Suppression of sympathetic nervous system during fasting.

Two days of fasting in rats significantly reduces the turnover of norepinephrine in the heart. In contrast to the effects of ganglionic blockade in fed controls, similar blockade in fasted animals is without significant effect on [3H]-norepinephrine retention or endogenous norepinephrine in the heart. These data are consistent with suppression of centrally mediated sympathetic activity in the fasted state. The decrease in norepinephrine turnover during fasting is completely reversed by 1 day of refeeding.

Impaired suppression of sympathetic activity during fasting in the gold thioglucose-treated mouse.

Sympathetic activity in rats and mice is diminished by fasting and increased by sucrose feeding. The central neural mechanisms coordinating changes in the functional state of sympathetic nerves with changes in dietary intake are unknown, but a role for neurons in the ventromedial hypothalamus (VMH) is suggested by the existence of sympathetic connections within the VMH and the importance of this region in the regulation of feeding behavior. To investigate the potential role of the VMH in dietary regulation of sympathetic activity [(3)H]norepinephrine turnover was measured in the hearts of fasted and sucrose-fed mice after treatment with gold thioglucose (AuTG). In control mice, norepinephrine (NE) turnover was 1.60+/-0.92 ng NE/heart per h (95% confidence limits) after 1 d of fasting and 4.58+/-0.98 after 3 d of sucrose feeding, although, in AuTG-treated mice, cardiac NE turnover in fasting was 5.45+/-1.56 and with sucrose feeding, 5.44+/-0.76. Experiments with ganglionic blockade indicate that the absence of dietary effect on NE turnover in AuTG-treated mice reflects a corresponding lack of change in central sympathetic outflow. AuTG administration, therefore, disrupts dietary regulation of sympathetic activity by abolishing the suppression of sympathetic activity that occurs with fasting. This effect of AuTG is unrelated to duration of fasting (up to 3 d) and is specific for AuTG because neither treatment with another gold thio compound (gold thiomalate) nor the presence of genetic obesity (ob/ob) prevented fasting suppression of sympathetic activity. Moreover, AuTG treatment did not impair sympathetic activation by cold exposure (4 degrees C) nor adrenal medullary stimulation by 2-deoxy-d-glucose. Thus, AuTG treatment selectively impairs dietary regulation of sympathetic activity, possibly by destruction of neurons in the VMH.

Excretion and metabolism of catecholamines by the isolated perfused rat kidney.

The excretion and metabolism of labeled epinephrine and norepinephrine by the isolated, perfused rat kidney were studied. The excretion of both catecholamines significantly exceeded the amount filtered, thus providing direct evidence of net tubular secretion. Renal clearance of epinephrine was significantly greater than that of norepinephrine. Tubular secretion was a linear function of the concentration of unbound catecholamine in the medium with no demonstrable tubular maximum at the concentrations studied. The isolated kidney removed catecholamines from the medium by metabolism as well as excretion in the urine. O-Methylation was the major metabolic route and O-methylated metabolites were rapidly excreted and concentrated in urine. Preferential excretion and metabolism of epinephrine were confirmed in double-label experiments in which [14C]epinephrine and [3H]norepinephrine were perfused together. The ratio of 14C:3H in urine exceeded that in perfusion medium for total radioactivity as well as for catecholamines and O-methylated amines. The present study thus provides direct evidence for (a) net tubular secretion of epinephrine and norepinephrine with a direct relationship between secretion and medium concentration; (b) significant renal metabolism of both epinephrine and norepinephrine with O-methylation as the major metabolic route; and (c) preferential excretion and metabolism of epinephrine.

Sympathoadrenal activity in fasting pregnant rats. Dissociation of adrenal medullary and sympathetic nervous system responses.

The pattern of urinary catecholamine excretion in fasting differs in pregnant and nonpregnant rats, which suggests that the sympathoadrenal response to fasting is altered by pregnancy. In fasting nonpregnant animals, urinary norepinephrine (NE) excretion decreases and epinephrine (E) excretion remains unchanged, whereas the excretion of both catecholamines rises significantly with refeeding. In contrast, fasting third-trimester pregnant rats exhibit a 420% increase in urinary E and a 345% increase in urinary NE, elevations which fall with refeeding. Specific evaluation of sympathoadrenal activity in fasting pregnant rats reveals stimulation of the adrenal medulla and suppression of sympathetic nerves. In fasting third-trimester rats the adrenal content of E is 37% lower in innervated adrenals as compared with contralateral denervated glands, which indicates the presence of neurally-mediated adrenal medullary activation. Adrenalectomy completely abolishes the fasting-induced rise in urinary E and NE in pregnant rats. Studies with 2-deoxy-D-glucose suggest that stimulation of the adrenal medulla results from hypoglycemia, which is present after 3 d of fasting in pregnant rats (plasma glucose 36.7 mg/dl). Sympathetic nervous system activity, as measured by [(3)H]NE turnover in the heart, decreases in fasting pregnant rats despite hypoglycemia, a response similar to that seen in fasting nonpregnant animals where plasma glucose is maintained above 50 mg/dl. The calculated NE turnover rate is 44% lower in 2-d fasted pregnant rats than in fed pregnant animals (17.6 +/- 1.3 vs. 31.3 +/- 1.8 ng NE/heart per h, respectively). Thus adrenal medullary and sympathetic nervous system responses in fasting pregnant rats appear to be dissociated, which suggests that diet-induced changes in sympathetic activity and stimulation of the adrenal medulla by hypoglycemia may be independently regulated.

Effect of protein on sympathetic nervous system activity in the rat. Evidence for nutrient-specific responses.

Increased energy intake activates the sympathetic nervous system (SNS) in animals and man. While dietary carbohydrate and fat stimulate, the impact of dietary protein on the SNS is not well defined. The present studies examine the effect of protein ingestion on sympathetic function based upon the measurement of [3H]norepinephrine (NE) turnover in heart and interscapular brown adipose tissue (IBAT) as the index of SNS activity. In these experiments, animals were pair-fed mixtures of laboratory chow and refined preparations of casein, sucrose, and lard to permit comparisons among nutrients with total energy intake held constant or with additional energy provided in the form of a single nutrient. After 5 d of eating a 2:1 mixture of chow and either casein or sucrose cardiac, [3H]NE turnover was less (P less than 0.005) in casein-fed rats (6.4%/h and 28.9 ng NE/h) than in animals given sucrose (11.2%/h and 46.5 ng NE/h). Similar results were obtained in IBAT and in experiments using 1:1 mixtures of chow and casein/sucrose. Casein-fed animals also displayed slower rates of NE turnover than lard-fed rats in both heart (7.8%/h vs. 13.2, P less than 0.001) and IBAT (7.0%/h vs. 12.8, P less than 0.01). Addition of casein (50% increase in energy intake) to a fixed chow ration raised NE turnover slightly, but not significantly, in heart (an average increase of 15% in six experiments). Thus, in distinction to SNS activation seen with dietary carbohydrate or fat, the SNS response to dietary protein is minimal in both heart and IBAT, indicating that the effect of increased energy intake on the SNS is dependent upon diet composition.

Sympathoadrenal responses to acute and chronic hypoxia in the rat.

The sympathoadrenal responses to acute and chronic hypoxic exposure at 10.5 and 7.5% oxygen were determined in the rat. Cardiac norepinephrine (NE) turnover was used to assess sympathetic nervous system (SNS) activity, and urinary excretion of epinephrine (E) was measured as an index of adrenal medullary activity. The responses of the adrenal medulla and SNS were distinct and dependent upon the degree and duration of hypoxic exposure. Chronic hypoxia at 10.5% oxygen increased cardiac NE turnover by 130% after 3, 7, and 14 d of hypoxic exposure. Urinary excretion of NE was similarly increased over this time interval, while urinary E excretion was marginally elevated. In contrast, acute exposure to moderate hypoxia at 10.5% oxygen was not associated with an increase in SNS activity; in fact, decreased SNS activity was suggested by diminished cardiac NE turnover and urinary NE excretion over the first 12 h of hypoxic exposure, and by a rebound increase in NE turnover after reexposure to normal oxygen tension. Adrenal medullary activity, on the other hand, increased substantially during acute exposure to moderate hypoxia (2-fold increase in urinary E excretion) and severe hypoxia (greater than 10-fold). In distinction to the lack of effect of acute hypoxic exposure (10.5% oxygen), the SNS was markedly stimulated during the first day of hypoxia exposure at 7.5% oxygen, an increase that was sustained throughout at least 7 d at 7.5% oxygen. These results demonstrate that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure. The response to acute hypoxic exposure is more complicated; during the first 12 h of exposure at 10.5% oxygen, the SNS is not stimulated and appears to be restrained, while adrenal medullary activity is enhanced. Acute exposure to a more severe degree of hypoxia (7.5% oxygen), however, is associated with stimulation of both the SNS and adrenal medulla.

Effect of dietary fat on sympathetic nervous system activity in the rat.

Previous studies from our laboratory have demonstrated that dietary intake affects the sympathetic nervous system (SNS); carbohydrate intake, in particular, has been shown to stimulate sympathetic activity. The present studies were undertaken to characterize the effect of dietary fat on SNS activity in the rat. Sympathetic activity was assessed by measurement of norepinephrine (NE) turnover in heart, interscapular brown adipose tissue (IBAT), and pancreas and by excretion of NE in the urine. When fed a fat-enriched diet (50% chow, 50% lard), fractional NE turnover in heart (k) increased from 6.3 +/- 0.6% h in ad lib. fed controls to 14.7 +/- 1.3% h in the high-fat group (P less than 0.001); calculated NE turnover rate increased from 24.5 +/- 2.4 ng/heart per h to 36.8 +/- 3.5 (P less than 0.05). Urinary NE excretion more than doubled after 6 d of the same high fat diet (P less than 0.001). Ganglionic blockade produced a greater effect on NE turnover in fat-fed, as compared with chow-fed animals, consistent with increased sympathetic activity in the fat-fed group. When fat absorption was blocked with a bile acid binding resin (cholestyramine), the same high-fat diet did not increase cardiac NE turnover, indicating that fat absorption is required for the stimulatory effect on sympathetic activity. In another series of experiments, in which chow (and hence protein) intake was held constant, the effect of fat and isocaloric sucrose supplements on NE turnover was assessed in heart, IBAT, and pancreas. The caloric value of the supplements was 50, 100, and 335% of the chow in the different experiments. An effect of fat on NE turnover in heart and IBAT was demonstrable at the lowest level of fat supplement. Fat increased pancreatic NE turnover when added in amounts sufficient to double the caloric intake. The stimulatory effect of sucrose and fat on NE turnover in heart and IBAT was similar. These experiments demonstrate that fat increases SNS activity in the rat and that the magnitude of the effect is similar to that of sucrose. The results imply that fat may contribute to dietary thermogenesis in this species.

Effect of diet and cold exposure on norepinephrine turnover in brown adipose tissue of the rat.

Brown adipose tissue (BAT) is an important site of adaptive changes in thermogenesis in the rat. The sympathetic nervous system, which richly supplies BAT, is thought to play an important role in the regulation of BAT thermogenesis because catecholamines stimulate and beta adrenergic blocking agents inhibit oxygen consumption in this tissue. The present studies were carried out to assess directly sympathetic activity in BAT in response to cold exposure and to changes in dietary intake, both of which alter heat production in the rat. Sympathetic activity was determined from the rate of norepinephrine (NE) turnover in interscapular brown adipose tissue (IBAT) after preliminary experiments validated the use of NE turnover techniques in IBAT. Acute exposure to 4 degrees C increased NE turnover in IBAT 4- to 12-fold compared with ambient temperature controls, depending upon the interval over which the turnover measurement was made, while in the heart NE turnover doubled in response to the same cold stimulus. In animals exposed to cold continuously for 10 d before study, NE turnover measurements in IBAT and in the heart were elevated comparably to those obtained during acute exposure. Alterations in feeding were also associated with changes in NE turnover in IBAT. Fasting for 2 d decreased NE turnover in IBAT (-35% from 29.2+/-4.2 ng NE/h to 18.9+/-5.9) and in heart (-52%). In animals fed a "cafeteria" diet, a model of voluntary overfeeding in the rat, NE turnover was increased in both IBAT (+108% from 24.8+/-4.5 ng NE/h to 51.7+/-6.8) and heart (+66%). Because ganglionic blockade exerted a greater effect on NE turnover in IBAT in cafeteria-fed rats than in controls, the increase in NE turnover in IBAT with this overfeeding regimen reflects enhanced central sympathetic outflow. Thus NE turnover techniques can be satisfactorily applied to the assessment of sympathetic nervous system activity in IBAT. The experiments reported here demonstrate changes in sympathetic activity in IBAT that parallel known adaptive changes in heat production in the rat. These studies, therefore, support the concept that the increased thermogenesis of chronic cold exposure and of cafeteria feeding occur by similar mechanisms and imply an important role for the sympathetic nervous system, mediated in part through BAT, in the regulation of energy balance in the rat.

Effect of protein ingestion on urinary dopamine excretion. Evidence for the functional importance of renal decarboxylation of circulating 3,4-dihydroxyphenylalanine in man.

Since dietary protein increases urinary dopamine (DA) excretion in animals, this study was undertaken to assess the role of DA production in the acute changes in renal function following protein ingestion in man. Excretion of DA, sodium, potassium, water, solute, and creatinine were measured in six normal men in 30-min intervals over 5 h after oral ingestion of protein and/or carbidopa, an inhibitor of DA formation from 3,4-dihydroxyphenylalanine (DOPA). Overall, protein increased urinary DA 50% (P = 0.031) while carbidopa reduced it 70% (P less than 0.0001), although suppression of DA excretion by carbidopa was not uniform over the 5 h of observation. Carbidopa doubled the level of DOPA in venous plasma and greatly magnified the DOPA response to protein. Inhibition of decarboxylase activity reduced excretion of sodium, potassium, solute and water after protein ingestion. These results indicate that extraneuronal DOPA decarboxylation in kidney contributes to acute protein-induced changes in renal function in man and suggest a general role for the decarboxylation of circulating DOPA in the expression of dopaminergic effects on the kidney in vivo.

High plasma norepinephrine concentrations at birth in infants of diabetic mothers.

Analysis of plasma norepinephrine (NE) concentrations in umbilical artery and vein from infants of diabetic and nondiabetic mothers revealed high plasma NE values in those of diabetic mothers. While birth weight and arterial plasma NE did not correlate in infants of nondiabetic mothers (r = 0.07, NS), birth weight and plasma NE were related inversely in infants of diabetic mothers (r = -0.73, P less than 0.05).

Impaired in vivo insulin clearance in patients with severe target-cell resistance to insulin.

The concentration of insulin in plasma is determined by both its rate of secretion and its rate of clearance from the plasma compartment. The effect of marked insulin resistance on insulin clearance in vivo has not been determined in man. We have employed the euglycemic insulin clamp technique to measure insulin sensitivity and insulin clearance in 16 control subjects and in 4 subjects with marked target-cell resistance to insulin. Two insulin-resistant patients had reduced receptor concentration on peripheral mononuclear cells, and two patients had normal receptor number and affinity. During 80-mU/m2/min insulin clamp studies, the clearance rate in each insulin-resistant patient was lower than that in any controls; the mean insulin clearance rate was 511 +/- 74 ml/m2/mon in control subjects and 205 ml/m2/min (P less than 0.001) in insulin-resistant patients. These findings demonstrate an association between marked target-cell resistance to insulin and impaired in vivo insulin clearance, and suggest an important role for receptor-mediated pathways in insulin clearance in vivo.

Surrogate decision-maker preferences for medical care of severely demented nursing home patients.

BACKGROUND: In the absence of advanced directives, physicians treating demented patients rely on surrogates to help make medical care decisions. METHOD: We surveyed family members of severely demented nursing home residents to determine preferences for medical intervention in five hypothetical situations involving tube feeding, hospitalization, intensive care unit admission, mechanical ventilation, and cardiopulmonary resuscitation. RESULTS: Only 11.8% of surrogates rejected all interventions. Cardiopulmonary resuscitation and tube feeding were accepted least frequently (31.6% and 36.4%, respectively). Mechanical ventilation, hospitalization, and intensive care unit admission were accepted by 43.6%, 63.4%, and 75.2%, respectively. There was no correlation between previous surrogate experience with an intervention and its acceptance. Nearly 70% of surrogates indicated that decisions were independent of any previously expressed resident views. CONCLUSIONS: In this study, surrogates of even the most demented nursing home patients prefer hospital level services including intensive care unit care for the treatment of acute illness. Efforts to control access to services on ethical or economic grounds may meet with resistance.

Hypertension in obesity and NIDDM. Role of insulin and sympathetic nervous system.

An important link exists between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension. Most patients with NIDDM are obese; the incidence of hypertension in obesity and NIDDM is substantial, approaching 50% in some studies. Furthermore, hypertension is known to contribute to the increased cardiovascular morbidity and mortality in patients with obesity and NIDDM. Despite the obvious clinical importance, the pathogenesis of hypertension in obesity and NIDDM remains poorly understood. Recent studies have identified hyperinsulinemia and insulin resistance as important threads that tie hypertension, obesity, and NIDDM together. The hypothesis is developed that insulin-mediated sympathetic stimulation contributes to blood pressure elevation in both obesity and NIDDM. Recruited as a mechanism to limit weight gain and restore energy balance, insulin resistance and sympathetic stimulation increase blood pressure by enhancing renal Na+ reabsorption and stimulating the cardiovascular system. In this article, we review the evidence on which this hypothesis is based.

Effects of 2-deoxy-D-glucose on the cardiac sympathetic nerves and the adrenal medulla in the rat: further evidence for a dissociation of sympathetic nervous system and adrenal medullary responses.

In rats and mice, fasting suppresses and sucrose overfeeding stimulates sympathetic nervous system (SNS) activity. Fasting hypoglycemia in rats suppresses SNS activity while stimulating adrenal medullary catecholamine release. Administration of 2-deoxy-D-glucose (2-DG), an inhibitor of intracellular glucose metabolism, also stimulates the adrenal medulla. The studies reported here were undertaken to determine the SNS response to chronic 2-DG administration and to test the hypothesis that diet-induced changes in SNS activity are related to central nervous system glucose metabolism. Ingestion of 2-DG caused an increase in urinary epinephrine excretion and significant depletion of adrenal epinephrine content, both indices of adrenal medullary stimulation. Chronic sc injections of 2-DG in animals with normal or increased food consumption caused simultaneous suppression of cardiac sympathetic nerve activity, as evidenced by diminished cardiac [3H]norepinephrine turnover, and stimulation of adrenal medullary epinephrine release. Parenteral 2-DG administration to adrenalectomized rats also caused suppression of cardiac sympathetic activity. Thus, this response to neuroglycopenia is independent of adrenal medullary catecholamine release. These results indicate that central nervous system glucose metabolism may mediate diet-induced changes in SNS activity.

Hyperinsulinemia: possible role in obesity-induced hypertension.

Data in support of the hypothesis that insulin-mediated sympathetic stimulation contributes to the hypertension that occurs in association with obesity are presented. The relation between insulin and the sympathetic nervous system derives from the effect of diet on sympathetic activity. Fasting suppresses but overfeeding stimulates the sympathetic nervous system. Insulin-mediated glucose metabolism within central neurons sensitive to insulin and glucose appears to be one important signal in this relation between diet and sympathetic activity. In the obese, hyperinsulinemia and hypertension track together in epidemiological studies. Evidence from a human population-based study (the Normative Aging Study) indicates that the abdominal form of obesity is associated with both hyperinsulinemia and increased urinary norepinephrine excretion. Elevations in urinary norepinephrine excretion, moreover, were highest in those with the highest fasting levels of insulin and glucose. These observations are consistent with the hypothesis that insulin-mediated sympathetic stimulation is a mechanism recruited in the obese to increase metabolic rate and restore energy balance; concomitant increases in sympathetic stimulation of the heart, vasculature, and kidney result in hypertension, which, according to this formulation, is an unfortunate by-product of the cardiovascular response to a metabolic adaptation.

Relation of obesity and diet to sympathetic nervous system activity.

The hypothesis that dietary intake and obesity stimulate the sympathetic nervous system was investigated in a cross-sectional study of 572 men aged 43-85 years from the Normative Aging Study. Habitus was represented by body mass index, as a measure of overall adiposity, and by the ratio of abdomen-to-hip circumference (abdomen/hip ratio), as a measure of centripetal fat distribution. Sympathetic activity was assessed by measurement of 24-hour urinary norepinephrine excretion. Increased body mass index and total caloric intake were independently associated with increased 24-hour urinary norepinephrine excretion (p = 0.0001 and p = 0.0055, respectively). In addition, mean urinary norepinephrine excretion was higher in subjects classified as either hyperglycemic (serum fasting glucose greater than or equal to 113 mg/dl) and hyperinsulinemic (serum fasting insulin greater than or equal to 19 microIU/ml) (p = 0.0023) or in subjects classified as either hyperglycemic or hyperinsulinemic (p = 0.0063) than the mean urinary norepinephrine excretion in normal subjects. These relations were demonstrated to be independent of age, smoking status, and physical activity. Our results are consistent with the hypothesis that insulin mediates sympathetic stimulation in response to dietary intake and increases sympathetic nervous system activity in the obese.

Counterregulatory responses to insulin-induced glucose reduction in the elderly.

The impact of age on counterregulatory responses to moderate reductions in blood glucose induced by a constant insulin infusion (20 mU/m2 X min) was studied in normal young (n = 7; aged 20-42 yr) and old (n = 7; aged 66-77 yr) nonobese subjects. Insulin was infused until the whole blood glucose level fell to or below 60 mg/dl. This required an infusion time of 39 +/- 3 (+/- SE) min in the young and 36 +/- 3 min in the old. Mean basal glucose [young, 88 +/- 2 (+/- SE); old, 88 +/- 2 mg/dl), minimum glucose (young, 51 +/- 2; old, 54 +/- 1 mg/dl), time to nadir (young, 48 +/- 3; old, 44 +/- 3), and time to recovery were similar in both groups. Maximal (young, 40.3 +/- 2.3; old, 42.1 +/- 3.3 microU/ml) insulin levels were also similar. Basal and maximal levels of glucagon, epinephrine, and GH were similar in the two groups. Although basal norepinephrine values were higher in the old subjects (young, 243 +/- 38; old, 364 +/- 23 pg/ml; P = 0.02), increments above basal during reduction in blood glucose were not affected by age. Basal cortisol values were similar (young, 13.7 +/- 1.4; old, 14.0 +/- 0.7 micrograms/dl), but maximum cortisol responses were slightly greater in the old subjects (young, 14.6 +/- 1.0; old, 17.7 +/- 0.9 micrograms/dl; P = 0.03). These studies indicate that hormonal responses and counterregulatory efficiency during modest reductions in blood glucose are preserved in healthy elderly subjects.

Altered dopaminergic responses in hypertension.

Biogenic amine metabolism may be altered in hypertension and thus contribute to its pathophysiology. This report describes an abnormality in dopamine excretion in hypertensive subjects in the postabsorptive state that persists despite an increase in dietary precursors for dopamine supplied by a protein meal. We studied seven normotensive and six nonmedicated hypertensive men after two different meals: 60 g protein and a noncaloric electrolyte-equivalent broth. Overall mean sodium excretion was 56% higher in the hypertensive group throughout both meal studies (p less than 0.01), implying higher chronic dietary sodium intake. Despite this, overall urinary excretion of dopamine tended to be lower in hypertensive than in normotensive subjects (p = 0.06). Hypertensive also differed from normotensive subjects in their response to protein feeding. In the normotensive subjects there was a 23% increase in urinary dopamine excretion (p less than 0.05), which was not seen after the noncaloric meal. In the hypertensive subjects, there was no change in urinary dopamine after the protein meal. In the normotensive subjects there was a 74% increase in sodium excretion (p less than 0.01) after the protein meal, but no significant change was seen in the hypertensive subjects. There were no differences in baseline renal plasma flow or glomerular filtration rate between the groups and no statistically significant differences between the groups in their renal hemodynamic responses to the meals. In summary, hypertensive subjects have less renal dopamine production for the amount of sodium ingested and a decreased renal dopamine production in response to a protein load as compared with normotensive subjects, consistent with a renal defect in conversion of DOPA to dopamine.

Relationship of dietary saturated fatty acids and body habitus to serum insulin concentrations: the Normative Aging Study.

The purpose of this study was to examine the relationship of body mass index, abdomen-hip ratio, and dietary intake to fasting and postprandial insulin concentrations among 652 men aged 43-85 y, followed in the Normative Aging Study. Log-transformed fasting insulin was significantly associated with body mass index, abdomen-hip ratio, total fat energy, and saturated fatty acid energy, with correlation coefficients ranging from 0.14 for total fat to 0.45 for body mass index. When multivariate models were used, body mass index, abdomen-hip ratio, and saturated fatty acid intake were statistically significant independent predictors of both fasting and postprandial insulin concentrations, after age, cigarette smoking, and physical activity were adjusted for. If saturated fatty acids as a percentage of total energy were to decrease from 14% to 8%, there would be an 18% decrease in fasting insulin and a 25% decrease in postprandial insulin. These data suggest that overall adiposity, abdominal obesity, and a diet high in saturated fatty acids are independent predictors for both fasting and postprandial insulin concentrations.

Relationship of catecholamine excretion to body size, obesity, and nutrient intake in middle-aged and elderly men.

Catecholamine release from sympathetic nerves and the adrenal medulla is influenced by diet under controlled research conditions. To test whether diet affects catecholamine excretion in free-living men, the urinary content of dopamine (DA), epinephrine (Epi), or norepinephrine (NE) was measured in 24-h collections provided by 572 participants of the Normative Aging Study of the Veterans Administration. Average daily intakes of energy and macronutrients were assessed by means of a semiquantitative food frequency questionnaire and sodium intake by quantitation of sodium excretion. Catecholamine excretion was also examined in relation to anthropometric variables. Because DA and Epi excretion were inversely related to age, all subsequent analyses included adjustments for age. Although DA and NE were positively related to measures of body size and fatness, Epi was negatively related to body fatness. Excretion rates of all three catecholamines were directly related to total energy intake and inversely related to energy-adjusted CHO consumption.