Jovanovic-Peterson L, Meisel B, Bevier W, Peterson C M
Sansum Medical Research Foundation, Santa Barbara, CA 93105, USA.
Am J Perinatol. 1997 Apr;14(4):181-6. doi: 10.1055/s-2007-994123.
Women with gestational diabetes tend to progress to noninsulin-dependent diabetes (NIDDM) with a high cumulative incidence relative to the general population. These women have also been shown to be insulin resistant and may represent a variant of the insulin resistance syndrome or Syndrome X. Our previous studies indicated that administered insulin was associated with an increase in blood pressure in women with gestational diabetes, raising the question that insulin levels per se contribute to blood pressure in these women. We developed a means by which the insulin levels of a given pregnant individual might be estimated called the Fraction of Circulating Insulin Level Relative to Normal (FOCILRN = C-PEPTIDE/2.0 + TOTAL DAILY INSULIN DOSE/CALCULATED DAILY INSULIN REQUIREMENT BASED ON WEIGHT AND GESTATIONAL WEEK). The formula was applied to 15 nonhypertensive pregnant women of comparable obese phenotype (Rubenesque) with varying degrees of glucose tolerance (4 normal, 5 gestational diabetes treated with diet alone, 4 gestational diabetes treated with insulin, and 2 noninsulin-dependent diabetes). Blood pressure was quantified at the beginning of the study (gestational weeks 24-34) and again 4-8 weeks later using a 24-hr monitor. Correlation analysis was used to test for a relationship between the FOCILRN and blood pressure. The increase in mean arterial pressure was found to be continuous and linear with increasing insulin exposure as quantified by FOCILRN. The correlation was significant for all subjects (r = 0.961, p < 0.001) and remained significant even with removal of patients with NIDDM (r = 0.857, p < 0.001). The nighttime heart rate, systolic and diastolic blood pressures were found to be significantly correlated with FOCILRN (r = 0.651, p < 0.01, r = 0.724, p < 0.001, and r = 0.831, p < 0.001, respectively). The difference between the maximum and minimum diastolic blood pressure values between 12:00 AM and 6:00 AM between sessions 1 and 2 significantly differed among the groups with women on insulin having the highest FOCILRN having the least variation in blood pressure. In nonhypertensive women of obese phenotype (Rubenesque), increasing insulin exposure is associated with increasing mean arterial blood pressure and less variability of nocturnal blood pressure. These data provide support for the hypothesis that insulin may mediate blood pressure response in genetically vulnerable individuals. The identification of the Rubenesque phenotype during gestation may be a clinically useful marker for individuals at risk for Syndrome X.
妊娠糖尿病女性相较于普通人群，发展为非胰岛素依赖型糖尿病（NIDDM）的累积发病率较高。这些女性也已被证明存在胰岛素抵抗，可能代表胰岛素抵抗综合征或X综合征的一种变体。我们之前的研究表明，给予胰岛素会使妊娠糖尿病女性的血压升高，这就提出了一个问题，即胰岛素水平本身是否会导致这些女性的血压升高。我们开发了一种方法来估计特定孕妇的胰岛素水平，称为循环胰岛素水平相对于正常水平的分数（FOCILRN = C肽/2.0 + 每日胰岛素总剂量/根据体重和孕周计算的每日胰岛素需求量）。该公式应用于15名具有相似肥胖体型（鲁本斯体型）、不同程度糖耐量的非高血压孕妇（4名血糖正常者、5名单纯饮食治疗的妊娠糖尿病患者、4名胰岛素治疗的妊娠糖尿病患者和2名非胰岛素依赖型糖尿病患者）。在研究开始时（妊娠24 - 34周）使用24小时监测仪测量血压，4 - 8周后再次测量。采用相关分析来检验FOCILRN与血压之间的关系。结果发现，平均动脉压的升高与FOCILRN所量化的胰岛素暴露增加呈连续线性关系。所有受试者的相关性均显著（r = 0.961，p < 0.001），即使去除非胰岛素依赖型糖尿病患者，相关性仍然显著（r = 0.857，p < 0.001）。发现夜间心率、收缩压和舒张压与FOCILRN显著相关（分别为r = 0.651，p < 0.01；r = 0.724，p < 0.001；r = 0.831，p < 0.001）。在第1次和第2次测量期间，凌晨12点至6点之间舒张压的最大值和最小值之差在各组之间存在显著差异，使用胰岛素的女性FOCILRN最高，其血压变化最小。在具有肥胖体型（鲁本斯体型）的非高血压女性中，胰岛素暴露增加与平均动脉血压升高以及夜间血压变异性降低有关。这些数据为胰岛素可能在基因易感性个体中介导血压反应的假说提供了支持。在妊娠期识别鲁本斯体型可能是X综合征风险个体的一个临床有用标志物。
