ESPE2023 Rapid Free Communications Fat, metabolism and obesity 1 (6 abstracts)
Reduced central sensitivity to thyroid hormones in children and adolescents with overweight or obesity and impaired glucose tolerance.
Domenico Corica 1 , Procolo Di Bonito 2 , Maria Rosaria Licenziati 3 , Anna Di Sessa 4 , Emanuele Miraglia Del Giudice 4 , Maria Felicia Faienza 5 , Valeria Calcaterra 6,7 , Francesca Franco 8 , Giulio Maltoni 9 , Giuliana Valerio 10 & Malgorzata Wasniewska 1
1Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy. 2Department of Internal Medicine, “S. Maria delle Grazie” Hospital, Pozzuoli, Italy. 3Neuro-endocrine diseases and Obesity Unit, Department of Neurosciences, Santobono-Pausilipon Children's Hospital, Napoli, Italy. 4Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Napoli, Italy. 5Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, Italy. 6Pediatric Department, Buzzi Children's Hospital, Milano, Italy. 7Department of Internal Medicine, University of Pavia, Pavia, Italy. 8Pediatric Department, Azienda Sanitaria Universitaria Friuli Centrale, Hospital of Udine, Udine, Italy. 9Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 10Department of Movement Sciences and Wellbeing, University of Napoli “Parthenope”, Napoli, Italy
Background: Thyroid hormones (TH) play multiple effects on glucose metabolism. Some recent studies carried out in adult patients suggested an association between altered sensitivity to TH and type 2 diabetes, obesity, and metabolic syndrome. No studies are currently available on the presence of altered sensitivity to the action of TH in youths with prediabetes.
Objective: To evaluate the relationship between sensitivity to TH and impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or glycosylated hemoglobin (HbA1c) ≥ 5.7% in youths with overweight/obesity (OW/OB).
Materials and Methods: This cross-sectional study included 805 Caucasian youths with OW or OB (aged 6-18 years) recruited at seven Italian centers for the care of OW/OB. Inclusion criteria were: TH within the normal range, anti-thyroid antibody negativity, data availability for fasting glucose and insulin, oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1c), lipids, blood pressure (BP). Exclusion criteria were: thyroid diseases, subclinical hypothyroidism, genetic or endocrine obesity, diabetes mellitus, chronic diseases, pharmacological treatment. The fT3/fT4 ratio was evaluated to assess peripheral sensitivity, while TSH index (TSHI), Thyrotroph T4 Resistance Index (TT4RI), Thyroid Feedback Quantile-based Index (TFQI) and Parametric TFQI were calculated to assess central sensitivity. Prediabetes was defined as any of the following phenotypes: IGT or IFG or high HbA1c.
Results: Youths with IGT (n=72) showed higher levels of TSH (3.08±0.98 vs 2.68±0.98 mIU/L, P=0.001), TSHI (3.06±0.51 vs 2.85±0.53;P =0.001), TT4RI (46.00±17.87 vs 38.65±16.27;P<0.0001), TFQI [1.00 (0.97-1.00) vs 1.00 (0.99-1.00)]; P=0.034), PTFQI (0.67±0.20 vs 0.60±0.22; P=0.007) compared to youths without IGT (n=733), independently of centers and age. No differences were observed for fT3/fT4-ratio. The others phenotypes of prediabetes were not associated with altered sensitivity to TH. Odds ratio of IGT rise of 1-7-fold for each increase of 1 mIU/L in TSH (P=0.010), 1 unit in TSH Index (P=0.004), TT4RI (P=0.003) or PTFQI (P=0.018), independently of centers, age, and prepubertal stage (Model 1). This result was confirmed by adjusting the logistic regression model for family history of type 2 diabetes, HOMA-IR, TG/HDL ratio, systolic BP, obesity, IFG and high HbA1c (Model 2).
Conclusions: IGT was associated with a reduced central sensitivity to TH in youths with OW/OB. Our finding suggests that IGT phenotype, known to be associated with an altered cardiometabolic risk profile, has also been associated with an impaired TH homeostasis in youths with OW/OB.
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