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
- Sara F. Michaliszyn1,
- Andrea Mari2,
- SoJung Lee1,
- Fida Bacha3,
- Hala Tfayli4,
- Lama Farchoukh1,
- Ele Ferrannini5 and
- Silva Arslanian1,6⇑
- 1Division of Weight Management, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA
- 2CNR Institute of Biomedical Engineering, Padova, Italy
- 3Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX
- 4Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
- 5Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, Pisa, Italy
- 6Division of Pediatric Endocrinology, Diabetes and Metabolism, Children’s Hospital of Pittsburgh, Pittsburgh, PA
- Corresponding author: Silva A. Arslanian, .
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.
- Received December 30, 2013.
- Accepted May 30, 2014.
- © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.