Metabolic Signature Differentiated Diabetes Mellitus from Lipid Disorder in Elderly Taiwanese

Aging is a complex progression of biological processes and is the causal contributor to the development of diabetes mellitus (DM). DM is the most common degenerative disease and is the fifth leading cause of death in Taiwan, where the trend of DM mortality has been steadily increasing. Metabolomics, important branch of systems biology, has been mainly utilized to understand endogenous metabolites in biological systems and their dynamic changes as they relate to endogenous and exogenous factors. The purpose of this study was to elucidate the metabolomic profiles in elderly people and its relation to lipid disorder (LD). We collected 486 elderly individuals aged ≥65 years and performed untargeted and targeted metabolite analysis using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography—mass spectrometry (LC/MS). Several metabolites, including branched-chain amino acids, alanine, glutamate and alpha-aminoadipic acid were elevated in LD compared to the control group. Based on multivariate analysis, four metabolites were selected in the best model to predict DM progression: phosphatidylcholine acyl-alkyl (PC ae) C34:3, PC ae C44:3, SM C24:1 and PCae C36:3. The combined area under the curve (AUC) of those metabolites (0.82) was better for DM classification than individual values. This study found that targeted metabolic signatures not only distinguish the LD within the control group but also differentiated DM from LD in elderly Taiwanese. These metabolites could indicate the nutritional status and act as potential metabolic biomarkers for the elderly in Taiwan

Dietary Leucine Supplement Ameliorates Hepatic Steatosis and Diabetic Nephropathy in db/db Mice

Dietary leucine supplementation has been explored for the therapeutic intervention of obesity and obesity-induced metabolic dysfunctions. In this study, we aim to examine the effects of dietary leucine supplementation in db/db mice. Mice were treated with or without leucine (1.5% w/v) in drinking water for 12 weeks. The leucine supplement was found to reduce insulin resistance and hepatic steatosis in db/db mice. Using Nuclear Magnetic Resonance (NMR)-based lipidomics, we found that the reduction of hepatic triglyceride synthesis was correlated with attenuated development of fatty liver. In addition, diabetic nephropathy (DN) was also ameliorated by leucine. Using liquid chromatography–time-of-flight mass spectrometry (LC-TOF MS)-based urine metabolomics analysis, we found that the disturbance of the tricarboxylic acid (TCA) cycle was reversed by leucine. The beneficial effects of leucine were probably due to AMP-activated protein kinase (AMPK) activation in the liver and kidneys of db/db mice. Thus, dietary leucine supplementation may potentially be a nutritional intervention to attenuate hepatic steatosis and early DN in type II diabetes