Plasma metabolomic profiles reveal sex-specific response to an oral glucose tolerance test in late middle-aged adults

Abstract

Sex is a key determinant of human phenotype, with males and females exhibiting distinct anthropometric and metabolic features that influence disease susceptibility. This study investigated sex-specific metabolic differences in late middle-aged adults without diagnosed metabolic diseases, both in the fasting state and during an oral glucose tolerance test (OGTT). Using data from the NutriTech project, we analyzed plasma metabolomic responses during the OGTT, along with detailed assessments of body composition and fasting clinical parameters. Females exhibited 28 % greater total adipose tissue, mainly subcutaneous, whereas males had more intra-abdominal fat and higher energy expenditure. Females showed elevated fasting levels of fatty acids-particularly very-long-chain fatty acids- leptin, and adiponectin. Males had slightly higher fasting glycemia (∼ 5 %) and a more pronounced glycemic increase during the OGTT (17 %), along with elevated insulin levels. In both fasting and postprandial states, males showed higher circulating levels (p < 0.05) of aromatic and branched-chain amino acids (BCAA) and their catabolites. Conversely, females had higher sphingomyelins levels during fasting and throughout the OGTT, and increased postprandial levels of secondary bile acids (p < 0.05). These sex-specific metabolic features in late middle-aged adults may enhance our understanding of metabolic disease risk and support the development of more targeted prevention strategies. CLINICAL TRIAL REGISTRATION NUMBER: NCT01684917.

Keywords: Bile acids; Nutritional challenge; Postprandial metabolism; Sphingomyelins.