Effects of intragastric administration of L-tryptophan on the glycaemic response to a nutrient drink in men with type 2 diabetes - impacts on gastric emptying, glucoregulatory hormones and glucose absorption.

2021-01-05
Nutrition & diabetes 11(1)
- Maryam Hajishafiee
- Rachel A Elovaris
- Karen L Jones
- Leonie K Heilbronn
- Michael Horowitz
- Sally D Poppitt
- Christine Feinle-Bisset

PubMed: 33414406
DOI: 10.1038/s41387-020-00146-9

Study Design

Type: Randomized Controlled Trial (RCT)
Population: Twelve men with T2D (age: 63±2 years, HbA1c: 49.7±2.5 mmol/mol, BMI: 30±1 kg/m²)
Methods: Randomised, double-blind fashion; intragastric administration of 3g or 1.5g tryptophan, or control (0.9% saline), 30 min before a mixed-nutrient drink; gastric emptying quantified using two-dimensional ultrasound
Blinding: Double-blind
Funding: Unclear

Background

The rate of gastric emptying and glucoregulatory hormones are key determinants of postprandial glycaemia. Intragastric administration of L-tryptophan slows gastric emptying and reduces the glycaemic response to a nutrient drink in lean individuals and those with obesity. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D).

Methods

Twelve men with T2D (age: 63 ± 2 years, HbA1c: 49.7 ± 2.5 mmol/mol, BMI: 30 ± 1 kg/m²) received, on three separate occasions, 3 g ('Trp-3') or 1.5 g ('Trp-1.5') tryptophan, or control (0.9% saline), intragastrically, in randomised, double-blind fashion, 30 min before a mixed-nutrient drink (500 kcal, 74 g carbohydrates), containing 3 g 3-O-methyl-D-glucose (3-OMG) to assess glucose absorption. Venous blood samples were obtained at baseline, after tryptophan, and for 2 h post-drink for measurements of plasma glucose, C-peptide, glucagon and 3-OMG. Gastric emptying of the drink was quantified using two-dimensional ultrasound.

Results

Tryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04), but did not affect fasting glucose. In response to the drink, Trp-3 lowered plasma glucose from t = 15-30 min and from t = 30-45 min compared with control and Trp-1.5, respectively (both P < 0.05), with no differences in peak glucose between treatments. Gastric emptying tended to be slower after Trp-3, but not Trp-1.5, than control (P = 0.06). Plasma C-peptide, glucagon and 3-OMG increased on all days, with no major differences between treatments.

Conclusions

In people with T2D, intragastric administration of 3 g tryptophan modestly slows gastric emptying, associated with a delayed rise, but not an overall lowering of, postprandial glucose.

Research Insights

L-Tryptophan→Increased Blood Glucose Levels
Plasma ... 3-OMG increased on all days, with no major differences between treatments
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')
L-Tryptophan→Increased C-peptide Level
Tryptophan alone stimulated C-peptide (P=0.002)
Effect
Beneficial
Effect size
Small
Dose
3 g ('Trp-3')
L-Tryptophan→Increased Glucagon Level
Tryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04)
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')
L-Tryptophan→Increased Plasma Glucagon Level
Tryptophan alone stimulated ... glucagon (P=0.04)
Effect
Neutral
Effect size
Small
Dose
3 g ('Trp-3')
L-Tryptophan→Reduced Fasting Blood Glucose Level
Tryptophan alone stimulated C-peptide and glucagon, but did not affect fasting glucose
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')
L-Tryptophan→Reduced Fasting Glucose
did not affect fasting glucose
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')
L-Tryptophan→Reduced Glucose Absorption
Plasma C-peptide, glucagon and 3-OMG increased on all days, with no major differences between treatments
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')
L-Tryptophan→Reduced Peak Glucose
with no differences in peak glucose between treatments
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')
L-Tryptophan→Reduced Postprandial Glucose
with no differences in peak glucose between treatments.
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')
L-Tryptophan→Reduced Postprandial Glucose Level
Trp-3 lowered plasma glucose from t=15-30 min and from t=30-45 min compared with control and Trp-1.5, respectively (both P < 0.05), with no differences in peak glucose between treatments
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')
L-Tryptophan→Slowed Gastric Emptying
Gastric emptying tended to be slower after Trp-3, but not Trp-1.5, than control (P=0.06)
Effect
Neutral
Effect size
Small
Dose
1.5 g ('Trp-1.5')