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Article ; Online: The Amelioration of Detrimental Biochemical Anomalies by Supplementing B, C, and E Vitamins in Subjects with Type 2 Diabetes Mellitus May Reduce the Rate of Development of Diabetic Retinopathy.

Pramanik, Subhasish / Banerjee, Kaustav / Mondal, Lakshmi Kanta

2022 Volume 2022, Page(s) 3886710

Abstract: Excessive intracellular glucose in insulin-independent tissues including nerve, nephron, lens, and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) ... ...

Abstract	Excessive intracellular glucose in insulin-independent tissues including nerve, nephron, lens, and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation, and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of the retina, resulting in the breakdown of the inner blood-retinal barrier and the initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, the development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B vitamins, vitamin C, and vitamin E along with antidiabetic medication for five years demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only antihyperglycemic drugs.
MeSH term(s)	Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Retinopathy/metabolism ; Glucose ; Glycation End Products, Advanced ; Humans ; Hypoglycemic Agents/therapeutic use ; Vascular Endothelial Growth Factor A ; Vitamin E/therapeutic use ; Vitamins/therapeutic use
Chemical Substances	Glycation End Products, Advanced ; Hypoglycemic Agents ; Vascular Endothelial Growth Factor A ; Vitamins ; Vitamin E (1406-18-4) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-09-01
Publishing country	England
Document type	Clinical Trial ; Journal Article
ZDB-ID	2711897-6
ISSN	2314-6753 ; 2314-6753
ISSN (online)	2314-6753
ISSN	2314-6753
DOI	10.1155/2022/3886710
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Article: Decreased Levels of miR-126 and miR-132 in Plasma and Vitreous Humor of Non-Proliferative Diabetic Retinopathy Among Subjects with Type-2 Diabetes Mellitus.

Pramanik, Subhasish / Saha, Chinmay / Chowdhury, Subhankar / Bose, Chiranjit / Bhattacharyya, Nitai P / Mondal, Lakshmi Kanta

Diabetes, metabolic syndrome and obesity : targets and therapy

2022 Volume 15, Page(s) 345–358

Abstract: Purpose: Diabetic retinopathy (DR), the leading cause of blindness among working adults, is an urgent public health problem as diabetes mellitus (DM) is increasing at an alarming rate. Hyperglycemia-induced endothelial dysfunction is the principal ... ...

Abstract	Purpose: Diabetic retinopathy (DR), the leading cause of blindness among working adults, is an urgent public health problem as diabetes mellitus (DM) is increasing at an alarming rate. Hyperglycemia-induced endothelial dysfunction is the principal contributing factor leading to the development of microangiopathy. Altered levels of microRNA (miR), the negative regulator of protein-coding genes, have been observed and considered to be markers for DR. Present study aimed to find out whether miR levels in plasma could be effective biomarkers to differentiate between type 2 diabetes mellitus (T2DM) with non-proliferative retinopathy (NPDR) from T2DM with no-DR (DNR). Methods: We recruited 50 T2DM subjects comprising 31 NPDR and 19 DNR individuals. Surrogate markers of systemic oxidative stress and vascular endothelial growth factor (VEGF) were measured in plasma. Levels of miR-126 and miR-132 were determined in plasma and vitreous fluid using real-time PCR. Results: We observed that levels of miR-126 and miR-132 were decreased in NPDR subjects in comparison to DNR. Plasma levels of miRs were inversely correlated with secreted levels of VEGF and oxidative stress marker. The levels of these miRs showed discriminating ability between NPDR and DNR. Conclusion: Circulating miRs 126 and 132 in plasma or vitreous may serve as biomarkers for early diabetic retinopathy risk prediction, provided validated in a larger cohort and other forms of retinal vasculopathy or retinopathy in the future.
Language	English
Publishing date	2022-02-04
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2494854-8
ISSN	1178-7007
ISSN	1178-7007
DOI	10.2147/DMSO.S346097
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Article ; Online: Effects of Lunar Phases on Foot Temperature, Oxidative Stress, and Inflammation in Type 2 Diabetic Subjects.

Bhattacharjee, Koena / Pramanik, Subhasish / Chowdhury, Sutanu Dutta / Basu, Barnali Ray / Mondal, Lakshmi Kanta

Endocrine, metabolic & immune disorders drug targets

2022 Volume 23, Issue 6, Page(s) 832–842

Abstract: Background: It has been observed that the lunar phases alter the fasting plasma glucose (FPG) level in type-2 diabetic (T2DM) subjects. Diabetic peripheral neuropathy (DPN) was also reported to be associated with elevated foot temperature (FT), ... ...

Abstract	Background: It has been observed that the lunar phases alter the fasting plasma glucose (FPG) level in type-2 diabetic (T2DM) subjects. Diabetic peripheral neuropathy (DPN) was also reported to be associated with elevated foot temperature (FT), oxidative stress, and inflammation in T2DM subjects. Objectives: The purpose of the present study was to evaluate the changes in FT, oxidative stress, and inflammation levels and assess the relationship of FT with oxidative stress, antioxidant enzyme activity, and inflammatory markers in T2DM subjects at different lunar phases. Methods: The plasma glucose, glycated hemoglobin, and dorsal and plantar surface temperatures of the feet by infrared dermal thermometer were measured in 88 randomly selected T2DM subjects at different lunar phases. The levels of oxidative stress and inflammation were assessed by measuring malondialdehyde (MDA), glucose 6-phosphate dehydrogenase (G6PDH), and tumor necrosis factoralpha (TNF-α). Results: The FTs, MDA, and TNF-α were significantly increased, and G6PDH activity was significantly decreased in the new moon (NM) and full moon (FM) than in the third quarter (TQ) and first quarter (FQ) for both sexes. The FTs, MDA, and TNF-α levels were significantly positively correlated, whereas G6PDH activity was significantly negatively correlated with FPG at NM and FM in both sexes. The MFT was significantly positively correlated with MDA and TNF-α and significantly negatively correlated with G6PDH at NM and FM in T2DM subjects. Conclusion: The lunar phases showed a prominent influence on the FT, oxidative stress, and inflammatory status in T2DM subjects, which might be due to the existence of biological rhythm interaction with lunar electromagnetic radiations.
MeSH term(s)	Male ; Female ; Humans ; Moon ; Temperature ; Blood Glucose ; Diabetes Mellitus, Type 2/diagnosis ; Tumor Necrosis Factor-alpha ; Oxidative Stress ; Antioxidants/metabolism ; Inflammation/diagnosis
Chemical Substances	Blood Glucose ; Tumor Necrosis Factor-alpha ; Antioxidants
Language	English
Publishing date	2022-12-07
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2228325-0
ISSN	2212-3873 ; 1871-5303
ISSN (online)	2212-3873
ISSN	1871-5303
DOI	10.2174/1871530323666221205112054
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Article ; Online: Effects of lunar cycle on fasting plasma glucose, heart rate and blood pressure in type 2 diabetic patients.

Chowdhury, Sutanu Dutta / Pramanik, Subhasish / Bhattacharjee, Koena / Mondal, Lakshmi Kanta

Chronobiology international

2020 Volume 38, Issue 2, Page(s) 270–277

Abstract: The purpose of this study was to investigate the influence of lunar phases on fasting plasma glucose, heart rate, and blood pressure in type 2 diabetic patients. The present cross-sectional study was carried out during four phases, i.e., full moon (FM), ... ...

Abstract	The purpose of this study was to investigate the influence of lunar phases on fasting plasma glucose, heart rate, and blood pressure in type 2 diabetic patients. The present cross-sectional study was carried out during four phases, i.e., full moon (FM), first quarter (FQ), new moon (NM), and third quarter (TQ), of the lunar month. The study was conducted on 42 randomly selected patients (22 males and 20 females) from the Diabetes Clinic of Calcutta Medical College. Fasting plasma glucose (FPG) of each subject was determined and heart rate (HR) and blood pressure (BP) were measured at rest and during static exercise conditions, i.e., performance of a standard handgrip dynamometer test. The FPG level during the NM and FM was significantly higher (
MeSH term(s)	Aged ; Blood Glucose ; Blood Pressure ; Circadian Rhythm ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; Fasting ; Female ; Hand Strength ; Heart Rate ; Humans ; India ; Male ; Moon
Chemical Substances	Blood Glucose
Language	English
Publishing date	2020-12-13
Publishing country	England
Document type	Journal Article
ZDB-ID	998996-1
ISSN	1525-6073 ; 0742-0528
ISSN (online)	1525-6073
ISSN	0742-0528
DOI	10.1080/07420528.2020.1842754
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Article ; Online: Biochemical scenario behind initiation of diabetic retinopathy in type 2 diabetes mellitus.

Mondal, Lakshmi Kanta / Bhaduri, Gautam / Bhattacharya, Basudev

Indian journal of ophthalmology

2018 Volume 66, Issue 4, Page(s) 535–540

Abstract: Purpose: Despite the disease having similar glycemic status and duration microangiopathy in some patients develop within few years whereas it doesn't appear as a health complication in some diabetics for a considerable period. This study is undertaken ... ...

Abstract	Purpose: Despite the disease having similar glycemic status and duration microangiopathy in some patients develop within few years whereas it doesn't appear as a health complication in some diabetics for a considerable period. This study is undertaken to assess the hyperglycemia-induced biochemical background behind the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (DM). Methods: Following proper diagnosis, 100 patients of type 2 DM of 10-12 years duration having no DR, and 42 patients of type 2 DM of the same duration and glycemic status as the second group, with mild retinopathy were recruited in the study. Lactic acid, glutamate, malondialdehyde (MDA), nitrate, advanced glycation end-products (AGEs), peripheral blood mononuclear cell reactive oxygen species (ROS), vascular endothelial growth factor (VEGF), and its receptor 2 (VEGFR2) in these two groups were produced in an assay following standard methodology. Results: Biochemical markers of anaerobic glycolysis, lipid peroxidation, AGEs, glutamate concentration, oxidative stress, and expression of VEGF and its VEGFR2 with significantly elevated markings were found in them who developed earliest stage of DR rather than them who had not. Conclusion: Hyperglycemia-induced anomalous glucose metabolism, lipid peroxidation, advanced glycation, glutamate toxicity, and oxidative stress create a background where apoptosis of retinal capillary endothelial cells invite increased expression of VEGF and VEGFR2, these being the crucial factors behind the development of diabetic microangiopathy.
MeSH term(s)	Adult ; Biomarkers/blood ; Blood Glucose/metabolism ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood ; Diabetic Retinopathy/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Glutamic Acid/blood ; Glycation End Products, Advanced/blood ; Glycemic Index ; Humans ; Lactic Acid/blood ; Male ; Malondialdehyde/blood ; Nitrates/blood ; Reactive Oxygen Species/blood ; Vascular Endothelial Growth Factor A/blood ; Vascular Endothelial Growth Factor Receptor-2/blood
Chemical Substances	Biomarkers ; Blood Glucose ; Glycation End Products, Advanced ; Nitrates ; Reactive Oxygen Species ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Lactic Acid (33X04XA5AT) ; Glutamic Acid (3KX376GY7L) ; Malondialdehyde (4Y8F71G49Q) ; KDR protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
Language	English
Publishing date	2018-03-27
Publishing country	India
Document type	Journal Article
ZDB-ID	187392-1
ISSN	1998-3689 ; 0301-4738
ISSN (online)	1998-3689
ISSN	0301-4738
DOI	10.4103/ijo.IJO_1121_17
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Article: Do different lipid components accelerate the pathogenesis and severity of Diabetic Retinopathy?

Mondal, Lakshmi Kanta / Pramanik, Subhasish / Chowdhury, Subhankar / Bose, Chiranjit / Bera, Debgopal / Saha, Ayindrila / Bhattacharjee, Koena

International journal of retina and vitreous

2022 Volume 8, Issue 1, Page(s) 39

Abstract: Background: To assess the association of lipid and lipid-derived toxic molecules in pathogenesis and severity of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM).: Methods: The present cross-sectional study included 14 healthy individuals ...

Abstract	Background: To assess the association of lipid and lipid-derived toxic molecules in pathogenesis and severity of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Methods: The present cross-sectional study included 14 healthy individuals (HC) without T2DM, 22 T2DM subjects without DR (DNR), 24 T2DM subjects with mild non-proliferative DR (MNPDR), and 24 T2DM subjects with high-risk proliferative DR (HRPDR). All subjects underwent plasma and vitreous analysis for estimation of total lipid (TL), free fatty acid (FFA), lipid peroxides (LPOs) like malondialdehyde (MDA), 4-Hydroxy-noneal (HNE), the advanced lipoxidation end product (ALE) like Hexanoyl-lysine (HLY) and vascular endothelial growth factor (VEGF) following standard spectrophotometric and enzyme-linked immunosorbent assay (ELISA) methods respectively. Results: The concentration of TL, FFA, markers of lipid peroxidation and lipoxidation as well as VEGF in plasma and vitreous were found to be significantly elevated stepwise inT2DM subjects (HRPDR > MNPDR > DNR) compared to healthy controls (HC).Further, plasma conventional lipid components like total cholesterol (TCH), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG), FFA and TL showed their significant positive correlations with vitreous level of different LPOs, ALE and VEGF in the DR group. Conclusion: Total lipid and lipid-derived detrimental biomolecules ultimately result in increased secretion of VEGF and thus not only add as associated mediators in the pathogenesis of DR, these also accelerate the severity of microangiopathy in T2DM.
Language	English
Publishing date	2022-06-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2836254-8
ISSN	2056-9920
ISSN	2056-9920
DOI	10.1186/s40942-022-00390-4
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Article: Visual contrast sensitivity could be an early marker of diabetic retinopathy.

Pramanik, Subhasish / Chowdhury, Subhankar / Ganguly, Upasana / Banerjee, Anindita / Bhattacharya, Basudev / Mondal, Lakshmi Kanta

Heliyon

2020 Volume 6, Issue 10, Page(s) e05336

Abstract: The present study aimed to explore the early predictive marker of diabetic retinopathy (DR) and to elucidate the associated demographic, metabolic, and ocular factors. We enrolled 43 type 2 diabetic subjects with mild non-proliferative retinopathy (MNPDR) ...

Abstract	The present study aimed to explore the early predictive marker of diabetic retinopathy (DR) and to elucidate the associated demographic, metabolic, and ocular factors. We enrolled 43 type 2 diabetic subjects with mild non-proliferative retinopathy (MNPDR), 30 diabetic subjects with no retinopathy (DNR), and 35 healthy controls (HC). The study groups showed no significant alteration in central macular thickness (CMT) and visual acuity (VA). The contrast sensitivity (CS) score was found to be significantly lower among DNR and MNPDR subjects compared to HCs (p < 0.0001). Between MNPDR and DNR subjects, the CS score was significantly lower in the former (p = 0.0036). CS score discriminated DNR subjects from HC, with 74% accuracy for the optimal threshold 0.71. The associated area under the ROC curve (AUC) is 0.82 (p < 0.0001) while the discrimination rule has 66% sensitivity and 80% specificity. The CS score also discriminated MNPDR subjects from DNR with 64% accuracy for the optimal threshold 0.53. The associated AUC is 0.65 (p < 0.023) and the rule has 86% sensitivity and 33% specificity. According to best subset regression analysis, not only glycaemic parameters but also lipid parameters [low-density lipoprotein cholesterol (LDL-C) (p = 0.045) and triglycerides (TG) (p = 0.0005)] were found to be significant predictors of CS. CMT (p = 0.058) was another marginally significant predictor of CS. CS may be used as an early predictive marker for DR. So, not only hyperglycemia, but also hyperlipidemia seems to significantly affect retinal CS function in diabetes.
Language	English
Publishing date	2020-10-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2020.e05336
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Article: Efficacy and Cost-Effectiveness of Anti-VEGF for Treating Diabetic Retinopathy in the Indian Population.

Pramanik, Subhasish / Mondal, Lakshmi Kanta / Paine, Suman Kalyan / Jain, Sneha / Chowdhury, Subhankar / Ganguly, Upasana / Ghosh, Sayantan / Bose, Chiranjit / Bhattacharjee, Koena / Bhaduri, Gautam

Clinical ophthalmology (Auckland, N.Z.)

2021 Volume 15, Page(s) 3341–3350

Abstract: Purpose: In the present study, we aimed to evaluate the efficacy, safety, and cost-effectiveness of the anti-vascular endothelial growth factor (anti-VEGF), namely ranibizumab (RBZ) or bevacizumab (BVZ), after either focal or grid or scatter laser ... ...

Abstract	Purpose: In the present study, we aimed to evaluate the efficacy, safety, and cost-effectiveness of the anti-vascular endothelial growth factor (anti-VEGF), namely ranibizumab (RBZ) or bevacizumab (BVZ), after either focal or grid or scatter laser photocoagulation, for the treatment of diabetic macular edema (DME) in the Indian population. Methods: Retrospective data were collected in the Regional Institute of Ophthalmology, Kolkata, India between January 2018 and June 2019. Seventy-seven eyes received 3 consecutive monthly intravitreal injections of RBZ (0.5 mg) and were followed by prompt laser photocoagulation (within 7-10 days after the third injection). Similarly, 51 eyes received 3 consecutive monthly intravitreal injections of BVZ (1.25 mg), an off-label drug, and were followed by prompt laser therapy. Safety assessments of the therapy, as well as surrogate markers of biochemical derangements related to diabetic retinopathy (DR), were also investigated at the end of 12 months. Results: Seventy-seven subjects who were given a treatment of RBZ+laser therapy showed average 6.87±5.53 letters gain in their best-corrected visual acuity (BCVA) score, whereas the ones treated with off-label BVZ+ laser therapy demonstrated improvement in BCVA of an average 6.82±5.76 letters in "Early Treatment Diabetic Retinopathy Study" (ETDRS) chart. The study also highlights the cost-effectiveness of both RBZ+laser and BVZ+laser therapies for the treatment of DME in DR. The results demonstrated that a subject has to pay 20.951 times more cost (in INR) for RBZ+laser therapy compared to BVZ+laser therapy, to get an almost similar outcome. Conclusion: BVZ is found to be the more attractive option for treating DME in DR for its cost-friendliness over RBZ in terms of BCVA outcome, as well as the safety perspectives, at least for the economically backward population in developing countries, like India.
Language	English
Publishing date	2021-08-10
Publishing country	New Zealand
Document type	Journal Article
ISSN	1177-5467
ISSN	1177-5467
DOI	10.2147/OPTH.S317771
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Article ; Online: Hyperlipidemia-Mediated Increased Advanced Lipoxidation End Products Formation, an Important Factor Associated with Decreased Erythrocyte Glucose-6-Phosphate Dehydrogenase Activity in Mild Nonproliferative Diabetic Retinopathy.

Choudhuri, Subhadip / Roy, Pijush Kanti / Mitra, Bhaskar / Sen, Susruta / Sarkar, Rajarshi / Das, Mandrita / Biswas, Debashree / Ghosh, Prithwijit / Biswas, Ajoy / Chakraborty, Shaibal / Mondal, Lakshmi Kanta

Canadian journal of diabetes

2017 Volume 41, Issue 1, Page(s) 82–89

Abstract: Objectives: The present study aimed to evaluate the role of hyperlipidemia in increased formation of advanced lipoxidation end products (ALEs) and to evaluate whether there is any relationship between ALEs generation and erythrocyte glucose-6-phosphate ... ...

Abstract	Objectives: The present study aimed to evaluate the role of hyperlipidemia in increased formation of advanced lipoxidation end products (ALEs) and to evaluate whether there is any relationship between ALEs generation and erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity in cases of mild nonproliferative diabetic retinopathy (MNPDR). Methods: In this study, we enrolled 100 patients with type 2 diabetes and MNPDR, 100 subjects with type 2 diabetes but without retinopathy (DNR) and 90 normal individuals without diabetes as healthy controls (HCs). Erythrocyte nicotinamide dinucleotide phosphate (NADPH), G6PD activity, serum total cholesterol, low- and high-density lipoprotein (LDL, HDL) and triglyceride levels were determined by photometric assay. Serum malondialdehyde (MDA) protein adduct and hexanoyl-lysine (HEL) were measured by an enzyme-linked immunosorbent assay (ELISA). Results: A robust linear relationship was observed between MDA protein adduct and LDL or cholesterol or triglyceride levels, and HEL and LDL or cholesterol or triglyceride levels in subjects with MNPDR (p=0.0001). A significant inverse association was observed between erythrocyte G6PD activity and serum MDA protein adductor HEL levels in subjects with MNPDR (p=0.0001). Conclusions: Hyperlipidemia is an important factor that is associated with increased ALEs formation in persons with MNPDR. Increased ALEs generation was associated with decreased G6PD activity and low NADPH levels in cases of MNPDR, suggesting their detrimental role in the occurrence of early NPDR.
MeSH term(s)	Adult ; Advanced Oxidation Protein Products/blood ; Biomarkers/blood ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Diabetic Retinopathy/blood ; Diabetic Retinopathy/diagnosis ; Diabetic Retinopathy/epidemiology ; Erythrocytes/metabolism ; Female ; Glucosephosphate Dehydrogenase/blood ; Humans ; Hyperlipidemias/blood ; Hyperlipidemias/diagnosis ; Hyperlipidemias/epidemiology ; Male ; Middle Aged ; Oxidation-Reduction
Chemical Substances	Advanced Oxidation Protein Products ; Biomarkers ; Glucosephosphate Dehydrogenase (EC 1.1.1.49)
Language	English
Publishing date	2017-02
Publishing country	Canada
Document type	Journal Article
ISSN	2352-3840
ISSN (online)	2352-3840
DOI	10.1016/j.jcjd.2016.07.007
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Article ; Online: Role of N-ε- carboxy methyl lysine, advanced glycation end products and reactive oxygen species for the development of nonproliferative and proliferative retinopathy in type 2 diabetes mellitus.

Choudhuri, Subhadip / Dutta, Deep / Sen, Aditi / Chowdhury, Imran Hussain / Mitra, Bhaskar / Mondal, Lakshmi Kanta / Saha, Avijit / Bhadhuri, Gautam / Bhattacharya, Basudev

Molecular vision

2013 Volume 19, Page(s) 100–113

Abstract: Purpose: The aim of the present study was to evaluate the collective role of N-epsilon-carboxy methyl lysine (N(ε)-CML), advanced glycation end-products (AGEs), and reactive oxygen species (ROS) for the development of retinopathy among type 2 diabetic ... ...

Abstract	Purpose: The aim of the present study was to evaluate the collective role of N-epsilon-carboxy methyl lysine (N(ε)-CML), advanced glycation end-products (AGEs), and reactive oxygen species (ROS) for the development of retinopathy among type 2 diabetic subjects. Methods: Seventy type 2 diabetic subjects with nonproliferative diabetic retinopathy (NPDR), 105 subjects with proliferative diabetic retinopathy (PDR), and 102 patients with diabetes but without retinopathy (DNR) were enrolled in this study. In addition, 95 normal individuals without diabetes were enrolled as healthy controls in this study. Serum and vitreous N(ε)-CML and AGEs were measured by enzyme-linked immunosorbent assay. The peripheral blood mononuclear cell (PBMC) ROS level was measured by flow cytometric analysis. Serum and PBMC total thiols were measured by spectrophotometry. Results: Serum AGEs and N(ε)-CML levels were significantly elevated in subjects with PDR (p<0.0001) and NPDR (p=0.0297 and p<0.0001, respectively) compared to DNR subjects. Further vitreous AGEs and N(ε)-CML levels were found to be significantly high among PDR subjects compared to the control group (p<0.0001). PBMC ROS production was found to be strikingly high among NPDR (p<0.0001) and PDR (p<0.0001) subjects as compared to the DNR group. Serum and PBMC total thiol levels were remarkably decreased in NPDR (p<0.0001 and p=0.0043, respectively) and PDR (p=0.0108 and p=0.0332 respectively) subjects than those were considered as DNR. Conclusions: Our findings suggest that N(ε)-CML and ROS are the key modulators for the development of nonproliferative retinopathy among poorly controlled type 2 diabetic subjects. Furthermore, AGEs under persistent oxidative stress and the deprived antioxidant state might instigate the pathogenic process of retinopathy from the nonproliferative to the proliferative state.
MeSH term(s)	Adult ; Aged ; Case-Control Studies ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Diabetic Retinopathy/etiology ; Diabetic Retinopathy/metabolism ; Diabetic Retinopathy/pathology ; Female ; Glycation End Products, Advanced/blood ; Glycation End Products, Advanced/metabolism ; Humans ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/pathology ; Lysine/analogs & derivatives ; Lysine/blood ; Lysine/metabolism ; Male ; Middle Aged ; Reactive Oxygen Species/blood ; Sulfhydryl Compounds/blood ; Vitreous Body/metabolism
Chemical Substances	Glycation End Products, Advanced ; Reactive Oxygen Species ; Sulfhydryl Compounds ; N(6)-carboxymethyllysine (70YDX3Z2O7) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2013-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2017540-1
ISSN	1090-0535 ; 1090-0535
ISSN (online)	1090-0535
ISSN	1090-0535
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