Pancreatic Lipomatosis Is a Structural Marker in Nondiabetic Children With Mutations in Carboxyl-Ester Lipase

• Published in: Diabetes (New York, N.Y.) Vol. 56; no. 2; pp. 444 - 449
• Main Authors: RAEDER, Helge, HALDORSEN, Ingfrid S, ERSLAND, Lars, GRFÜNER, Renate, TAXT, Torfinn, SØVIK, Oddmund, MOLVEN, Anders, NJØLSTAD, Pal R
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2007
• Subjects: Adolescent; Adult; Age; Atrophy; Biological and medical sciences; Carboxylesterase - genetics; Care and treatment; Child; Child, Preschool; Dermatology; Diabetes; Diabetes mellitus; Diabetes Mellitus - diagnostic imaging; Diabetes Mellitus - genetics; Diabetes Mellitus - pathology; Diabetes. Impaired glucose tolerance; Disease; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Families & family life; Female; Gene mutation; Gene mutations; Genetic aspects; Glucose; Humans; Insulin; Investigations; Lipomatosis - genetics; Magnetic Resonance Imaging; Male; Medical sciences; Mutation; Pancreas; Pancreas - diagnostic imaging; Pancreas - pathology; Pancreatic beta cells; Pancreatic Diseases - genetics; Pancreatic Elastase - deficiency; Tumors of the skin and soft tissue. Premalignant lesions; Ultrasonic imaging; Ultrasonography; Endocrinopathy; Human; Skin disease; Enzyme; Diabetes mellitus; Triacylglycerol lipase; Lipomatosis; Esterases; Carboxylic ester hydrolases; Hydrolases; Adipose tissue disorders; Benign neoplasm; Mutation; Pancreas; Child
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db06-0859

Pancreatic Lipomatosis Is a Structural Marker in Nondiabetic Children With Mutations in Carboxyl-Ester Lipase Helge Ræder 1 , Ingfrid S. Haldorsen 2 , Lars Ersland 3 , Renate Grüner 4 , Torfinn Taxt 4 , Oddmund Søvik 1 , Anders Molven 5 6 and Pål R. Njølstad 1 7 1 Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Bergen, Norway 2 Section for Radiology, Department of Surgery, University of Bergen, Bergen, Norway 3 Department of Clinical Engineering, Haukeland University Hospital, Bergen, Norway 4 Department of Biomedicine, University of Bergen, Bergen, Norway 5 Section for Pathology, the Gade Institute, University of Bergen, Norway 6 Department of Pathology, Haukeland University Hospital, Bergen, Norway 7 Department of Pediatrics, Haukeland University Hospital, Bergen, Norway Address correspondence and reprint requests to Prof. Pål Rasmus Njølstad, MD PhD, Section for Pediatrics, Department of Clinical Medicine, University of Bergen, N-5020 Bergen, Norway. E-mail: pal.njolstad{at}uib.no Abstract Both pancreatic volume reduction and lipomatosis have been observed in subjects with diabetes. The underlying molecular and pathological mechanisms are, however, poorly known, and it has been speculated that both features are secondary to diabetes. We have recently described pancreatic atrophy and lipomatosis in diabetic subjects of two Norwegian families with a novel syndrome of diabetes and exocrine pancreatic dysfunction caused by heterozygous carboxyl-ester lipase ( CEL ) mutations. To explore the early pathological events in this syndrome, we performed radiological examinations of the pancreas in nondiabetic mutation carriers with signs of exocrine dysfunction. In a case series study at a tertiary hospital, we evaluated 11 nondiabetic and mutation-positive children with fecal elastase deficiency and 11 age- and sex-matched control subjects using ultrasound and magnetic resonance imaging (MRI) to estimate pancreatic fat content. The pancreata of nondiabetic mutation carriers exhibited increased reflectivity on ultrasound and had MRI findings indicative of lipomatosis. Apparently, carriers of heterozygous CEL mutations accumulate fat in their pancreas before the anticipated development of diabetes. Our findings suggest that lipomatosis of the pancreas reflects early events involved in the pathogenesis of diabetes and exocrine pancreatic dysfunction syndrome. MRI, magnetic resonance imaging VIBE, volume interpolated breath-hold examination Footnotes Additional information can be found in an online appendix at http://dx.doi.org/10.2337/db06-0859 . The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted October 26, 2006. Received June 23, 2006. DIABETES