Diurnal Pattern of Insulin Action in Type 1 Diabetes

Implications for a Closed-Loop System

  1. Ananda Basu1
  1. 1Department of Endocrinology, Mayo Clinic, Rochester, Minnesota
  2. 2Department of Information Engineering, University of Padova, Padova, Italy
  3. 3Division of Gastroenterology, Mayo Medical School, Rochester, Minnesota
  4. 4Department of Health Sciences Research, Mayo Medical School, Rochester, Minnesota
  1. Corresponding author: Ananda Basu, basu.ananda{at}mayo.edu.
  1. L.H., C.D.M., and D.K.N. contributed equally to this work.

Abstract

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.

Footnotes

  • Received December 14, 2012.
  • Accepted February 19, 2013.

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  1. Diabetes vol. 62 no. 7 2223-2229
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