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

Abstract

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 less than 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 less than 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 less than 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 set-point of glucose regulation amplified by counterregulatory mechanisms activated by the fasting condition.

Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity.

“…These conditions were chosen because they are known to result in concurrent stimulation of MGU and liver glucose uptake in nondiabetic humans (27,28). In addition, they mimic those commonly observed in diabetic individuals between meals and during the night (61)(62)(63)(64). Under these conditions, whole body glucose disposal was lower and EGP was higher in the diabetic than in the nondiabetic subjects.…”

Effects of breakfast meal composition on second meal metabolic responses in adults with type 2 diabetes mellitus

“…Graphical checks of normality were made by quantile-quantile (Q-Q) plots for each treatment, and for the entire test period. The hypothesis of log AUC values for each of the diets was formally verified by the Shapiro-Wilk test, P-values exceeded 0.77 (Shapiro et al, 1991).…”

Diurnal rhythm in endogenous glucose production is a major contributor to fasting hyperglycaemia in type 2 diabetes. Suprachiasmatic deficit or limit cycle behaviour?

“…One study reported diurnal variations in the concentrations and fluxes of glucose and other metabolites in diabetic, but not control, subjects [22]; another found elevated morning glucose levels in both diabetic and control subjects, although these were significantly attenuated in the latter group [23]; and still others observed no additional increase in glycaemia in overnight-fasted diabetic subjects [24,25]. These nocturnal increases in glucose may be related to the dawn phenomenon [26,27], although this usually starts later than the rise in EGP described here and is likely related to postprandial counter-regulatory effects.…”