THE RUBENESQUE PREGNANCY - A PROGRESSION TOWARDS HIGHER BLOOD-PRESSURE CORRELATES WITH A MEASURE OF ENDOGENOUS AND EXOGENOUS INSULIN LEVELS

Women with gestational diabetes tend to progress to noninsulin-depende nt diabetes (NIDDM) with a high cumulative incidence relative to the g eneral population. These women have also been shown to be insulin resi stant and may represent a variant of the insulin resistance syndrome o r Syndrome X. Our previous studies indicated that administered insulin was associated with an increase in blood pressure in women with gesta tional diabetes, raising the question that insulin levels per se contr ibute to blood pressure in these women. We developed a means by which the insulin levels of a given pregnant individual might be estimated c alled the Fraction of Circulating Insulin Level Relative to Normal (FO CILRN = C-PEPTIDE/2.0 + TOTAL DAILY INSULIN DOSE/CALCULATED DAILY INSU LIN REQUIREMENT BASED ON WEIGHT AND GESTATIONAL WEEK). The formula was applied to 15 nonhypertensive pregnant women of comparable obese phen otype (Rubenesque) with varying degrees of glucose tolerance (4 normal , 5 gestational diabetes treated with diet alone, 4 gestational diabet es treated with insulin, and 2 noninsulin-dependent diabetes). Blood p ressure was quantified at the beginning of the study (gestational week s 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 b lood pressure. The increase in mean arterial pressure was found to be continuous and linear with increasing insulin exposure as quantified b y FOCILRN. The correlation was significant for all subjects (r = 0.961 , p < 0.001) and remained significant even with removal of patients wi th NIDDM (r = 0.857, p < 0.001). The nighttime heart rate, systolic an d 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 min imum diastolic blood pressure values between 12:00 AM and 6:00 AM betw een sessions 1 and 2 significantly differed among the groups with wome n on insulin having the highest FOCILRN having the least variation in blood pressure. In nonhypertensive women of obese phenotype (Rubenesqu e), increasing insulin exposure is associated with increasing mean art erial blood pressure and less variability of nocturnal blood pressure. These data provide support for the hypothesis that insulin may mediat e blood pressure response in genetically vulnerable individuals. The i dentification of the Rubenesque phenotype during gestation may be a cl inically useful marker for individuals at risk for Syndrome X.