Effects of a Small Protein and Lipid Preload on Glucose Tolerance in Subjects With Impaired Glucose Homeostasis

Effects of a Small Protein and Lipid Preload on Glucose Tolerance in Subjects With Impaired Glucose Homeostasis

Mechanisms Through Which a Small Protein and Lipid Preload Improves Glucose Tolerance in Subjects With Impaired Glucose Homeostasis

The purpose of this study is: to measure the size of the effect on glucose tolerance of a small mixed protein and lipid meal given as a pre-load in individuals with different glucose tolerance status to investigate the underlying mechanisms by accurately evaluating beta cell function, insulin sensitivity, insulin clearance and glucose kinetics (oral absorption, endogenous production, rate of utilization) together with gut hormones plasma concentration.

As supported by experimental and clinical data, oral carbohydrate tolerance is influenced by the coingestion of nutrients through multiple mechanisms. The ingestion itself, the contact with the gastric mucosa, the arrival into the intestine and the subsequent digestion are known to produce neural reflexes, hormonal responses and plasma substrates gradients which, by modulating gastric emptying, insulin secretion and insulin clearance participate in the regulation of postprandial glycaemia. The size of this effect is influenced by a number of factors: the specific nutrient chemical characteristics (fat vs protein and composition) and their physical properties (solid vs liquid), the timing (pre-load vs coingestion) and finally the individual glucose tolerance status. To our knowledge, the effect on glucose excursions of a combination of protein and fat given before carbohydrate is still unknown and also unknown is the contribution of different mechanisms involved in the control of glucose homeostasis in subjects with different degrees of glucose tolerance.

During the "control" study, each subject ingest 500 ml of water 30 minutes before a standard 75 g Oral Glucose Tolerance Test

During the "preload" study, each subject ingest a small mixed meal 30 minutes before a standard 75 g Oral Glucose Tolerance Test. The meal is composed by 50 g of parmesan cheese, one small size boiled egg and 300 ml of water (250 kcal, 23 g protein, 17 g fat and 2 g of carbohydrate).

Insulin sensitivity, estimated from glucose and insulin levels during the Oral Glucose Tolerance Test with the use of Oral Glucose Insulin Sensitivity index

The Oral Glucose Insulin Sensitivity index (OGIS; equation for a 2-h oral glucose test with a glucose dose of 75 g) is the mean glucose clearance change (basal vs OGTT 60-120 min), divided by the mean plasma insulin concentration gradient over the same time interval.

Glucose fluxes (intestinal glucose absorption, endogenous glucose production, rate of disappearance of plasma glucose), assessed by modeling glucose tracers enrichments using a standard double tracers technique

Beta cells function parameters (glucose sensitivity, rate sensitivity, potentiation factor ratio), calculated by modeling insulin secretion and glucose concentration.

Inclusion Criteria: healthy, prediabetic or diet-controlled type 2 diabetic patients Subjects ≥ 18 and ≤65 years of age Lean, Overweight or Obese (BMI: 18 to 35 kg/m2) Normal liver and kidney function Normal thyroid function Read and understood the informed consent form and signed it voluntarily Exclusion Criteria: Liver, heart, kidney, lung, infectious, neurological, psychiatric, immunological or neoplastic diseases. Type 1 or insulin treated diabetes. Pregnancy or lactation Illicit drug abuse or alcoholism Subject treated with insulin or treatment Subjects taking anoretic drugs Subjects on steroid treatment Subjects after bariatric surgery.

Trico D, Frascerra S, Baldi S, Mengozzi A, Nesti L, Mari A, Natali A. The insulinotropic effect of a high-protein nutrient preload is mediated by the increase of plasma amino acids in type 2 diabetes. Eur J Nutr. 2019 Sep;58(6):2253-2261. doi: 10.1007/s00394-018-1778-y. Epub 2018 Jul 14.

Trico D, Baldi S, Tulipani A, Frascerra S, Macedo MP, Mari A, Ferrannini E, Natali A. Mechanisms through which a small protein and lipid preload improves glucose tolerance. Diabetologia. 2015 Nov;58(11):2503-12. doi: 10.1007/s00125-015-3710-9. Epub 2015 Jul 30.