Abstract
While the risk factors for Type 2 diabetes (T2DM) are known, early predictive markers of transition from normal to a prediabetes state are unidentified. We studied the basal metabolism and metabolic response to a mixed-meal challenge in 110 healthy subjects in the age group of 18 to 40 years (Male:Female = 1:1); grouped into first degree relatives of patients with T2DM (n = 30), those with a body mass index >23 kg/m2 but <30 kg/m2 (n = 30), those with prediabetes (n = 20) and normal controls (n = 30). We performed an untargeted metabolomics analysis of plasma and related that with clinical and biochemical parameters, markers of inflammation, and insulin sensitivity. Similar to prediabetes subjects, overweight subjects had insulin resistance and significantly elevated levels of C-peptide, adiponectin and glucagon and lower level of ghrelin. Metabolites such as MG(22:2(13Z, 16Z)/0:0/0:0) and LysoPC (15:0) were reduced in overweight and prediabetes subjects. Insulin sensitivity was significantly lower in men. Fasting levels of uric acid, xanthine, and glycochenodeoxycholic-3-glucuronide were elevated in men. However, both lysophospholipids and antioxidant defense metabolites were higher in women. Impaired postprandial metabolism and insulin sensitivity in overweight normoglycemic young adults indicates a risk of developing hyperglycemia. Our results also indicate a higher risk of diabetes in young men.
Highlights
Type 2 Diabetes mellitus (T2DM) is a progressive disease characterized by insulin resistance and a relative or absolute deficiency of insulin production
The baseline profile was similar in NC and False Discovery Rate (FDR) group while overweight and prediabetes subjects had a dissimilar profile compared to the normal controls (Fig. 1a–d)
Our study reveals early metabolic changes associated with insulin resistance in normoglycemic young adults who are overweight but not yet obese
Summary
Type 2 Diabetes mellitus (T2DM) is a progressive disease characterized by insulin resistance and a relative or absolute deficiency of insulin production. Insulin resistance is the early sign towards the onset of T2DM in most of the individuals. In a recent study in individuals with normal fasting blood glucose, information from a discrete set of 19 metabolites was found to improve prediction of T2DM.This study identified nitrogen metabolism pathway and its components as important in the pathogenesis of T2DM6. An earlier Framingham offspring study of patients with new onset of T2DM that used a targeted metabolomic approach observed that plasma levels of five branched-chain amino acids; leucine, isoleucine, tyrosine, valine, and phenylalanine could be useful to predict diabetes. The objectives of our study were to explore metabolic changes in healthy young adults with known risk factors such as family history and overweight and susceptible to develop T2DM and identify early metabolic changes if any in them
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
