Alterations in Adipose Tissue Distribution, Cell Morphology, and Function Mark Primary Insulin Hypersecretion in Youth With Obesity.
Document Type
Article
Publication Date
6-1-2024
Original Citation
Tricò D,
Chiriacò M,
Nouws J,
Vash-Margita A,
Kursawe R,
Tarabra E,
Galderisi A,
Natali A,
Giannini C,
Hellerstein M,
Ferrannini E,
Caprio S.
Alterations in Adipose Tissue Distribution, Cell Morphology, and Function Mark Primary Insulin Hypersecretion in Youth With Obesity. Diabetes. 2024;73(6):941-52.
Keywords
JGM, Humans, Adolescent, Male, Female, Insulin Resistance, Insulin, Adipose Tissue, Insulin-Secreting Cells, Leptin, Glucose Tolerance Test, Child, Adipocytes, Pediatric Obesity, Obesity, Glucose Clamp Technique, Adiposity
JAX Source
Diabetes. 2024;73(6):941-52.
ISSN
1939-327X
PMID
37870826
DOI
https://doi.org/10.2337/db23-0450
Abstract
Excessive insulin secretion independent of insulin resistance, defined as primary hypersecretion, is associated with obesity and an unfavorable metabolic phenotype. We examined the characteristics of adipose tissue of youth with primary insulin hypersecretion and the longitudinal metabolic alterations influenced by the complex adipo-insular interplay. In a multiethnic cohort of adolescents with obesity but without diabetes, primary insulin hypersecretors had enhanced model-derived β-cell glucose sensitivity and rate sensitivity but worse glucose tolerance, despite similar demographics, adiposity, and insulin resistance measured by both oral glucose tolerance test and euglycemic-hyperinsulinemic clamp. Hypersecretors had greater intrahepatic and visceral fat depots at abdominal MRI, hypertrophic abdominal subcutaneous adipocytes, higher free fatty acid and leptin serum levels per fat mass, and faster in vivo lipid turnover assessed by a long-term 2H2O labeling protocol. At 2-year follow-up, hypersecretors had greater fat accrual and a threefold higher risk for abnormal glucose tolerance, while individuals with hypertrophic adipocytes or higher leptin levels showed enhanced β-cell glucose sensitivity. Primary insulin hypersecretion is associated with marked alterations in adipose tissue distribution, cellularity, and lipid dynamics, independent of whole-body adiposity and insulin resistance. Pathogenetic insight into the metabolic crosstalk between β-cell and adipocyte may help to identify individuals at risk for chronic hyperinsulinemia, body weight gain, and glucose intolerance.