Abnormalities in the ultradian oscillations of insulin secretion and glucose levels in Type 2 (non-insulin-dependent) diabetic patients

Abstract

To investigate the temporal organization of insulin secretion and glucose concentration during fasting in Type 2 (non-insulin-dependent) diabetes mellitus, we studied seven patients with Type 2 diabetes, eight obese non-diabetic control subjects and eight normal weight non-diabetic subjects. Blood sampling for glucose, insulin and C-peptide was performed at 15-min intervals during a 24-h period of fasting for the diabetic and the obese control subjects and during an 8-h fasting period for the normal subjects. Insulin secretion rates were calculated from the peripheral C-peptide concentration profiles. Ultradian oscillations of glucose levels and insulin secretion rates were evident during fasting in all subjects. An additional study with blood sampling at 2-min intervals for 8 h further indicated that this ultradian periodicity is expressed independently of rapid 10-15 min insulin oscillations. There were no differences between diabetic and non-diabetic subjects in the frequency of the ultradian oscillations of insulin secretion (which averaged 12-15 oscillations per 24 h) and in the rate of concomitancy of oscillations of insulin secretion with oscillations in glucose levels, which averaged 63-65%. The relative amplitudes of both the insulin and glucose oscillations were also similar in diabetic and nondiabetic subjects. The major abnormality in patients with Type 2 diabetes was evidenced by spectral analysis, and confirmed by calculations of the distributions of inter-pulse intervals. It consisted of a slowing of the glucose oscillations, without a similar slowing of the oscillations in insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

24-hour glucose profiles during continuous or oscillatory insulin infusion. Demonstration of the functional significance of ultradian insulin oscillations.

“…Thus, the ultradian oscillations in glucose levels and insulin secretion which have been observed in man and in laboratory animals under a variety of experimental conditions (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) may have functional significance in terms of improved efficiency of glucose regulation for a given rate of insulin delivery. The difference in glucose levels between the two modes of infusion averaged 1 mmol/liter, a clinically meaningful value.…”

“…Ultradian oscillations in glucose concentrations and insulin secretion have been observed in man and in laboratory animals in a variety of conditions, including fasting (3,4), constant glucose infusion (5)(6)(7)(8), continuous enteral nutrition (9,10), meal ingestion (11)(12)(13), and oral glucose loads (14). These oscillations are disrupted in impaired glucose tolerance ( 15 ), abdominal obesity (16), and non-insulin-dependent diabetes (15,17,18), suggesting that they may be important for the maintenance of normal glucose homeostasis.…”

Failure of physiological plasma glucose excursions to entrain high-frequency pulsatile insulin secretion in type 2 diabetes.

“…A number of studies have demonstrated increasing failure of glucose entrainment in individuals with impaired glucose tolerance and type 2 diabetes (14,23,24). Conversely, a substantial improvement in ␤-cell responsiveness to oscillatory glucose infusion after in vivo antidiabetic treatment with troglitazone (25) and glucagon-like peptide 1 has been reported (26).…”

Complex dynamics and multistability in a damped harmonic oscillator with delayed negative feedback

“…Examples include finger position, 27 pupil area in drowsy subjects, 28 and insulin levels in healthy individuals. 29 Since time delays are thought to be important features of the control mechanisms for these processes, it is tempting to speculate that these time series might reflect twotori generated by the control mechanism. However, it is not presently possible to eliminate the alternate possibility that the two frequencies represent the interaction of two distinct control mechanisms.…”