Gibson J M, Westwood M, Lauszus F F, Klebe J G, Flyvbjerg A, White A
Department of Medicine and School of Biological Sciences, University of Manchester, England, UK.
Diabetes. 1999 Feb;48(2):321-6. doi: 10.2337/diabetes.48.2.321.
During pregnancy, IGFs and their binding proteins (IGFBPs) are important for the growth of fetal and maternal tissues. IGFBP-1 normally circulates as a single, highly phosphorylated species (hpIGFBP-1). However, in pregnancy there are lesser phosphorylated isoforms (lpIGFBP-1) with decreased affinity for IGF-I, allowing for increased IGF bioavailability. Because regulation of IGFBP-1 is abnormal in type 1 diabetes, we examined the impact of this on IGFBP-1 and its phosphorylation status in diabetic pregnancy. We assessed IGFBP-1 in relation to birth weight, maternal weight gain, duration of diabetes, glycemic control, and the presence or absence of retinopathy in 44 diabetic and 11 nondiabetic subjects. We found that in type 1 diabetic patients there was a significant negative relationship between hpIGFBP-1 and birth weight (r = -0.42, P < 0.01) and between the ratio of hpIGFBP-1 to lpIGFBP-1 and birth weight (r = -0.38, P = 0.02) by week 18 of gestation. Multiple regression analysis confirmed that hpIGFBP-1 was the best single predictor of birth weight (R2 = 0.3, P = 0.001) in diabetic subjects using models including other parameters known to influence fetal size. In contrast to hpIGFBP-1 levels, lpIGFBP-1 levels were not associated with birth weight, but were significantly related to initial maternal BMI and maternal weight throughout gestation in diabetic subjects (r = -0.57, P < 0.001). hpIGFBP-1 levels were positively related to duration of diabetes (r = 0.38, P < 0.01). Diabetic subjects had significantly higher hpIGFBP-1 and lpIGFBP-1 levels than nondiabetic subjects (hpIGFBP-1: 215 +/- 21 vs. 108 +/- 13 microg/l, P = 0.01; lpIGFBP-1: 139 +/- 12 vs. 66 +/- 5 microg/l, P < 0.001), but the ratio of hpIGFBP-1 to lpIGFBP-1 was similar in both groups (2.1 +/- 0.3 [diabetic] vs. 1.7 +/- 0.2 [nondiabetic], NS). In summary, maternal IGFBP-1 levels were higher in diabetic than in normal pregnancies. Diabetic subjects with prolonged duration of diabetes and retinopathy had higher total IGFBP-1 levels than those with shorter disease duration. Thus hpIGFBP-1 in diabetic pregnancy is positively related to the duration of diabetes and inversely related to fetal growth, with lpIGFBP-1 being related to maternal weight and BMI. The ratio of hpIGFBP-1 to lpIGFBP-1 may be a more robust indicator of fetal outcome, since it was consistent between diabetic and nondiabetic subjects. Measurement of the different phosphorylated isoforms of IGFBP-1 may increase the usefulness of IGFBP-1 as a predictor of fetal growth in both normal and diabetic pregnancy.
在孕期，胰岛素样生长因子（IGFs）及其结合蛋白（IGFBPs）对胎儿和母体组织的生长至关重要。IGFBP - 1通常以单一的、高度磷酸化的形式（hpIGFBP - 1）循环。然而，在孕期存在磷酸化程度较低的异构体（lpIGFBP - 1），其对IGF - I的亲和力降低，从而使IGF的生物利用度增加。由于1型糖尿病患者中IGFBP - 1的调节异常，我们研究了其对糖尿病妊娠中IGFBP - 1及其磷酸化状态的影响。我们评估了44例糖尿病患者和11例非糖尿病患者中IGFBP - 1与出生体重、母体体重增加、糖尿病病程、血糖控制以及视网膜病变的有无之间的关系。我们发现，在1型糖尿病患者中，妊娠18周时hpIGFBP - 1与出生体重之间存在显著的负相关（r = -0.42，P < 0.01），hpIGFBP - 1与lpIGFBP - 1的比值与出生体重之间也存在负相关（r = -0.38，P = 0.02）。多元回归分析证实，在使用包含其他已知影响胎儿大小的参数的模型时，hpIGFBP - 1是糖尿病患者出生体重的最佳单一预测指标（R2 = 0.3，P = 0.001）。与hpIGFBP - 1水平相反，lpIGFBP - 1水平与出生体重无关，但与糖尿病患者的初始母体BMI和整个孕期的母体体重显著相关（r = -0.57，P < 0.001）。hpIGFBP - 1水平与糖尿病病程呈正相关（r = 0.38，P < 0.01）。糖尿病患者的hpIGFBP - 1和lpIGFBP - 1水平显著高于非糖尿病患者（hpIGFBP - 1：215±21 vs. 108±13μg/l，P = 0.01；lpIGFBP - 1：139±12 vs. 66±5μg/l，P < 0.001），但两组中hpIGFBP - 1与lpIGFBP - 1的比值相似（糖尿病组为2.1±0.3，非糖尿病组为1.7±0.2，无显著性差异）。总之，糖尿病孕妇的母体IGFBP - 1水平高于正常妊娠。糖尿病病程长且有视网膜病变的患者总IGFBP - 1水平高于病程短的患者。因此，糖尿病妊娠中的hpIGFBP - 1与糖尿病病程呈正相关，与胎儿生长呈负相关，lpIGFBP - 1与母体体重和BMI相关。hpIGFBP - 1与lpIGFBP - 1的比值可能是更可靠的胎儿结局指标，因为它在糖尿病患者和非糖尿病患者中是一致的。测量IGFBP - 1的不同磷酸化异构体可能会增加IGFBP - 1作为正常和糖尿病妊娠中胎儿生长预测指标的有用性。
