Endocrine Abstracts

Background: Postprandial hyperglycemia is an independent risk factor for cardiovascular disease and all-cause mortality. This excess cardiovascular risk may be partly explained by the impairment in endothelial function that typically follows an acute increase in plasma glucose levels. Recently, nutritional interventions focused on the sequence of macronutrient consumption within the meal have been proposed to normalize postprandial glycemia in subjects with abnormal glucose tolerance (AGT). We therefore aimed to establish whether and by which mechanisms a protein- and fat-rich nutrient preload attenuates glucose-induced endothelial dysfunction in individuals with AGT.

Methods: In this randomized controlled trial, the endothelial function was assessed by the reactive hyperemia index (RHI) using an EndoPAT device at fasting, 60 min and 120 min during two 75 g oral glucose tolerance tests (OGTTs) preceded by either a mixed nutrient preload (one boiled egg, 50 g parmesan cheese, 300 ml water) or a water preload (500 ml water; control OGTT). A total of 30 volunteers were recruited, including 22 patients with impaired glucose tolerance (IGT, n = 13) or diet-controlled type 2 diabetes (T2D, n = 9), who were classified as AGT. A group of 8 subjects with normal glucose tolerance underwent the control OGTT and was used as reference. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, free fatty acids (FFA), arginine, branched chain amino acid (BCAA), and total amino acids (AA) were measured during the tests.

Results: The RHI negatively correlated with fasting plasma glucose (r = −0.29, P = 0.04). During the control OGTT, the RHI decreased by 9% (P = 0.02) and its deterioration was associated with the time-course of plasma glucose levels (β = −0.03, P = 0.015). In individuals with AGT, the nutrient preload attenuated the decline in the RHI (P = 0.04) and markedly reduced postprandial glycemia (P = 0.0003) compared with the control OGTT. The beneficial effect of the nutrient preload on the RHI was proportional to the improvement in glucose tolerance (r = 0.52, P = 0.02). Furthermore, it was associated with the increase in plasma GLP-1 (r = 0.47, P = 0.04) and arginine levels (r = 0.64, P = 0.04).

Conclusions: A mixed protein- and fat-rich nutrient preload attenuates postprandial endothelial dysfunction in individuals with AGT by lowering plasma glucose excursions and by increasing GLP-1 and arginine levels, both of which are known upregulators of the nitric oxide vasodilator system.