Insulin Resistance is Associated with Gut Permeability Without the Direct Influence of Obesity in Young Adults
Lusikelelwe Mkumbuzi, Mvuyisi M O Mfengu, Godwill A Engwa, Constance R Sewani-Rusike, Lusikelelwe Mkumbuzi, Mvuyisi M O Mfengu, Godwill A Engwa, Constance R Sewani-Rusike
Abstract
Objective: Recent findings have associated insulin resistance and obesity with increased gut permeability. However, it still remains unclear whether obesity may be the underlining factor for the association between gut permeability and insulin resistance. This study investigated the relationship between gut permeability, measures of obesity, and markers of insulin resistance in young adults.
Materials and methods: A cross-sectional quantitative study which enrolled 151 young South African adults was conducted. Anthropometric measurements were performed to assess obesity. Adiponectin, leptin, and zonulin, a marker for gut permeability, were assayed. Insulin and fasting glucose were assayed and used to determine insulin resistance (HOMA-IR), insulin sensitivity (%S) and beta cell function (%B).
Results: Decreased adiponectin and increased leptin were associated (p<0.05) with obesity. HOMA-IR inversely correlated (p<0.05) with adiponectin but positively with leptin to adiponectin (Lept/ADP) ratio (p<0.05) in females. Markers of insulin resistance were not associated (p>0.05) with obesity. Overweight/obese (O/O) females had a significantly (p<0.01) higher zonulin concentration than lean females. Zonulin positively associated (p<0.05) with body mass index and visceral fat, as well as with HOMA-IR and insulin concentration. Lept/ADP ratio, an inflammatory marker, was associated with risk of insulin resistance. Increased insulin, a maker for insulin resistance, was associated with risk of gut permeability.
Conclusion: Insulin resistance was associated with gut permeability without a direct influence by obesity in young adults. The lack of relationship between obesity and insulin resistance was possibly mediated by the contribution of obesity to gut permeability. This finding suggests that gut permeability may be a potential independent risk factor for the development of insulin resistance in healthy obese young adults.
Keywords: gut permeability; inflammation; insulin resistance; obesity.
Conflict of interest statement
The authors report no conflicts of interest for this work.
© 2020 Mkumbuzi et al.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7457818/bin/DMSO-13-2997-g0001.jpg)
Figure 2
Plasma leptin level between overweight/obese…
Figure 2
Plasma leptin level between overweight/obese and lean subjects. Data is expressed as mean…
Figure 3
Leptin to adiponectin ratio between…
Figure 3
Leptin to adiponectin ratio between overweight/obese and lean subjects. Data is expressed as…
Figure 4
Plasma zonulin between lean and…
Figure 4
Plasma zonulin between lean and overweight/obese subjects. Data is expressed as mean ±…
Figure 5
Mediation effect and summary of…
Figure 5
Mediation effect and summary of findings. ( A ) Mediation effect of gut…
- Gut permeability is associated with hypertension and measures of obesity but not with Endothelial Dysfunction in South African youth.Ntlahla EE, Mfengu MM, Engwa GA, Nkeh-Chungag BN, Sewani-Rusike CR. Ntlahla EE, et al. Afr Health Sci. 2021 Sep;21(3):1172-1184. doi: 10.4314/ahs.v21i3.26. Afr Health Sci. 2021. PMID: 35222580 Free PMC article.
- Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population.Ayina CN, Noubiap JJ, Etoundi Ngoa LS, Boudou P, Gautier JF, Mengnjo MK, Mbanya JC, Sobngwi E. Ayina CN, et al. Lipids Health Dis. 2016 May 17;15:96. doi: 10.1186/s12944-016-0264-x. Lipids Health Dis. 2016. PMID: 27189377 Free PMC article.
- Zonulin level, a marker of intestinal permeability, is increased in association with liver enzymes in young adolescents.Kim JH, Heo JS, Baek KS, Kim SY, Kim JH, Baek KH, Kim KE, Sheen YH. Kim JH, et al. Clin Chim Acta. 2018 Jun;481:218-224. doi: 10.1016/j.cca.2018.03.005. Epub 2018 Mar 12. Clin Chim Acta. 2018. PMID: 29544751
- Relationship of adipokine to insulin sensitivity and glycemic regulation in obese women--the effect of body weight reduction by caloric restriction.Golubović MV, Dimić D, Antić S, Radenković S, Djindjić B, Jovanović M. Golubović MV, et al. Vojnosanit Pregl. 2013 Mar;70(3):284-91. doi: 10.2298/vsp1303284v. Vojnosanit Pregl. 2013. PMID: 23607240
- Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.Bernardo AP, Oliveira JC, Santos O, Carvalho MJ, Cabrita A, Rodrigues A. Bernardo AP, et al. Clin J Am Soc Nephrol. 2015 Dec 7;10(12):2205-12. doi: 10.2215/CJN.03170315. Epub 2015 Oct 27. Clin J Am Soc Nephrol. 2015. PMID: 26507143 Free PMC article.
- High Fructose Causes More Prominent Liver Steatohepatitis with Leaky Gut Similar to High Glucose Administration in Mice and Attenuation by Lactiplantibacillus plantarum dfa1.Ondee T, Pongpirul K, Udompornpitak K, Sukkummee W, Lertmongkolaksorn T, Senaprom S, Leelahavanichkul A. Ondee T, et al. Nutrients. 2023 Mar 17;15(6):1462. doi: 10.3390/nu15061462. Nutrients. 2023. PMID: 36986190 Free PMC article.
- Metabolic-Dysfunction-Associated Fatty Liver Disease and Gut Microbiota: From Fatty Liver to Dysmetabolic Syndrome.Abenavoli L, Scarlata GGM, Scarpellini E, Boccuto L, Spagnuolo R, Tilocca B, Roncada P, Luzza F. Abenavoli L, et al. Medicina (Kaunas). 2023 Mar 17;59(3):594. doi: 10.3390/medicina59030594. Medicina (Kaunas). 2023. PMID: 36984595 Free PMC article. Review.
- Low-fat dairy consumption improves intestinal immune function more than high-fat dairy in a diet-induced swine model of insulin resistance.She Y, Wang K, Makarowski A, Mangat R, Tsai S, Willing BP, Proctor SD, Richard C. She Y, et al. Eur J Nutr. 2023 Mar;62(2):699-711. doi: 10.1007/s00394-022-03013-8. Epub 2022 Oct 5. Eur J Nutr. 2023. PMID: 36197467
- Bacterial DNAemia in Older Participants and Nonagenarian Offspring and Association With Redox Biomarkers: Results From MARK-AGE Study.Giacconi R, D'Aquila P, Malavolta M, Piacenza F, Bürkle A, Villanueva MM, Dollé MET, Jansen E, Grune T, Gonos ES, Franceschi C, Capri M, Gradinaru D, Grubeck-Loebenstein B, Sikora E, Stuetz W, Weber D, Toussaint O, Debacq-Chainiaux F, Hervonen A, Hurme M, Slagboom PE, Schön C, Bernhardt J, Breusing N, Duncan T, Passarino G, Bellizzi D, Provinciali M. Giacconi R, et al. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):42-50. doi: 10.1093/gerona/glac154. J Gerontol A Biol Sci Med Sci. 2023. PMID: 35914804 Free PMC article.
- The intestinal immune system and gut barrier function in obesity and ageing.Shemtov SJ, Emani R, Bielska O, Covarrubias AJ, Verdin E, Andersen JK, Winer DA. Shemtov SJ, et al. FEBS J. 2022 Jun 21:10.1111/febs.16558. doi: 10.1111/febs.16558. Online ahead of print. FEBS J. 2022. PMID: 35727858 Review.
-
- Gutiérrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular mechanisms of insulin resistance: an update. Gac Med Mex. 2017;153:197–209.
-
- International Diabetes Federation. IDF Diabetes Atlas. 7th ed. Int Diabetes Fed; 2015. Available from:: http://www.idf.org/diabetesatlas. Accessed January2, 2016.
-
- SEMDSA Type 2 Diabetes Guidelines Expert Committee. The 2017 SEMDSA guideline for the management of type 2 diabetes. JEMDSA. 2017;22(1):S1–S196.
- Full Text Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7457818/bin/DMSO-13-2997-g0002.jpg)
Figure 3
Leptin to adiponectin ratio between…
Figure 3
Leptin to adiponectin ratio between overweight/obese and lean subjects. Data is expressed as…
Figure 4
Plasma zonulin between lean and…
Figure 4
Plasma zonulin between lean and overweight/obese subjects. Data is expressed as mean ±…
Figure 5
Mediation effect and summary of…
Figure 5
Mediation effect and summary of findings. ( A ) Mediation effect of gut…
- Gut permeability is associated with hypertension and measures of obesity but not with Endothelial Dysfunction in South African youth.Ntlahla EE, Mfengu MM, Engwa GA, Nkeh-Chungag BN, Sewani-Rusike CR. Ntlahla EE, et al. Afr Health Sci. 2021 Sep;21(3):1172-1184. doi: 10.4314/ahs.v21i3.26. Afr Health Sci. 2021. PMID: 35222580 Free PMC article.
- Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population.Ayina CN, Noubiap JJ, Etoundi Ngoa LS, Boudou P, Gautier JF, Mengnjo MK, Mbanya JC, Sobngwi E. Ayina CN, et al. Lipids Health Dis. 2016 May 17;15:96. doi: 10.1186/s12944-016-0264-x. Lipids Health Dis. 2016. PMID: 27189377 Free PMC article.
- Zonulin level, a marker of intestinal permeability, is increased in association with liver enzymes in young adolescents.Kim JH, Heo JS, Baek KS, Kim SY, Kim JH, Baek KH, Kim KE, Sheen YH. Kim JH, et al. Clin Chim Acta. 2018 Jun;481:218-224. doi: 10.1016/j.cca.2018.03.005. Epub 2018 Mar 12. Clin Chim Acta. 2018. PMID: 29544751
- Relationship of adipokine to insulin sensitivity and glycemic regulation in obese women--the effect of body weight reduction by caloric restriction.Golubović MV, Dimić D, Antić S, Radenković S, Djindjić B, Jovanović M. Golubović MV, et al. Vojnosanit Pregl. 2013 Mar;70(3):284-91. doi: 10.2298/vsp1303284v. Vojnosanit Pregl. 2013. PMID: 23607240
- Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.Bernardo AP, Oliveira JC, Santos O, Carvalho MJ, Cabrita A, Rodrigues A. Bernardo AP, et al. Clin J Am Soc Nephrol. 2015 Dec 7;10(12):2205-12. doi: 10.2215/CJN.03170315. Epub 2015 Oct 27. Clin J Am Soc Nephrol. 2015. PMID: 26507143 Free PMC article.
- High Fructose Causes More Prominent Liver Steatohepatitis with Leaky Gut Similar to High Glucose Administration in Mice and Attenuation by Lactiplantibacillus plantarum dfa1.Ondee T, Pongpirul K, Udompornpitak K, Sukkummee W, Lertmongkolaksorn T, Senaprom S, Leelahavanichkul A. Ondee T, et al. Nutrients. 2023 Mar 17;15(6):1462. doi: 10.3390/nu15061462. Nutrients. 2023. PMID: 36986190 Free PMC article.
- Metabolic-Dysfunction-Associated Fatty Liver Disease and Gut Microbiota: From Fatty Liver to Dysmetabolic Syndrome.Abenavoli L, Scarlata GGM, Scarpellini E, Boccuto L, Spagnuolo R, Tilocca B, Roncada P, Luzza F. Abenavoli L, et al. Medicina (Kaunas). 2023 Mar 17;59(3):594. doi: 10.3390/medicina59030594. Medicina (Kaunas). 2023. PMID: 36984595 Free PMC article. Review.
- Low-fat dairy consumption improves intestinal immune function more than high-fat dairy in a diet-induced swine model of insulin resistance.She Y, Wang K, Makarowski A, Mangat R, Tsai S, Willing BP, Proctor SD, Richard C. She Y, et al. Eur J Nutr. 2023 Mar;62(2):699-711. doi: 10.1007/s00394-022-03013-8. Epub 2022 Oct 5. Eur J Nutr. 2023. PMID: 36197467
- Bacterial DNAemia in Older Participants and Nonagenarian Offspring and Association With Redox Biomarkers: Results From MARK-AGE Study.Giacconi R, D'Aquila P, Malavolta M, Piacenza F, Bürkle A, Villanueva MM, Dollé MET, Jansen E, Grune T, Gonos ES, Franceschi C, Capri M, Gradinaru D, Grubeck-Loebenstein B, Sikora E, Stuetz W, Weber D, Toussaint O, Debacq-Chainiaux F, Hervonen A, Hurme M, Slagboom PE, Schön C, Bernhardt J, Breusing N, Duncan T, Passarino G, Bellizzi D, Provinciali M. Giacconi R, et al. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):42-50. doi: 10.1093/gerona/glac154. J Gerontol A Biol Sci Med Sci. 2023. PMID: 35914804 Free PMC article.
- The intestinal immune system and gut barrier function in obesity and ageing.Shemtov SJ, Emani R, Bielska O, Covarrubias AJ, Verdin E, Andersen JK, Winer DA. Shemtov SJ, et al. FEBS J. 2022 Jun 21:10.1111/febs.16558. doi: 10.1111/febs.16558. Online ahead of print. FEBS J. 2022. PMID: 35727858 Review.
-
- Gutiérrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular mechanisms of insulin resistance: an update. Gac Med Mex. 2017;153:197–209.
-
- International Diabetes Federation. IDF Diabetes Atlas. 7th ed. Int Diabetes Fed; 2015. Available from:: http://www.idf.org/diabetesatlas. Accessed January2, 2016.
-
- SEMDSA Type 2 Diabetes Guidelines Expert Committee. The 2017 SEMDSA guideline for the management of type 2 diabetes. JEMDSA. 2017;22(1):S1–S196.
- Full Text Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7457818/bin/DMSO-13-2997-g0003.jpg)
Figure 4
Plasma zonulin between lean and…
Figure 4
Plasma zonulin between lean and overweight/obese subjects. Data is expressed as mean ±…
Figure 5
Mediation effect and summary of…
Figure 5
Mediation effect and summary of findings. ( A ) Mediation effect of gut…
- Gut permeability is associated with hypertension and measures of obesity but not with Endothelial Dysfunction in South African youth.Ntlahla EE, Mfengu MM, Engwa GA, Nkeh-Chungag BN, Sewani-Rusike CR. Ntlahla EE, et al. Afr Health Sci. 2021 Sep;21(3):1172-1184. doi: 10.4314/ahs.v21i3.26. Afr Health Sci. 2021. PMID: 35222580 Free PMC article.
- Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population.Ayina CN, Noubiap JJ, Etoundi Ngoa LS, Boudou P, Gautier JF, Mengnjo MK, Mbanya JC, Sobngwi E. Ayina CN, et al. Lipids Health Dis. 2016 May 17;15:96. doi: 10.1186/s12944-016-0264-x. Lipids Health Dis. 2016. PMID: 27189377 Free PMC article.
- Zonulin level, a marker of intestinal permeability, is increased in association with liver enzymes in young adolescents.Kim JH, Heo JS, Baek KS, Kim SY, Kim JH, Baek KH, Kim KE, Sheen YH. Kim JH, et al. Clin Chim Acta. 2018 Jun;481:218-224. doi: 10.1016/j.cca.2018.03.005. Epub 2018 Mar 12. Clin Chim Acta. 2018. PMID: 29544751
- Relationship of adipokine to insulin sensitivity and glycemic regulation in obese women--the effect of body weight reduction by caloric restriction.Golubović MV, Dimić D, Antić S, Radenković S, Djindjić B, Jovanović M. Golubović MV, et al. Vojnosanit Pregl. 2013 Mar;70(3):284-91. doi: 10.2298/vsp1303284v. Vojnosanit Pregl. 2013. PMID: 23607240
- Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.Bernardo AP, Oliveira JC, Santos O, Carvalho MJ, Cabrita A, Rodrigues A. Bernardo AP, et al. Clin J Am Soc Nephrol. 2015 Dec 7;10(12):2205-12. doi: 10.2215/CJN.03170315. Epub 2015 Oct 27. Clin J Am Soc Nephrol. 2015. PMID: 26507143 Free PMC article.
- High Fructose Causes More Prominent Liver Steatohepatitis with Leaky Gut Similar to High Glucose Administration in Mice and Attenuation by Lactiplantibacillus plantarum dfa1.Ondee T, Pongpirul K, Udompornpitak K, Sukkummee W, Lertmongkolaksorn T, Senaprom S, Leelahavanichkul A. Ondee T, et al. Nutrients. 2023 Mar 17;15(6):1462. doi: 10.3390/nu15061462. Nutrients. 2023. PMID: 36986190 Free PMC article.
- Metabolic-Dysfunction-Associated Fatty Liver Disease and Gut Microbiota: From Fatty Liver to Dysmetabolic Syndrome.Abenavoli L, Scarlata GGM, Scarpellini E, Boccuto L, Spagnuolo R, Tilocca B, Roncada P, Luzza F. Abenavoli L, et al. Medicina (Kaunas). 2023 Mar 17;59(3):594. doi: 10.3390/medicina59030594. Medicina (Kaunas). 2023. PMID: 36984595 Free PMC article. Review.
- Low-fat dairy consumption improves intestinal immune function more than high-fat dairy in a diet-induced swine model of insulin resistance.She Y, Wang K, Makarowski A, Mangat R, Tsai S, Willing BP, Proctor SD, Richard C. She Y, et al. Eur J Nutr. 2023 Mar;62(2):699-711. doi: 10.1007/s00394-022-03013-8. Epub 2022 Oct 5. Eur J Nutr. 2023. PMID: 36197467
- Bacterial DNAemia in Older Participants and Nonagenarian Offspring and Association With Redox Biomarkers: Results From MARK-AGE Study.Giacconi R, D'Aquila P, Malavolta M, Piacenza F, Bürkle A, Villanueva MM, Dollé MET, Jansen E, Grune T, Gonos ES, Franceschi C, Capri M, Gradinaru D, Grubeck-Loebenstein B, Sikora E, Stuetz W, Weber D, Toussaint O, Debacq-Chainiaux F, Hervonen A, Hurme M, Slagboom PE, Schön C, Bernhardt J, Breusing N, Duncan T, Passarino G, Bellizzi D, Provinciali M. Giacconi R, et al. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):42-50. doi: 10.1093/gerona/glac154. J Gerontol A Biol Sci Med Sci. 2023. PMID: 35914804 Free PMC article.
- The intestinal immune system and gut barrier function in obesity and ageing.Shemtov SJ, Emani R, Bielska O, Covarrubias AJ, Verdin E, Andersen JK, Winer DA. Shemtov SJ, et al. FEBS J. 2022 Jun 21:10.1111/febs.16558. doi: 10.1111/febs.16558. Online ahead of print. FEBS J. 2022. PMID: 35727858 Review.
-
- Gutiérrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular mechanisms of insulin resistance: an update. Gac Med Mex. 2017;153:197–209.
-
- International Diabetes Federation. IDF Diabetes Atlas. 7th ed. Int Diabetes Fed; 2015. Available from:: http://www.idf.org/diabetesatlas. Accessed January2, 2016.
-
- SEMDSA Type 2 Diabetes Guidelines Expert Committee. The 2017 SEMDSA guideline for the management of type 2 diabetes. JEMDSA. 2017;22(1):S1–S196.
- Full Text Sources
- Medical
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7457818/bin/DMSO-13-2997-g0004.jpg)
Figure 5
Mediation effect and summary of…
Figure 5
Mediation effect and summary of findings. ( A ) Mediation effect of gut…
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7457818/bin/DMSO-13-2997-g0005.jpg)
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Source: PubMed