The Rubenesque pregnancy: a progression towards higher blood pressure correlates with a measure of endogenous and exogenous insulin levels

Abstract

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.