National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Am J Physiol Endocrinol Metab. 2021 Dec 1;321(6):E795-E801. doi: 10.1152/ajpendo.00281.2021. Epub 2021 Oct 25.
Gluconeogenesis (GNG), the formation of glucose from noncarbohydrate precursors, requires adenosine triphosphate (ATP). Previous studies have estimated the energetic cost of GNG in humans based on theoretical calculations of rates of GNG, moles of oxygen consumption by GNG, and average oxygen consumption. Few human studies have measured the energy expenditure (EE) due to GNG. We estimated EE attributable to GNG in patients with three insulin resistance conditions and high GNG rates (insulin receptor pathogenic variants, lipodystrophy, and type 2 diabetes) and obesity without diabetes. Fractional GNG was measured by incorporation of deuterium from body water into newly formed glucose, endogenous glucose production (EGP) as glucose appearance following administration of [6,6-H]glucose, and total GNG as fractional GNG × EGP. EE was measured by indirect calorimetry and compared with predicted EE from the Mifflin St. Jeor equation. EE attributable to GNG was estimated using linear regression after accounting for age and fat-free mass (FFM). EE in patients with insulin resistance was significantly higher than predicted by the Mifflin St. Jeor equation. GNG correlated with resting EE (REE). EE attributable to GNG in patients with insulin resistance was almost one-third of REE, substantially higher than theorized in healthy subjects. Our findings demonstrate that GNG is a significant contributor to EE in insulin-resistant states. Prediction equations may underestimate caloric needs in patients with insulin resistance. Therefore, targeting caloric needs to account for higher EE due to increased GNG should be considered in energy balance studies in patients with insulin resistance. Gluconeogenesis is an energy-requiring process that is upregulated in diabetes, contributing to hyperglycemia. Previous studies have estimated that gluconeogenesis accounts for less than 10% of resting energy expenditure. This study estimates the energy expenditure attributable to gluconeogenesis in uncommon and severe forms of insulin resistance and common, milder forms of insulin resistance. In these populations, gluconeogenesis accounts for almost one-third of resting energy expenditure, substantially higher than previously theorized in the literature.
糖异生（GNG）是指从非碳水化合物前体生成葡萄糖的过程，需要三磷酸腺苷（ATP）。先前的研究基于 GNG 速率、GNG 消耗的氧摩尔数和平均耗氧量的理论计算来估计人类 GNG 的能量成本。很少有人类研究测量 GNG 引起的能量消耗（EE）。我们在胰岛素抵抗条件下 GNG 速率较高（胰岛素受体致病性变异、脂肪营养不良和 2 型糖尿病）和肥胖但无糖尿病的患者中估计了归因于 GNG 的 EE。通过将来自身体水的氘掺入新形成的葡萄糖中来测量分数 GNG，通过给予 [6,6-H]葡萄糖后葡萄糖出现来测量内源性葡萄糖生成（EGP），以及通过分数 GNG×EGP 来测量总 GNG。EE 通过间接热量法测量，并与 Mifflin St. Jeor 方程预测的 EE 进行比较。在考虑年龄和去脂体重（FFM）后，使用线性回归估计归因于 GNG 的 EE。胰岛素抵抗患者的 EE 明显高于 Mifflin St. Jeor 方程的预测值。GNG 与静息 EE（REE）相关。胰岛素抵抗患者归因于 GNG 的 EE 几乎占 REE 的三分之一，明显高于健康受试者的理论值。我们的研究结果表明，GNG 是胰岛素抵抗状态下 EE 的重要贡献者。预测方程可能低估了胰岛素抵抗患者的热量需求。因此，在胰岛素抵抗患者的能量平衡研究中，应考虑针对因 GNG 增加而导致的更高 EE 来确定热量需求。糖异生是一个耗能过程，在糖尿病中上调，导致高血糖。先前的研究估计，糖异生占静息能量消耗的不到 10%。本研究估计了在罕见和严重的胰岛素抵抗形式以及常见和较轻的胰岛素抵抗形式中归因于糖异生的能量消耗。在这些人群中，糖异生占静息能量消耗的近三分之一，明显高于文献中先前的理论值。
