Diurnal Pattern of Insulin Action in Type 1 diabetes: Implications for a Closed Loop System.

We have recently demonstrated a diurnal pattern to insulin action (SI) in healthy individuals with higher SI at breakfast than dinner. To determine if such a pattern exists in type 1 diabetes we studied 19 C-peptide negative subjects (HbA1c 7.1±0.6%) on insulin pump therapy with normal gastric emptying. Identical mixed meals were ingested during breakfast (B), lunch (L) or dinner (D) at 0700, 1300 and 1900 in randomized Latin Square order on three 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. While 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 B than L. There were no differences in meal glucose appearance or glucose disappearance between meals. Although there was no statistical difference (p=0.34) in SI between meals in type 1 diabetes participants, the diurnal pattern of SI taken across the three meals in its entirety, did differ (p=0.016) from healthy subjects. While the pattern in healthy subjects showed decreasing SI between B and L, the reverse SI pattern was observed in type 1 diabetes. The results suggest that in contrast to healthy subjects, SI diurnal pattern in type 1 diabetes is individual specific, hence cannot be extrapolated to the type 1 diabetes population as a whole thus implying that Artificial Pancreas algorithms may need to be personalized.