0021-972x/92/7502-0508$03.00/0 Journal of Clinical Endocrinology and Metabolism Copyright 0 1992 by The Endocrine Society
Polycystic Ovary Despite Profound
Vol. 75, No. 2 Printed in U.S.A.
Syndrome: Lack of Hypertension Insulin Resistance*
SEBASTIAN ZIMMERMANN, ROBERT A. PHILLIPS?, DIANE T. FINEGOODS, CRAIG WILKENFELD, MARIA RICHARD GORLIN, AND LAWRENCE R. KRAKOFF
ANDREA DUNAIFS, ARDELJAN,
Divisions of Cardiology and Endocrinology, Department of Medicine, Mount Sinai School of Medicine, and the Departments of Medicine and Physiology, University of Alberta (D.T.F.), Edmonton, Alberta, Canada ABSTRACT It has been hypothesized that insulin resistance and hyperinsulinemia contribute to the development of arterial hypertension. To further investigate this relationship, we compared arterial blood pressure in controls and women with polycystic ovary syndrome (PCO), an insulinresistant state. Fourteen PC0 women and 18 normal control women of similar age, body mass index, and race were studied. Plasma glucose and insulin levels were determined in an oral glucose tolerance test. The insulin sensitivity (Si) index was determined by the minimal model method. Systolic and diastolic blood pressures were measured by 24-h ambulatory monitoring. Left ventricular mass was assessed by echo-
I
cardiography. The two groups had comparable fasting glucose levels, but the 2-h postload glucose was higher in PC0 (8.0 f 0.5 US. 5.6 + 0.3 mmol/L; P < 0.001). Compared to controls, PC0 women were significantly more insulin resistant by fasting insulin, 2-h insulin concentrations, and St (28.3 f 6.7 vs. 68.3 + 10.0 min-‘/nmol.mL; P < 0.01). Average ambulatory systolic (121? 2 vs. 118 & 2 mm Hg) and diastolic (76 Ifr 2 vs. 73 + 2 mm Hg) blood pressures were similar for PC0 and control women. No difference was found in left ventricular mass. Therefore, despite profound insulin resistance and hyperinsulinemia, women with PC0 do not have increased arterial pressure or left ventricular mass. (J Clin Endocrinol Metub 75: 508-513, 1992)
resistance,characterized by increased plasma insulin with normal glucose tolerance, has been demonstrated in nonobese hypertensive subjects (1, 2). In some Caucasianpopulations the degree of insulin resistance is related to the level of blood pressure (3-5). However, this relation is not uniform in all ethnic groups. The Pimas,Native Americans with a high prevalence of type II diabetes and insulin resistance,have no relationship between insulin and blood pressure. Similarly, a correlation between insulin action and blood pressurehas not been demonstrated in nonhypertensive African-Americans (6). Polycystic ovary syndrome (PCO) is a common disorder of women, characterized by chronic anovulation and hyperandrogenism as well as hyperinsulinemia and insulin resistance in the majority of affected subjects (7-11). However, unbiased and systematic evaluation of blood pressure has not been previously undertaken in this group. Therefore, to investigate the relationship of insulin resistance and hypertension we compared insulin action and blood pressure in women with PC0 and normal controls,
Materials and Methods
NSULIN
Received July 22, 1991. Address all correspondence and requests for reprints to: Dr. Robert A. Phillips, Divisions of Hypertension and Cardiology, Box 1085, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, New York 10029. * Presented in part at the 64th Scientific Sessions of the American Heart Association, Anaheim, CA, November 11-14, 1991. This work was supported by Grant RR-00071 from the NIH to the General Clinical Research Center and by the Heart Research Foundation (New York, NY). t Supported in part by grants from the Heart Research Foundation and the Sosnoff Foundation (New York, NY). $ Supported in part by Grant DK-40605 from the NIH and a grant from the American Diabetes Assocation. 5 Scholar of the Alberta Heritage Foundation for Medical Research.
Subjects Thirty-two healthy women of Caucasian or Caribbean (Dominican or Puerto Rican) origin, with an age range of 20-42 yr, were studied. All were nonsmokers, did not engage in regular physical exercise, and had stable weight throughout the course of the study. None was hypertensive, diabetic, or known to have any systemic illness. Oral contraceptives or fertility agents, if used, had not been taken for a minimum of 3 months before the study. Control subjects had 27- to 32-day menstrual cycles, and it was determined that they were ovulatory, based on a plasma progesterone level greater than 16 nmol/L in the luteal phase of their cycle. There was no difference in the menstrual or fertility history of obese and nonobese controls. Fourteen subjects had a diagnosis of PCO, which was based on biochemical documentation of hyperandrogenemia in conjunction with oligomenorrhea or six or fewer menses per yr (12). PC0 women were documented to be nonovulatory by plasma progesterone levels below 6.2 nmol/L 21 days after menses, if present. Hyperprolactinemia was excluded, and Cushing’s syndrome was excluded when clinically suspected by a 1-mg overnight dexamethasone suppression test or a normal 24-h urine for free cortisol determination. Nonclassical steroid 21hydroxylase deficiency was excluded by a l-h ACTH stimulation test in all PC0 women (13). Of the PC0 women, 10 were obese [body mass index (BMI), >27 kg/m’], and 4 were nonobese (BMI, >27 kg/m2, corresponds to an obesity level of 20% overweight based on 1959 Metropolitan Life Insurance tables for women). Eighteen healthy euthyroid and ovulatory women (12 obese and 6 nonobese) without hirsutism or elevated plasma androgen levels were selected as control subjects and matched to PC0 women for age, BMI, waist/hip ratio, and ethnicity.
Oral glucose tolerance
test
All subjects had a standard oral glucose tolerance test to assess glucose tolerance. After ingesting a 1.67-mol carbohydrate diet for 3 days and fasting for lo-12 h overnight, they received a 0.42-mol glucose load. Blood was sampled at 0, 30, 60, 90, and 120 min for determination of plasma glucose and insulin levels, 508
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PC0 AND Minimal
HYPERTENSION
model method
Insulin action was determined using Bergman’s minimal model, a method equivalent to the euglycemic glucose clamp for assessment of overall insulin sensitivity (14). Women ate a 300-mg carbohydrate diet for 3 days and fasted overnight (12 h) before a modified frequent sampling iv glucose tolerance test (FSIGT). After placement of two iv catheters, four basal samples were collected over 15 min, after which glucose (1.7 mmol/kg, iv bolus) was injected over 1 min. Twenty minutes after glucose administration, tolbutamide was given as an iv bolus (1.85 mmol in PC0 women, who were expected to be insulin resistant, and 1.1 mmol in control subjects). Blood specimens (3 cc) were collected at the following intervals: 0, 2, 3, 4, 5, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 90, and 100 min, then every 20 min thereafter until 300 min, to allow glucose levels to return to baseline. The insulin sensitivity index (Si) was calculated with the MINMOD computer program (copyright R. N. Bergman), from the insulin and glucose dvnamics obtained durine the FSIGT (15). The computer uro&-am applies the minimal model by considering the insulin dynam;c as input and finding the set of constant parameters (including Si) that results in the best fit of the plasma glucose curve during the glucose injection. Yang et al. (16) previously demonstrated that glucose alone does not result in an optimal insulin dynamic, Injection of tolbutamide, an insulin secretagogue, improves the insulin dynamic and significantly reduces the coefficient of variation of the Si estimate (16). To obtain an optimal insulin dynamic in all subjects, a differential tolbutamide dose (i.e. 1.1 mmol in the presumed insulin-sensitive normal women and 1.85 mmol in the presumed insulin-resistant PC0 women) was used, and subjects were excluded from the study if their integrated insulin output was less than 7.175 x lo3 pmol/L. min, since this level of insulin response is unacceptable for minimal model analysis (16).
509
Statistics All data are expressed as the mean + SE. Since ethnic differences influence the relationship between insulin resistance and blood pressure (6), we used a factorial design (24) for comparison to adjust for the four more Caucasians in our control group. The relation between the variables was analyzed by simple correlation. All statistical analyses were performed with programs from the SAS Institute (Cary, NC).
Results Clinical
and hormonal
characteristics
The two groups of PC0 women and controls consistedof young, moderately obese women, who were comparable in age, degree of overweight (BMI), body fat topography (waist/ hip ratio), and ethnic origin (Table 1). As part of their syndrome, PC0 women were expected to have significantly elevated levels of total and unbound plasma testosterone and androstenedione (Table 2). No difference was found in plasma norepinephrine, plasma renin, or atria1 natriuretic peptide concentrations (Table 2). Plasma epinephrine was significantly higher in PCO, but within the physiological range. Insulin
action and glucose metabolism
Twenty-four-hour blood pressure monitoring was performed using the SpaceLabs 90202 device (SpaceLabs, Inc., Redmond, WA) (17). Subjects were monitored on a day of typical weekly activity. Since blood pressure is not known to be affected by the menstrual cycle, control subjects were studied at random phases of the cycle. For calibration, the device was connected to an aneroid sphygmomanometer with a Y-tube. Three consecutive measurements were taken, 5 min apart (casual blood pressure), in a seated position and calibrated to the monitor readings. Recordings were made every 20 min until 2400 h (midnight) and every 60 min from 2400-0600 h.
PC0 and controls differed significantly in their response to oral glucose. In the fasting state, plasma glucose levels were similar in the two groups, and all women were normoglycemic. However, plasma insulin was higher in PC0 (Table 3 and Fig. 1). Two hours after the glucose load, the plasma glucose level in the PC0 group was nearly 1.4 times that in controls, but plasma insulin was approximately 5 times that in the control group, confirming that PC0 women are hyperinsulinemic (22). Of the PC0 group, one woman had noninsulin-dependent diabetes mellitus, and two had impaired glucose tolerance, according to the National Dia-
Echocardiography
TABLE
Blood pressure
Two-dimensionally guided M-mode echocardiography was performed with an ATL Mark 600 or ATL Ultramark 6 scanner (Advanced Technology Laboratories, Inc., Bothell, WA), using a 2.5- or 3.0-mHz transducer. Studies were either recorded on videotape or directly stored in digital form on floppy disks. Studies were performed and analyzed bv two echocardioerauhers who were unaware of the subjects PC0 scatus or blood p&sure. Left ventricular mass was measured and calculated according to the Penn convention (18). All studies were digitized for analysis (Color Vue II, Nova MicroSonics, Advanced Technology Laboratory)
1. Clinical
characteristics
of PC0
and controls
PC0 (n = 14) Age
Values
are the mean
TABLE
2. Hormones
or
31 * 1117 80 f 30 rtr 0.77 +
1 4 2 0.02
+ SE. in PC0
women
and controls
PC0 Testosterone (nmol/L) UT (nmol/L) Androstenedione (nmol/L) DHEAS (umol/L) Norepinephrine (nmol/L) Epinephrine (pmol/L) Plasma renin (rig/L . s) ANP bg/mL)
Controls (n = 18)
30 + 1 717 79 k 6 31 + 2 0.82 + 0.02
(yr)
Race (caucasian/hispanic) Wt (kg) BMI (kg/m*) Waist/hip ratio
Assays Blood samples for plasma epinephrine, norepinephrine, PRA, and atria1 natriuretic peptide (ANP) determinations were drawn from an indwelling forearm venous catheter after subjects had been supine for at least 30 min. Plasma catecholamines were determined by high pressure liquid chromatography with a cation exchange column-and an electrochemical detector (19). The following were determined by previously reported methods: PRA (20); ANPI(21); insulin (11, 22); and plasma levels of testosterone, androstenedione, testosterone, nonsex hormone-binding globulin (unbound) testosterone, and dehydroepiandrosterone sulfate (22, 23). Plasma glucose was determined by the glucose oxidase technique with a Beckman Glucose Analyzer 2 (Fullerton, CA).
women
1.9 0.5 7.9 4.5 1.1 158 1.3 23
+ f f + f + + i
P value
Controls
0.1 0.05 0.8 0.6 0.1 21 0.3 4
1.0 0.2 4.7 4.6 1.3 98 1.0 30
+ + * + + + + +
0.1 0.03 0.4 0.4 0.1 16 0.1 5
Values are the mean f SE. ANP, Atria1 natriuretic peptide; dehydroepiandrosterone sulfate; UT, nonsex hormone-binding lin-bound (unbound) testosterone.
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co.01 co.01 co.01 NS NS co.05 NS NS DHEAS, globu-
ZIMMERMANN
510 TABLE
3. Insulin
action
in PC0
women
Controls
P value
5.1 + 0.2 8.0 + 0.5
4.9 f 0.1 5.6 f 0.3
NS
Polycystic Ovary Despite Profound
Vol. 75, No. 2 Printed in U.S.A.
Syndrome: Lack of Hypertension Insulin Resistance*
SEBASTIAN ZIMMERMANN, ROBERT A. PHILLIPS?, DIANE T. FINEGOODS, CRAIG WILKENFELD, MARIA RICHARD GORLIN, AND LAWRENCE R. KRAKOFF
ANDREA DUNAIFS, ARDELJAN,
Divisions of Cardiology and Endocrinology, Department of Medicine, Mount Sinai School of Medicine, and the Departments of Medicine and Physiology, University of Alberta (D.T.F.), Edmonton, Alberta, Canada ABSTRACT It has been hypothesized that insulin resistance and hyperinsulinemia contribute to the development of arterial hypertension. To further investigate this relationship, we compared arterial blood pressure in controls and women with polycystic ovary syndrome (PCO), an insulinresistant state. Fourteen PC0 women and 18 normal control women of similar age, body mass index, and race were studied. Plasma glucose and insulin levels were determined in an oral glucose tolerance test. The insulin sensitivity (Si) index was determined by the minimal model method. Systolic and diastolic blood pressures were measured by 24-h ambulatory monitoring. Left ventricular mass was assessed by echo-
I
cardiography. The two groups had comparable fasting glucose levels, but the 2-h postload glucose was higher in PC0 (8.0 f 0.5 US. 5.6 + 0.3 mmol/L; P < 0.001). Compared to controls, PC0 women were significantly more insulin resistant by fasting insulin, 2-h insulin concentrations, and St (28.3 f 6.7 vs. 68.3 + 10.0 min-‘/nmol.mL; P < 0.01). Average ambulatory systolic (121? 2 vs. 118 & 2 mm Hg) and diastolic (76 Ifr 2 vs. 73 + 2 mm Hg) blood pressures were similar for PC0 and control women. No difference was found in left ventricular mass. Therefore, despite profound insulin resistance and hyperinsulinemia, women with PC0 do not have increased arterial pressure or left ventricular mass. (J Clin Endocrinol Metub 75: 508-513, 1992)
resistance,characterized by increased plasma insulin with normal glucose tolerance, has been demonstrated in nonobese hypertensive subjects (1, 2). In some Caucasianpopulations the degree of insulin resistance is related to the level of blood pressure (3-5). However, this relation is not uniform in all ethnic groups. The Pimas,Native Americans with a high prevalence of type II diabetes and insulin resistance,have no relationship between insulin and blood pressure. Similarly, a correlation between insulin action and blood pressurehas not been demonstrated in nonhypertensive African-Americans (6). Polycystic ovary syndrome (PCO) is a common disorder of women, characterized by chronic anovulation and hyperandrogenism as well as hyperinsulinemia and insulin resistance in the majority of affected subjects (7-11). However, unbiased and systematic evaluation of blood pressure has not been previously undertaken in this group. Therefore, to investigate the relationship of insulin resistance and hypertension we compared insulin action and blood pressure in women with PC0 and normal controls,
Materials and Methods
NSULIN
Received July 22, 1991. Address all correspondence and requests for reprints to: Dr. Robert A. Phillips, Divisions of Hypertension and Cardiology, Box 1085, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, New York 10029. * Presented in part at the 64th Scientific Sessions of the American Heart Association, Anaheim, CA, November 11-14, 1991. This work was supported by Grant RR-00071 from the NIH to the General Clinical Research Center and by the Heart Research Foundation (New York, NY). t Supported in part by grants from the Heart Research Foundation and the Sosnoff Foundation (New York, NY). $ Supported in part by Grant DK-40605 from the NIH and a grant from the American Diabetes Assocation. 5 Scholar of the Alberta Heritage Foundation for Medical Research.
Subjects Thirty-two healthy women of Caucasian or Caribbean (Dominican or Puerto Rican) origin, with an age range of 20-42 yr, were studied. All were nonsmokers, did not engage in regular physical exercise, and had stable weight throughout the course of the study. None was hypertensive, diabetic, or known to have any systemic illness. Oral contraceptives or fertility agents, if used, had not been taken for a minimum of 3 months before the study. Control subjects had 27- to 32-day menstrual cycles, and it was determined that they were ovulatory, based on a plasma progesterone level greater than 16 nmol/L in the luteal phase of their cycle. There was no difference in the menstrual or fertility history of obese and nonobese controls. Fourteen subjects had a diagnosis of PCO, which was based on biochemical documentation of hyperandrogenemia in conjunction with oligomenorrhea or six or fewer menses per yr (12). PC0 women were documented to be nonovulatory by plasma progesterone levels below 6.2 nmol/L 21 days after menses, if present. Hyperprolactinemia was excluded, and Cushing’s syndrome was excluded when clinically suspected by a 1-mg overnight dexamethasone suppression test or a normal 24-h urine for free cortisol determination. Nonclassical steroid 21hydroxylase deficiency was excluded by a l-h ACTH stimulation test in all PC0 women (13). Of the PC0 women, 10 were obese [body mass index (BMI), >27 kg/m’], and 4 were nonobese (BMI, >27 kg/m2, corresponds to an obesity level of 20% overweight based on 1959 Metropolitan Life Insurance tables for women). Eighteen healthy euthyroid and ovulatory women (12 obese and 6 nonobese) without hirsutism or elevated plasma androgen levels were selected as control subjects and matched to PC0 women for age, BMI, waist/hip ratio, and ethnicity.
Oral glucose tolerance
test
All subjects had a standard oral glucose tolerance test to assess glucose tolerance. After ingesting a 1.67-mol carbohydrate diet for 3 days and fasting for lo-12 h overnight, they received a 0.42-mol glucose load. Blood was sampled at 0, 30, 60, 90, and 120 min for determination of plasma glucose and insulin levels, 508
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PC0 AND Minimal
HYPERTENSION
model method
Insulin action was determined using Bergman’s minimal model, a method equivalent to the euglycemic glucose clamp for assessment of overall insulin sensitivity (14). Women ate a 300-mg carbohydrate diet for 3 days and fasted overnight (12 h) before a modified frequent sampling iv glucose tolerance test (FSIGT). After placement of two iv catheters, four basal samples were collected over 15 min, after which glucose (1.7 mmol/kg, iv bolus) was injected over 1 min. Twenty minutes after glucose administration, tolbutamide was given as an iv bolus (1.85 mmol in PC0 women, who were expected to be insulin resistant, and 1.1 mmol in control subjects). Blood specimens (3 cc) were collected at the following intervals: 0, 2, 3, 4, 5, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 90, and 100 min, then every 20 min thereafter until 300 min, to allow glucose levels to return to baseline. The insulin sensitivity index (Si) was calculated with the MINMOD computer program (copyright R. N. Bergman), from the insulin and glucose dvnamics obtained durine the FSIGT (15). The computer uro&-am applies the minimal model by considering the insulin dynam;c as input and finding the set of constant parameters (including Si) that results in the best fit of the plasma glucose curve during the glucose injection. Yang et al. (16) previously demonstrated that glucose alone does not result in an optimal insulin dynamic, Injection of tolbutamide, an insulin secretagogue, improves the insulin dynamic and significantly reduces the coefficient of variation of the Si estimate (16). To obtain an optimal insulin dynamic in all subjects, a differential tolbutamide dose (i.e. 1.1 mmol in the presumed insulin-sensitive normal women and 1.85 mmol in the presumed insulin-resistant PC0 women) was used, and subjects were excluded from the study if their integrated insulin output was less than 7.175 x lo3 pmol/L. min, since this level of insulin response is unacceptable for minimal model analysis (16).
509
Statistics All data are expressed as the mean + SE. Since ethnic differences influence the relationship between insulin resistance and blood pressure (6), we used a factorial design (24) for comparison to adjust for the four more Caucasians in our control group. The relation between the variables was analyzed by simple correlation. All statistical analyses were performed with programs from the SAS Institute (Cary, NC).
Results Clinical
and hormonal
characteristics
The two groups of PC0 women and controls consistedof young, moderately obese women, who were comparable in age, degree of overweight (BMI), body fat topography (waist/ hip ratio), and ethnic origin (Table 1). As part of their syndrome, PC0 women were expected to have significantly elevated levels of total and unbound plasma testosterone and androstenedione (Table 2). No difference was found in plasma norepinephrine, plasma renin, or atria1 natriuretic peptide concentrations (Table 2). Plasma epinephrine was significantly higher in PCO, but within the physiological range. Insulin
action and glucose metabolism
Twenty-four-hour blood pressure monitoring was performed using the SpaceLabs 90202 device (SpaceLabs, Inc., Redmond, WA) (17). Subjects were monitored on a day of typical weekly activity. Since blood pressure is not known to be affected by the menstrual cycle, control subjects were studied at random phases of the cycle. For calibration, the device was connected to an aneroid sphygmomanometer with a Y-tube. Three consecutive measurements were taken, 5 min apart (casual blood pressure), in a seated position and calibrated to the monitor readings. Recordings were made every 20 min until 2400 h (midnight) and every 60 min from 2400-0600 h.
PC0 and controls differed significantly in their response to oral glucose. In the fasting state, plasma glucose levels were similar in the two groups, and all women were normoglycemic. However, plasma insulin was higher in PC0 (Table 3 and Fig. 1). Two hours after the glucose load, the plasma glucose level in the PC0 group was nearly 1.4 times that in controls, but plasma insulin was approximately 5 times that in the control group, confirming that PC0 women are hyperinsulinemic (22). Of the PC0 group, one woman had noninsulin-dependent diabetes mellitus, and two had impaired glucose tolerance, according to the National Dia-
Echocardiography
TABLE
Blood pressure
Two-dimensionally guided M-mode echocardiography was performed with an ATL Mark 600 or ATL Ultramark 6 scanner (Advanced Technology Laboratories, Inc., Bothell, WA), using a 2.5- or 3.0-mHz transducer. Studies were either recorded on videotape or directly stored in digital form on floppy disks. Studies were performed and analyzed bv two echocardioerauhers who were unaware of the subjects PC0 scatus or blood p&sure. Left ventricular mass was measured and calculated according to the Penn convention (18). All studies were digitized for analysis (Color Vue II, Nova MicroSonics, Advanced Technology Laboratory)
1. Clinical
characteristics
of PC0
and controls
PC0 (n = 14) Age
Values
are the mean
TABLE
2. Hormones
or
31 * 1117 80 f 30 rtr 0.77 +
1 4 2 0.02
+ SE. in PC0
women
and controls
PC0 Testosterone (nmol/L) UT (nmol/L) Androstenedione (nmol/L) DHEAS (umol/L) Norepinephrine (nmol/L) Epinephrine (pmol/L) Plasma renin (rig/L . s) ANP bg/mL)
Controls (n = 18)
30 + 1 717 79 k 6 31 + 2 0.82 + 0.02
(yr)
Race (caucasian/hispanic) Wt (kg) BMI (kg/m*) Waist/hip ratio
Assays Blood samples for plasma epinephrine, norepinephrine, PRA, and atria1 natriuretic peptide (ANP) determinations were drawn from an indwelling forearm venous catheter after subjects had been supine for at least 30 min. Plasma catecholamines were determined by high pressure liquid chromatography with a cation exchange column-and an electrochemical detector (19). The following were determined by previously reported methods: PRA (20); ANPI(21); insulin (11, 22); and plasma levels of testosterone, androstenedione, testosterone, nonsex hormone-binding globulin (unbound) testosterone, and dehydroepiandrosterone sulfate (22, 23). Plasma glucose was determined by the glucose oxidase technique with a Beckman Glucose Analyzer 2 (Fullerton, CA).
women
1.9 0.5 7.9 4.5 1.1 158 1.3 23
+ f f + f + + i
P value
Controls
0.1 0.05 0.8 0.6 0.1 21 0.3 4
1.0 0.2 4.7 4.6 1.3 98 1.0 30
+ + * + + + + +
0.1 0.03 0.4 0.4 0.1 16 0.1 5
Values are the mean f SE. ANP, Atria1 natriuretic peptide; dehydroepiandrosterone sulfate; UT, nonsex hormone-binding lin-bound (unbound) testosterone.
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co.01 co.01 co.01 NS NS co.05 NS NS DHEAS, globu-
ZIMMERMANN
510 TABLE
3. Insulin
action
in PC0
women
Controls
P value
5.1 + 0.2 8.0 + 0.5
4.9 f 0.1 5.6 f 0.3
NS
