IRS1 G972R Missense Polymorphism Is Associated With Failure to Oral Antidiabetes Drugs in White Patients With Type 2 Diabetes From Italy

  1. Vincenzo Trischitta1,2,8
  1. 1Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
  2. 2Department of Experimental Medicine, Sapienza University, Rome, Italy
  3. 3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  4. 4Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
  5. 5Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
  6. 6Institute of Agricultural Biology and Biotechnology, CNR, Pisa, Italy
  7. 7Clinical Unit of Endocrinology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
  8. 8Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
  1. Corresponding author: Sabrina Prudente, s.prudente{at}, or Vincenzo Trischitta, vincenzo.trischitta{at}


This study tried to replicate in a large sample of white patients with type 2 diabetes (T2D) from Italy a previously reported association of the IRS1 G972R polymorphism with failure to oral antidiabetes drugs (OAD). A total of 2,409 patients from four independent studies were investigated. Case subjects (n = 1,193) were patients in whom, because of uncontrolled diabetes (i.e., HbA1c >8%), insulin therapy had been added either on, or instead of, maximal or near-maximal doses of OAD, mostly metformin and sulfonylureas; control subjects (n = 1,216) were patients with HbA1c <8% in the absence of insulin therapy. The IRS1 G972R polymorphism was typed by TaqMan allele discrimination. In all samples, individuals carrying the IRS1 R972 risk variant tended to be more frequent among case than control subjects, though reaching statistical significance only in one case. As no IRS1 G972R-by-study sample interaction was observed, data from the four samples were analyzed together; a significant association was observed (allelic odds ratio [OR] 1.30, 95% CI 1.03–1.63). When our present data were meta-analyzed with those obtained in a previous study, an overall R972 allelic OR of 1.37 (1.12–1.69) was observed. This study confirms in a large and ethnically homogeneous sample that IRS1 G972R polymorphism is associated with failure to OAD among patients with T2D.

  • Received December 31, 2013.
  • Accepted March 31, 2014.

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