Diurnal Pattern of Insulin Action in Type 1 Diabetes
Implications for a Closed-Loop System
- Ling Hinshaw1,
- Chiara Dalla Man2,
- Debashis K. Nandy1,
- Ahmed Saad1,
- Adil E. Bharucha3,
- James A. Levine1,
- Robert A. Rizza1,
- Rita Basu1,
- Rickey E. Carter4,
- Claudio Cobelli2,
- Yogish C. Kudva1 and
- Ananda Basu1⇑
- 1Department of Endocrinology, Mayo Clinic, Rochester, Minnesota
- 2Department of Information Engineering, University of Padova, Padova, Italy
- 3Division of Gastroenterology, Mayo Medical School, Rochester, Minnesota
- 4Department of Health Sciences Research, Mayo Medical School, Rochester, Minnesota
- Corresponding author: Ananda Basu, .
L.H., C.D.M., and D.K.N. contributed equally to this work.
We recently demonstrated a diurnal pattern to insulin action (i.e., insulin sensitivity [SI]) in healthy individuals with higher SI at breakfast than at dinner. To determine whether such a pattern exists in type 1 diabetes, we studied 19 subjects with C-peptide–negative diabetes (HbA1c 7.1 ± 0.6%) on insulin pump therapy with normal gastric emptying. Identical mixed meals were ingested during breakfast, lunch, and dinner at 0700, 1300, and 1900 h in randomized Latin square of order on 3 consecutive days when measured daily physical activity was equal. The triple tracer technique enabled measurement of glucose fluxes. Insulin was administered according to the customary insulin:carbohydrate ratio for each participant. Although postprandial glucose excursions did not differ among meals, insulin concentration was higher (P < 0.01) and endogenous glucose production less suppressed (P < 0.049) at breakfast than at lunch. There were no differences in meal glucose appearance or in glucose disappearance between meals. Although there was no statistical difference (P = 0.34) in SI between meals in type 1 diabetic subjects, the diurnal pattern of SI taken across the three meals in its entirety differed (P = 0.016) from that of healthy subjects. Although the pattern in healthy subjects showed decreasing SI between breakfast and lunch, the reverse SI pattern was observed in type 1 diabetic subjects. The results suggest that in contrast to healthy subjects, SI diurnal pattern in type 1 diabetes is specific to the individual and cannot be extrapolated to the type 1 diabetic population as a whole, implying that artificial pancreas algorithms may need to be personalized.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-1759/-/DC1.
See accompanying commentary, p. 2173.
- Received December 14, 2012.
- Accepted February 19, 2013.
- © 2013 by the American Diabetes Association.
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