Increased intestinal permeability to oral chromium (51Cr) -EDTA in human Type 2 diabetes
Objective In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low‐grade systemic inflammation. This has yet to be demonstrated in humans. The objec...
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Published in | Diabetic medicine Vol. 31; no. 5; pp. 559 - 563 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Blackwell Publishing Ltd
01.05.2014
Blackwell Wiley Subscription Services, Inc |
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Abstract | Objective
In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low‐grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes.
Methods
We examined intestinal permeability using chromium (51Cr)‐EDTA urinary recovery in twenty well‐controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI.
Results
Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high‐sensitivity C‐reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010).
Conclusion
This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes.
What's new?
There is increasing evidence linking an inflammatory cascade originating in the gut with systemic inflammation and the development of metabolic disease.
An early and key feature of this cascade is an increase in intestinal permeability, although this has yet to be demonstrated in human diabetes.
In this proof of concept study, we demonstrate for the first time an increase in intestinal permeability in people with Type 2 diabetes. |
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AbstractList | There is increasing evidence linking an inflammatory cascade originating in the gut with systemic inflammation and the development of metabolic disease.
An early and key feature of this cascade is an increase in intestinal permeability, although this has yet to be demonstrated in human diabetes.
In this proof of concept study, we demonstrate for the first time an increase in intestinal permeability in people with Type 2 diabetes. Objective In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes. Methods We examined intestinal permeability using chromium (51Cr)-EDTA urinary recovery in twenty well-controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI. Results Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high-sensitivity C-reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010). Conclusion This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes. What's new? There is increasing evidence linking an inflammatory cascade originating in the gut with systemic inflammation and the development of metabolic disease. An early and key feature of this cascade is an increase in intestinal permeability, although this has yet to be demonstrated in human diabetes. In this proof of concept study, we demonstrate for the first time an increase in intestinal permeability in people with Type 2 diabetes. [PUBLICATION ABSTRACT] In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes. We examined intestinal permeability using chromium ((51) Cr)-EDTA urinary recovery in twenty well-controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI. Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high-sensitivity C-reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010). This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes. Objective In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low‐grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes. Methods We examined intestinal permeability using chromium (51Cr)‐EDTA urinary recovery in twenty well‐controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI. Results Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high‐sensitivity C‐reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010). Conclusion This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes. What's new? There is increasing evidence linking an inflammatory cascade originating in the gut with systemic inflammation and the development of metabolic disease. An early and key feature of this cascade is an increase in intestinal permeability, although this has yet to be demonstrated in human diabetes. In this proof of concept study, we demonstrate for the first time an increase in intestinal permeability in people with Type 2 diabetes. In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes.OBJECTIVEIn animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes.We examined intestinal permeability using chromium ((51) Cr)-EDTA urinary recovery in twenty well-controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI.METHODSWe examined intestinal permeability using chromium ((51) Cr)-EDTA urinary recovery in twenty well-controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI.Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high-sensitivity C-reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010).RESULTSIntestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high-sensitivity C-reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010).This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes.CONCLUSIONThis is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes. |
Author | Robertson, M. D. Horton, F. Wright, J. Hinton, P. J. Smith, L. |
Author_xml | – sequence: 1 givenname: F. surname: Horton fullname: Horton, F. organization: Department of Nuclear Medicine, Royal Surrey County Hospital, Guildford, UK – sequence: 2 givenname: J. surname: Wright fullname: Wright, J. organization: Nutrition, Metabolism and Diabetes Research Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK – sequence: 3 givenname: L. surname: Smith fullname: Smith, L. organization: Nutrition, Metabolism and Diabetes Research Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK – sequence: 4 givenname: P. J. surname: Hinton fullname: Hinton, P. J. organization: Department of Nuclear Medicine, Royal Surrey County Hospital, Guildford, UK – sequence: 5 givenname: M. D. surname: Robertson fullname: Robertson, M. D. email: m.robertson@surrey.ac.uk organization: Nutrition, Metabolism and Diabetes Research Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK |
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Keywords | Endocrinopathy Type 2 diabetes Human Obesity Nutrition Digestive system Nutrition disorder Gut Oral administration Metabolic diseases Permeability EDTA Chromium Endocrinology Nutritional status |
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References_xml | – reference: Peled Y, Watz C, Gilat T. Measurement of intestinal permeability using 51Cr-EDTA. Am J Gastroenterol 1985; 80: 770-773. – reference: Clemente-Postigo M, Queipo-Ortuno MI, Murri M, Boto-Ordonez M, Perez-Martinez P, Andres-Lacueva C et al. Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients. J Lipid Res 2012; 53: 973-978. – reference: Creely SJ, McTernan PG, Kusminski CM. Fisher fM, Da Silva NF, Khanolkar M et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab 2007; 292: E740-747. – reference: Secondulfo M, de Magistris L, Sapone A, Di Monda G, Esposito P, Carratu R. Intestinal permeability and diabetes mellitus type 2. Minerva Gastroenterol Dietol 1999; 45: 187-192. – reference: Suzuki T, Hara H. Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats. Nutr Metab 2010; 7: 19. – reference: Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57: 1470-1481. – reference: Brenner C, Simmonds RE, Wood S, Rose V, Feldmann M, Turner J. TLR signalling and adapter utilization in primary human in vitro differentiated adipocytes. Scand J Immunol 2012; 76: 359-370. – reference: Bjarnason I, Peters TJ, Veall N. 51Cr-EDTA test for intestinal permeability. Lancet 1984; 2: 523. – reference: Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012; 489: 242-249. – reference: Harte AL, Varma MC, Tripathi G, McGee KC, Al-Daghri NM, Al-Attas OS et al. High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects. Diabetes Care 2012; 35: 375-382. – reference: Suenaert P, Bulteel V, Lemmens L, Noman M, Geypens B, Van Assche G et al. Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease. Am J Gastroenterol 2002; 97: 2000-2004. – reference: Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol 2006; 101: 1288-1294. – reference: Anderson AD, Jain PK, Fleming S, Poon P, Mitchell CJ, MacFie J. Evaluation of a triple sugar test of colonic permeability in humans. Acta Physiol Scand 2004; 182: 171-177. – reference: Amar J, Burcelin R, Ruidavets JB, Cani PD, Fauvel J, Alessi MC et al. Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr 2008; 87: 1219-1223. – reference: de Kort S, Keszthelyi D, Masclee AA. Leaky gut and diabetes mellitus: what is the link? Obes Rev 2011; 12: 449-458. – reference: Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R et al. Increased intestinal permeability and tight junction alterations in non-alcoholic fatty liver disease. Hepatology 2009; 49: 1877-1887. – reference: Spruss A, Kanuri G, Stahl C, Bischoff SC, Bergheim I. Metformin protects against the development of fructose-induced steatosis in mice: role of the intestinal barrier function. Lab Invest 2012; 92: 1020-1032. – reference: Cani PD, Osto M, Geurts L, Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes 2012; 3: 279-288. – reference: Choi K, Lee SS, Oh SJ, Lim SY, Lim SY, Jeon WK et al. The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test. Clin Nutr 2007; 26: 57-62. – reference: DeMeo MT, Mutlu EA, Keshavarzian A, Tobin MC. Intestinal permeation and gastrointestinal disease. J Clin Gastroenterol 2002; 34: 385-396. – volume: 182 start-page: 171 year: 2004 end-page: 177 article-title: Evaluation of a triple sugar test of colonic permeability in humans publication-title: Acta Physiol Scand – volume: 292 start-page: E740 year: 2007 end-page: 747 article-title: Fisher fM, Da Silva NF, Khanolkar M . Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes publication-title: Am J Physiol Endocrinol Metab – volume: 97 start-page: 2000 year: 2002 end-page: 2004 article-title: Anti‐tumor necrosis factor treatment restores the gut barrier in Crohn's disease publication-title: Am J Gastroenterol – volume: 34 start-page: 385 year: 2002 end-page: 396 article-title: Intestinal permeation and gastrointestinal disease publication-title: J Clin Gastroenterol – volume: 49 start-page: 1877 year: 2009 end-page: 1887 article-title: Increased intestinal permeability and tight junction alterations in non‐alcoholic fatty liver disease publication-title: Hepatology – volume: 87 start-page: 1219 year: 2008 end-page: 1223 article-title: Energy intake is associated with endotoxemia in apparently healthy men publication-title: Am J Clin Nutr – volume: 101 start-page: 1288 year: 2006 end-page: 1294 article-title: Abnormal intestinal permeability in subgroups of diarrhea‐predominant irritable bowel syndromes publication-title: Am J Gastroenterol – volume: 12 start-page: 449 year: 2011 end-page: 458 article-title: Leaky gut and diabetes mellitus: what is the link? publication-title: Obes Rev – volume: 80 start-page: 770 year: 1985 end-page: 773 article-title: Measurement of intestinal permeability using Cr‐EDTA publication-title: Am J Gastroenterol – volume: 26 start-page: 57 year: 2007 end-page: 62 article-title: The effect of oral glutamine on 5‐fluorouracil/leucovorin‐induced mucositis/stomatitis assessed by intestinal permeability test publication-title: Clin Nutr – volume: 57 start-page: 1470 year: 2008 end-page: 1481 article-title: Changes in gut microbiota control metabolic endotoxemia‐induced inflammation in high‐fat diet‐induced obesity and diabetes in mice publication-title: Diabetes – volume: 7 start-page: 19 year: 2010 article-title: Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats publication-title: Nutr Metab – volume: 53 start-page: 973 year: 2012 end-page: 978 article-title: Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients publication-title: J Lipid Res – volume: 3 start-page: 279 year: 2012 end-page: 288 article-title: Involvement of gut microbiota in the development of low‐grade inflammation and type 2 diabetes associated with obesity publication-title: Gut Microbes – volume: 92 start-page: 1020 year: 2012 end-page: 1032 article-title: Metformin protects against the development of fructose‐induced steatosis in mice: role of the intestinal barrier function publication-title: Lab Invest – volume: 489 start-page: 242 year: 2012 end-page: 249 article-title: Functional interactions between the gut microbiota and host metabolism publication-title: Nature – volume: 76 start-page: 359 year: 2012 end-page: 370 article-title: TLR signalling and adapter utilization in primary human differentiated adipocytes publication-title: Scand J Immunol – volume: 35 start-page: 375 year: 2012 end-page: 382 article-title: High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects publication-title: Diabetes Care – volume: 2 start-page: 523 year: 1984 article-title: Cr‐EDTA test for intestinal permeability publication-title: Lancet – volume: 45 start-page: 187 year: 1999 end-page: 192 article-title: Intestinal permeability and diabetes mellitus type 2 publication-title: Minerva Gastroenterol Dietol – ident: e_1_2_8_16_1 doi: 10.1111/j.1365-201X.2004.01347.x – ident: e_1_2_8_3_1 doi: 10.1093/ajcn/87.5.1219 – volume: 80 start-page: 770 year: 1985 ident: e_1_2_8_18_1 article-title: Measurement of intestinal permeability using 51Cr‐EDTA publication-title: Am J Gastroenterol – ident: e_1_2_8_10_1 doi: 10.1097/00004836-200204000-00003 – ident: e_1_2_8_5_1 doi: 10.1111/j.1365-3083.2012.02744.x – ident: e_1_2_8_14_1 doi: 10.1002/hep.22848 – ident: e_1_2_8_7_1 doi: 10.1152/ajpendo.00302.2006 – ident: e_1_2_8_13_1 doi: 10.1111/j.1572-0241.2006.00672.x – ident: e_1_2_8_20_1 doi: 10.1186/1743-7075-7-19 – ident: e_1_2_8_4_1 doi: 10.1194/jlr.P020909 – ident: e_1_2_8_15_1 doi: 10.1016/j.clnu.2006.07.003 – ident: e_1_2_8_11_1 doi: 10.1016/S0140-6736(84)92601-1 – ident: e_1_2_8_8_1 doi: 10.2337/dc11-1593 – ident: e_1_2_8_19_1 doi: 10.2337/db07-1403 – volume: 45 start-page: 187 year: 1999 ident: e_1_2_8_9_1 article-title: Intestinal permeability and diabetes mellitus type 2 publication-title: Minerva Gastroenterol Dietol – ident: e_1_2_8_17_1 doi: 10.1111/j.1467-789X.2010.00845.x – ident: e_1_2_8_2_1 doi: 10.4161/gmic.19625 – ident: e_1_2_8_21_1 doi: 10.1038/labinvest.2012.75 – ident: e_1_2_8_6_1 doi: 10.1038/nature11552 – ident: e_1_2_8_12_1 doi: 10.1111/j.1572-0241.2002.05914.x |
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In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins,... There is increasing evidence linking an inflammatory cascade originating in the gut with systemic inflammation and the development of metabolic disease. An... In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing... Objective In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins,... |
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SubjectTerms | Administration, Oral Biological and medical sciences Biomarkers - metabolism C-Reactive Protein - metabolism Case-Control Studies Cell Membrane Permeability - physiology Chromium Radioisotopes - administration & dosage Chromium Radioisotopes - urine Diabetes Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - urine Diabetes. Impaired glucose tolerance Edetic Acid - administration & dosage Edetic Acid - urine Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Humans Interleukin-6 - blood Intestinal Absorption - physiology Intestinal Mucosa - metabolism Intestines - cytology Male Medical sciences Middle Aged Tumor Necrosis Factor-alpha - blood Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: endocrinology |
Title | Increased intestinal permeability to oral chromium (51Cr) -EDTA in human Type 2 diabetes |
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