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.
Keywords
Gestational diabetes - blood pressure - insulin resistance - circulating insulin levels
