Relationship between Decreased Serum Superoxide Dismutase Activity and Metabolic Syndrome: Synergistic Mediating Role of Insulin Resistance and β-Cell Dysfunction

The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders...

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Published inOxidative medicine and cellular longevity Vol. 2020; no. 2020; pp. 1 - 10
Main Authors Li, Wei, Xu, Lingling, Li, Yu-xiu, Ping, Fan, Zeng, Jingbo, He, Shuli, Ma, Chunxiao, Li, Pingping, Lv, Lu, Ma, Chifa, Liu, Yiwen, Zhang, Huabing
Format Journal Article
LanguageEnglish
Published Cairo, Egypt Hindawi Publishing Corporation 2020
Hindawi
John Wiley & Sons, Inc
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Abstract The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06±16.89 U/mL vs. 56.25±22.61 U/mL, P=0.001) and exhibited a descending trend across sequential increase of MS component number (P for trend=0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β-cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β-cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β-cell dysfunction partially mediate the relationship between decreased SOD activity and MS.
AbstractList The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06±16.89 U/mL vs. 56.25±22.61 U/mL, P=0.001) and exhibited a descending trend across sequential increase of MS component number (P for trend=0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β-cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β-cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β-cell dysfunction partially mediate the relationship between decreased SOD activity and MS.
The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06 ± 16.89 U/mL vs. 56.25 ± 22.61 U/mL, P = 0.001) and exhibited a descending trend across sequential increase of MS component number ( P  for trend = 0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β -cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β -cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β -cell dysfunction partially mediate the relationship between decreased SOD activity and MS.
The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06 ± 16.89 U/mL vs. 56.25 ± 22.61 U/mL, = 0.001) and exhibited a descending trend across sequential increase of MS component number (  for trend = 0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and -cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and -cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and -cell dysfunction partially mediate the relationship between decreased SOD activity and MS.
The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06 ± 16.89 U/mL vs. 56.25 ± 22.61 U/mL, P = 0.001) and exhibited a descending trend across sequential increase of MS component number (P for trend = 0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β-cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β-cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β-cell dysfunction partially mediate the relationship between decreased SOD activity and MS.The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06 ± 16.89 U/mL vs. 56.25 ± 22.61 U/mL, P = 0.001) and exhibited a descending trend across sequential increase of MS component number (P for trend = 0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β-cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β-cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β-cell dysfunction partially mediate the relationship between decreased SOD activity and MS.
The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects ( 62.06 ± 16.89  U/mL vs. 56.25 ± 22.61  U/mL, P = 0.001 ) and exhibited a descending trend across sequential increase of MS component number ( P   for   trend = 0.031 ). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β -cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β -cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β -cell dysfunction partially mediate the relationship between decreased SOD activity and MS.
Author Ma, Chunxiao
Ma, Chifa
Xu, Lingling
Li, Yu-xiu
Lv, Lu
Ping, Fan
Li, Wei
He, Shuli
Liu, Yiwen
Li, Pingping
Zhang, Huabing
Zeng, Jingbo
AuthorAffiliation 3 Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing 100050, China
5 Department of Endocrinology, Fuxing Hospital, The Eighth Clinical Medical College, Capital Medical University, Beijing 100038, China
1 Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
2 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medical Sciences and Peking Union Medical College, Beijing 100050, China
4 Department of Nutrition, Peking Union Medical College Hospital, Beijing 100730, China
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Snippet The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related...
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SubjectTerms Adult
Age
Aged
Aged, 80 and over
Aging
Biomarkers - metabolism
Blood pressure
Calories
Cellular Senescence
Cholesterol
Data collection
Diet
Female
Glucose
Glutathione
Humans
Hypertension
Inflammation - pathology
Insulin Resistance
Insulin-Secreting Cells - pathology
Lipids
Logistic Models
Male
Males
Metabolic syndrome
Metabolic Syndrome - blood
Metabolic Syndrome - metabolism
Metabolomics
Middle Aged
Mitochondrial DNA
Multivariate Analysis
Oxidative Stress
Pathogenesis
Risk Factors
Software
Studies
Superoxide Dismutase - blood
Triglycerides - metabolism
Variables
Variance analysis
Vitamins
Young Adult
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Title Relationship between Decreased Serum Superoxide Dismutase Activity and Metabolic Syndrome: Synergistic Mediating Role of Insulin Resistance and β-Cell Dysfunction
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