Diurnal pattern of insulin action in type 1 diabetes: implications for a closed-loop system

Diabetes. 2013 Jul;62(7):2223-9. doi: 10.2337/db12-1759. Epub 2013 Feb 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose*
  • C-Peptide / blood
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood*
  • Insulin Aspart / therapeutic use
  • Male
  • Middle Aged
  • Motor Activity / physiology
  • Postprandial Period

Substances

  • Blood Glucose
  • C-Peptide
  • Hypoglycemic Agents
  • Insulin
  • Insulin Aspart