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

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，改善青少年1型糖尿病（T1DM）患者的血糖控制。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。代谢异常如餐后高血糖和高胰高血糖素血症被认为是导致T1DM患者血糖控制不良的原因。双胍类药物二甲双胍可改善T1DM患者的胰岛素抵抗，降低胰岛素需氧量。西格列汀是一种口服降糖药，通过增加内源性活性GLP-1的循环，作为肠促胰岛素增强剂。胰促胰岛素GLP-1通过刺激内源性胰岛素分泌和抑制胰高血糖素降低餐后高血糖。我们建议研究二甲双胍和西格列汀作为辅助药物对青少年T1DM患者标准胰岛素治疗的降血糖效果。我们假设在青少年T1DM患者中，联合使用二甲双胍和西格列汀作为辅助标准胰岛素治疗将比单独使用胰岛素或单独使用每种药物更能降低餐后高血糖。为了了解这些药物的降糖作用及其与胰岛素的联合作用，我们将研究这些药物降糖的机制。通过口服降糖药治疗多种代谢异常，我们可能能够改善青少年T1DM患者的血糖控制。

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.