Role of the ENPP1 K121Q Polymorphism in Glucose Homeostasis
- Roberto Baratta1,
- Paola Rossetti1,
- Sabrina Prudente23,
- Fabrizio Barbetti4,
- Dora Sudano1,
- Angela Nigro1,
- Maria Grazia Farina1,
- Fabio Pellegrini25,
- Vincenzo Trischitta2367 and
- Lucia Frittitta1
- 1Unit of Endocrinology, Department of Internal and Specialistic Medicine, University of Catania Medical School, Garibaldi Hospital, Catania, Italy
- 2Research Unit of Diabetes and Endocrine Diseases, Casa Sollievo della Sofferenza (CSS) Scientific Institute, San Giovanni Rotondo, Italy
- 3CSS-Mendel Institute, Rome, Italy
- 4Bambino Gesù Pediatric Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
- 5Unit of Biostatistics, Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Chieti, Italy
- 6Unit of Endocrinology, CSS Scientific Institute, San Giovanni Rotondo, Italy
- 7Department of Clinical Sciences, Sapienza University, Rome, Italy
- Corresponding author: Lucia Frittitta, lfritti{at}unict.it
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 × 10−2) different across K121Q genotype groups and higher in QQ than KK individuals (P = 5 × 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 × 10−7) and KQ (30.5 ± 1.5; P = 3.2 × 10−6) individuals. KQ individuals also showed a reduced insulin sensitivity index compared with KK subjects (P = 3.6 × 10−2). The disposition index was lower in QQ carriers than in KQ and KK individuals (P = 8 × 10−3 and 4 × 10−4, respectively) and lower in KQ than in KK individuals (P = 3 × 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 × 10−3 and 2 × 10−2, respectively) and disposition index (P = 2 × 10−2 and 7 × 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.
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 5 September 2008.
V.T. and L.F. equally supervised the study.
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- Accepted August 26, 2008.
- Received December 27, 2007.
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