Glucocorticoid receptor gene polymorphisms are associated with reduced first-phase glucose-stimulated insulin secretion and disposition index in women, but not in men

D.H. van Raalte, N. van Leeuwen, A.M.C. Bik-Simonis, G. Nijpels, T.W. van Haeften, S.A. Schafer, D.I. Boomsma, M.H.H. Kramer, R.J. Heine, J.A. Maassen, H. Staiger, F. Machicao, H.U. Häring, P.E. Slagboom, G. Willemsen, E.J.C. de Geus, J.M. Dekker, A. Fritsche, E.M.W. Eekhoff, M. DiamantL.M. Hart

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Aim Glucocorticoids are efficacious anti-inflammatory agents, but, in susceptible individuals, these drugs may induce glucose intolerance and diabetes by affecting β-cell function and insulin sensitivity. We assessed whether polymorphisms in the glucocorticoid receptor gene NR3C1 associate with measures of β-cell function and insulin sensitivity derived from hyperglycaemic clamps in subjects with normal or impaired glucose tolerance. Methods A cross-sectional cohort study was conducted in four academic medical centres in the Netherlands and Germany. Four hundred and forty-nine volunteers (188 men; 261 women) were recruited with normal glucose tolerance (n=261) and impaired glucose tolerance (n=188). From 2-h hyperglycaemic clamps, first- and second-phase glucose-stimulated insulin secretion, as well as insulin sensitivity index and disposition index, were calculated. All participants were genotyped for the functional NR3C1 polymorphisms N363S (rs6195), BclI (rs41423247), ER22/23EK (rs6189/6190), 9β A/G (rs6198) and ThtIIII (rs10052957). Associations between these polymorphisms and β-cell function parameters were assessed. Results In women, but not in men, the N363S polymorphism was associated with reduced disposition index (P=1.06 10
Original languageEnglish
Pages (from-to)e211-e216
JournalDiabetic Medicine
Volume29
Issue number8
DOIs
Publication statusPublished - 2012

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