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Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity
Alfonso Galderisi, Domenico Tricò, Jessica Lat, Stephanie Samuels, Ram Weiss, Michelle Van Name, Bridget Pierpont, Nicola Santoro, Sonia Caprio
Alfonso Galderisi, Domenico Tricò, Jessica Lat, Stephanie Samuels, Ram Weiss, Michelle Van Name, Bridget Pierpont, Nicola Santoro, Sonia Caprio
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Research Article Endocrinology Metabolism

Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity

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Abstract

In youths with obesity, the gut hormone potentiation of insulin secretion — the incretin effect — is blunted. We explored the longitudinal impact of the incretin effect during pubertal transition on β cell function and insulin sensitivity. Youths with obesity and 2-hour glucose level ≥ 120 mg/dL underwent a 3-hour oral glucose-tolerance test (OGTT) and an isoglycemic i.v. glucose infusion to quantify the incretin effect. After 2 years, 30 of 39 participants had a repeated OGTT and were stratified into 3 tertiles according to the baseline incretin effect. The high–incretin effect group demonstrated a longitudinal increase in β cell function (disposition index, minimal model [DIMM]), with greater insulin sensitivity at follow-up and stable insulin secretion (φtotal). A lower incretin effect at baseline was associated with higher 1-hour and 2-hour glucose level at follow-up. The high–incretin effect group displayed a greater increase of GLP-17–36 than the moderate- and low-incretin group at baseline, while such a difference did not persist after 2 years. Glucagon suppression was reduced at follow-up in those with low-baseline incretin in respect to the high-incretin group. The incretin effect during pubertal transition affected the longitudinal trajectory of β cell function and weight in youths with obesity.

Authors

Alfonso Galderisi, Domenico Tricò, Jessica Lat, Stephanie Samuels, Ram Weiss, Michelle Van Name, Bridget Pierpont, Nicola Santoro, Sonia Caprio

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Figure 4

The incretin effect during pubertal transition on longitudinal glucose metrics and BMI.

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The incretin effect during pubertal transition on longitudinal glucose m...
(A–C) Linear regression analysis of incretin effect and fasting (A), 1-hour (B), and 2-hour (C) glucose. Data are represented as naturally log-transformed measures. Linear regression analysis r and P value are reported per each variable. (D) Baseline incretin effect by 2-hour glucose level at follow-up. Data are expressed as median and IQR (25th, 75th). Kruskal-Wallis test has been adopted for comparison. (E) ROC analyses for the binary outcome 2-hour glucose level of ≥ 120 mg/dL at follow-up. The analysis includes baseline incretin effect, baseline fasting, and 2-hour glucose level and baseline BMI as predictors.

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