Abstract
Background: The Wnt pathway is known to influence body composition during early human development by regulating bone formation, myogenesis and adipogenesis. We have recently shown that DKK1 is related to measures of adiposity in nondiabetic African ancestry males. Whether these relationships are true across sexes and/or in other human populations remains unknown. In this study we evaluated the relationship of DKK1 with adiposity in a sample of male and female, mixed race, nondiabetic North American individuals. Methods: Fasting serum DKK1 levels were measured using ELISAs in 201 nondiabetic subjects (age range 30.7-60 years, BMI range 19.9-64.0 kg/m2) recruited from the general population via television advertisement and mass mailing. The subjects were predominantly female (85%) and Caucasian (63%). Anthropometrics were obtained and markers of inflammation and glucose metabolism were measured from fasting serum samples. Spearman and partial Spearman correlation analysis was used to determine the association of DKK1 with measures of adiposity and insulin resistance. Results: Circulating DKK1 was positively associated with BMI (r=0.30, p<0.001) and waist circumference (r=0.25, p<0.001), independent of age, race and sex. In addition, DKK1 was positively associated with fasting serum insulin level (r=0.18, p<0.01) and HOMA-IR (r=0.19, p<0.01) in age, sex and race adjusted models. However, these associations were no longer significant after adjustment for BMI. Conclusion: This is the first study looking at correlation of DKK1 with adiposity in North American nondiabetic individuals. Our findings suggest that the link between DKK1 and insulin resistance maybe mediated indirectly through total and regional adiposity and that DKK1 could be a potential early biomarker for diabetes in high risk individuals. These findings support our findings in African ancestry males and add to the evidence favoring potential role of Wnt modulators in adiposity regulation in humans. Disclosure H. Ali: None. E. Oczypok: None. I. Miljkovic: None. R. Cvejkus: None. J.M. Zmuda: None. J. DeLany: None. E.E. Kershaw: Research Support; Self; Regeneron Pharmaceuticals. Funding National Institutes of Health (T32DK007252); Endocrine Fellows Foundation
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