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Impaired Modulation of Hepatic Glucose Output Overnight after a 72-h Fast in Normal Man^*

J. N. CLORE, S. T. HELM, J. E. NESTLER and W. G. BLACKARD

Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University Richmond, Virginia 23298-0111

Address requests for reprints to: John N. Clore, M.D., Box 111, MCV Station, Medical College of Virginia, Richmond, Virginia 23298–0111.

We have previously reported a 25% fall in glucose utilization (Rd) and glucose production (Ra) in normal volunteers during an overnight fast, when glycogenolysis accounts for approximately 70% of hepatic glucose output (HGO). This reduction in Ra and Rd was positively correlated with reductions in glycerol and FFA. To determine if a similar fall in HGO occurs after a prolonged fast when HGO depends solely upon gluconeogenesis, seven normal male volunteers were fasted for 72 h. Glucose kinetics were then assessed overnight using a [3-³H]glucose infusion from 2200–0800 h. Plasma glucose (3.6 ± 0.1 mM), immunoreactive insulin (2.7 ± 0.4 mU/L), C-peptide (0.22 ± 0.03 nmol/L), Rd (1.30 ± 0.03 mg/kg·min), and Ra (1.28 ± 0.03 mg/kg·min) were suppressed, and plasma glucagon (98.8 ± 13.2 pmol/L) was elevated compared to values obtained during the overnight fast, but none of these parameters changed overnight after the 3-day fast. Plasma lactate (0.98 ± 0.09 mmol/L) and alanine (0.18 ± 0.03 mmol/L) levels were also unchanged throughout the night. Plasma glycerol (0.14 ± 0.03 mmol/L) and FFA (0.98 ± 0.07 mmol/L) were significantly elevated compared to values during the overnight fast, but failed to fall during the study as had been observed during a 14-h fast. We conclude that the modulation of HGO observed during an overnight fast does not occur during prolonged fasting. The lack of nocturnal modulation of HGO when plasma FFA and glycerol levels are fixed at elevated concentrations supports a role of FFA and/or glycerol in the modulation of HGO during an overnight fast.

^* This work was supported in part by NIH Grants RR-00065 and DK-18903. Portions of this study were presented in abstract form at the 24th Annual Meeting of the European Association for the Study of Diabetes, September 1988, Paris, France.

Recipient of a Clinical Associate Physician Award from the NIH.

Received June 30, 1989.

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