PMID- 34861061
OWN - NLM
STAT- MEDLINE
DCOM- 20220318
LR  - 20220318
IS  - 1098-2825 (Electronic)
IS  - 0887-8013 (Print)
IS  - 0887-8013 (Linking)
VI  - 36
IP  - 1
DP  - 2022 Jan
TI  - Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM, 
      diabetic neuropathy, diabetic retinopathy, and obesity.
PG  - e24163
LID - 10.1002/jcla.24163 [doi]
LID - e24163
AB  - INTRODUCTION: Chronic hyperglycemia activates the inflammatory pathways and 
      oxidative stress mechanisms with consequent damage to nerve tissue and retina. 
      The Keap1-Nrf2 pathway acts as one of the most important antioxidant pathways of 
      the organism. Variants of Keap1 could affect susceptibility to diabetes and its 
      complications. METHODS: In a case-control study, 400 individuals included type 2 
      diabetes mellitus (T2DM) patients without complication, with neuropathy, with 
      retinopathy, and healthy individuals were investigated. The levels of glutathione 
      (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant 
      capacity (TAC) were measured using chemical methods. Using the PCR-RFLP method, 
      the Keap1 (rs11085735) variants were identified. RESULTS: Neuropathic patients 
      had significantly lower levels of GSH, GPx, and TAC and higher levels of total 
      oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM 
      patients without complication and controls. Lower levels of GSH and GPx and a 
      higher level of MDA were observed in patients with retinopathy compared with 
      controls. Obesity was associated with significantly lower GPx activity and higher 
      TOS. A significantly higher Keap1 AA genotype was found in patients with 
      neuropathy than T2DM without complication and controls. The presence of Keap1 AA 
      genotype correlated with lower GPx activity compared to CC genotype. CONCLUSIONS: 
      Our study suggests the role of reduced antioxidant system and Keap1 variants in 
      the pathogenesis of T2DM and its complications of neuropathy and retinopathy and 
      also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters 
      in diabetic patients, especially those with complication and their treatment with 
      antioxidants is suggested.
CI  - (c) 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley 
      Periodicals LLC.
FAU - Khalili, Farnaz
AU  - Khalili F
AD  - Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Vaisi-Raygani, Asad
AU  - Vaisi-Raygani A
AD  - Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Shakiba, Ebrahim
AU  - Shakiba E
AD  - Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Kohsari, Maryam
AU  - Kohsari M
AUID- ORCID: 0000-0002-1817-9147
AD  - Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Dehbani, Maryam
AU  - Dehbani M
AD  - Medical Biology Research Center, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Naseri, Rozita
AU  - Naseri R
AD  - Department of Internal Medicine, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Asadi, Soheila
AU  - Asadi S
AD  - Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Rahimi, Ziba
AU  - Rahimi Z
AD  - Medical Biology Research Center, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Rahimi, Mehrali
AU  - Rahimi M
AD  - Department of Internal Medicine, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
FAU - Rahimi, Zohreh
AU  - Rahimi Z
AUID- ORCID: 0000-0001-7589-3307
AD  - Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
AD  - Medical Biology Research Center, Kermanshah University of Medical Sciences, 
      Kermanshah, Iran.
LA  - eng
GR  - 97937/Kermanshah University of Medical Sciences/
PT  - Journal Article
DEP - 20211203
PL  - United States
TA  - J Clin Lab Anal
JT  - Journal of clinical laboratory analysis
JID - 8801384
RN  - 0 (KEAP1 protein, human)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/complications/epidemiology/genetics
MH  - *Diabetic Neuropathies/epidemiology/genetics
MH  - *Diabetic Retinopathy/epidemiology/genetics
MH  - Female
MH  - Humans
MH  - Kelch-Like ECH-Associated Protein 1/*genetics
MH  - Male
MH  - Middle Aged
MH  - Obesity/complications/epidemiology/genetics
MH  - *Oxidative Stress
PMC - PMC8761405
OTO - NOTNLM
OT  - diabetic neuropathy
OT  - diabetic retinopathy
OT  - keap1 variants
OT  - oxidative stress
OT  - type 2 diabetes
COIS- None.
EDAT- 2021/12/04 06:00
MHDA- 2022/03/19 06:00
PMCR- 2021/12/03
CRDT- 2021/12/03 17:34
PHST- 2021/11/15 00:00 [revised]
PHST- 2021/09/04 00:00 [received]
PHST- 2021/11/23 00:00 [accepted]
PHST- 2021/12/04 06:00 [pubmed]
PHST- 2022/03/19 06:00 [medline]
PHST- 2021/12/03 17:34 [entrez]
PHST- 2021/12/03 00:00 [pmc-release]
AID - JCLA24163 [pii]
AID - 10.1002/jcla.24163 [doi]
PST - ppublish
SO  - J Clin Lab Anal. 2022 Jan;36(1):e24163. doi: 10.1002/jcla.24163. Epub 2021 Dec 3.