title: β-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes.
abstract: Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (βCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-βCGS to the 2-h hyperglycemic clamp-βCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia.
authors.affiliation: Division of Weight Management, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Sara F
authors.initials: SF
authors.lastname: Michaliszyn
authors.affiliation: CNR Institute of Biomedical Engineering, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: Division of Weight Management, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: SoJung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX.
authors.forename: Fida
authors.initials: F
authors.lastname: Bacha
authors.affiliation: Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Hala
authors.initials: H
authors.lastname: Tfayli
authors.affiliation: Division of Weight Management, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Lama
authors.initials: L
authors.lastname: Farchoukh
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, Pisa, Italy.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.affiliation: Division of Weight Management, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA Division of Pediatric Endocrinology, Diabetes and Metabolism, Children's Hospital of Pittsburgh, Pittsburgh, PA silva.arslanian@chp.edu.
authors.forename: Silva
authors.initials: S
authors.lastname: Arslanian
mesh_terms: D000293:Adolescent; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D011236:Prediabetic State / Q000378:metabolism
chemical_list: D054795:Incretins