HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Karlberg, N. Articles by Lipsanen-Nyman, M. Search for Related Content PubMed PubMed Citation Articles by Karlberg, N. Articles by Lipsanen-Nyman, M. Social Bookmarking                What's this?

Insulin Resistance Syndrome in Subjects With Mutated RING Finger Protein TRIM37

¹ Hospital for Children and Adolescents, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
² Department of Medical Genetics, Folkhälsan Institute of Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
³ Neuroscience Center, Folkhälsan Institute of Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

We evaluated the glucose and lipid metabolism in 65 patients (aged 1.1–55 years) with mulibrey (muscle-liver-brain-eye) nanism (MUL), which is a monogenic disorder with prenatal-onset growth failure and typical clinical characteristics. MUL is caused by mutations in the TRIM37 gene, encoding a peroxisomal protein (TRIM37) with E3 ubiquitin-ligase activity. The subjects underwent clinical evaluation, abdominal ultrasonography, and laboratory measurements, including a 3-h oral glucose tolerance test. The results showed a dramatic change in glucose and lipid metabolism with age in MUL subjects. While the children had low fasting glucose and insulin levels, 90% of the adults had high fasting and postload insulin values (up to 1,450 mU/l). A 10-fold decrease in the fasting glucose-to-insulin ratio and a 4-fold decrease in whole-body insulin sensitivity index were observed. Insulin resistance, fatty liver, high serum leptin, hypertension, and acantosis nigricans were already evident in many slim prepubertal children. Half of the adults had type 2 diabetes, and an additional 42% showed impaired glucose tolerance. Seventy percent fulfilled the National Cholesterol Education Program criteria for metabolic syndrome. The peroxisomal targeting and the functional link of TRIM37 to the ubiquitin-proteosome pathway may provide novel clues to the development of metabolic syndrome.

Abbreviations: IGT, impaired glucose tolerance; IRS, insulin resistance syndrome; MUL, mulibrey (muscle-liver-brain-eye) nanism; OGTT, oral glucose tolerance test; SDS, SD score; SGA, small for gestational age

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Karlberg, H. Jalanko, and M. Lipsanen-Nyman Growth and Growth Hormone Therapy in Subjects With Mulibrey Nanism Pediatrics, July 1, 2007; 120(1): e102 - e111. [Abstract] [Full Text] [PDF]