Abstract
Background and objectivesDelivery of nutrients directly to the small intestine, either via enteral feeding tube or by gastric bypass surgery, is associated with increased levels of appetite-suppressing and glucoregulatory hormones, including GLP-1, and reduced appetite. Achieving these changes non-invasively using formulated foods may be of therapeutic benefit in individuals with obesity and related comorbidities. The aim of this pilot study was to determine the effect of a single dose of a novel delayed-release nutrient (DRN) on glucose, GLP-1, c-peptide, insulin, and appetite in adults with obesity and type 2 diabetes.Subjects and methodsWe formulated an all-natural, generally recognized as safe (‘GRAS”) DRN and conducted a randomized prospective crossover trial. Nineteen adults with obesity and type 2 diabetes underwent paired 3-h meal tolerance tests (MTT) in randomized order 1–4 weeks apart. Subjects ingested a single dose of DRN and the same nutrients as unformulated powders (UN).ResultsFor DRN compared with UN, the maximal concentration (Cmax) was significantly lower for glucose, c-peptide, and insulin, and the time of maximal concentration (Tmax) was significantly delayed. While Tmax for GLP-1 was also significantly delayed following DRN compared with UN (45 min later; p = 0.26), Cmax did not differ significantly. GLP-1 rose significantly during the last 90 min of the 3-h MTT (β1 = 0.16 pg/mL/min, p = 0.025), while following UN it decreased (β1 = −0.21 pg/mL/min, p = 0.0026) (p difference = 0.0003). There were minimal differences in seven measures of appetite and adverse symptoms between DRN and UN.ConclusionsWe conclude that nutrient can be formulated using all-natural ingredients to induce a delayed rise in GLP-1. Further testing is needed to determine the amount and site of nutrient release, when maximum GLP-1 levels occur, and if modification of the formulation specifications and dose are associated with appetite and glucose control.
Highlights
Increased distal nutrient delivery is considered to initiate multiple gut-based neurohormonal pathways, including intestinal L-cell activation, that mediate the metabolic benefit of gastric bypass surgery[1,2,3,4,5]
For delayed-release nutrient (DRN) compared with unformulated powders (UN), the maximal concentration (Cmax) was significantly lower for glucose, c-peptide, and insulin, and the time of maximal concentration (Tmax) was significantly delayed
While Tmax for GLP-1 was significantly delayed following DRN compared with UN (45 min later; p = 0.26), Cmax did not differ significantly
Summary
Increased distal nutrient delivery is considered to initiate multiple gut-based neurohormonal pathways, including intestinal L-cell activation, that mediate the metabolic benefit of gastric bypass surgery[1,2,3,4,5]. We hypothesized that a formulation designed to release nutrient rapidly in the small intestine would simulate the appearance of nutrient in the small intestine, which occurs after gastric bypass surgery, and with nutrient administration by post-pyloric enteral feeding tube, and thereby increase GLP-1 release[10] We propose that such a nutrient formulation could be ingested before, or even in place of, a regular meal to reduce appetite and caloric intake and improve glucose control. Delivery of nutrients directly to the small intestine, either via enteral feeding tube or by gastric bypass surgery, is associated with increased levels of appetite-suppressing and glucoregulatory hormones, including GLP-1, and reduced appetite Achieving these changes non-invasively using formulated foods may be of therapeutic benefit in individuals with obesity and related comorbidities. The aim of this pilot study was to determine the effect of a single dose of a novel delayed-release nutrient (DRN) on glucose, GLP-1, c-peptide, insulin, and appetite in adults with obesity and type 2 diabetes
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