Noah Gruber1,2, Moran Rathaus3, Idit Ron3, Rinat Livne3, Sharon Sheinvald4, Ehud Barhod3, Rina Hemi3, Amit Tirosh5,3, Orit Pinhas-Hamiel4,5, Amir Tirosh6,7. 1. Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel. noah.gruber@sheba.health.gov.il. 2. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. noah.gruber@sheba.health.gov.il. 3. The Dalia and David Arabov Diabetes Research Center, Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel-Hashomer, Israel. 4. Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel. 5. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 6. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Amir.Tirosh@sheba.health.gov.il. 7. The Dalia and David Arabov Diabetes Research Center, Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel-Hashomer, Israel. Amir.Tirosh@sheba.health.gov.il.
Abstract
AIMS/HYPOTHESIS: Fatty acid-binding protein 4 (FABP4) is an adipokine with a key regulatory role in glucose and lipid metabolism. We prospectively evaluated the role of FABP4 in the pathophysiology of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes. METHODS: Clinical and laboratory data were prospectively collected from consecutive children presenting with new-onset type 1 diabetes. In addition to blood chemistry and gases, insulin, C-peptide, serum FABP4 and NEFA were collected upon presentation and 48 h after initiation of insulin treatment. In a mouse model of type 1 diabetes, glucose, insulin, β-hydroxybutyrate and weight were compared between FABP4 knockout (Fabp4-/-) and wild-type (WT) mice. RESULTS: Included were 33 children (mean age 9.3 ± 3.5 years, 52% male), of whom 14 (42%) presented with DKA. FABP4 levels were higher in the DKA group compared with the non-DKA group (median [IQR] 10.1 [7.9-14.2] ng/ml vs 6.3 [3.9-7] ng/ml, respectively; p = 0.005). The FABP4 level was positively correlated with HbA1c at presentation and inversely correlated with venous blood pH and bicarbonate levels (p < 0.05 for all). Following initiation of insulin therapy, a marked reduction in FABP4 was observed in all children. An FABP4 level of 7.22 ng/ml had a sensitivity of 86% and a specificity of 78% for the diagnosis of DKA, with an area under the receiver operating characteristic curve of 0.78 (95% CI 0.6, 0.95; p = 0.008). In a streptozotocin-induced diabetes mouse model, Fabp4-/- mice exhibited marked hypoinsulinaemia and hyperglycaemia similar to WT mice but displayed no significant increase in β-hydroxybutyrate and were protected from ketoacidosis. CONCLUSIONS/ INTERPRETATION: FABP4 is suggested to be a necessary regulator of ketogenesis in insulin-deficient states.
AIMS/HYPOTHESIS: Fatty acid-binding protein 4 (FABP4) is an adipokine with a key regulatory role in glucose and lipid metabolism. We prospectively evaluated the role of FABP4 in the pathophysiology of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes. METHODS: Clinical and laboratory data were prospectively collected from consecutive children presenting with new-onset type 1 diabetes. In addition to blood chemistry and gases, insulin, C-peptide, serum FABP4 and NEFA were collected upon presentation and 48 h after initiation of insulin treatment. In a mouse model of type 1 diabetes, glucose, insulin, β-hydroxybutyrate and weight were compared between FABP4 knockout (Fabp4-/-) and wild-type (WT) mice. RESULTS: Included were 33 children (mean age 9.3 ± 3.5 years, 52% male), of whom 14 (42%) presented with DKA. FABP4 levels were higher in the DKA group compared with the non-DKA group (median [IQR] 10.1 [7.9-14.2] ng/ml vs 6.3 [3.9-7] ng/ml, respectively; p = 0.005). The FABP4 level was positively correlated with HbA1c at presentation and inversely correlated with venous blood pH and bicarbonate levels (p < 0.05 for all). Following initiation of insulin therapy, a marked reduction in FABP4 was observed in all children. An FABP4 level of 7.22 ng/ml had a sensitivity of 86% and a specificity of 78% for the diagnosis of DKA, with an area under the receiver operating characteristic curve of 0.78 (95% CI 0.6, 0.95; p = 0.008). In a streptozotocin-induced diabetes mouse model, Fabp4-/- mice exhibited marked hypoinsulinaemia and hyperglycaemia similar to WT mice but displayed no significant increase in β-hydroxybutyrate and were protected from ketoacidosis. CONCLUSIONS/ INTERPRETATION: FABP4 is suggested to be a necessary regulator of ketogenesis in insulin-deficient states.
Authors: Haiming Cao; Motohiro Sekiya; Meric Erikci Ertunc; M Furkan Burak; Jared R Mayers; Ariel White; Karen Inouye; Lisa M Rickey; Baris C Ercal; Masato Furuhashi; Gürol Tuncman; Gökhan S Hotamisligil Journal: Cell Metab Date: 2013-05-07 Impact factor: 27.287
Authors: Amy C Wotherspoon; Ian S Young; David R McCance; Chris C Patterson; Michael J A Maresh; Donald W M Pearson; James D Walker; Valerie A Holmes Journal: Diabetes Care Date: 2016-09-14 Impact factor: 19.112