Role of the ENPP1 K121Q polymorphism in glucose homeostasis

Roberto Baratta, Paola Rossetti, Sabrina Prudente, Fabrizio Barbetti, Dora Sudano, Angela Nigro, Maria Grazia Farina, Fabio Pellegrini, Vincenzo Trischitta, Lucia Frittitta

Research output: Contribution to journalArticle

Abstract

OBJECTIVE-To study the role of the ENPP1 Q121 variant on glucose homeostasis in whites from Italy. RESEARCH DESIGN AND METHODS-We conducted case- control studies in 764 adults (from two independent samples of 289 nonobese and 485 obese individuals) and 240 overweight/ obese children undergoing oral glucose tolerance testing (OGTT). Early-phase insulin secretion and insulin sensitivity (the insulinogenic index and the insulin sensitivity index) and their interplay (the disposition index) were calculated. RESULTS-In adult subjects, glucose profiles during OGTT were significantly (P = 2 X 10 -2) different across K121Q genotype groups and higher in QQ than KK individuals (P = 5 X 10-2). The insulinogenic index was significantly reduced in QQ (18.5 ±3.4) compared with both KK (31.6±1.0; P = 2.2 X 10-7) and KQ (30.5 ±1.5; P = 3.2 X 10-6) individuals. KQ individuals also showed a reduced insulin sensitivity index compared with KK subjects (P = 3.6 X 10-2). The disposition index was lower in QQ carriers than in KQ and KK individuals (P = 8 X 10-3 and 4 X 10-4, respectively) and lower in KQ than in KK individuals (P=3 X 10-2). Data obtained in overweight/obese children were very similar to those observed in adults, with QQ individuals showing (compared with KQ and KK subjects) a reduced insulinogenic index (P=7 X 10-3 and 2 X 10-2, respectively) and disposition index (P=2 X 10-2 and 7 X 10-3, respectively). CONCLUSIONS-Homozygous carriers of the ENPP1 Q121 variant are characterized by an altered glucose homeostasis. Reduced early-phase insulin secretion and inefficient interplay between insulin secretion and sensitivity, which occur at early ages, are major determinants of this defect.

Original languageEnglish
Pages (from-to)3360-3364
Number of pages5
JournalDiabetes
Volume57
Issue number12
DOIs
Publication statusPublished - Dec 2008

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Baratta, R., Rossetti, P., Prudente, S., Barbetti, F., Sudano, D., Nigro, A., Farina, M. G., Pellegrini, F., Trischitta, V., & Frittitta, L. (2008). Role of the ENPP1 K121Q polymorphism in glucose homeostasis. Diabetes, 57(12), 3360-3364. https://doi.org/10.2337/db07-1830