Disorderly and nonstationary insulin secretion in relatives of
patients with non-insulin-dependent diabetes mellitus.
Schmitz, Ole, Niels P[phi]rksen, Birgit Nyholm, Christian Skjaerbaek,
Peter C. Butler, Johannes D. Veldhuis, Steven M. Pincus.
Department of Medicine M (Endocrinology and Diabetes), University
Hospital of Aarhus and Institute for Experimental Clinical Research,
University of Aarhus, DK-8000 Aarhus C, Denmark, Endocrine Research
Unit, Mayo Clinic, Rochester, Minnesota 55905, National Science
Foundation Center for Biological Timing, Endocrinology Division,
University of Virginia, Charlottesville, Virginia 22908; and 4990
Moose Hill Road, Guilford, Connecticut 06437
APStracts 3:0197E, 1996.
To further explore the role of the -cell as a pathogenic factor behind
non-insulin-dependent diabetes mellitus (NIDDM), insulin secretion at
modest hyperglycemia was examined in 15 healthy first-degree
relatives of NIDDM patients and 13 anthropometrically and age matched
controls. Oral glucose tolerance test was normal in all, but the
relatives had impaired insulin-stimulated glucose uptake
(P<0.05) as assessed by the euglycemic clamp technique. During
a constant intravenous glucose infusion (4.0 or 4.5 mg/kg/min) for
135 minutes we performed a time-series analysis of serum insulin in
samples obtained at one-minute intervals for 75 minutes (time, 60 to
135 min). Plasma glucose was comparable in the two groups (8.2+/-0.3
and 7.7+/-0.3 mmol/l, P=0.17; relatives vs controls), while AUC of
serum insulin during the study period was higher in the relatives
(P<0.05). The recently introduced scale- and model-independent
statistic, Approximate Entropy (ApEn), as well as the coefficient of
variation for a 6 (9 and 15) point moving average (MA) were applied
to test regularity and stationarity of insulin secretion,
respectively. Both ApEn and 6 (9 and 15) point MA were able to
significantly discern the insulin time-series of the two groups
(P<0.05), demonstrating a higher degree of irregularity and
nonstationarity among the offspring. Moreover, when combining the two
complementary sets of statistics into a single "index of
nonpulsatility", an even more notable distinction was available
(P<0.01). No relationship was found between the altered
insulin secretion and the insulin resistance or the circulating
insulin levels. In conclusion, this approach demonstrates that the
stimulated insulin secretion of glucose tolerant relatives of NIDDM
patients is characterized by disorderliness. Whether this
experimental and statistic model can predict the risk for developing
a clinically important -cell dysfunction and eventually NIDDM remains
to be clarified.
Received 15 April 1996; accepted in final form 18 September 1996.
APS Manuscript Number E191-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996