Severe Insulin Resistance and Hypertriglyceridemia After Childhood Total Body Irradiation |
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| Affiliation: | 1. Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;2. Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom;1. Endocrinology and Metabolism Institute, Cleveland Clinic Foundation, Cleveland, Ohio;2. Education Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio;3. Yale Pediatric Endocrinology Department, Yale University School of Medicine, New Haven, Connecticut;4. Yale Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut;5. Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio;1. Endocrinology and Reproductive Physiology Laboratory, Department of Physiology, University of Calcutta, West Bengal, India;2. Department of Zoology, D.M. College of Science, Manipur, India;3. Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts;1. Department of Orthopedic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;2. Maccabi Healthcare Services, Israel;3. Center for Clinical Quality and Safety, Jerusalem, Israel;4. Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;1. University of Maryland School of Medicine, Baltimore, Maryland;2. Baltimore Washington Medical Center Baltimore, Maryland;3. University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;4. Boston University Medical Center, Boston, Massachusetts;1. Sapienza University of Rome Experimental Medicine Department Medical Physiopathology, Food Science and Endocrinology Section Food Science and Human Nutrition Research Unit;1. Hattiesburg Clinic, Hattiesburg, Mississippis;2. Strelitz Diabetes Center for Endocrine and Metabolic Disorders, Eastern Virginia Medical School, Norfolk, Virginia |
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| Abstract: | ObjectiveTo 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.MethodsFasting 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.ResultsBoth 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.ConclusionThough 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. (Endocr Pract. 2013;19:51-58) |
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