Effects of combined intraduodenal administration of lauric acid and l-tryptophan on postprandial plasma glucose, glucoregulatory hormones and gastric emptying in type 2 diabetes: a double-blind, randomised, crossover study

In a randomised, blinded (investigators and participants), crossover study performed in the University of Adelaide Clinical Research Facility, 11 men with type 2 diabetes (age: 69 ± 7 years; HbA₁c: 51 ± 5 mmol/mol [6.8 ± 0.3%]; BMI: 28 ± 1 kg/m²), each received, on four separate occasions, 45 min intraduodenal infusions of C12 (1.26 kJ/min), Trp (0.42 kJ/min), C12+Trp (1.68 kJ/min), or 0.9% saline (control), 30 min before a mixed-nutrient drink (350 ml, 2092 kJ (500 kcal), 74 g carbohydrate) containing 100 mg ¹³C-acetate. Plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and CCK concentrations were measured at baseline, following treatments alone, and for 180 min post-drink. Gastric emptying was assessed via ¹³C-acetate breath test.

C12+Trp, but not C12 or Trp, reduced overall (p=0.02) and peak (mmol/l; control: 11.1 ± 0.6, Trp: 10.3 ± 0.5, C12: 10.7 ± 0.6, C12+Trp: 9.8 ± 0.5; p=0.01) plasma glucose. C12+Trp slowed gastric emptying (p=0.001), and increased pre-drink plasma GLP-1, GIP and CCK (all p<0.05), without affecting insulin or C-peptide. No treatment effects were observed postprandially.

In type 2 diabetes, intraduodenal C12+Trp lowers postprandial glucose, probably primarily by slowing of gastric emptying and mediated by GLP-1 and CCK. These findings support further exploration of nutrient-based gastrointestinal strategies to optimise glycaemic management in type 2 diabetes.

Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) ACTRN12623000778684

JAS and VB were each supported by Adelaide Scholarship International stipends, provided by the University of Adelaide (JAS, 2021–2025; VB, 2017–2020) and CFB by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (Grant 1103020, 2016–2023). The research was supported by a Diabetes Australia Research Project Grant (2021–2022) to CFB.

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