Intermittent versus continuous enteral nutrition attenuates increases in insulin and leptin during short-term bed rest

Abstract

Purpose: To compare endocrine responses to intermittent vs continuous enteral nutrition provision during short-term bed rest.

Methods: Twenty healthy men underwent 7 days of bed rest, during which they were randomized to receive enteral nutrition (47%E as carbohydrate, 34%E as fat, 16%E as protein and 3%E as fibre) in a continuous (CONTINUOUS; n = 10; 24 h day-1 at a constant rate) or intermittent (INTERMITTENT; n = 10; as 4 meals per day separated by 5 h) pattern. Daily plasma samples were taken every morning to assess metabolite/hormone concentrations.

Results: During bed rest, plasma leptin concentrations were elevated to a lesser extent with INTERMITTENT vs CONTINUOUS (iAUC: 0.42 ± 0.38 vs 0.95 ± 0.48 nmol L-1, respectively; P = 0.014) as were insulin concentrations (interaction effect, P < 0.001) which reached a peak of 369 ± 225 pmol L-1 in CONTINUOUS, compared to 94 ± 38 pmol L-1 in INTERMITTENT (P = 0.001). Changes in glucose infusion rate were positively correlated with changes in fasting plasma GLP-1 concentrations (r = 0.44, P = 0.049).

Conclusion: Intermittent enteral nutrition attenuates the progressive rise in plasma leptin and insulinemia seen with continuous feeding during bed rest, suggesting that continuous feeding increases insulin requirements to maintain euglycemia. This raises the possibility that hepatic insulin sensitivity is impaired to a greater extent with continuous versus intermittent feeding during bed rest. To attenuate endocrine and metabolic changes with enteral feeding, an intermittent feeding strategy may, therefore, be preferable to continuous provision of nutrition. This trial was registered on clinicaltrials.gov as NCT02521025.

Keywords: Glucagon; Glucagon-like peptide-1; Glucose; Insulin; Insulin sensitivity; Metabolism.

Conflict of interest statement

LJCvL has received research grants, consulting fees, speaking honoraria, or a combination of these, from Friesland Campina and Nutricia Research. JTG has received research support from Arla Foods Ingredients, Lucozade Ribena Suntory and Kenniscentrum Suiker en Voeding. JTG currently receives funding from the Medical Research Council (MR/P002927/1) and the Biotechnology and Biological Sciences Research Council (BB/R018928/1). None of the other authors have disclosed any conflicts of interest.

Figures

Fig. 1

Plasma glucose (a), insulin (b), GLP-1 (c), glucagon (d), ghrelin (e) and leptin (f) concentrations during 24 h of bed rest in a representative participant (n = 1), with enteral nutrition provided in either an intermittent (INTERMITTENT) or continuous (CONTINUOUS) pattern. Dashed vertical lines indicate when nutrition was provided in the intermittent condition. GLP-1 glucagon-like peptide-1

Fig. 2

Plasma concentrations of glucose (a), insulin (b), glucagon (c) and the insulin-to-glucagon ratio (d) before (day 0) and during 7 days of bed rest, and with enteral nutrition provided in either an intermittent (INTERMITTENT; n = 10) or continuous (CONTINUOUS; n = 10) pattern. Data are means ± 95% CI. *difference between INTERMITTENT and CONTINUOUS, P < 0.05

Fig. 3

Plasma concentrations of GLP-1 (a glucagon-like peptide-1), ghrelin (b), and leptin (c) concentrations before (day 0) and during 7 days of bed rest, and with enteral nutrition provided in either an intermittent (INTERMITTENT; n = 10) or continuous (CONTINUOUS; n = 10) pattern. Data are presented as group means ± 95% CI. *P < 0.05 for INTERMITTENT vs CONTINUOUS

Fig. 4

Relationship between plasma ghrelin concentration and appetite ratings during day 7 of bed rest conducted with enteral nutrition provided in either an intermittent (INTERMITTENT) or continuous (CONTINUOUS) pattern

Fig. 5

Change in fasting plasma glucose (a) insulin (b), glucagon (c), GLP-1 (d), ghrelin (e) and leptin (f) concentrations after 7 days of bed rest with enteral nutrition provided in either an intermittent (INTERMITTENT) or continuous (CONTINUOUS) pattern. GLP-1, glucagon-like peptide-1. Individual data are presented (n = 10 per group) alongside group means ± 95% CI

Fig. 6

Glucose infusion rate during a hyper-insulinemic, euglycemic clamp before (PRE) and after (POST) 7 days of bed rest with enteral nutrition (a), as previously reported (Dirks et al. 2019a). Relationship between the change in fasting plasma GLP-1 concentration and glucose infusion rate after 7 days of bed rest conducted with enteral nutrition provided in either an intermittent (INTERMITTENT) or continuous (CONTINUOUS) pattern (b)