The Impact of a Fat-Dominant Preload Before a Carbohydrate-Rich Meal on Glucose Homeostasis in Patients Without Diabetes After Sleeve Gastrectomy: A Proof-of-Concept, Randomised, Open-Label, Crossover Study

Whelehan, Gráinne; Herring, Louisa Y.; Tziannou, Aikaterina; Henson, Joseph; Thackray, Alice E.; Bowrey, David; Abraham, Jenny; Menon, Vinod; Idris, Iskandar; Waller, Helen; Stensel, David J.; Webb, David R.; Yates, Thomas; Davies, Melanie J.; Papamargaritis, Dimitris

doi:10.3390/nu18030469

Open AccessArticle

The Impact of a Fat-Dominant Preload Before a Carbohydrate-Rich Meal on Glucose Homeostasis in Patients Without Diabetes After Sleeve Gastrectomy: A Proof-of-Concept, Randomised, Open-Label, Crossover Study

by

Gráinne Whelehan

^1,2,3

,

Louisa Y. Herring

^1,2

,

Aikaterina Tziannou

¹

,

Joseph Henson

¹,

Alice E. Thackray

^3,4

,

David Bowrey

⁵,

Jenny Abraham

⁶,

Vinod Menon

^6,7,

Iskandar Idris

⁷

,

Helen Waller

^1,3,

David J. Stensel

^3,4,8,9

,

David R. Webb

^1,2,3,

Thomas Yates

^1,2,3,

Melanie J. Davies

^1,2,3

and

Dimitris Papamargaritis

^1,2,10,*

¹

Diabetes Research Centre, University of Leicester, Leicester LE1 7RH, UK

²

Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester LE5 4PW, UK

³

NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester LE5 4PW, UK

⁴

National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, UK

⁵

Department of Surgery, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, UK

⁶

Department of General Surgery, University Hospitals Coventry & Warwickshire NHS Trust Coventry, Coventry CV2 2DX, UK

⁷

Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK

⁸

Faculty of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan

⁹

Department of Sports Science and Physical Education, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong

¹⁰

Department of Diabetes and Endocrinology, Kettering General Hospital NHS Trust, Kettering NN16 8UZ, UK

^*

Author to whom correspondence should be addressed.

Nutrients 2026, 18(3), 469; https://doi.org/10.3390/nu18030469

Submission received: 5 January 2026 / Revised: 27 January 2026 / Accepted: 29 January 2026 / Published: 31 January 2026

(This article belongs to the Special Issue Diet and Nutrition in Bariatric Interventions)

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Abstract

Background/Objectives: Sleeve gastrectomy (SG) improves glycaemic control; however, it also markedly accelerates gastric emptying, which can lead to exaggerated postprandial glucose and insulin excursions and, in some cases, postprandial hyperinsulinaemic hypoglycaemia. In non-surgical populations, fat preloads can reduce postprandial glycaemia by slowing gastric emptying, but their effects after SG are unclear. Methods: Ten adults >1-year post-SG completed a randomised, open-label, crossover study involving two mixed-meal tolerance tests (MMTTs), preceded (−30 min) by either a moderate, fat-dominant preload (28 g Brazil nuts) or 100 mL water (control). Blood samples were collected over three hours to assess plasma glucose, insulin, c-peptide, and total glucagon-like peptide-1 (GLP-1). Hypoglycaemia and dumping symptoms were assessed using validated questionnaires. Nadir plasma glucose concentration was the primary outcome. Results: Nadir plasma glucose was identical between conditions (both 3.8 mmol/L; 95% CI: −0.4, 0.3, p = 0.849), and neither peak glucose nor overall postprandial glucose exposure (incremental area under the curve iAUC_{0–180 min}) differed between the preload and water conditions. Insulin and c-peptide concentrations immediately before the MMTT were higher after the fat-dominant preload (both p < 0.001). Overall insulin and c-peptide responses during the MMTT (iAUC_{0–180 min}) remained comparable between conditions (95% CI −225, 2665; p = 0.442 and −67,787, 70,263; 0.968), but peak values for both hormones were higher after the preload (95% CI 2.9, 79.1, p = 0.038 and 17.3, 2402.7, p = 0.040, respectively). Total GLP-1 was also elevated prior to the MMTT (95% CI 1.6, 22.8, p = 0.028), while its early and overall postprandial responses did not differ (both p > 0.05). Ratings of hypoglycaemia and dumping symptoms were similar for both study arms. Discussion: A moderate, fat-dominant preload consumed before a mixed meal did not alter nadir or overall postprandial glucose in adults without diabetes after SG. However, the preload was associated with higher peak insulin secretion, a finding that should be interpreted with caution, as the study was not powered for secondary outcomes. Given the unique gastrointestinal physiology after SG, further research is needed to determine how different nutrient compositions or timing approaches influence postprandial glucose homeostasis in this population.

Keywords: bariatric surgery; sleeve gastrectomy; preload; fat-dominant; glucose; insulin; glucose homeostasis; c-peptide; glucagon-like peptide-1

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MDPI and ACS Style

Whelehan, G.; Herring, L.Y.; Tziannou, A.; Henson, J.; Thackray, A.E.; Bowrey, D.; Abraham, J.; Menon, V.; Idris, I.; Waller, H.; et al. The Impact of a Fat-Dominant Preload Before a Carbohydrate-Rich Meal on Glucose Homeostasis in Patients Without Diabetes After Sleeve Gastrectomy: A Proof-of-Concept, Randomised, Open-Label, Crossover Study. Nutrients 2026, 18, 469. https://doi.org/10.3390/nu18030469

AMA Style

Whelehan G, Herring LY, Tziannou A, Henson J, Thackray AE, Bowrey D, Abraham J, Menon V, Idris I, Waller H, et al. The Impact of a Fat-Dominant Preload Before a Carbohydrate-Rich Meal on Glucose Homeostasis in Patients Without Diabetes After Sleeve Gastrectomy: A Proof-of-Concept, Randomised, Open-Label, Crossover Study. Nutrients. 2026; 18(3):469. https://doi.org/10.3390/nu18030469

Chicago/Turabian Style

Whelehan, Gráinne, Louisa Y. Herring, Aikaterina Tziannou, Joseph Henson, Alice E. Thackray, David Bowrey, Jenny Abraham, Vinod Menon, Iskandar Idris, Helen Waller, and et al. 2026. "The Impact of a Fat-Dominant Preload Before a Carbohydrate-Rich Meal on Glucose Homeostasis in Patients Without Diabetes After Sleeve Gastrectomy: A Proof-of-Concept, Randomised, Open-Label, Crossover Study" Nutrients 18, no. 3: 469. https://doi.org/10.3390/nu18030469

APA Style

Whelehan, G., Herring, L. Y., Tziannou, A., Henson, J., Thackray, A. E., Bowrey, D., Abraham, J., Menon, V., Idris, I., Waller, H., Stensel, D. J., Webb, D. R., Yates, T., Davies, M. J., & Papamargaritis, D. (2026). The Impact of a Fat-Dominant Preload Before a Carbohydrate-Rich Meal on Glucose Homeostasis in Patients Without Diabetes After Sleeve Gastrectomy: A Proof-of-Concept, Randomised, Open-Label, Crossover Study. Nutrients, 18(3), 469. https://doi.org/10.3390/nu18030469

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The Impact of a Fat-Dominant Preload Before a Carbohydrate-Rich Meal on Glucose Homeostasis in Patients Without Diabetes After Sleeve Gastrectomy: A Proof-of-Concept, Randomised, Open-Label, Crossover Study

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