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Submitted on October 22, 2004
Accepted on August 1, 2005
The Division of Geriatric Medicine, the Department of Medicine, University of British Columbia, Vancouver, BC (GSM); the Department of Medicine, the Mayo Clinic, Rochester, Mn (JDV); and the Department of Surgery, University of Massachusetts Medical School, MA (DE)
* To whom correspondence should be addressed. E-mail: dariush.elahi{at}umassmed.edu.
Context: Insulin is secreted in a pulsatile fashion with measurable orderliness (low entropy). Normal aging and diabetes in middle-aged patients is characterized by alterations in pulsatile insulin release.
Objectives: We undertook the current studies to determine if disruptions in pulsatile insulin release also accompany diabetes in the elderly.
Design: Two studies were performed. In the first study, insulin values were sampled every minute for 1 h under fasting conditions. In the second study, subjects underwent a 2 h hyperglycemic glucose clamp (glucose 5.4 mM above basal). From 60-120 min, insulin was sampled every 1 min. Secretory pulse analysis was conducted using a multiparameter deconvolution technique.
Setting: General clinical research center and outpatient visits
Patients: Volunteers were healthy young (n = 10, BMI=23 ± 1kg/m2, age=23 ± 1 yr) and elderly (n = 10, BMI=24 ± 1kg/m2, age=78 ± 2 yr) volunteers and elderly patients with diabetes (n = 8, BMI=28 ± 1kg/m2, age=73 ± 2 yr).
Intervention: Five of the older patients with type 2 diabetes (BMI=29 ± 1kg/m2, age=72 ± 2 yr) were treated with continuous sc GLP-1 (7-36) amide infusion for 6 weeks, and a second 2 h hyperglycemic clamp was performed.
Main Outcome Measures: Insulin burst mass, pulsatile insulin secretion and entropy
Results: Under fasting conditions, elderly patients with diabetes had a reduction in insulin burst mass (P < 0.05) that was similar to normal elderly. During hyperglycemia, elderly patients with diabetes had an even greater impairment in insulin burst mass (P < 0.05), basal (P < 0.05) and pulsatile insulin secretion (P < 0.05) than normal elderly. Approximate entropy, a measure of irregularity of insulin release, was increased to a greater extent in older diabetes patients than normal elderly, signifying loss of orderliness of insulin secretion (P < 0.05). In response to treatment with GLP-1 insulin burst mass (P < 0.05) and pulsatile insulin secretion (P < 0.05) improved significantly in elderly patients with diabetes.
Conclusions: We conclude that, alterations in pulsatile insulin release can be improved in elderly patients with diabetes by the administration of sc GLP-1
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  C. W. Chia and J. M. Egan Incretin-Based Therapies in Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3703 - 3716. [Abstract] [Full Text] [PDF]
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