title: Phenotypical heterogeneity linked to adipose tissue dysfunction in patients with Type 2 diabetes.
abstract: Adipose tissue (AT) inflammation leads to increased free fatty acid (FFA) efflux and ectopic fat deposition, but whether AT dysfunction drives selective fat accumulation in specific sites remains unknown. The aim of the present study was to investigate the correlation between AT dysfunction, hepatic/pancreatic fat fraction (HFF, PFF) and the associated metabolic phenotype in patients with Type 2 diabetes (T2D). Sixty-five consecutive T2D patients were recruited at the Diabetes Centre of Sapienza University, Rome, Italy. The study population underwent clinical examination and blood sampling for routine biochemistry and calculation of insulin secretion [homoeostasis model assessment of insulin secretion (HOMA-β%)] and insulin-resistance [homoeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (ADIPO-IR)] indexes. Subcutaneous (SAT) and visceral (VAT) AT area, HFF and PFF were determined by magnetic resonance. Some 55.4% of T2D patients had non-alcoholic fatty liver disease (NAFLD); they were significantly younger and more insulin-resistant than non-NAFLD subjects. ADIPO-IR was the main determinant of HFF independently of age, sex, HOMA-IR, VAT, SAT and predicted severe NAFLD with the area under the receiver operating characteristic curve (AUROC)=0.796 (95% confidence interval: 0.65-0.94, P=0.001). PFF was independently associated with increased total adiposity but did not correlate with AT dysfunction, insulin resistance and secretion or NAFLD. The ADIPO-IR index was capable of predicting NAFLD independently of all confounders, whereas it did not seem to be related to intrapancreatic fat deposition; unlike HFF, higher PFF was not associated with relevant alterations in the metabolic profile. In conclusion, the presence and severity of AT dysfunction may drive ectopic fat accumulation towards specific targets, such as VAT and liver, therefore evaluation of AT dysfunction may contribute to the identification of different risk profiles among T2D patients.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University, 00161 Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barchetta
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University, 00161 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelico
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University, 00161 Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Ben
authors.affiliation: Department of Radiological Sciences, Oncology and Pathology, Sapienza University, 00161 Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Di Martino
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University, 00161 Rome, Italy.
authors.forename: Flavia Agata
authors.initials: FA
authors.lastname: Cimini
authors.affiliation: Endocrinology and Diabetes, Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bertoccini
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University, 00161 Rome, Italy.
authors.forename: Licia
authors.initials: L
authors.lastname: Polimeni
authors.affiliation: Department of Radiological Sciences, Oncology and Pathology, Sapienza University, 00161 Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Catalano
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University, 00161 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fraioli
authors.affiliation: Microscopic and Ultrastructural Anatomy (CIR), University Campus Bio-Medico, 00128 Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Del Vescovo
authors.affiliation: Microscopic and Ultrastructural Anatomy (CIR), University Campus Bio-Medico, 00128 Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Morini
authors.affiliation: Endocrinology and Diabetes, Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy.
authors.forename: Marco Giorgio
authors.initials: MG
authors.lastname: Baroni
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University, 00161 Rome, Italy gisella.cavallo@uniroma1.it.
authors.forename: Maria Gisella
authors.initials: MG
authors.lastname: Cavallo
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism; D010641:Phenotype
chemical_list: D007328:Insulin
keywords: adipose tissue dysfunction; non-alcoholic fatty liver disease (NAFLD); pancreatic fat; type 2 diabetes (T2D)