OBJECTIVE Hyperinsulinaemic women with the polycystic ovary syndrome (PCOS) may be at increased risk of vascular disease later in life, mediated by blood pressure or lipid abnormalities or by elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity. PAI-1 may also be involved in ovarian follicle development and ovarian connective tissue remodelling. We measured plasma PAI-1 activity and 24-hour ambulatory blood pressure records in women with and without PCOS.

DESIGN Cross-sectional study of three groups.

PATIENTS Twenty-four non-obese women with a classic ovarian ultrasound appearance of PCO and extreme menstrual disturbance (Group 1), 26 matched controls with a normal menstrual cycle and an ultrasound appearance of PCO (Group 2) and 10 matched controls with a normal menstrual cycle and normal ovarian ultrasound (Group 3).

MEASUREMENTS Twenty-four hour ambulatory blood pressure recordings (Spacelabs 90207), ovarian ultrasonography, fasting plasma insulin and glucose, plasma PAI-1 activity, HDL and total cholesterol, triglycerides, gonadotrophins and testosterone. Family history of premature vascular disease.

RESULTS Median fasting plasma insulin was significantly higher in Group 1 (45 .8 pmol/l, range 12.9–161.9) than in Group 2 (28.1 pmol/l; range 13.6–91; P <0.05) or Group 3 (26.0 pmol/l; range 13.5–63.3; P <0.05). There were no differences between groups in 24-hour, daytime or night-time ambulatory blood pressure measurements, and no relation between plasma insulin and any blood pressure variable.  Mean plasma PAI-1 activity was higher in Group 1 (10.0 ±7.1 AU/l) than in Group 2 (6.0 ±4.6 AU/l P < 0.05) or Group 3 (5.1 ± 3.5 AU/l; P =0.06). There was a significant independent direct relation between fasting plasma insulin and PAI-activity (r = 0.41, R2 = 0.154; F1,59 = 11.38; P = 0.001). Groups did not differ in parental history of premature vascular disease, or in mean HDL or fasting triglyceride levels.

CONCLUSIONS The only measurable vascular risk factor associated with hyperinsulinaemia and menstrual disturbance in non-obese women with PCOS is an elevated plasma PAI-1 activity. These women did not differ from controls in ambulatory blood pressure profiles, lipid measurements or in a parental history of premature vascular disease. PAI-1 and plasminogen are involved in ovarian follicle maturation and the present finding suggests a biologically plausible link between hyperinsulinaemia, anovulation and vascular risk in PCOS.

Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI-1) activity in lean women with and without the polycystic ovary syndrome.

Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women

To define the physiological relationships between cardiovascular function, glucose regulation, and insulin secretion, we submitted nine young normotensive subjects to ambulatory blood pressure monitoring and blood sampling at 20-minute intervals for 24 hours to measure glucose, insulin, C peptide, cortisol, and growth hormone. Subjects ingested three identical carbohydrate-rich meals in the morning (8:30 AM), early afternoon (2 PM), and evening (8 PM). On the following day, they underwent an intravenous glucose tolerance test for quantification of insulin sensitivity. Significant postmeal increases in systolic pressure averaging 18 +/- 10 mm Hg in the morning, 18 +/- 8 mm Hg in the early afternoon, and 26 +/- 19 mm Hg in the evening were observed. Postprandial variations in diastolic pressure and heart rate were significant only for the morning meal. The magnitude of the postprandial increases in systolic pressure was correlated with the amount of insulin secreted in the morning but not later in the day. Pulses of growth hormone consistently occurred 3 to 4 hours after the morning and midday meals, as well as after the onset of sleep. Our findings indicate that under normal conditions, there is a quantitative relationship between postprandial insulin secretion and blood pressure.

Diurnal Variations in Cardiovascular Function and Glucose Regulation in Normotensive Humans

Insulin resistance is generally interpreted as the physiological state under which insulin causes a reduced glucose-lowering effect. Hyperinsulinaemia is considered to be a result of insulin resistance. Many recent studies have suggested that hyperinsulinaemia and/or insulin resistance is associated with an elevated blood pressure, whereas several other studies have found a modest or no association. Many factors (e.g. adiposity, age, ethnic difference) have been suggested to confound the insulin-blood pressure relationship. Insulin is thought to raise blood pressure by a few possible mechanisms (e.g. stimulating sympathetic nervous system activity, enhancing renal tubular sodium reabsorption). On the other hand, insulin has also been reported to possess a vasodilatory property. Neither an insulin infusion within a physiological range nor continuously sustained hyperinsulinaemia in patients with insulinoma are associated with elevated blood pressure. Therefore, the relationship between insulin and blood pressure is still under discussion. Among the antihypertensive drugs, angiotensin converting enzyme (ACE) inhibitors seem to have marginal effects of improving insulin sensitivity, but whether this effect would lead to a better prognosis for diabetic patients remains to be proven. Lipid lowering drugs appear to show no benefit in lowering blood glucose.

The link between insulin resistance and hypertension : effects of antihypertensive and antihyperlipidaemic drugs on insulin sensitivity

Hyperinsulinemia, Family History of Hypertension, and Essential Hypertension

In order to investigate the relationship between ambulatory blood pressure values and fasting plasma insulin, non-invasive, 24-h blood pressure monitoring was performed in 32 young normotensive males. Systolic and diastolic blood pressures were averaged for awake and asleep periods. Fasting plasma insulin levels correlated significantly with both asleep (r = 0.61; P less than 0.001) and awake (r = 0.44; P less than 0.02) systolic blood pressure, but not with casual systolic blood pressure (r = 0.27). There were no significant associations between awake, asleep and casual diastolic blood pressure, and fasting plasma insulin levels (r = 0.15, 0.05 and 0.21, respectively). These results support the hypothesis that insulin may be a physiological determinant of blood pressure.

Relationship between fasting plasma insulin and ambulatory blood pressure in young, non-obese normotensive subjects.

In order to investigate the relation of ambulatory blood pressure values to fasting plasma insulin, non-invasive 24-hour blood pressure monitoring was performed in 32 young normotensive males. Systolic and diastolic blood pressures were averaged for awake and asleep periods. Fasting plasma insulin levels correlated significantly with both asleep (r = 0.61; p < 0.001) and awake systolic blood pressures (r = 0.44; p < 0.02) but not with casual systolic blood pressure (r = 0.27). There were no significant associations of awake, asleep and causal diastolic blood pressures values with fasting plasma insulin levels (r = 0.15, 0.05 and 0.21, respectively). These results support the hypothesis that insulin may be a physiological determinant of blood pressure.

A Kubasik

Papers

Relationship between fasting plasma insulin and ambulatory blood pressure in young, non-obese normotensive subjects.

Levels of insulin in serum during fasting and circadian blood pressure profile in young health men