Levitt Katz L E, Satin-Smith M S, Collett-Solberg P, Thornton P S, Baker L, Stanley C A, Cohen P
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, USA.
J Pediatr. 1997 Aug;131(2):193-9. doi: 10.1016/s0022-3476(97)70153-7.
The diagnosis of hypoglycemia caused by hyperinsulinism may be difficult because insulin levels are not uniformly elevated at the time of hypoglycemia. Insulin-like growth factor binding protein-1 (IGFBP-1) is a 28 kd protein whose secretion is acutely inhibited by insulin. We hypothesized that serum levels of IGFBP-1 would be a useful marker of hyperinsulinism. We measured IGFBP-1 levels during the course of standardized fasting studies in hospitalized children; 36 patients became hypoglycemic during the fasting studies, and samples obtained at the point of hypoglycemia were analyzed. On the basis of the currently used diagnostic criteria, 13 children had hyperinsulinism, 16 had ketotic hypoglycemia or no disorder, 3 had hypopituitarism or isolated growth hormone deficiency, 2 had glycogen storage disease type 1 and 2 had fatty acid oxidation disorders. In control subjects (children with ketotic hypoglycemia or no disorder), IGFBP-1 levels rose during fasting to a mean of 343.8 +/- 71.3 ng/ml in the sample drawn at the time of hypoglycemia. Mean IGFBP-1 levels at hypoglycemia for the entire group with hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different from levels seen in control subjects (p < 0.0001). In children with moderately controlled hyperinsulinism (fasting tolerance > 4 hours), mean IGFBP-1 levels at the time of hypoglycemia were 71.5 +/- 16.9 ng/ml. IGFBP-1 levels in the children with poorly controlled hyperinsulinism (fasting tolerance < 4 hours) failed to rise during fasting, with a mean of 30.1 +/- 10.4 ng/ml in the final sample. IGFBP-1 levels were inversely correlated with serum insulin and C-peptide levels (r = -0.71 and -0.72, respectively; p < 0.0001). Patients with other endocrinologic or metabolic diseases that result in fasting hypoglycemia demonstrated a rise in IGFBP-1 levels similar to that seen in ketotic hypoglycemia. Low serum levels of IGFBP-1 at the time of hypoglycemia provide an additional marker of insulin action that might help to differentiate hyperinsulinism from other hypoglycemic disorders.
因高胰岛素血症导致的低血糖症诊断可能存在困难，因为在低血糖发作时胰岛素水平并非均一性升高。胰岛素样生长因子结合蛋白-1（IGFBP-1）是一种28kd的蛋白质，其分泌会被胰岛素急性抑制。我们推测血清IGFBP-1水平可能是高胰岛素血症的一个有用标志物。我们在住院儿童的标准化禁食研究过程中测量了IGFBP-1水平；36名患者在禁食研究期间出现低血糖，对低血糖发作时采集的样本进行了分析。根据目前使用的诊断标准，13名儿童患有高胰岛素血症，16名患有酮症性低血糖或无病症，3名患有垂体功能减退或孤立性生长激素缺乏，2名患有1型糖原贮积病，2名患有脂肪酸氧化障碍。在对照受试者（患有酮症性低血糖或无病症的儿童）中，禁食期间IGFBP-1水平升高，在低血糖发作时采集的样本中平均为343.8±71.3ng/ml。整个高胰岛素血症组在低血糖发作时的IGFBP-1平均水平为52.4±11.5ng/ml，与对照受试者的水平有显著差异（p<0.0001）。在高胰岛素血症得到适度控制的儿童（禁食耐受时间>4小时）中，低血糖发作时的IGFBP-1平均水平为71.5±16.9ng/ml。高胰岛素血症控制不佳的儿童（禁食耐受时间<4小时）在禁食期间IGFBP-1水平未能升高，最终样本中的平均水平为30.1±10.4ng/ml。IGFBP-1水平与血清胰岛素和C肽水平呈负相关（r分别为-0.71和-0.72；p<0.0001）。因其他内分泌或代谢疾病导致禁食性低血糖的患者，其IGFBP-1水平升高情况与酮症性低血糖患者相似。低血糖发作时血清IGFBP-1水平较低，为胰岛素作用提供了一个额外的标志物，可能有助于将高胰岛素血症与其他低血糖症区分开来。
