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Biomedical subjects

B Falkner

Publications and source records attributed to B Falkner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group.

Because obesity-associated hypertension has unique hemodynamic and hormonal profiles, certain classes of antihypertensive agents may be more effective than others as monotherapy. Thus, we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week, multicenter, double-blind trial in 232 obese patients with hypertension. Patients with an office diastolic pressure between 90 and 109 mm Hg were randomized to treatment with daily doses of lisinopril (10, 20, or 40 mg), hydrochlorothiazide (12.5, 25, or 50 mg), or placebo. Mean body mass indexes were similar for all patients. At week 12, lisinopril and hydrochlorothiazide effectively lowered office diastolic (-8.3 and -7.7 versus -3.3 mm Hg, respectively; P<.005) and systolic (-9.2 and -10.0 versus -4.6 mm Hg, respectively; P<.05) pressures compared with placebo. Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo (P<.001). Significant dose-response differences were observed between treatments. Sixty percent of patients treated with lisinopril had an office diastolic pressure <90 mm Hg compared with 43% of patients treated with hydrochlorothiazide (P<.05). Responses to therapies differed with both race and age. Neither treatment significantly affected insulin or lipid profiles; however, plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril (+0.31 versus -0.21 mmol/L; P<.001). Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline. In conclusion, lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension. Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics, may have a more rapid rate of response, and may offer advantages in patients at high risk of metabolic disorders.

Adult↗
PubMed1996

Gender differences in insulin-induced free fatty acid suppression: studies in an African American population.

This study of African Americans (AA) was designed to investigate gender differences in insulin-induced free fatty acid (FFA) suppression. Sixty AA (34 women, mean age 34 +/- 7.6 years, and 26 men, mean age 30 +/- 2.9 years) participated. All subjects had an oral glucose tolerance test (OGTT). Nineteen women and 18 men also underwent a euglycemic hyperinsulinemic clamp (IC) study. Plasma insulin and FFA concentrations were obtained during both tests at 0, 60, and 120 min. While there was no gender difference in body mass index (P = 0.21), women had greater percent body fat (P < 0.001) calculated by the Siri formula. There was no gender difference in fasting FFA levels, but during the OGTT, women compared to men had significantly greater FFA suppression. Both nonobese and obese women suppressed FFA concentration by 88%, and nonobese and obese men suppressed FFA concentration by 80 and 66% respectively. This gender difference in FFA suppression was significant (P = 0.001) and independent of obesity and insulin concentration. During the IC studies, there were no gender or obesity differences in FFA suppression, with women and men suppressing FFA levels by 87-89% (P = 0.7). Fasting insulin concentrations were higher in obese vs. nonobese (P = 0.03), but fasting FFA concentrations were not different (P = 0.15). For nonobese and obese females, fasting FFA levels were 0.55 +/- 0.24 and 0.44 +/- 0.26 mEq/L, respectively, and for nonobese and obese males, 0.45 +/- 0.2 and 0.35 +/- 0.18 mEq/L, respectively. In women, development of obesity may be enhanced by greater sensitivity to insulin-induced FFA suppression as measured during an OGTT. To detect gender differences in FFA metabolism, the OGTT is superior to the IC. The lack of elevation in fasting FFA levels in obese AA women and men has not been reported in other racial groups and may indicate a greater adipocyte sensitivity to insulin in AA.

Adipocytes↗
PubMed1996

Hypertension in pediatric patients.

The importance of hypertension in the pediatric population has not been as well-appreciated as in adults. This may be due in part to the much lower prevalence of hypertension in children. Nevertheless, hypertension is an important clinical problem in pediatrics, and the approach to its management differs from that in adults in several major respects. Compared with adults, a much greater percentage of hypertension in children is caused by secondary, potentially correctable, disease states. Elevated blood pressure in children may also represent the early expression of primary or essential hypertension. In addition, the technique of blood pressure measurement, the definitions of high blood pressure, and the classifications of blood pressure values in children are different than in adults. These factors dictate a pediatric approach to detection, evaluation, and management of hypertension in children and adolescents.

Adolescent↗
PubMed1996

Effect of estrogen withdrawal on blood pressure and insulin resistance in sucrose-fed juvenile rats.

We have previously shown that juvenile Sprague-Dawley rats, fed a diet in which complex carbohydrates are replaced by sucrose, develop insulin resistance and hypertension. These conditions develop despite the absence of genetic predisposition to either. When studied with the euglycemic hyperinsulinemic clamp technique, these rats have reduced insulin-stimulated glucose utilization, but normal suppression of hepatic glucose output. In the young sucrose-fed rats, it was noted that the degree of blood pressure elevation was greater in males than in females. The purpose of this study was to test the hypothesis that estrogen withdrawal increases insulin resistance and hypertension. Female rats were randomized at weaning (3 weeks of life) to receive control diet or sucrose diet. Animals were assessed with weekly weight and indirect tail-cuff blood pressure. At 8 weeks of life, the sucrose-fed rats were randomized to receive bilateral oophorectomy or sham surgery (anesthesia and uterine horn exposure without removal of the ovaries). At 13 to 14 weeks of life, all animals were fasted overnight, and had an oral glucose tolerance test while conscious. Weight and weight gain were not different among the groups over the 11 week study period. Animals fed the sucrose diet developed significantly higher blood pressure than animals fed the control diet; oophorectomized animals had higher blood pressure than sham-operated animals (P <.0001). Sucrose-fed oophorectomized animals developed fasting and glucose-stimulated hyperinsulinemia. Estrogen withdrawal augments blood pressure in juvenile rats made insulin resistant and hypertensive with a sucrose diet. Estrogen withdrawal in these animals also induces fasting and glucose-stimulated hyperinsulinemia, which are signs of worsening insulin resistance. Androgen:estrogen imbalance increases metabolic dysfunction and worsens hypertension in this animal model.

Animals↗
PubMed1996

The role of cardiovascular reactivity as a mediator of hypertension in African Americans.

Observations on the adverse effect of chronic environmental stress on blood pressure in individuals, and the incidence of hypertension in populations, have raised the possibility that aberrant physiological responses to stressful stimuli may play a role in the development of human hypertension. A variety of investigations, both clinical and experimental, have been conducted to explore a neurogenic dimension in the pathogenesis of hypertension. Reactivity is defined as the change in blood pressure, heart rate, or other hemodynamic parameters in response to physical or mental stimuli. Data from clinical studies have shown that reactivity is a stable measurement within individuals. Augmented reactivity is observed in patients with hypertension compared with normotensive subjects, and can also be detected in the young, often associated with other risk factors for hypertension. Racial differences in reactivity have been shown, with enhanced vascular reactivity observed among blacks compared with greater cardiac reactivity in whites. Neither stress, nor reactivity to stress has been shown to have a causal role in the development of hypertension. Although augmented stress-induced reactivity is strongly associated with groups having a greater risk for future hypertension, the role that reactivity plays in this process remains to be delineated.

Black People↗
PubMed1995

Effect of angiotensin converting enzyme inhibitor (lisinopril) on insulin sensitivity and sodium transport in mild hypertension.

The purpose of this study was to determine whether antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril would alter cell Na+ transport kinetics, metabolic parameters associated with insulin resistance, or both in young adults with mild hypertension. Sixteen young adults (mean age 29 +/- 4 years) were treated with placebo for 8 weeks, then with lisinopril for 12 weeks. Metabolic risk factors examined included plasma lipid levels, plasma insulin concentration during an oral glucose tolerance test, and insulin sensitivity determined by an euglycemic hyperinsulinemic clamp procedure. Red blood cells were assayed for Na+/H+ exchange, Na+/Li+ exchange, Na(+)-K+ pump activity, and Na(+)-K(+)-Cl- cotransport before and during treatment. Blood pressure decreased from 142 +/- 4/98 +/- 2 mm Hg before treatment to 131 +/- 3/85 +/- 1 mm Hg during lisinopril treatment (P < .001). During lisinopril treatment, there was a significant reduction in total cholesterol (from 177 +/- 8 to 161 +/- 8 mg/dL, P < .008), in low density lipoprotein-cholesterol (from 107 +/- 7 to 91 +/- 7 mg/dL, P < .002), and in insulin at 60 min into the oral glucose tolerance test (from 132 +/- 18 to 99 +/- 15 microU/mL, P < .05). There was a marginally significant increase in insulin sensitivity during lisinopril treatment (P < .08). The assays of cell Na+ transport showed a significant reduction in maximal activity (Vmax) for Na+/H+ exchange (from 33.7 +/- 3.8 to 19.7 +/- 2.6 mmol/L cell/h, P < .003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Hypertension in children and adolescents.

The absolute levels of blood pressure (BP) that define hypertension differ in children and adults. Extensive epidemiological data on growth and blood pressure in children and adolescents now provide values for normal ranges of blood pressure throughout childhood. Hypertension in the young is defined as systolic or diastolic blood pressure that is repeatedly above the 95th percentile for age and sex. Regular measurement of blood pressure and use of the reference values now enable accurate detection of hypertension in both symptomatic and asymptomatic children and adolescents. When hypertension is confirmed by repeated blood pressure measurements, decisions must be made regarding further evaluation for diagnosis of a possible underlying cause for the hypertension. In general, the younger the child and the higher the blood pressure, the more likely that a secondary cause, such as a renal parenchymal or renovascular lesion, for the hypertension will be identified. Mild elevations of blood pressure in the young may also be due to early expression of primary or essential hypertension. In children and adolescents, essential hypertension is characterized by blood pressure variability, a family history of hypertension, and, frequently, obesity. Pharmacologic therapy to control significant and severe hypertension is indicated for cardiovascular and renal protection. When early essential hypertension is the likely diagnosis in children or adolescents with mild blood pressure elevation, emphasis is directed at life-style changes including dietary modification, weight control, and increase in physical activity.

Adolescent↗
PubMed1995

Insulin sensitivity, lipids, and blood pressure in young American blacks.

The purpose of this study was to determine whether insulin resistance was linked with alterations in plasma lipids in adult young blacks with borderline hypertension. Ninety-four American blacks participated (46 men, 48 women, age range 28 to 33 years). Within this group of 94 subjects, there were 60 normotensive (Nt) subjects and 36 subjects with borderline hypertension (BHt), defined as blood pressure > 135/85 mm Hg. None of the subjects were diabetic or receiving antihypertension medication. All participants had blood pressure and anthropometric measurements, a fasting lipid profile, an oral glucose tolerance test, and a euglycemic hyper-insulinemic clamp. Insulin-stimulated glucose utilization (M), determined by insulin clamp, was significantly lower in the BHt subjects compared with the Nt subjects (men, Nt 6.91 +/- 0.62 versus BHt 5.54 +/- 0.65; women, Nt 5.97 +/- 0.47 versus BHt 3.79 +/- 0.38 mg.kg-1.min-1, P = .006). When M was corrected for adiposity and expressed in milligrams per kilogram of fat free mass (M'), the difference between Nt and BHt remained significant (P = .006). There was a significant correlation of M' with systolic blood pressure (r = .393, P < .0001), HDL-C (r = .382, P < .0001), triglyceride level (r = 308, P < .001), apolipoprotein A-I (r = .190, P = .033), and apolipoprotein B stepwise multiple linear regression analysis, HDL-C emerged as the most significant lipid component in the model for insulin resistance. These data suggest that in American blacks with mild hypertension, the risk for cardiovascular disease may be augmented in the presence of insulin resistance.

Adult↗
PubMed1995

Albuminuria in association with insulin and sodium-lithium countertransport in young African Americans with borderline hypertension.

The purpose of this study was to determine whether early nephropathy, evidenced by urinary albumin excretion, can be detected in young African American subjects with only borderline hypertension, and whether there is a relationship of albuminuria with insulin resistance and with sodium-lithium countertransport activity. Clinically well young African American men and women including normotensive (blood pressure < 135/85 mm Hg, n = 41) and borderline hypertensive (blood pressure > or = 135/85 mm Hg, n = 26) individuals were studied. Each subject underwent an oral glucose tolerance test and euglycemic hyperinsulinemic clamp study. Albuminuria was measured on timed urine collections. Sodium-lithium countertransport activity was assayed in fresh red blood cells at 280 mmol/L Na+ for full saturation of external Na+ sites. The sum of insulin levels during glucose tolerance was significantly greater in the borderline hypertensive compared with the normotensive subjects (P = .014), and insulin-stimulated glucose utilization during the clamp was significantly lower in borderline hypertensive compared with normotensive subjects (P = .016). Albuminuria was greater in borderline hypertensive compared with normotensive subjects (P = .002). Albuminuria was significantly correlated with fasting plasma insulin concentration (r = .44, P < .002) and the sum of insulins during the glucose tolerance test (r = .45, P < .002). Sodium-lithium countertransport correlated with albuminuria (r = .31, P < .05) as well as significantly with insulin-stimulated glucose utilization during the clamp (r = .44, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Gender differences in insulin-stimulated glucose utilization among African-Americans.

The purpose of this study was to determine whether there are gender differences in plasma insulin levels or insulin resistance in young adult African-Americans. Male (n = 53) and female (n = 45) subjects (age 23 to 28 years) included normotensives (N, blood pressure [BP] < 135/85 mm Hg) and borderline hypertensives (BH, BP > 135/85 mm Hg). Plasma insulin concentration was measured during an oral glucose tolerance test (OGTT) in all subjects. In 50 cases, insulin clamps were performed. Plasma estradiol and free testosterone were analyzed in a subsample (n = 15) of women. Data were analyzed for BP and gender groups by two-way ANOVA. Compared to men, women in each BP group had higher plasma insulin: glucose ratios (P < .01) and sums of insulin on OGTT (P < .02). The insulin clamp data also demonstrated significantly lower insulin-stimulated glucose utilization (M) in women compared to men in each BP group (N males 7.28 +/- 0.72 v N females 4.94 +/- 1.2 mg/kg-min; BH males 5.28 +/- .56 v BH females 2.59 +/- 0.50 mg/kg-min; P < .004 for gender differences). Analysis of the sex hormone data found a significant correlation in the ratio of free testosterone/estradiol (T/E) with plasma glucose, insulin, insulin/glucose, and systolic BP (P < .05), and no correlation of T/E with body mass index or triceps skinfold thickness. These data indicate that there are significant gender differences in plasma insulin levels and in insulin sensitivity in African-Americans. The relationship of plasma insulin to sex hormones suggests that in females, hyperinsulinemia cosegregates with increased androgenicity.

Adult↗
PubMed1994

The effect of excess dietary sucrose on growth, blood pressure, and metabolism in developing Sprague-Dawley rats.

To determine the effects of sucrose-enriched feeds on somatic growth, blood pressure development, and insulin-stimulated glucose metabolism, Sprague-Dawley rat pups (n = 94) were randomly assigned at weaning (3 wk) to a control diet (15% sucrose, by calories, n = 48) or an isocaloric diet in which starch is replaced by sucrose (66% sucrose, by calories, n = 46). Weight and blood pressure were followed until 13 wk. Chronic catheters were placed in a subset of male animals (n = 13), fasting glucose production was measured, and euglycemic hyperinsulinemic clamps were performed while the rats were in the conscious, nonstressed state. There was no difference in weight gain between control and sucrose rats in each sex group. Blood pressure in sucrose rats was significantly higher than in control rats after 4 wk of diet (7 wk of age, p < 0.001) in both sex groups and persisted for the duration of sucrose-enriched feeds. Insulin resistance was confirmed in sucrose rats with the euglycemic hyperinsulinemic clamp technique. In juvenile rats that have no genetic predisposition to hypertension, excess dietary sucrose induced high blood pressure without obesity. Sucrose feeding also induced insulin resistance. The sucrose-fed Sprague-Dawley weanling rat provides a model

Aging↗
PubMed1993

Insulin resistance in the conscious spontaneously hypertensive rat: euglycemic hyperinsulinemic clamp study.

To determine whether spontaneously hypertensive rats (SHR) are insulin resistant when compared with their genetic control, Wistar-Kyoto rats (WKY), insulin-stimulated glucose utilization was studied in both strains with the euglycemic hyperinsulinemic clamp technique. This methodology can determine if insulin resistance is present and whether it is due to ineffective stimulation of peripheral glucose utilization, or to incomplete suppression of (hepatic) endogenous glucose production (EGP) by insulin, or both. Twelve WKY and 15 SHR (all male) had long-term catheters surgically placed. After surgical recovery, fasting metabolic parameters were measured in the conscious, unstressed state. Clamp studies were then performed on nine WKY and eight SHR. EGP was measured before and during euglycemic hyperinsulinemia with the tracer-dilution technique (6-3H-glucose). Indices of fasting metabolism (plasma glucose, insulin, and hepatic EGP) were not different between WKY and SHR. During the clamp studies, the glucose infusion rate (GIR) required to maintain euglycemia was significantly lower in SHR (SHR, 0.055 +/- 0.003 v WKY, 0.106 +/- 0.001 mmol/kg.min-1; P < .001). EGP was completely suppressed during euglycemic hyperinsulinemia in all WKY and in six of eight SHR. We conclude that conscious, nonstressed SHR are insulin resistant when compared with WKY. Attenuated insulin-stimulated peripheral glucose utilization implicates skeletal muscle, and not liver, as the primary site of insulin resistance in SHR.

Animals↗
PubMed1993

Racial differences in blood pressure among urban adolescents.

The purpose of this study was to determine if there are racial differences in the blood pressure patterns among urban adolescents. Blood pressure (BP) was measured according to Task Force guidelines in health-screening and education sessions conducted in urban public and parochial high schools. The prevalence of BP > or = 95th% (HBP) on initial screening was determined in a population of 3,349 students. Differences in prevalence of HBP among race, sex, and age groups were tested for significance by chi 2 analysis. The overall prevalence of HBP in this urban adolescent population was 8.1%. Significant race differences were present in females (blacks = 6.6% versus non-Hispanics = 2.9%, p < 0.01). Within the black females, HBP occurred more frequently among the girls attending predominantly black public schools (7.7%) compared to an interracial parochial school (2.0%) p < 0.001. This difference could not be explained by weight, height, or the occurrence of obesity. The observed BP differences within black females, by school, may reflect a family-environment effect on cardiovascular risk.

Adolescent↗
PubMed1993

Renovascular hypertension in children.

Renal arteriography remains the only study to identify and define correctly both location and extent of renal artery stenosis. Because other studies do not adequately identify all children who have renal artery disease, it is reasonable to perform renal arteriography in those children with severe hypertension who do not have another readily identifiable cause for their hypertension. On the other hand, in children with less profound elevation of blood pressure in whom there is no other definable cause, it is possible to defer renal angiography. In these children with mild or moderate hypertension, studies such as the captopril 99mTc-DTPA scan or intravenous digital subtraction angiography may identify those for whom arteriography is more likely to have abnormal results.

Child↗
PubMed1993

Insulin-stimulated glucose utilization and borderline hypertension in young adult blacks.

The purpose of this investigation was to determine whether there is a relation between impaired insulin-stimulated glucose utilization, or insulin resistance, and blood pressure (BP) in a young adult black population. Clinically well, young black men and women, including normotensive (BP < 135/85 mm Hg, n = 23) and borderline hypertensive (BP > or = 135/85 mm Hg, n = 27) individuals, were studied. Each subject had an oral glucose tolerance test (OGTT) and underwent a euglycemic hyperinsulinemic clamp procedure. A two-way analysis of variance demonstrated a significantly greater fasting insulin plasma concentration (P < .02) and sum of insulin levels during the OGTT (P = .04) in the borderline hypertensive compared with normotensive subjects. In both BP groups, women had significantly higher fasting plasma insulin levels than men (P < .02 and P = .009). Body mass index was a significantly covariate of the plasma insulin concentration. Data obtained from the clamp demonstrated significant insulin resistance in borderline hypertensive compared with normotensive subjects (4.69 +/- 0.50 versus 6.57 +/- 0.63 mg/kg per minute, P = .002). A stepwise multiple linear regression analysis demonstrated that there are significant multiple correlations of insulin resistance with body mass index, clamped insulin level, BP group, and systolic BP (multiple R = .7862, P < .001). Application of this analysis to the nonobese sample (n = 33) found significant correlations of insulin resistance with sex, BP group, and systolic BP (multiple R = .6817, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Red blood cell sodium-proton exchange in hypertensive blacks with insulin-resistant glucose disposal.

To define the potential pathogenic role of hyperinsulinemia as a mediator of alterations in sodium transport, we have examined red blood cell Na(+)-H+ and Na(+)-Li+ exchanges in a young adult black population characterized for blood pressure and insulin-mediated glucose disposal. Normotensive and mildly hypertensive blacks (blood pressure, 120 +/- 2/76 +/- 2 and 139 +/- 3/94 +/- 2 mm Hg, respectively) with a mean age of 26.1 years were studied for insulin sensitivity with the euglycemic hyperinsulinemic clamp (molar index of insulin sensitivity, M/I = moles glucose metabolized/insulin in milliliters of plasma). Na(+)-H+ exchange (U = mmol/L cell.h) was measured before and after the insulin clamp as a function of cell pH to determine the maximum transport rate. In the normotensive subjects, 18 were insulin sensitive (M/I = 9.37 +/- 0.6 x 10(4)) and 4 were insulin resistant (M/I = 3.64 +/- 0.6 x 10(4)). In the hypertensive subjects, 4 were insulin sensitive (M/I = 9.15 +/- 1.1 x 10(4)) and 16 were insulin resistant (M/I = 3.02 +/- 0.3 x 10(4)). The maximum rate of Na(+)-H+ exchange was significantly higher in all hypertensive vs normotensive individuals (35 +/- 3 vs 23 +/- 3 U, P < .005). Na(+)-H+ exchange activity was higher in insulin-resistant vs insulin-sensitive hypertensive subjects (40 +/- 3 vs 20 +/- 2 U, P < .001) but not in insulin-resistant normotensive subjects. Na(+)-Li+ exchange was not different in hypertensive and normotensive individuals but was higher in all insulin-resistant compared with all insulin-sensitive subjects (0.26 +/- 0.03 vs 0.16 +/- 0.02 U, P < .01). Na(+)-Li+ exchange also was higher in insulin-resistant vs insulin-sensitive normotensive subjects (0.35 +/- 0.03 vs 0.15 +/- 0.02 U, P < .001) and in insulin-resistant hypertensive subjects vs insulin-sensitive normotensive subjects (0.24 +/- 0.03 vs 0.15 +/- 0.02 U, P < .001). A stepwise multiple regression analysis for all variables revealed that with Na(+)-H+ exchange as a dependent variable the main determinant was blood pressure, which in turn had insulin sensitivity as the main determinant. In conclusion, these results indicate that in hypertensive blacks, insulin-resistant glucose disposal is strongly associated with elevated red blood cell Na(+)-H+ exchange activity. Thus, despite impaired insulin-mediated glucose disposal, cellular Na+ gain via enhanced activity of Na(+)-H+ exchange is not blunted in hypertensive blacks.

Adult↗