Research Article Details
| Article ID: | A45348 |
| PMID: | 25079479 |
| Source: | J Pediatr Gastroenterol Nutr |
| Title: | Hepatic steatosis is prevalent in stillborns delivered to women with diabetes mellitus. |
| Abstract: | OBJECTIVE: Maternal diabetes is a risk factor for pregnancy complications, including stillbirth and macrosomia. Evolving data suggest that diabetes during pregnancy also has long-term consequences for offspring, putting them at risk for obesity and the metabolic syndrome in childhood. Because nonalcoholic fatty liver disease is known to occur in adults and children with insulin resistance, we hypothesized that altered lipid metabolism in fetuses of diabetic mothers may manifest with hepatic steatosis. METHODS: We undertook a retrospective autopsy study to compare the presence and degree of hepatic steatosis between stillborns delivered to women with pregestational or gestational diabetes mellitus (gestational age 20-40 weeks; n = 33) and age-matched nondiabetic control stillbirth cases (n = 48), the latter enriched for maternal obesity, macrosomia, and similar cause of demise. RESULTS: Histopathologic hepatic steatosis was significantly more prevalent and severe in the diabetic subjects (26/33, 78.8%) than in the controls (8/48, 16.6%) (P < 0.001). Within the diabetic cohort, the severity of steatosis was related directly to gestational age, birth weight, and liver weight, with no correlation of presence or severity of steatosis in the control group to maternal or fetal factors, including maternal body mass index or fetal macrosomia. Although macrosomic stillborns were more common in diabetic women with %hemoglobin A1c >6 and body mass index >30 kg/m, fetal steatosis was independent of glycemic control, maternal obesity, type of diabetes, ethnicity, or fetal sex in our cohort. CONCLUSIONS: This study is the first to our knowledge to demonstrate a specific association between fetal hepatic steatosis and maternal diabetes. |
| DOI: | 10.1097/MPG.0000000000000520 |
| 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 |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| 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 |