Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy
Pentose phosphate pathway (PPP) represents a potentially 'protective' mechanism in hyperglycaemia due to shunting of glycolytic intermediates into PPP reactions. We hypothesized that thiamine status (plasma and erythrocyte levels of thiamine and its esters) together with genetic variabilit...
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| Veröffentlicht in: | Nephrology, dialysis, transplantation dialysis, transplantation, 2011-04, Vol.26 (4), p.1229-1236 |
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| creator | PACAL, Lukáš TOMANDL, Josef MUZIK, Jan KANKOVA, Kateřina SVOJANOVSKY, Jan KRUSOVA, Darja STEPANKOVA, Soňa REHOROVA, Jitka OLSOVSKY, Jindřich BELOBRADKOVA, Jana TANHÄUSEROVA, Veronika TOMANDLOVA, Marie |
| description | Pentose phosphate pathway (PPP) represents a potentially 'protective' mechanism in hyperglycaemia due to shunting of glycolytic intermediates into PPP reactions. We hypothesized that thiamine status (plasma and erythrocyte levels of thiamine and its esters) together with genetic variability in key PPP enzymes-transketolase (TKT), transaldolase and TKT-like-might contribute to the progression of diabetic nephropathy (DN) and mortality of diabetics.
A total of 240 diabetic subjects with variable degree of kidney disease were included at baseline and were followed up for a median of 26 (IQR 21-50) months. Concentrations of thiamine in plasma and whole blood and TKT-catalysed reaction were determined by HPLC. Single-nucleotide polymorphisms (SNPs) (n = 14) were genotyped by means of PCR using TaqMan chemistry (Applied Biosystems, Foster City, CA, USA).
Significant differences in pTh, pThDP, eryThDP and eryTKT between DN-stage groups were ascertained (P < 0.05) with advancing stage of DN being accompanied with increasing values of pTh, pThDP and eryTKT but not eryThDP. A highly significant negative correlation (r = - 0.41, P < 0.001) was found between pThDP and eryThDP, and the tertiles of the ratio of eryThDP/pThDP were significantly associated with all-cause mortality rates (P = 0.0072). We also identified significant differences in the rate of DN progression between different pTDP tertile groups (P = 0.0017). No significant genetic effects were found.
The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality. |
| doi_str_mv | 10.1093/ndt/gfq550 |
| format | Article |
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A total of 240 diabetic subjects with variable degree of kidney disease were included at baseline and were followed up for a median of 26 (IQR 21-50) months. Concentrations of thiamine in plasma and whole blood and TKT-catalysed reaction were determined by HPLC. Single-nucleotide polymorphisms (SNPs) (n = 14) were genotyped by means of PCR using TaqMan chemistry (Applied Biosystems, Foster City, CA, USA).
Significant differences in pTh, pThDP, eryThDP and eryTKT between DN-stage groups were ascertained (P < 0.05) with advancing stage of DN being accompanied with increasing values of pTh, pThDP and eryTKT but not eryThDP. A highly significant negative correlation (r = - 0.41, P < 0.001) was found between pThDP and eryThDP, and the tertiles of the ratio of eryThDP/pThDP were significantly associated with all-cause mortality rates (P = 0.0072). We also identified significant differences in the rate of DN progression between different pTDP tertile groups (P = 0.0017). No significant genetic effects were found.
The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfq550</identifier><identifier>PMID: 20826743</identifier><identifier>CODEN: NDTREA</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Aged ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Associated diseases and complications ; Biological and medical sciences ; Cross-Sectional Studies ; Diabetes. Impaired glucose tolerance ; Diabetic Nephropathies - enzymology ; Diabetic Nephropathies - genetics ; Diabetic Nephropathies - mortality ; Emergency and intensive care: renal failure. Dialysis management ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Erythrocytes - enzymology ; Female ; Follow-Up Studies ; Genotype ; Glucose - metabolism ; Humans ; Intensive care medicine ; Male ; Medical sciences ; Middle Aged ; Pentose Phosphate Pathway ; Pentosephosphates - metabolism ; Polymorphism, Single Nucleotide - genetics ; Survival Rate ; Thiamine - metabolism ; Transaldolase - genetics ; Transketolase - genetics</subject><ispartof>Nephrology, dialysis, transplantation, 2011-04, Vol.26 (4), p.1229-1236</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c352t-8e24c880f3efd16aa435f74cd6aa3f9c3bd083af595a53f94a6813d074be43253</citedby><cites>FETCH-LOGICAL-c352t-8e24c880f3efd16aa435f74cd6aa3f9c3bd083af595a53f94a6813d074be43253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24073133$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20826743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PACAL, Lukáš</creatorcontrib><creatorcontrib>TOMANDL, Josef</creatorcontrib><creatorcontrib>MUZIK, Jan</creatorcontrib><creatorcontrib>KANKOVA, Kateřina</creatorcontrib><creatorcontrib>SVOJANOVSKY, Jan</creatorcontrib><creatorcontrib>KRUSOVA, Darja</creatorcontrib><creatorcontrib>STEPANKOVA, Soňa</creatorcontrib><creatorcontrib>REHOROVA, Jitka</creatorcontrib><creatorcontrib>OLSOVSKY, Jindřich</creatorcontrib><creatorcontrib>BELOBRADKOVA, Jana</creatorcontrib><creatorcontrib>TANHÄUSEROVA, Veronika</creatorcontrib><creatorcontrib>TOMANDLOVA, Marie</creatorcontrib><title>Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy</title><title>Nephrology, dialysis, transplantation</title><addtitle>Nephrol Dial Transplant</addtitle><description>Pentose phosphate pathway (PPP) represents a potentially 'protective' mechanism in hyperglycaemia due to shunting of glycolytic intermediates into PPP reactions. We hypothesized that thiamine status (plasma and erythrocyte levels of thiamine and its esters) together with genetic variability in key PPP enzymes-transketolase (TKT), transaldolase and TKT-like-might contribute to the progression of diabetic nephropathy (DN) and mortality of diabetics.
A total of 240 diabetic subjects with variable degree of kidney disease were included at baseline and were followed up for a median of 26 (IQR 21-50) months. Concentrations of thiamine in plasma and whole blood and TKT-catalysed reaction were determined by HPLC. Single-nucleotide polymorphisms (SNPs) (n = 14) were genotyped by means of PCR using TaqMan chemistry (Applied Biosystems, Foster City, CA, USA).
Significant differences in pTh, pThDP, eryThDP and eryTKT between DN-stage groups were ascertained (P < 0.05) with advancing stage of DN being accompanied with increasing values of pTh, pThDP and eryTKT but not eryThDP. A highly significant negative correlation (r = - 0.41, P < 0.001) was found between pThDP and eryThDP, and the tertiles of the ratio of eryThDP/pThDP were significantly associated with all-cause mortality rates (P = 0.0072). We also identified significant differences in the rate of DN progression between different pTDP tertile groups (P = 0.0017). No significant genetic effects were found.
The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality.</description><subject>Adult</subject><subject>Aged</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Associated diseases and complications</subject><subject>Biological and medical sciences</subject><subject>Cross-Sectional Studies</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diabetic Nephropathies - enzymology</subject><subject>Diabetic Nephropathies - genetics</subject><subject>Diabetic Nephropathies - mortality</subject><subject>Emergency and intensive care: renal failure. Dialysis management</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Erythrocytes - enzymology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genotype</subject><subject>Glucose - metabolism</subject><subject>Humans</subject><subject>Intensive care medicine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pentose Phosphate Pathway</subject><subject>Pentosephosphates - metabolism</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Survival Rate</subject><subject>Thiamine - metabolism</subject><subject>Transaldolase - genetics</subject><subject>Transketolase - genetics</subject><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkcFu1DAQhi0EotvChQdAviAkpFA7thPniCqgSJUqofYczTrjjSGxU9uLFN6j74u7u8BprJlv_t-an5A3nH3krBOXfsiXO_ugFHtGNlw2rKqFVs_Jpgx5xRTrzsh5Sj8YY13dti_JWc103bRSbMjj9zAhDZbm0cHsPNKUIe8TBT_QHXrMztBfEB1s3eTySp2nOYJPPzGHCRIewJBHjHRBn0PpLGNIywgZqVlNUUf_e50xHVbHMo5hFzElF_yT8VCkDy4elzGGBfK4viIvLEwJX5_qBbn_8vnu6rq6uf367erTTWWEqnOlsZZGa2YF2oE3AFIo20ozlKewnRHbgWkBVnUKVGlIaDQXA2vlFqWolbgg74-65U8Pe0y5n10yOE3gMexTrxvGteqEKOSHI2liSCmi7ZfoZohrz1n_lEJfUuiPKRT47Ul2v51x-If-PXsB3p0ASAYmWw5qXPrPSdYKXlz_AA9KlNc</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>PACAL, Lukáš</creator><creator>TOMANDL, Josef</creator><creator>MUZIK, Jan</creator><creator>KANKOVA, Kateřina</creator><creator>SVOJANOVSKY, Jan</creator><creator>KRUSOVA, Darja</creator><creator>STEPANKOVA, Soňa</creator><creator>REHOROVA, Jitka</creator><creator>OLSOVSKY, Jindřich</creator><creator>BELOBRADKOVA, Jana</creator><creator>TANHÄUSEROVA, Veronika</creator><creator>TOMANDLOVA, Marie</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20110401</creationdate><title>Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy</title><author>PACAL, Lukáš ; TOMANDL, Josef ; MUZIK, Jan ; KANKOVA, Kateřina ; SVOJANOVSKY, Jan ; KRUSOVA, Darja ; STEPANKOVA, Soňa ; REHOROVA, Jitka ; OLSOVSKY, Jindřich ; BELOBRADKOVA, Jana ; TANHÄUSEROVA, Veronika ; TOMANDLOVA, Marie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-8e24c880f3efd16aa435f74cd6aa3f9c3bd083af595a53f94a6813d074be43253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Associated diseases and complications</topic><topic>Biological and medical sciences</topic><topic>Cross-Sectional Studies</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diabetic Nephropathies - enzymology</topic><topic>Diabetic Nephropathies - genetics</topic><topic>Diabetic Nephropathies - mortality</topic><topic>Emergency and intensive care: renal failure. Dialysis management</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Erythrocytes - enzymology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Genotype</topic><topic>Glucose - metabolism</topic><topic>Humans</topic><topic>Intensive care medicine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pentose Phosphate Pathway</topic><topic>Pentosephosphates - metabolism</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Survival Rate</topic><topic>Thiamine - metabolism</topic><topic>Transaldolase - genetics</topic><topic>Transketolase - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PACAL, Lukáš</creatorcontrib><creatorcontrib>TOMANDL, Josef</creatorcontrib><creatorcontrib>MUZIK, Jan</creatorcontrib><creatorcontrib>KANKOVA, Kateřina</creatorcontrib><creatorcontrib>SVOJANOVSKY, Jan</creatorcontrib><creatorcontrib>KRUSOVA, Darja</creatorcontrib><creatorcontrib>STEPANKOVA, Soňa</creatorcontrib><creatorcontrib>REHOROVA, Jitka</creatorcontrib><creatorcontrib>OLSOVSKY, Jindřich</creatorcontrib><creatorcontrib>BELOBRADKOVA, Jana</creatorcontrib><creatorcontrib>TANHÄUSEROVA, Veronika</creatorcontrib><creatorcontrib>TOMANDLOVA, Marie</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PACAL, Lukáš</au><au>TOMANDL, Josef</au><au>MUZIK, Jan</au><au>KANKOVA, Kateřina</au><au>SVOJANOVSKY, Jan</au><au>KRUSOVA, Darja</au><au>STEPANKOVA, Soňa</au><au>REHOROVA, Jitka</au><au>OLSOVSKY, Jindřich</au><au>BELOBRADKOVA, Jana</au><au>TANHÄUSEROVA, Veronika</au><au>TOMANDLOVA, Marie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><addtitle>Nephrol Dial Transplant</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>26</volume><issue>4</issue><spage>1229</spage><epage>1236</epage><pages>1229-1236</pages><issn>0931-0509</issn><eissn>1460-2385</eissn><coden>NDTREA</coden><abstract>Pentose phosphate pathway (PPP) represents a potentially 'protective' mechanism in hyperglycaemia due to shunting of glycolytic intermediates into PPP reactions. We hypothesized that thiamine status (plasma and erythrocyte levels of thiamine and its esters) together with genetic variability in key PPP enzymes-transketolase (TKT), transaldolase and TKT-like-might contribute to the progression of diabetic nephropathy (DN) and mortality of diabetics.
A total of 240 diabetic subjects with variable degree of kidney disease were included at baseline and were followed up for a median of 26 (IQR 21-50) months. Concentrations of thiamine in plasma and whole blood and TKT-catalysed reaction were determined by HPLC. Single-nucleotide polymorphisms (SNPs) (n = 14) were genotyped by means of PCR using TaqMan chemistry (Applied Biosystems, Foster City, CA, USA).
Significant differences in pTh, pThDP, eryThDP and eryTKT between DN-stage groups were ascertained (P < 0.05) with advancing stage of DN being accompanied with increasing values of pTh, pThDP and eryTKT but not eryThDP. A highly significant negative correlation (r = - 0.41, P < 0.001) was found between pThDP and eryThDP, and the tertiles of the ratio of eryThDP/pThDP were significantly associated with all-cause mortality rates (P = 0.0072). We also identified significant differences in the rate of DN progression between different pTDP tertile groups (P = 0.0017). No significant genetic effects were found.
The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>20826743</pmid><doi>10.1093/ndt/gfq550</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Nephrology, dialysis, transplantation, 2011-04, Vol.26 (4), p.1229-1236 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Associated diseases and complications Biological and medical sciences Cross-Sectional Studies Diabetes. Impaired glucose tolerance Diabetic Nephropathies - enzymology Diabetic Nephropathies - genetics Diabetic Nephropathies - mortality Emergency and intensive care: renal failure. Dialysis management Endocrine pancreas. Apud cells (diseases) Endocrinopathies Erythrocytes - enzymology Female Follow-Up Studies Genotype Glucose - metabolism Humans Intensive care medicine Male Medical sciences Middle Aged Pentose Phosphate Pathway Pentosephosphates - metabolism Polymorphism, Single Nucleotide - genetics Survival Rate Thiamine - metabolism Transaldolase - genetics Transketolase - genetics |
| title | Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy |
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