Unpredictable feeding impairs glucose tolerance in growing lambs

Abstract

Irregular eating is associated with insulin resistance and metabolic disease in adults but may affect young, growing children differently. We investigated the metabolic effects of unpredictable feeding in female juvenile lambs randomly assigned to receive, for six weeks, maintenance feed given twice daily in equal portions (Control Group, C; n = 24) or the same weekly feed amount in aliquots of variable size at unpredictable times (Unpredictable Group, U; n = 21). Intravenous glucose tolerance tests (IVGTT), insulin tolerance tests (ITT), and measurement of diurnal plasma cortisol concentrations were performed pre and post the dietary intervention. Groups were compared using t test and RM ANOVA. Weight gain was similar in both groups (C 18 ± 2%; U 16 ± 2% of initial body weight). Glucose area under the curve (AUC) was unchanged in C (AUC pre 818 ± 34, post 801 ± 33 mmol.min.l(-1)), but increased by 20% in U (pre 830 ± 25, post 1010 ± 19 mmol.min.l(-1); p<0.0001), with an inadequate insulin response to glucose load (log(AUC insulin first 40 minutes) post intervention C 1.49 ± 0.04 vs U 1.36 ± 0.04 ng.min.ml(-1); p = 0.03). Insulin tolerance and diurnal variation of plasma cortisol concentrations were not different between groups. Unpredictable feeding impairs insulin response to glucose in growing lambs despite high quality food and normal weight gain. Irregular eating warrants investigation as a potentially remediable risk factor for disordered glucose metabolism.

Figure 1. Glucose and insulin responses to intravenous glucose tolerance test.

Plasma glucose (A,B) and insulin (D,E) concentrations and area under the curve (AUC) (C,F) during intravenous glucose tolerance test (IVGTT) before (A,D) and after (B,E) the six week dietary intervention, in regularly fed (C) and unpredictably fed (U) sheep. Values are mean±SEM. ***p<0.001 for difference between C and U groups ###p<0.001 for difference pre and post intervention within an experimental group Log(AUC40) Insulin = log area under the curve for insulin response in the first 40 minutes after the glucose bolus.

Figure 2. Glucose and free fatty acid response to insulin tolerance test.

Plasma glucose (A,B) and free fatty acid (ffa)(C,D) concentrations during insulin tolerance test (ITT) before (A,C) and after (B,D) the six week dietary intervention in regularly fed (C) and unpredictably fed (U) sheep. Values are mean±SEM. ** p<0.01 for difference between C and U groups in the timing of nadir plasma glucose concentration. Time effect p<0.001, group × time interaction p<0.001; group effect p = 0.06 for plasma free fatty acid (ffa) concentrations after the intervention (D).

Figure 3. Effect of unpredictable feeding on diurnal cortisol concentrations.

Diurnal plasma cortisol concentrations, before (A) and after (B) the six week dietary intervention in regularly fed (C) and unpredictably fed (U) sheep. Values are mean±SEM. There are no significant differences between groups. Solid lines parallel to the x axis reflect periods of darkness.