β-Cell Impairment and Clinically Meaningful Alterations in Glycemia in Obese Youth Across the Glucose Tolerance Spectrum

Authors

Joon Young Kim
Hala Tfayli
Fida Bacha
SoJung Lee
Nour Gebara
Silva Arslanian

Publication Date

11-1-2020

Journal

Metabolism

DOI

10.1016/j.metabol.2020.154346

PMID

32835760

PMCID

PMC7897751

PubMedCentral® Full Text Version

Post-print

Published Open-Access

no

Keywords

Black or African American, Blood Glucose, Child, Diabetes Mellitus, Type 2, Fasting, Female, Glucose Clamp Technique, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Insulin-Secreting Cells, Male, Pediatric Obesity, White People, Young Adult, β-cell function, Clamp, Glucose area under the curve, OGTT, Glucose tolerance, Youth

Abstract

Background/aims: In obese youth, it is not clear what degree of β-cell impairment translates to glucose dysregulation commensurate with shifts from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes. We aimed to investigate the quantitative relationship between β-cell (clamp-measured disposition index [DI]) and OGTT glucose area under the curve (G-AUC) in obese youth across the spectrum of glucose tolerance.

Methods: Data from 152 youth (58 African-American [AA] and 94 American-White [AW]; 73 NGT, 48 IGT, and 31 type 2 diabetes) who completed a 3-h hyperinsulinemic (80 mu/m2/min)-euglycemic clamp, and a 2-h hyperglycemic (225 mg/dL) clamp synchronized with a 2-h OGTT were examined.

Results: In IGT vs. NGT, 36% lower DI corresponded to 27% higher G-AUC; in type 2 diabetes vs. IGT, 65% lower DI related to 25% higher G-AUC, and in type 2 diabetes vs. NGT, 78% lower DI paralleled 59% higher G-AUC. Although AA vs. AW youth had larger decrements in DI, from NGT to IGT and from NGT to type 2 diabetes, they displayed comparable increments in G-AUC.

Conclusion: At least ~35-50% recovery in β-cell function might be needed to have clinically meaningful improvement in G-AUC commensurate with conversion to better glucose tolerance. Mechanism(s) protective against dysglycemia might be operative in AA vs. AW youth despite greater declines in DI. Treatments aiming to improve β-cell function should focus on degree of change in DI commensurate with clinically meaningful changes in glycemia, reflective of restoration of glucose tolerance.