title: Severe insulin resistance and hypertriglyceridemia after childhood total body irradiation.
abstract: OBJECTIVE
  To characterize the metabolic phenotype of 2 cases of normal weight young women who developed type 2 diabetes (T2D), severe insulin resistance (insulin requirement >200 units/day), marked hypertriglyceridemia (>2000 mg/dL), and hepatic steatosis beginning 9 years after undergoing total body irradiation (TBI) and bone marrow transplantation for childhood cancer.
  
  
  METHODS
  Fasting plasma glucose, insulin, free fatty acids (FFAs), leptin, adiponectin, resistin, TNFα, and IL-6 were measured in each case and in 8 healthy women; Case 1 was also assessed after initiating pioglitazone. Coding regions and splice junctions of PPARG, LMNA, and AKT2 were sequenced in Case 1 and of PPARG in Case 2 to evaluate for familial partial lipodystrophies. Genotyping of APOE was performed in Case 1 to rule out type III hyperlipoproteinemia.
  
  
  RESULTS
  Both cases had elevated plasma levels of insulin, leptin, resistin, and IL-6, high-normal to elevated TNFα, and low to low-normal adiponectin in keeping with post-receptor insulin resistance and adipose tissue inflammation. Case 1 experienced a biochemical response to pioglitazone. No causative mutations for partial lipodystrophies or type III hyperlipoproteinemia were identified.
  
  
  CONCLUSIONS
  Though metabolic derangements have previously been reported in association with TBI, few cases have described insulin resistance and hypertriglyceridemia as severe as that seen in our patients. We speculate that early childhood TBI may impede adipose tissue development leading to metabolic complications from an attenuated ability of adipose tissue to accommodate caloric excess, and propose that this extreme metabolic syndrome be evaluated for as a late complication of TBI.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. sarah.mayson@uphs.upenn.edu
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Mayson
authors.forename: Victoria E R
authors.initials: VE
authors.lastname: Parker
authors.forename: Mark H
authors.initials: MH
authors.lastname: Schutta
authors.forename: Robert K
authors.initials: RK
authors.lastname: Semple
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
mesh_terms: D000293:Adolescent; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D009447:Neuroblastoma / Q000532:radiotherapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000532:radiotherapy; D052243:Resistin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha