Research Article Details
| Article ID: | A00246 |
| PMID: | 35167495 |
| Source: | JCI Insight |
| Title: | Ethnic and gender differences in hepatic lipid content and related cardiometabolic parameters in lean individuals. |
| Abstract: | BACKGROUND: NAFLD affects 25-30% of the US and European populations and is associated with insulin resistance (IR), T2D, increased cardiovascular risk and is defined by hepatic triglyceride content (HTG) > 5.56%. However, it is unknown whether HTG content less than 5.56% is associated with cardiometabolic risk factors and whether there are ethnic [Asian Indian (AI) vs. non-Asian Indian (non-AI)] and/or gender differences in these parameters in lean individuals. METHODS: We prospectively recruited 2,331 individuals and measured HTG, using 1H MRS, and plasma concentrations of triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, and uric acid. Insulin sensitivity was assessed using HOMA-IR and the Matsuda Insulin Sensitivity Index (ISI). RESULTS: The 95th percentile for HTG in lean non-AI individuals was 1.85%. Plasma insulin, triglycerides, total cholesterol, LDL cholesterol and uric acid concentrations were increased and HDL decreased in individuals with HTG content > 1.85% and ≤ 5.56% compared to those individuals with HTG content ≤ 1.85% and was associated with increased IR. Mean HTG was lower in lean non-AI women compared to lean non-AI men, whereas lean AI men and women had a 40-100% increase in HTG when compared to non-AI men and women which was associated with increased cardiometabolic risk factors. CONCLUSIONS: We found that the 95th percentile of HTG in lean non-AI individuals was 1.85% and that HTG concentrations above this threshold were associated with IR and cardiovascular risk factors. Premenopausal women are protected from these changes whereas young lean AI men and women manifest increased HTG content and associated cardiometabolic risk factors. FUNDING: Supported by grants from the United States Department of Health and Human Resources (NIH/NIDDK): R01 DK113984, P30 DK45735, U24 DK59635 and UL1 RR024139 and the Novo Nordisk Foundation (NNF18CC0034900). |
| DOI: | 10.1172/jci.insight.157906 |
| 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 | |
|---|---|---|---|---|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |