Deconvolution Analysis of Rapid Insulin Pulses before and after Six Weeks of Continuous Subcutaneous Administration of Glucagon-Like Peptide-1 in Elderly Patients with Type 2 Diabetes

Abstract

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. We undertook the current studies to determine whether disruptions in pulsatile insulin release also accompany diabetes in the elderly. 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. The study was conducted in a general clinical research center and during outpatient visits. Volunteers were healthy young [n = 10; body mass index (BMI), 23 +/- 1 kg/m2; age, 23 +/- 1 yr] and elderly (n = 10; BMI, 24 +/- 1 kg/m2; age, 78 +/- 2 yr) volunteers and elderly patients with diabetes (n = 8; BMI, 28 +/- 1 kg/m2; age, 73 +/- 2 yr). Five of the older patients with type 2 diabetes (BMI, 29 +/- 1 kg/m2; age, 72 +/- 2 yr) were treated with continuous sc glucagon-like peptide-1 (GLP-1) (7-36) amide infusion for 6 wk, and a second 2-h hyperglycemic clamp was performed. Insulin burst mass, pulsatile insulin secretion, and entropy were measured. 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) and 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. We conclude that alterations in pulsatile insulin release can be improved in elderly patients with diabetes by the administration of sc GLP-1.