Research Article Details
| Article ID: | A23546 |
| PMID: | 23692373 |
| Source: | Diabet Med |
| Title: | Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation. |
| Abstract: | BACKGROUND: Childhood cancer survivors may develop a number of endocrine complications linked to organ failure, such as hypogonadism, diabetes and growth hormone deficiency. However, increasing evidence now suggests that total body irradiation treatment, specifically, is linked with future risk of insulin resistance, hepatic steatosis and dyslipidaemia, possibly because total body irradiation affects adipocyte differentiation and impairs subcutaneous adipose tissue depot expansion during times of positive energy balance. CASE REPORT: We describe a 20-year-old woman who developed pancreatitis with severe hypertriglyceridaemia (serum triglycerides > 300 mmol/l) that required plasmapheresis. She had received total body irradiation prior to her bone marrow transplant at age 6 years for relapsed acute lymphoblastic leukaemia. She developed ovarian failure at age 12 years. At age 15 years she was noted to have hyperglycaemia, increased blood pressure, hepatic steatosis and mild hypertriglyceridaemia. She presented with severe hypertriglyceridaemia and eruptive xanthoma, and developed pancreatitis 12 h after admission. She was treated with plasmapheresis and intravenous insulin and made an excellent recovery. We implicate and discuss total body irradiation as the major contributing factor to her severe hypertriglyceridaemia, compounded by worsening glycaemic control, oestrogen deficiency and a changing adult lifestyle. CONCLUSION: Children who have received total body irradiation are at risk of diabetes and an exaggerated form of the metabolic syndrome with hypertriglyceridaemia, which can be life-threatening. We suggest that survivors of total body irradiation treatment require careful lifelong monitoring of their metabolic status. |
| DOI: | 10.1111/dme.12234 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D160 | Growth Hormone | Biological drug | DB00052 | GHR ligand; PRLR ligand | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D343 | Somatropin | Biological drug | DB00052 | GHR ligand; PRLR ligand | Hormone replacement drug | Under clinical trials | Details |