GLUCONEOGENESIS IN VERY LOW BIRTH WEIGHT INFANTS

早产儿管理的改进大大提高了他们的存活率。此前，营养管理在极低出生体重(VLBW)婴儿中并不是高度优先的，因为大多数婴儿在生命早期死亡。因此，我们对这些存活婴儿的营养管理的改进已经落后于心肺治疗的进步。极低出生体重儿容易发生低血糖；因此，为了提供足够的卡路里和预防低血糖，作为标准的全胃肠外营养(TPN)的一部分，常规地以高速率(大约60mumol/kg min，是这些婴儿测量的葡萄糖周转率的两倍)输注葡萄糖，这通常会导致高血糖。与低血糖一样，高血糖也会对患者的预后产生重大的短期和长期不良影响。本应用的具体焦点是确定标准全肠外营养中提供的底物对糖原分解和糖异生(GNG)产生葡萄糖以及葡萄糖利用的个体和集体作用。这些研究将确定：a.接受TPN治疗的血糖正常的VLBW婴儿是否完全抑制了他们的葡萄糖产生，而那些高血糖的婴儿是否有不完全的葡萄糖产生抑制和/或葡萄糖利用减少；b.当VLBW婴儿以较低的速率(17mumol/kg min)供应葡萄糖时：1.静脉注射。脂类(IntralipidR)增加GNG和葡萄糖的产生，如果是，这是通过β-氧化为GNG提供能量还是提供甘油作为3-碳前体的结果；2.甘油是否以剂量依赖的方式增加极低出生体重儿的GNG和葡萄糖的产生；3.是否静脉注射。氨基酸溶液(TrophAmineR)和/或生糖氨基酸谷氨酰胺和丙氨酸将增加GNG和葡萄糖的产生；以及4.胰高血糖素是否会增加内源和外源底物来源的GNG和葡萄糖的产生。最终目的将是利用这些信息设计成分(底物和可能的激素)的替代混合物，通过利用婴儿的糖异生途径降低这些婴儿的低血糖和高血糖的风险，同时提供足够的底物来维持正常的生长和发育。

Improvements in the management of premature infants have resulted in a dramatic increase in their survival. Previously, nutritional management was not of high priority in very low birth weight (VLBW) infants since most died early in life. As a result, our refinement of the nutritional management of these surviving infants has lagged behind the advancements in cardio-respiratory therapy. VLBW infants are susceptible to hypoglycemia; thus, to provide sufficient calories and to prevent hypoglycemia, glucose is routinely infused at high rates (approximately 60 mumol/kg min, twice that of measured glucose turnover rates in these infants) as part of standard total parenteral nutrition (TPN) which frequently results in hyperglycemia. Like hypoglycemia, hyperglycemia can have significant short and long term adverse impact on their outcomes. The specific focus of the present application is to determine the individual and collective roles of the substrates provided in standard total parenteral nutrition on glucose production from glycogenolysis and gluconeogenesis (GNG) and glucose utilization. These studies will determine: a. Whether VLBW infants receiving TPN who are normoglycemic suppress their glucose production completely and those who are hyperglycemic have incomplete suppression of glucose production and/or reduced glucose utilization; b. When VLBW infants are supplied glucose at a reduced rate (17 mumol/kg min): 1. Do i.v. lipids (IntralipidR) increase GNG and glucose production and if so is this the result of providing energy for GNG through beta-oxidation or providing glycerol as a 3-carbon precursor; 2. Whether glycerol increases GNG and glucose production in a dose dependent fashion in VLBW infants; 3. Whether i.v. amino acid solution (TrophAmineR) and/or the gluconeogenic amino acids, glutamine and alanine, will increase GNG and glucose production; and 4. Whether glucagon will increase GNG and glucose production from endogenous and exogenous substrate sources. The ultimate aim will be to utilize this information in designing alternative mixtures of constituents (substrates and possibly hormones) which will decrease the risk of both hypo- and hyperglycemia in these infants, by utilizing the infants' gluconeogenic pathway, while providing sufficient substrate to sustain normal growth and development.