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Increased Disorderliness of Basal Insulin Release, Attenuated Insulin Secretory Burst Mass, and Reduced Ultradian Rhythmicity of Insulin Secretion in Older Individuals¹

Division of Geriatric Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; the Department of Medicine and the Geriatric Research Education and Clinical Center, University of Maryland, Baltimore, Maryland 00000; the Department of Medicine, University of Virginia, Charlottesville, Virginia 00000; and the Department of Medicine, Harvard University, Boston, Massachusetts 00000

Address all correspondence and requests for reprints to: Dr. Graydon Meneilly, Division of Geriatric Medicine, Department of Medicine, VH&HSC-UBC Site–Room S139, Vancouver, British Columbia, Canada V6T 2B5.

Insulin is secreted in a pulsatile fashion. Rapid pulses are considered to be important for inhibiting hepatic glucose output, and ultradian pulses for stimulating peripheral glucose disposal. Aging is characterized by a progressive impairment in carbohydrate tolerance. We undertook the current studies to determine whether alterations in pulsatile insulin release accompany the age-related changes in carbohydrate metabolism. Healthy young (n = 8; body mass index, 21 ± 1 kg/m²; age, 24 ± 1 yr) and old (n = 9; body mass index, 24 ± 1 kg/m²; age, 77 ± 2 yr) volunteers underwent two studies. In the first study, insulin was sampled every 1 min for 150 min, and pulse analysis was conducted using a recently validated multiparameter deconvolution technique. In the second study, insulin was sampled every 10 min for 600 min, and insulin release was evaluated by Cluster analysis. In the 150-min studies, insulin secretory burst mass (P < 0.05) and amplitude (P < 0.01) were reduced in the elderly. In addition, approximate entropy, a measure of irregularity or disorderliness of insulin release, was increased in the aged (P < 0.01). In the 600-min studies, interpulse interval was greater in the aged (P < 0.05), and burst number was less (P < 0.05).

We conclude that normal aging is characterized by more disorderly insulin release, a reduction in the amplitude and mass of rapid insulin pulses, and a decreased frequency of ultradian pulses. Whether these alterations in insulin pulsatility contribute directly to the age-related changes in carbohydrate metabolism will require further study.

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