Features of melanocortin-4 receptor (MC4R) deficiency have been observed to be more pronounced in childhood. Longitudinal data from a population-based study were used to separate the phenotypic effects of MC4R deficiency during childhood and adulthood. The MC4R exon was sequenced in 6,760 individuals of predominantly Pima Indian heritage, and discovered mutations were functionally assessed in v...

BACKGROUND The relative roles of obesity, insulin resistance, insulin secretory dysfunction, and excess hepatic glucose production in the development of non-insulin-dependent diabetes mellitus (NIDDM) are controversial. We conducted a prospective study to determine which of these factors predicted the development of the disease in a group of Pima Indians. METHODS A body-composition assessment...

Parent-of-origin effects were observed in an Icelandic population for several genetic variants associated with type 2 diabetes, including those in KLF14 (rs4731702), MOB2 (rs2334499), and KCNQ1 (rs2237892, rs231362). We analyzed parent-of-origin effects for these variants, along with two others in KCNQ1 identified in previous genome-wide association studies (rs2237895, rs2299620), in 7,351 Pima...

Congenital retardation of renal development may increase the risk of renal disease, and this risk may be enhanced by diseases, such as diabetes, that damage the kidney. In this study, the prevalence of urinary albumin excretion, determined in 308 Pima Indians with type 2 diabetes, was 63% in subjects with low birth weight (<2,500 g), 41% in those with normal birth weight (2,500-4,499 g), and 64...

OBJECTIVE To investigate which anthropometric measurements of obesity best predict type 2 diabetes in a population of Pima Indians and whether additional information on diabetes risk could be obtained by combining measures of general obesity with measures of body fat distribution. RESEARCH DESIGN AND METHODS We conducted a prospective study of 624 men and 990 nonpregnant women >18 years of ag...

Adiponectin is a circulating protein secreted by adipocytes and is thought to have insulin-sensitizing effects. We present genetic analysis of adiponectin levels in 517 Pima Indians without diabetes (from 162 families, 750 sib-pairs). Adiponectin concentrations were heritable, with 39% of the variance of age- and sex-adjusted adiponectin potentially accounted for by additive genetic influences ...