Association of increased levels of MCP-1 and cathepsin-D in young onset type 2 diabetes patients (T2DM-Y) with severity of diabetic retinopathy.
OBJECTIVE
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.


CONCLUSIONS
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.
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.
Sruthi
S
Reddy
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.
Anandakumar
A
Amutha
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.
Ramachandran
R
Rajalakshmi
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.
Regin
R
Bhaskaran
Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Finny
F
Monickaraj
Neurogenomics Division, Translational Genomics Research Institute, (TGen), Phoenix, AZ, USA.
Sampathkumar
S
Rangasamy
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.
Ranjit Mohan
RM
Anjana
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.
Shiny
S
Abhijit
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.
Kuppan
K
Gokulakrishnan
Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Arup
A
Das
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.
Viswanathan
V
Mohan
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.
Muthuswamy
M
Balasubramanyam
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D002402:Cathepsin D / Q000097:blood*; D018932:Chemokine CCL2 / Q000097:blood*; D015986:Confounding Factors, Epidemiologic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007194:India; D008297:Male; D015203:Reproducibility of Results; D012307:Risk Factors; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult
D015415:Biomarkers; D002096:C-Peptide; D002402:Cathepsin D; D018932:Chemokine CCL2; D006442:Glycated Hemoglobin; C111835:CCL2 protein, human; C517652:hemoglobin A1c protein, human; C533922:CTSD protein, human
Biomarkers; Cathepsin-D; Diabetic Retinopathy; MCP-1; T2DM-Y