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Nocturnal Elevation of Glucose Levels during Fasting in Noninsulin-Dependent Diabetes^*

E. TIMOTHY SHAPIRO, KENNETH S. POLONSKY, GEORGES COPINSCHI, DANIÈLE BOSSON, HARTMUT TILLIL, JOHN BLACKMAN, GARY LEWIS and EVE VAN CAUTER

Department of Medicine, University of Chicago Chicago, Illinois 60637
Uniuersité Libre de Bruxelles School of Medicine Brussels, Belgium

Address all correspondence and requests for reprints to: Eve Van Cauter, Ph.D., Department of Medicine, Box 138, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637.

To define the spontaneous diurnal variations in glucose regulation during fasting in noninsulin-dependent diabetes (NIDDM), we measured circulating levels of glucose, insulin, C-peptide, GH, cortisol, and glucagon at 15-min intervals in 11 patients with untreated diabetes and 7 matched control subjects studied during a 24-h period. The rates of insulin secretion were derived from the concentrations of C-peptide by deconvolution using a two-compartment mathematical model for C-peptide distribution and metabolism.

In both groups of subjects, despite continued fasting, glucose levels stopped declining in the evening and subsequently rose throughout the night to reach a morning maximum. Elevated levels persisted until noon. The morning glucose maximum corresponded to a relative increase of 23.8 ± 5.5% above the evening nadir in NIDDM patients and 13.2 ± 4.6% in nondiabetic subjects (P < 0.05). In NIDDM patients, insulin levels and insulin secretion rates did not parallel the nocturnal glucose changes. In contrast, in control subjects, this nocturnal glucose rise coincided with a similar increase in insulin secretion rates.

Cortisol concentrations in patients with NIDDM were higher than those in control subjects throughout the study period (P < 0.001) and rose earlier in the evening than in control subjects, thus failing to demonstrate the normal nocturnal suppression. In both groups of subjects, the nighttime glucose elevation was temporally and quantitatively correlated with the circadian cortisol rise. GH secretion was increased in the evening and nighttime periods compared to the daytime values, and in NIDDM patients, but not in control subjects, the size of the morning glucose elevation was directly related to the magnitude of this increase in GH secretion (r = 0.88; P < 0.01). Glucagon concentrations were similar in both groups of subjects and remained essentially constant throughout the study period.

We hypothesize that the nocturnal glucose rise that occurs during fasting represents a normal diurnal variation in the setpoint of glucose regulation amplified by counterregulatory mechanisms activated by the fasting condition.

^* This work was supported in part by Grants DK-31842, DK-20595, and DK-41814 from the NIH, the General Clinical Research Center the University of Chicago (RR-00055), and a grant from the Belgian Fonds de la Recherche Scientifique Médicale.

Recipient of a Research Career Development Award from the NIH.

Received March 5, 1990.

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