DURATION OF THE HONEYMOON PHASE OF TYPE 1 DIABETES:

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 1型糖尿病是一种非常常见的疾病，仅在美国就有1/400人在18岁之前患病。它是糖尿病相关发病率和死亡率的不成比例的原因，因为它通常发病年龄较小，很难实现良好的血糖控制。尽管外源性胰岛素可以使患有这种疾病的儿童正常生长发育，但它不是治愈的方法。试图改变1型糖尿病患者高血糖发生的自身免疫过程的研究集中在保留内分泌胰腺的固有胰岛素分泌能力作为主要结果变量。可能保留残留的β细胞功能从而改善血糖控制的干预措施有可能对长期发病率和死亡率产生重大影响。 近年来，一些胰岛素类似物已经被开发出来，由于吸收机制的不同，它们具有不同的时间-作用曲线。与服用中效类似物NPH的儿童相比，我们有回顾性数据表明，服用长效类似物甘精的儿童在被诊断为1型糖尿病后至少前九个月的平均血糖控制情况明显更好。这与长期患有糖尿病的儿童形成对比，他们从NPH转向甘精，根据血红蛋白A1c值衡量，他们在平均血糖控制方面没有显著变化。因此，我们建议在6-18岁新诊断为1型糖尿病的患者中进行胰岛素甘精和NPH的随机试验，以解决这种差异是否由于更好地保存了胰腺的固有胰岛素分泌能力。为了评估服用甘精和NPH的患者之间的胰岛素储备是否存在差异，我们将在研究开始时以及在6个月和12个月时再次进行混合膳食耐量试验，并将C肽分泌作为主要的结果变量。如果发现差异，这可能会对未来对1型糖尿病患者的干预研究产生重大影响，因为未能控制胰岛素方案可能是此类研究中的一个潜在混杂变量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 1 diabetes is a very common disorder affecting 1/400 persons by the age of 18 years in the United States alone. It is responsible for a disproportionate percentage of the morbidity and mortality associated with diabetes because of its typically young age of onset and difficulty achieving good glycemic control. Although exogenous administration of insulin allows for normal growth and development in children with this condition, it is not a cure. Studies which have attempted to modify the autoimmune process which underlies the development of hyperglycemia in patients with type 1 diabetes have focused on the preservation of the innate insulin secretory capacity of the endocrine pancreas as the primary outcome variable. Interventions that might preserve residual beta-cell function and thereby improve glycemic control have the potential to have significant effects on long-term morbidity and mortality. In recent years, a number of insulin analogs have been developed which have varying time-action profiles due to varying mechanisms of absorption. In comparison to children on the moderate-acting analog NPH, we have retrospective data to suggest that children placed on the long-acting analog glargine achieve significantly better average glycemic control for at least the first nine months after diagnosis of type 1 diabetes. This contrasts to children with long-standing diabetes who are switched from NPH to glargine, who show no significant change in average glycemic control as measured by Hemoglobin A1c values. Therefore, we propose a randomized trial of insulins glargine and NPH in patients aged 6-18 years newly diagnosed with type 1 diabetes to address whether this difference is due to better preservation of the innate insulin secretory capacity of the pancreas. In order to evaluate whether there is a differnece in insulin reserve between patients treated with glargine vs NPH, we will perform mixed meal tolerance tests at study entry and again at 6 and 12 months, with C-peptide secretion as the primary outcome variable. If a difference is found, this could have significant implications for future intervention studies in patients with type 1 diabetes, as failing to control for insulin regimen could be a potential confounding variable in such studies.