Glucose lowering effect of metformin and sitagliptin in adolescents with Type 1

二甲双胍和西格列汀对青少年 1 型糖尿病的降血糖作用

• 批准号: 8354984
• 负责人: LUISA M RODRIGUEZ
• 金额: $ 7.32万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8354984
• 关键词: Adjuvant; Adolescent; Agonist; Biguanides; Blood Circulation; C-Peptide; Child; Combined Modality Therapy; Complex; Development; Enhancers; Glucagon; Glucose; Goals; Hyperglycemia; Hypoglycemic Agents; Injectable; Injection of therapeutic agent; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Metabolic; Metformin; Oral; Patients; Pharmaceutical Preparations; Plasma; Regimen; Testing; Triglycerides; enzyme activity; exenatide; glucagon-like peptide 1; glycemic control; hyperglucagonemia; improved; insulin secretion; receptor

DESCRIPTION (provided by applicant): Our long term goal is to improve glycemic control in adolescents with Type 1 diabetes mellitus (T1DM) through the use of oral hypoglycemic agents as adjuncts to insulin therapy. In T1DM pubertal development is associated with increased insulin resistance and worsening glycemic control. Metabolic abnormalities such as postprandial hyperglycemia and hyperglucagonemia are known to contribute to poor glycemic control in T1DM. The biguanide metformin can improve insulin resistance and decrease insulin requirements in patients with T1DM. Sitagliptin is an oral hypoglycemic agent that acts as an incretin enhancer by increasing the circulation of endogenous active GLP-1. The incretin GLP-1 lowers postprandial hyperglycemia by stimulating of endogenous insulin secretion and suppressing glucagon. We propose to examine the glucose lowering effect of metformin and sitagliptin as adjuvants to standard insulin therapy in adolescents with T1DM. We hypothesize that in adolescents with T1DM, the combined use of metformin and sitagliptin as adjuvants to standard insulin therapy will lower postprandial hyperglycemia more than insulin or the addition of each agent alone. To understand the glucose lowering effect of these agents and their combination with insulin we will examine the mechanisms by which these drugs lower glycemia. By targeting multiple metabolic abnormalities with oral hypoglycemic agents we might be able to improve glycemic control in adolescents with T1DM. PUBLIC HEALTH RELEVANCE: The objective is to study the glucose lowering effect of the oral medications: metformin, sitagliptin in adolescents with Type 1 diabetes mellitus.

描述（由申请人提供）：我们的长期目标是通过使用口服降糖药作为胰岛素治疗的辅助手段，改善 1 型糖尿病 (T1DM) 青少年的血糖控制。在 T1DM 中，青春期发育与胰岛素抵抗增加和血糖控制恶化有关。已知餐后高血糖和高胰高血糖素血症等代谢异常会导致 T1DM 血糖控制不佳。双胍类二甲双胍可以改善 T1DM 患者的胰岛素抵抗并降低胰岛素需求。西他列汀是一种口服降血糖药，通过增加内源性活性 GLP-1 的循环来充当肠促胰岛素增强剂。肠促胰岛素 GLP-1 通过刺激内源性胰岛素分泌和抑制胰高血糖素来降低餐后高血糖。我们建议检查二甲双胍和西他列汀作为标准胰岛素治疗的佐剂对 T1DM 青少年的降血糖作用。我们假设，在患有 T1DM 的青少年中，联合使用二甲双胍和西他列汀作为标准胰岛素治疗的佐剂，比胰岛素或单独添加每种药物更能降低餐后高血糖。为了了解这些药物的降血糖作用及其与胰岛素的组合，我们将研究这些药物降低血糖的机制。通过口服降糖药针对多种代谢异常，我们或许能够改善 1 型糖尿病青少年的血糖控制。 公共健康相关性：目的是研究口服药物二甲双胍、西他列汀对患有 1 型糖尿病的青少年的降血糖作用。