GLUCONEOGENESIS IN THE VERY LOW BIRTH WEIGHT INFANT

由于底物储存不足，VLBW婴儿低血糖的风险很高，因此难以维持正常血糖，但VLBW婴儿也存在葡萄糖不耐受。因此，当他们接受高输注速率的葡萄糖以防止低血糖和提供适当的能量摄入时，他们经常发生高血糖。本方案的第一个目的是确定VLBW婴儿如何利用糖异生途径维持正常血糖，同时以大约正常葡萄糖周转率的一半的速率接受葡萄糖作为总肠外营养（TPN）的一部分（即包括脂质和氨基酸）。由于糖异生（GNG）是一个复杂的过程，很难在体内研究，第二个目的是比较最近发表的三种使用[U-13C]葡萄糖，[2-13C]甘油和氧化氘测量GNG的方法。需要检验的假设有：1。作为TPN的一部分，以低于正常葡萄糖周转率（以防止高血糖）的速率接受葡萄糖的VLBW婴儿主要通过GNG维持正常血糖。2. TPN的脂质含量在支持糖异生方面比氨基酸更重要。3. 测量GNG的三种方法提供了相似的结果。研究对象：三组可比较的VLBW婴儿（n=20，胎龄2710.2周，出生体重996128克，出生后5.010.2天（平均se））接受TPN治疗（葡萄糖17.110.2 mmol/kg min，脂质1.610.1和蛋白2.210.1 mg/kg min），持续8-12小时。GNG通过[U-13C]葡萄糖（n=8）估算；[2-13C]甘油（n=6）或氧化氘（n=6）结果：所有婴儿血糖正常，血糖平均为3.010.1 mM，葡萄糖出现率（Ra）为28.811.1 mmol/kg min，葡萄糖生成率（GPR）为10.711.0 mmol/kg min，三组间均无差异。[U-13C]葡萄糖和[2-13C]甘油方法提供了几乎相同的糖异生估计，分别占葡萄糖Ra的2812%和2612%（即糖异生率分别为7.610.6和7.610.8 mmol/kg min），分别占GPR的7215和7319%。不包括甘油贡献的氧化氘估计值与用[2-13C]甘油法测量的非甘油贡献相当。甘油是主要的糖异生底物，占糖异生的6515%。由于[2-13C]甘油方法具有区分甘油和非甘油来源贡献的优势，我们选择使用这种方法来确定从TPN中提取氨基酸对葡萄糖Ra和糖异生的影响。受试者：一组6名婴儿（27.510.4孕周，1022157克，出生后年龄4.512天），即与上述受试者相当的婴儿，接受如上所述的葡萄糖和脂质，但没有氨基酸。对这些婴儿进行了8小时的研究。

Euglycemia is difficult to maintain in VLBW infants, since these infants are at a high risk of hypoglycemia due to inadequate substrate stores, but VLBW infants are also glucose intolerant. Therefore, they frequently develop hyperglycemia when they receive glucose at high infusion rates delivered both to prevent hypoglycemia and to provide an appropriate energy intake. The first purpose of this protocol is to determine how VLBW infants utilize the gluconeogenic pathway to maintain normoglycemia while receiving glucose at a rate about half the normal glucose turnover rate as part of total parenteral nutrition (TPN) (i.e including lipids and amino acids). Since gluconeogenesis (GNG) is a complex process, which is difficult to study in vivo, a second purpose is to compare three recently published methods to measure GNG using [U-13C]glucose, [2-13C]glycerol and deuterium oxide. The hypotheses to be tested are: 1. VLBW infants receiving glucose at a rate less than normal glucose turnover rate (to prevent hyperglycemia) as part of TPN maintain normoglycemia mainly via GNG. 2. The lipid content of TPN is more important in supporting gluconeogenesis than are the amino acids. 3. The three methods to measure GNG provide similar results. Subjects: Three comparable groups of VLBW infants (n=20; gestational age 2710.2 weeks; birth weight 996128 grams; postnatal age 5.010.2 days (mean1SE)) received TPN (glucose 17.110.2 mmol/kg min; lipid 1.610.1 and protein 2.210.1 mg/kg min) for 8-12 h. GNG was estimated by [U-13C]glucose (n=8); [2-13C]glycerol (n=6) or deuterium oxide (n=6). Results: All infants remained normoglycemic, blood glucose averaged 3.010.1 mM. Glucose appearance rate (Ra) was 28.811.1 mmol/kg min and glucose production rate (GPR), 10.711.0 mmol/kg min. None of these parameters varied between the three groups. The [U-13C]glucose and [2-13C]glycerol methods provided almost identical estimates of gluconeogenesis accounting for 2812 and 2612 % of glucose Ra (i.e. gluconeogenic rates of 7.610.6 and 7.610.8 mmol/kg min), respectively, and 7215 and 7319 % of GPR, respectively. The deuterium oxide estimate, which does not include the contribution from glycerol, was comparable to the non-glycerol contribution measured by the [2-13C]glycerol method. Glycerol was the major gluconeogenic substrate contributing 6515 % of gluconeogenesis. Since the [2-13C]glycerol method has the advantage of partitioning the contribution from glycerol and non-glycerol sources, we chose to use this method to determine the impact of withdrawal amino acids from TPN on glucose Ra and gluconeogenesis. Subjects: A group of six infants (27.510.4 gestational weeks; 1022157 grams; postnatal age 4.512 days) i.e. the infants were comparable to the subjects described above, received glucose and lipids as described above, but no amino acids. The infants were studied over 8 h.