 ± 1.1 μmol/kg·min) glucose disposal was lower during all three steps (p < 0.05- 0.005). Hepatic glucose production declined proportionally to plasma glucose concentration to a similar extent in all four groups of patients. In control subjects, hyperglycaemia stimulated glucose oxidation (+4.4 ± 0.7 μmol/kg·min) only at +11.2 mmol/l (p < 0.05), while non-oxidative glucose metabolism increased at each hyperglycaemic step (+3.1 ± 0.7; +3.5 ± 0.9, and +10.8 ± 1.7 μmol/kg·min; all p < 0.05). In diabetic patients, no increment in glucose oxidation was elicited even at the highest hyperglycaemic plateau (IDDM = + 0.5 ± 1.5; NIDDM = + 0.2 ± 0.6 μmol/kg·min) and non-oxidative glucose metabolism was hampered (IDDM = +1.8 ± 1.5, +3.1 ± 1.7, and +4.3 ± 1.8; NIDDM= +0.7 ± 0.6, 2.1 ± 0.9, and +7.0 ± 0.8 μmol/kg·min; p < 0.05-0.005). Blood lactate concentration increased and plasma non-esterified fatty acid (NEFA) fell in control (p < 0.05) but not in diabetic subjects. The increments in blood lactate were correlated with the increase in non-oxidative glucose disposal and with the decrease in plasma NEFA. In conclusion: 1) the ability of hyperglycaemia to promote glucose disposal is impaired in NIDDM and IDDM; 2) stimulation of glucose oxidation and non-oxidative glucose metabolism accounts for glucose disposal; 3) both pathways of glucose metabolism are impaired in diabetic patients; 4) impaired ability of hyperglycaemia to suppress plasma NEFA is present in these patients. These results suggest that glucose resistance, that is the ability of glucose itself to promote glucose utilization, is impaired in both IDDM and NIDDM patients.

KW - Glucose oxidation

KW - Glucose-mediated glucose metabolism

KW - Hyperglycaemia

KW - Mass action effect

KW - Non-oxidative glucose metabolism

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