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.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism