Obesity Connected Metabolic Changes in Type 2 Diabetic Patients Treated With Metformin

Shereen M Aleidi; Lina A Dahabiyeh; Xinyun Gu; Mohammed Al Dubayee; Awad Alshahrani; Hicham Benabdelkamel; Muhammad Mujammami; Liang Li; Ahmad Aljada; Anas M Abdel Rahman

doi:10.3389/fphar.2020.616157

Obesity Connected Metabolic Changes in Type 2 Diabetic Patients Treated With Metformin

Front Pharmacol. 2021 Feb 16:11:616157. doi: 10.3389/fphar.2020.616157. eCollection 2020.

Authors

Shereen M Aleidi¹, Lina A Dahabiyeh², Xinyun Gu³, Mohammed Al Dubayee⁴, Awad Alshahrani⁴, Hicham Benabdelkamel⁵, Muhammad Mujammami^{6

7}, Liang Li³, Ahmad Aljada⁸, Anas M Abdel Rahman^{8

9

10}

Affiliations

¹ Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman, Jordan.
² Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman, Jordan.
³ Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
⁴ College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
⁵ Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
⁶ Endocrinology and Diabetes Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
⁷ University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.
⁸ Department of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal University, Riyadh, Saudi Arabia.
⁹ Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
¹⁰ Department of Chemistry, Memorial University of Newfoundland, St. John's, NL, Canada.

Abstract

Metformin is widely used in the treatment of Type 2 Diabetes Mellitus (T2DM). However, it is known to have beneficial effects in many other conditions, including obesity and cancer. In this study, we aimed to investigate the metabolic effect of metformin in T2DM and its impact on obesity. A mass spectrometry (MS)-based metabolomics approach was used to analyze samples from two cohorts, including healthy lean and obese control, and lean as well as obese T2DM patients on metformin regimen in the last 6 months. The results show a clear group separation and sample clustering between the study groups due to both T2DM and metformin administration. Seventy-one metabolites were dysregulated in diabetic obese patients (30 up-regulated and 41 down-regulated), and their levels were unchanged with metformin administration. However, 30 metabolites were dysregulated (21 were up-regulated and 9 were down-regulated) and then restored to obese control levels by metformin administration in obese diabetic patients. Furthermore, in obese diabetic patients, the level of 10 metabolites was dysregulated only after metformin administration. Most of these dysregulated metabolites were dipeptides, aliphatic amino acids, nucleic acid derivatives, and urea cycle components. The metabolic pattern of 62 metabolites was persistent, and their levels were affected by neither T2DM nor metformin in obesity. Interestingly, 9 metabolites were significantly dysregulated between lean and obese cohorts due to T2DM and metformin regardless of the obesity status. These include arginine, citrulline, guanidoacetic acid, proline, alanine, taurine, 5-hydroxyindoleacetic acid, and 5-hydroxymethyluracil. Understanding the metabolic alterations taking place upon metformin treatment would shed light on possible molecular targets of metformin, especially in conditions like T2DM and obesity.

Keywords: amino acid, T2DM; body mass index-BMI; mass spectrometry-LC-MS/MS; metabolomics; metformin; obesity; type 2 diabete mellitus.