Sruthi Reddy1, Anandakumar Amutha1, Ramachandran Rajalakshmi1, Regin Bhaskaran1, Finny Monickaraj2, Sampathkumar Rangasamy3, Ranjit Mohan Anjana1, Shiny Abhijit1, Kuppan Gokulakrishnan1, Arup Das2, Viswanathan Mohan1, Muthuswamy Balasubramanyam4. 1. Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India. 2. Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, USA. 3. Neurogenomics Division, Translational Genomics Research Institute, (TGen), Phoenix, AZ, USA. 4. Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India.. Electronic address: balusignal@gmail.com.
Abstract
AIM: Young onset type 2 diabetes patients (T2DM-Y) have been shown to possess an increased risk of developing microvascular complications particularly diabetic retinopathy. However, the molecular mechanisms are not clearly understood. In this study, we investigated the serum levels of monocyte chemotactic protein 1 (MCP-1) and cathepsin-D in patients with T2DM-Y without and with diabetic retinopathy. METHODS: In this case-control study, participants comprised individuals with normal glucose tolerance (NGT=40), patients with type 2 diabetes mellitus (T2DM=35), non-proliferative diabetic retinopathy (NPDR=35) and proliferative diabetic retinopathy (PDR=35). Clinical characterization of the study subjects was done by standard procedures and MCP-1 and cathepsin-D were measured by ELISA. RESULTS: Compared to control individuals, patients with T2DM-Y, NPDR and PDR exhibited significantly (p<0.001) higher levels of MCP-1. Cathepsin-D levels were also significantly (p<0.001) higher in patients with T2DM-Y without and with diabetic retinopathy. Correlation analysis revealed a positive association (p<0.001) between MCP-1 and cathepsin-D levels. There was also a significant negative correlation of MCP1/cathepsin-D with C-peptide levels. The association of increased levels of MCP-1/cathepsin-D in patients with DR persisted even after adjusting for all the confounding factors. CONCLUSION: As both MCP-1 and cathepsin-D are molecular signatures of cellular senescence, we suggest that these biomarkers might be useful to predict the development of retinopathy in T2DM-Y patients.
AIM: Young onset type 2 diabetespatients (T2DM-Y) have been shown to possess an increased risk of developing microvascular complications particularly diabetic retinopathy. However, the molecular mechanisms are not clearly understood. In this study, we investigated the serum levels of monocyte chemotactic protein 1 (MCP-1) and cathepsin-D in patients with T2DM-Y without and with diabetic retinopathy. METHODS: In this case-control study, participants comprised individuals with normal glucose tolerance (NGT=40), patients with type 2 diabetes mellitus (T2DM=35), non-proliferative diabetic retinopathy (NPDR=35) and proliferative diabetic retinopathy (PDR=35). Clinical characterization of the study subjects was done by standard procedures and MCP-1 and cathepsin-D were measured by ELISA. RESULTS: Compared to control individuals, patients with T2DM-Y, NPDR and PDR exhibited significantly (p<0.001) higher levels of MCP-1. Cathepsin-D levels were also significantly (p<0.001) higher in patients with T2DM-Y without and with diabetic retinopathy. Correlation analysis revealed a positive association (p<0.001) between MCP-1 and cathepsin-D levels. There was also a significant negative correlation of MCP1/cathepsin-D with C-peptide levels. The association of increased levels of MCP-1/cathepsin-D in patients with DR persisted even after adjusting for all the confounding factors. CONCLUSION: As both MCP-1 and cathepsin-D are molecular signatures of cellular senescence, we suggest that these biomarkers might be useful to predict the development of retinopathy in T2DM-Y patients.
Authors: Jeanie B Tryggestad; Rachana D Shah; Barbara H Braffett; Fida Bacha; Samuel S Gidding; Rose A Gubitosi-Klug; Amy S Shah; Elaine M Urbina; Lorraine E Levitt Katz Journal: Pediatr Diabetes Date: 2020-07-02 Impact factor: 4.866
Authors: Matthijs A Velders; Fredrik Calais; Nina Dahle; Tove Fall; Emil Hagström; Jerzy Leppert; Christoph Nowak; Åke Tenerz; Johan Ärnlöv; Pär Hedberg Journal: Ups J Med Sci Date: 2019-08-20 Impact factor: 2.384