单基因胰岛素耐药性基因型分层治疗:系统性审查
Robert K Semple1,2, Kashyap A Patel3,4, Sungyoung Auh5
1Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Communications medicine
|October 4, 2023
概括
针对单一性胰岛素抵抗 (IR) 的干预措施显示出有前途,美特列普丁和 thiazolidinediones 改善了脂质变化中的代谢标志物. 证据质量低,需要进一步研究基因型特异性治疗方法.
科学领域:
- 内分泌学 在内分泌学.
- 代谢障碍 代谢障碍 代谢障碍
- 遗传学 遗传学 是一个
背景情况:
- 单一的胰岛素耐药性 (IR) 包括脂质和胰岛素信号缺陷.
- 遗传变异需要对治疗效果进行分层评估.
研究的目的:
- 评估药理和手术干预在单一性IR.的疗效.
- 根据遗传病因和脂质变类型对治疗效应进行分层.
主要方法:
- 对PubMed,MEDLINE和Embase数据库 (1987-2021) 的系统审查.
- 将报告个人层面干预效应的研究纳入单一性IR.
- 数据提取和分析,按基因分层,干预和脂质缩症分类.
主要成果:
- 在各种脂质变异类型和基因子组 (LMNA,PPARG,AGPAT2,BSCL2) 中,美特利普丁改善了甘油三和HbA1c.
- thiazolidinediones 改善了 HbA1c 和甘油三在一般化脂质疏松症和特定的遗传亚组中的情况.
- rhIGF-1在改善胰岛素受体 (INSR) 相关IR的HbA1c方面表现出有效性.
结论:
- 对基因型特定的单基因IR治疗的证据质量低至非常低.
- 梅特利普丁, thiazolidinediones 和 rhIGF-1 在特定的IR亚型中显示出潜在的益处.
- 对于许多基因型治疗组合的证据不够,这凸显了需要进一步调查的需要.
相关概念视频
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
215
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
215
01:16Insulin: Dosing Regimen and Adverse Effects
189
Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
189
01:22Diabetes Mellitus: Overview and Type I Subtype
2.7K
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
2.7K
01:22Diabetes Mellitus: Type 2 and Gestational
2.5K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
2.5K
01:24Glucagon-like Receptor Agonists
337
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
337
01:28Insulin: The Receptor and Signaling Pathways
1.2K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.2K