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Silbernagel, Guenther; Renner, Wilfried; Grammer, Tanja B.; Hügl, Sigrun R.; Bertram, Julia; Kleber, Marcus E.; Hoffmann, Michael M.; Winkelmann, Bernhard R.; März, Winfried; Boehm, Bernhard O.

Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagon‐like peptide 1

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  • Medientyp: E-Artikel
  • Titel: Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagon‐like peptide 1
  • Beteiligte: Silbernagel, Guenther; Renner, Wilfried; Grammer, Tanja B.; Hügl, Sigrun R.; Bertram, Julia; Kleber, Marcus E.; Hoffmann, Michael M.; Winkelmann, Bernhard R.; März, Winfried; Boehm, Bernhard O.
  • Erschienen: Wiley, 2011
  • Erschienen in: Diabetes/Metabolism Research and Reviews
  • Sprache: Englisch
  • DOI: 10.1002/dmrr.1194
  • ISSN: 1520-7552; 1520-7560
  • Schlagwörter: Endocrinology ; Endocrinology, Diabetes and Metabolism ; Internal Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Variants in <jats:italic>TCF7L2</jats:italic> have been associated with the age at onset of type 2 diabetes in Mexican Americans. However, there is a lack of data on this relationship in Caucasians. Furthermore, risk alleles in <jats:italic>TCF7L2</jats:italic> have been suggested to account for decreased conversion of proinsulin to insulin and decreased expression of GLP‐1. We investigated the effect of the allelic variants <jats:italic>rs1225537</jats:italic> and <jats:italic>rs7903146</jats:italic> in <jats:italic>TCF7L2</jats:italic> on the age at onset of type 2 diabetes, the plasma concentrations of proinsulin and GLP‐1, and the ratio of proinsulin to insulin in a German cohort.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We studied 3185 participants of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. Among these, 1021 subjects had type 2 diabetes. Data on age at onset of diabetes were available in 925 subjects. OGTTs were performed in a subgroup not previously known to have diabetes.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Carriers of the risk alleles in <jats:italic>rs1225537</jats:italic> and <jats:italic>rs7901346</jats:italic> had increased risk of type 2 diabetes and elevated HbA<jats:sub>1c</jats:sub> (all <jats:italic>p</jats:italic> &lt; 0.001). The risk alleles were also associated with early onset of type 2 diabetes, decreased insulin secretion and markedly increased proinsulin and proinsulin to insulin ratio (all <jats:italic>p</jats:italic> &lt; 0.03). GLP‐1 was not significantly related to the <jats:italic>TCF7L2</jats:italic> genotype.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our data demonstrate that <jats:italic>TCF7L2</jats:italic> variants are associated with an early age of onset of type 2 diabetes in Caucasians and affects the conversion of proinsulin to insulin. However, <jats:italic>TCF7L2</jats:italic> is not consistently associated with fasting GLP‐1. Copyright © 2011 John Wiley &amp; Sons, Ltd.</jats:p></jats:sec>