TY - JOUR
T1 - Increased lipolysis, diminished adipose tissue insulin sensitivity, and impaired b-cell function relative to adipose tissue insulin sensitivity in obese youth with impaired glucose tolerance
AU - Kim, Joon Young
AU - Nasr, Alexis
AU - Tfayli, Hala
AU - Bacha, Fida
AU - Michaliszyn, Sara F.
AU - Arslanian, Silva
N1 - Funding Information:
Acknowledgments. The authors thank the children who participated in this study and their parents, Nancy Guerra (Children’s Hospital of Pittsburgh) for her assistance, Resa Stauffer (Children’s Hospital of Pittsburgh) for her laboratory expertise, and the nursing staff of the Pediatric Clinical and Translational Research Center (Children’s Hospital of Pittsburgh) for their outstanding care of the participants and meticulous attention to the research. Funding. This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants K24-HD01357 and R01-HD27503 to S.A., National Center for Advancing Translational Sciences Clinical and Translational Science Award UL1TR000005, and National Center for Research Resources grant UL1RR024153 to the General Clinical Research Center. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. J.Y.K. and S.A. designed the study, analyzed the data, and wrote the manuscript. A.N. and S.F.M. collected and maintained the database and reviewed the manuscript. H.T. and F.B. contributed data and reviewed the manuscript. All authors approved the manuscript in its final version. S.A. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at the 77th Scientific Sessions of the American Diabetes Association, San Diego, CA, 9–13 June 2017.
Publisher Copyright:
© 2017 by the American Diabetes Association.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Despite evidence of insulin resistance and β-cell dysfunction in glucose metabolism in youth with prediabetes, the relationship between adipose tissue insulin sensitivity (ATIS) and β-cell function remains unknown. We investigated whole-body lipolysis, ATIS, and β-cell function relative to ATIS (adipose disposition index [DI]) in obese youth with impaired glucose tolerance (IGT) versus normal glucose tolerance (NGT). Whole-body lipolysis (glycerol appearance rate [GlyRa], [2H5]glycerol at baseline and during a hyperinsulinemic-euglycemic clamp), lipid oxidation (indirect calorimetry), insulin secretion (2-h hyperglycemic clamp), and body composition (dual-energy X-ray absorptiometry) were examined. Adipose DI was calculated as ATIS: (1/GlyRa 3 fasting insulin) 3 first-phase insulin secretion. Despite similar percent body fat, youth with IGT versus NGT had higher GlyRa, lower ATIS at baseline and during hyperinsulinemia, and higher lipid oxidation. Adipose DI was ∼43% lower in youth with IGT and correlated positively with glucose DI. The lower ATIS and diminished adipose DI in IGT versus NGT is in line with the compromised glucose metabolism reflected in impaired β-cell function relative to peripheral insulin resistance. We conclude that youth with IGT manifest a global decline in insulin sensitivity, including impaired insulin action in suppressing lipolysis and lipid oxidation, accompanied by β-cell dysfunction in fat and glucose metabolism, enhancing their risk of type 2 diabetes.
AB - Despite evidence of insulin resistance and β-cell dysfunction in glucose metabolism in youth with prediabetes, the relationship between adipose tissue insulin sensitivity (ATIS) and β-cell function remains unknown. We investigated whole-body lipolysis, ATIS, and β-cell function relative to ATIS (adipose disposition index [DI]) in obese youth with impaired glucose tolerance (IGT) versus normal glucose tolerance (NGT). Whole-body lipolysis (glycerol appearance rate [GlyRa], [2H5]glycerol at baseline and during a hyperinsulinemic-euglycemic clamp), lipid oxidation (indirect calorimetry), insulin secretion (2-h hyperglycemic clamp), and body composition (dual-energy X-ray absorptiometry) were examined. Adipose DI was calculated as ATIS: (1/GlyRa 3 fasting insulin) 3 first-phase insulin secretion. Despite similar percent body fat, youth with IGT versus NGT had higher GlyRa, lower ATIS at baseline and during hyperinsulinemia, and higher lipid oxidation. Adipose DI was ∼43% lower in youth with IGT and correlated positively with glucose DI. The lower ATIS and diminished adipose DI in IGT versus NGT is in line with the compromised glucose metabolism reflected in impaired β-cell function relative to peripheral insulin resistance. We conclude that youth with IGT manifest a global decline in insulin sensitivity, including impaired insulin action in suppressing lipolysis and lipid oxidation, accompanied by β-cell dysfunction in fat and glucose metabolism, enhancing their risk of type 2 diabetes.
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U2 - 10.2337/db17-0551
DO - 10.2337/db17-0551
M3 - Article
C2 - 28887312
AN - SCOPUS:85035325064
SN - 0012-1797
VL - 66
SP - 3085
EP - 3090
JO - Diabetes
JF - Diabetes
IS - 12
ER -