TY - JOUR
T1 - Irregular circulating insulin concentrations in type 2 diabetes mellitus
T2 - An inverse relationship between circulating free fatty acid and the disorderliness of an insulin time series in diabetic and healthy individuals
AU - Schmitz, Ole
AU - Juhl, Claus B.
AU - Hollingdal, Malene
AU - Veldhuis, Johannes D.
AU - Porksen, Niels
AU - Pincus, Steven M.
N1 - Funding Information:
From the Department of Medicine M (Endocrinology and Diabetes), Kommunehospitalet, University Hospitals of Aarhus, and Department of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark; and the Endocrinology Division, National Science Foundation Center for Biological Timing, University of Virginia, Charlottesville, VA. Submitted December 9, 1999; accepted July 28, 2000. Supported by the Danish Medical Research Council, the Danish Diabetes Association, the Dandy Foundation, the Foundation of Medical Research, County of Vejle, and the Novo Nordic Foundation, Novo Nordisk, Copenhagen. Address reprint requests to Ole Schmitz, MD, Department of Medicine M (Endocrinology and Diabetes), Kommunehospitalet, Aarhus University Hospital, 8000 Aarhus C, Denmark. Copyright © 2001 by W.B. Saunders Company 0026-0495/01/5001-0023$10.00/0 doi:10.1053/meta.2001.19524
PY - 2001
Y1 - 2001
N2 - Insulin is released in a high-frequency pulsatile secretory pattern, which is reflected as quantifiable oscillations in peripheral circulating insulin concentrations. Type 2 diabetes mellitus is characterized by a broad spectrum of abnormalities in β-cell function, including disturbed pulsatile insulin secretion as assessed by autocorrelation analysis. To achieve further insight into β-cell pathophysiology in type 2 diabetes, we examined the orderliness of the baseline serum insulin time series (blood collection every minute for 75 minutes) in 16 type 2 diabetics (fasting plasma glucose, 170 ± 10 mg/dL [mean ± SE]; serum free fatty acid [FFA], 0.794 ± 0.083 mmol/L; and known diabetes duration, 6 ± 2 years) and 15 healthy controls (serum FFA, 0.523 ± 0.055 mmol/L). We used approximate entropy (ApEn), a recently introduced scale- and model-independent measure of serial irregularity. ApEn was significantly increased in the type 2 diabetics compared with the controls (0.671 ± 0.016 v 0.653 ± 0.008, P = .04), indicating more irregular serum insulin time series in diabetics. Autocorrelation also discriminated between groups, although only when the data were pooled. Interestingly, an inverse relationship between ApEn and serum FFA was observed in the controls (r = -.63, P = .01) and diabetics (r = -.65, P < .01), whereas no relationships were found between ApEn and the age, body mass index (BMI), or plasma glucose. In conclusion, type 2 diabetes is characterized by an increased disorderliness of the fasting serum insulin time series, strongly suggesting perturbed rapid oscillatory insulin release. An inverse relationship between ApEn and fasting serum FFA among both groups might suggest a hitherto unknown stabilizing action of FFA on the high-frequency pulsatile insulin release process. This hypothesis needs to be tested in experimental designs that more specifically focus on this issue, eg, during changes in serum FFA.
AB - Insulin is released in a high-frequency pulsatile secretory pattern, which is reflected as quantifiable oscillations in peripheral circulating insulin concentrations. Type 2 diabetes mellitus is characterized by a broad spectrum of abnormalities in β-cell function, including disturbed pulsatile insulin secretion as assessed by autocorrelation analysis. To achieve further insight into β-cell pathophysiology in type 2 diabetes, we examined the orderliness of the baseline serum insulin time series (blood collection every minute for 75 minutes) in 16 type 2 diabetics (fasting plasma glucose, 170 ± 10 mg/dL [mean ± SE]; serum free fatty acid [FFA], 0.794 ± 0.083 mmol/L; and known diabetes duration, 6 ± 2 years) and 15 healthy controls (serum FFA, 0.523 ± 0.055 mmol/L). We used approximate entropy (ApEn), a recently introduced scale- and model-independent measure of serial irregularity. ApEn was significantly increased in the type 2 diabetics compared with the controls (0.671 ± 0.016 v 0.653 ± 0.008, P = .04), indicating more irregular serum insulin time series in diabetics. Autocorrelation also discriminated between groups, although only when the data were pooled. Interestingly, an inverse relationship between ApEn and serum FFA was observed in the controls (r = -.63, P = .01) and diabetics (r = -.65, P < .01), whereas no relationships were found between ApEn and the age, body mass index (BMI), or plasma glucose. In conclusion, type 2 diabetes is characterized by an increased disorderliness of the fasting serum insulin time series, strongly suggesting perturbed rapid oscillatory insulin release. An inverse relationship between ApEn and fasting serum FFA among both groups might suggest a hitherto unknown stabilizing action of FFA on the high-frequency pulsatile insulin release process. This hypothesis needs to be tested in experimental designs that more specifically focus on this issue, eg, during changes in serum FFA.
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U2 - 10.1053/meta.2001.19524
DO - 10.1053/meta.2001.19524
M3 - Article
C2 - 11172473
AN - SCOPUS:0035176023
SN - 0026-0495
VL - 50
SP - 41
EP - 46
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 1
ER -