Effects of aging on glucose regulation during wakefulness and sleep.

Glucose intolerance, reduced sleep efficiency, and disturbed circadian rhythmicity occur in aging. In normal young subjects, glucose regulation is modulated by sleep and circadian rhythmicity. To examine age-related alterations in the temporal pattern of glucose tolerance and insulin secretion, eight modestly overweight healthy older men, eight weight-matched young men, and six young lean men were studied during constant glucose infusion for 53 h. Levels of glucose, insulin, C-peptide, and growth hormone (GH) were measured every 20 min. Rates of insulin and GH secretion were calculated by deconvolution. In older volunteers, sleep ws shallow and more fragmented than in young subjects but was nevertheless associated with robust glucose elevations. However, postsleep increases of insulin secretion were markedly dampened. During wakefulness, the normal morning-to-evening increase in glucose was preserved in the elderly, but insulin secretion failed to increase proportionately. Thus decreased glucose tolerance in aging is associated with insulin resistance and also with a relative insensitivity of the beta-cell to the modulation of glucose regulation by sleep and circadian rhythmicity.

Oscillatory insulin secretion after pancreas transplant.

In vivo studies of beta-cell secretory function have demonstrated the existence of rapid insulin oscillations of small amplitude recurring every 8-15 min in normal subjects. This study evaluated the effects of pancreas transplant on rapid insulin oscillations. Samples for glucose, insulin, and C-peptide were drawn during constant glucose infusion at 2-min intervals for 90 min from six successful Px patients with type I diabetes mellitus, from six normal nondiabetic control subjects, and from three Kx subjects. A computerized algorithm (ULTRA) was used for pulse detection. In the Px group, the average insulin pulse period was significantly shorter than in both the control and Kx groups (Px 8.1 +/- 0.5, control 12.5 +/- 0.7, Kx 12.4 +/- 0.5 min, P < 0.0005). By contrast, the C-peptide pulse periods (Px 16.8 +/- 2.3, control 14.7 +/- 1.2, Kx 15.3 +/- 1.5 min) were similar in the three groups. Spectral analysis confirmed that the frequency of the insulin pulses was increased in the Px group. The absolute amplitude of the insulin pulses was greater in the Px group (P < 0.001) while the amplitude of the C-peptide pulses did not differ between the groups. Cross-correlation analysis demonstrated maximal correlation coefficients at a lag of 0 min between insulin and C-peptide (control r = 0.33, P < 0.0001; Kx r = 0.17, P = 0.06) and between insulin and glucose (control r = 0.21, P < 0.001; Kx r = 0.20, P < 0.02) in the control and Kx groups, respectively, whereas no significant correlations were observed at any lag in the Px group.(ABSTRACT TRUNCATED AT 250 WORDS)

Analytical problems in detecting rapid insulin secretory pulses in normal humans.

The present study was undertaken to define the optimal experimental and analytical conditions necessary to reproducibly detect, in the systemic blood, small-amplitude rapid oscillations (period 8-15 min) of insulin and C-peptide. Samples for insulin, C-peptide, and glucose were drawn at 2-min intervals for 2 h from six normal subjects during constant glucose infusion and from five of the same subjects under basal conditions. To reduce measurement error, insulin and C-peptide levels were measured 16 times at each time point. Three algorithms for pulse analysis (ULTRA, Cluster, PulseFit) were used to identify significant pulses, whereas autocorrelation and spectral analysis were used to identify potential regular periodic components in the data. In three of the five subjects studied under basal conditions, regular rapid oscillations could be consistently detected by autocorrelation when the analysis was based on eight replicates but not on duplicate series. In the remaining two basal studies and in all studies during glucose infusion, the majority of profiles did not have a significant periodic component. However, formal pulse analysis demonstrated that the number of pulses was similar during glucose infusion and basal conditions. Reproducibility was enhanced by increasing the number of replicates used in the analysis. We conclude that in the analysis of small-amplitude rapid insulin and C-peptide oscillations, the sensitivity and specificity of the analysis is likely to be enhanced by performing multiple estimations at each time point and by using a minimum of two contrasting analytical approaches for pulse detection, which incorporate a method evaluating periodicity in conjunction with a pulse detection program designed to evaluate each individual oscillation separately.