Biomedical subjects

R P Hoffman

Publications and source records attributed to R P Hoffman.

At least 19 recordsLinked to original sources

PubMed2001

Eating disorders in adolescents with type 1 diabetes. A closer look at a complicated condition.

The cultural drive to be thin can lead to eating disorders in many women and girls. In adolescent females with diabetes, the increased focus on eating and the weight gain associated with good glycemic control likely increase their susceptibility to abnormal eating. It is clear that nonspecified and subthreshold eating disorders, and possibly bulimia and anorexia, are more common in this group of patients. Good nutritional counseling to help patients avoid weight gain and family counseling to improve communication between patients and their families may help decrease this risk. Intentional insulin omission is a frequent means of preventing weight gain or increasing weight loss in adolescent females with type 1 diabetes. Eating disorders should be suspected in patients with recurrent diabetic ketoacidosis or poor glycemic control that is resistant to attempts at improvement. Treatment includes decreasing dietary restraint, promoting healthy eating, and either psychiatric counseling or psychologic intervention, or both.

Adolescent↗

PubMed2000

Latex hypersensitivity in a child with diabetes.

BACKGROUND: A 6-year-old girl who was diagnosed with diabetes mellitus 20 months previously developed erythematous, raised lesions at the site of her insulin injections. The reactions occurred when isophane and lispro insulin were administered individually or combined but not when insulin was obtained from the bottle after the septum had been removed. OBJECTIVES: To describe latex hypersensitivity in a child with diabetes and to review the literature. DESIGN: Case report. RESULTS: Findings from intradermal testing confirmed latex hypersensitivity. A change to insulin administration by insulin pen decreased the frequency of the reactions. CONCLUSION: Latex hypersensitivity should be considered in children with type 1 diabetes who develop local reactions to insulin injections.

Child↗

PubMed2000

Pubertal adolescent male-female differences in insulin sensitivity and glucose effectiveness determined by the one compartment minimal model.

Most studies of insulin sensitivity in puberty have been cross-sectional and have not been able to longitudinally address changes that might occur. In addition, these studies were unable to separate out glucose's ability to stimulate its own disposal (glucose effectiveness, S(G)) from insulin sensitivity (S(I)) or to separate the hepatic and peripheral effects of insulin. To address these problems, we used the frequently sampled i.v. glucose tolerance test with [6,6]D2 glucose to study S(G)* and S(I)* in 24 children (Tanner stage 1-3) at 6-mo intervals over an 18-mo period. Mean overnight GH and fasting GH binding protein (GHBP), IGF-1, and leptin levels were also measured. S(G)* did not differ between the sexes or Tanner stages. S(I)* did not differ between Tanner stages for either sex and was higher in boys than in girls. Hepatic insulin resistance did not differ between sexes or Tanner stages. S(G)* was not related to any of the other variables measured. S(I)* was negatively related to BMI, GHBP, IGF1, and leptin. These results demonstrate that insulin sensitivity is greater in prepubertal and early pubertal boys than in girls and is primarily determined by body mass effects.

Adolescent↗

PubMed1999

Effect of local sympathetic blockade on forearm blood flow and glucose uptake during hypoglycemia.

During hypoglycemia, hepatic glucose production increases and peripheral glucose utilization decreases. Systemic beta-adrenergic blockade during hypoglycemia increases peripheral glucose utilization. To explore the local effects of increased alpha- and beta-adrenergic activity on skeletal muscle glucose utilization, we measured arterial and venous plasma glucose concentrations, forearm blood flow (FBF), and forearm glucose uptake (FGU) during a hyperinsulinemic (40 mU/m2/min) stepped-hypoglycemic clamp with intrabrachial artery infusion of saline, phentolamine, propranolol, or combined phentolamine and propranolol. A control study was also performed with a euglycemic clamp and intraarterial saline. During hypoglycemia with saline and phentolamine, there were significant increases in FBF (130% +/- 38% and 180% +/- 35%, respectively) and FGU (120% +/- 51% and 230% +/- 150%, respectively). During hypoglycemia with propranolol and phentolamine + propranolol, FBF remained constant. FGU during hypoglycemia with propranolol was not different versus hypoglycemia with saline. No differences were found in these studies for forearm lactate output (FLO) or venous free fatty acid concentrations. These results demonstrate that local, as opposed to systemic, blockade during hypoglycemia does not alter peripheral glucose utilization.

Adrenergic alpha-Antagonists↗

PubMed1999

Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects.

The exact mechanisms for the decrease in R-R interval (RRI) during acute physiological hyperinsulinemia with euglycemia are unknown. Power spectral analysis of RRI and microneurographic recordings of muscle sympathetic nerve activity (MSNA) in 16 normal subjects provided markers of autonomic control during 90-min hyperinsulinemic/euglycemic clamps. By infusing propranolol and insulin (n = 6 subjects), we also explored the contribution of heightened cardiac sympathetic activity to the insulin-induced decrease in RRI. Slight decreases in RRI (P < 0.001) induced by sevenfold increases in plasma insulin could not be suppressed by propranolol. Insulin increased MSNA by more than twofold (P < 0.001), decreased the high-frequency variability of RRI (P < 0.01), but did not affect the absolute low-frequency variability of RRI. These results suggest that reductions in cardiac vagal tone and modulation contribute at least in part to the reduction in RRI during hyperinsulinemia. Moreover, more than twofold increases in MSNA occurring concurrently with a slight and not purely sympathetically mediated tachycardia suggest regionally nonuniform increases in sympathetic activity during hyperinsulinemia in humans.

Adrenergic beta-Antagonists↗

PubMed1998

Sympathetic nerve activity and insulin sensitivity in normotensive offspring of hypertensive parents.

Insulin resistance and elevated sympathetic nerve activity (SNA) are observed in young borderline hypertensive humans. A positive family history of hypertension (FH) is a strong risk factor for developing hypertension. To assess whether insulin resistance and increased sympathetic tone precede the onset of hypertension, we studied 17 young adults with and 17 without a documented family history of hypertension. Subjects were matched for age (33+/-0.4 years in FH positive and 32+/-0.5 years in FH negative; mean+/-SE) and body mass index (BMI, 25+/-1 kg/m2 in both FH positive and FH negative subjects). We measured blood pressure (BP), heart rate (HR), muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow, and insulin sensitivity (total glucose uptake determined by an euglycemic/hyperinsulinemic clamp using stable isotope tracer infusion), and calculated forearm vascular resistance (FVR). Mean BP and HR were similar in both groups (86+/-3 mm Hg and 61+/-2 beats/min, and 85+/-2 mm Hg and 62 +/-2 beats/min, respectively, in FH positive and negative respectively, P = ns). Baseline MSNA (24 +/-3 bursts/min in FH positive v 20+/-3 bursts/min in FH negative, P = ns) and total glucose uptake [0.104+/-0.014 mg/(kg x min x microU insulin/mL) in FH positive v 0.095+/-0.014 mg/(kg xmin x microU insulin/mL) in FH negative, P = ns] did not differ between the groups. Sympathetic and vascular responses to insulin were also similar in both groups. The increase in MSNA was 10+/-2 bursts/ min in FH positive and 10+/-1 bursts/min in FH negative, P = ns. Thus, age- and weight-matched offspring with and without a FH of hypertension did not vary in MSNA or insulin sensitivity. These findings suggest that in the absence of obesity and high arterial pressure, a FH of hypertension may not be accompanied by decreased insulin sensitivity or increased MSNA.

Adult↗

PubMed1997

Contrasting autonomic and hemodynamic effects of insulin in healthy elderly versus young subjects.

Acute increases in plasma insulin produce both sympathoexcitation and vasodilation in normal young adults. Aging is associated with insulin resistance and may alter the sympathetic or the vascular responses to insulin. Therefore, we assessed sympathetic and vascular responses to acute physiological increases in plasma insulin levels in 10 healthy, normotensive elderly (65+/-2 years) and 12 normal young (27+/-1 years) subjects matched for body mass index (25+/-1 kg/m2 in both groups). We measured muscle sympathetic nerve activity (microneurography), FBF (plethysmography), heart rate, and blood pressure and calculated forearm vascular resistance and insulin sensitivity (M value) during a 90-minute hyperinsulinemic/euglycemic clamp. M values were 4.3+/-0.4 mg x kg(-1) x min(-1) in the elderly and 8.4+/-1.4 mg x kg(-1) x min(-1) in the young subjects (P<.05). Baseline muscle sympathetic nerve activity was higher in the elderly subjects (33+/-3 versus 15+/-2 bursts per minute, P<.05); however, the absolute and percent increases in muscle sympathetic nerve activity were smaller in the elderly than in the young subjects (+10+/-1 versus +15+/-1 bursts per minute, or +37+/-11% versus +110+/-16%, P<.05). Forearm vascular resistance decreased with insulin from 46+/-2 to 31+/-3 units in the young but increased with insulin in the elderly subjects from 37+/-3 to 47+/-7 units (P<.05). Heart rate increased in young but not in elderly subjects. Insulin did not change blood pressure in either group. In conclusion, as opposed to vasodilation in young adults, insulin caused vasoconstriction in healthy elderly individuals. The failure of the vasodilator action of insulin in the elderly may permit even modest insulin-induced sympathoexcitation to elicit vasoconstriction. We speculate that the vasoconstrictor response to insulin may further potentiate insulin resistance in the elderly.

Adult↗

PubMed1996

Glucose effectiveness, peripheral and hepatic insulin sensitivity, in obese and lean prepubertal children.

OBJECTIVE: To determine whether prepubertal (Tanner I) obese children have diminished peripheral insulin sensitivity (IS) and to determine whether obesity affects the ability of glucose to stimulate its own disposal (glucose effectiveness, GE). DESIGN: Cross-sectional study of two groups. SUBJECTS: Seven obese (BMI > 75% for age, 26.1 +/- 2.1 kg/m2, age, 10.9 +/- 0.6 y, mean +/- SE) and six lean (BMI, 15.7 +/- 0.7 kg/m2, age, 10.3 +/- 0.7) children. METHODS: IS and GE by 3 h frequently sampled intravenous glucose tolerance test with 13% [6-6] D2-glucose in the glucose bolus (250 mg/kg), hepatic glucose production using Steele's non steady state equations and hepatic insulin resistance (HR) multiplying by the mean insulin level. RESULTS: IS was markedly lower (p < 0.01) in the obese group (0.27 +/- 0.08 (pmol l)/min) compared to the lean group (2.23 +/- 1.0 (pmol/l)min) whereas GE was higher (0.021 +/- 0.001 vs 0.015 +/- 0.001/min, p < 0.05). HR was increased in the obese (132 +/- 28 vs 58 +/- 14 mg/kg/min/pmol/l, p < 0.05). Obese children also had increased insulin secretion over the first 19 min (p > 0.01) following glucose although plasma glucose levels were higher (p < 0.01). CONCLUSION: These results show that obese prepubertal children have peripheral and hepatic insulin resistance. The increase in GE and insulin secretion may be compensatory responses to these defects in insulin action.

Aging↗

PubMed1995

Dissociation of sympathoexcitatory and vasodilator actions of modestly elevated plasma insulin levels.

OBJECTIVE: To determine sympathetic and vascular responses to modest increases in plasma insulin level. BACKGROUND: Most studies of sympathetic and vascular actions of insulin have evaluated high plasma insulin levels ( > 50 microU/ml). Those levels increase sympathetic nerve activity but also cause vasodilation. Hypertension and obesity are associated with only modestly elevated fasting insulin levels. METHODS: We investigated the effects of a 90 min low-dose hyperinsulinemic euglycemic clamp on muscle sympathetic nerve activity (microneurography), forearm vascular resistance (plethysmography), heart rate, blood pressure and central venous pressure. Insulin and vehicle sessions were performed in 12 normal subjects. RESULTS: Plasma insulin levels were elevated from values of 10 +/- 2 in the fasting state to 25 +/- 3 microU/ml during insulin infusion. Insulin levels did not change during vehicle administration. Muscle sympathetic nerve activity increased from 16 +/- 2 to 25 +/- 3 burst/min during the insulin session and did not change during vehicle administration. In contrast to muscle sympathetic nerve activity, forearm vascular resistance did not change during insulin administration (from 50 +/- 3 to 51 +/- 4 U). Forearm vascular resistance tended to fall during vehicle administration (from 45 +/- 2 to 37 +/- 3 U). There were no changes in heart rate, blood pressure and central venous pressure that could be attributed to insulin. CONCLUSIONS: Modest elevations of plasma insulin levels produce sympathetic activation similar to that caused by high levels, but, in contrast to high levels modest elevations in plasma insulin level do not decrease forearm vascular resistance. The present findings suggest a dissociation between sympathoexcitatory and vascular actions of insulin at low plasma levels.

Adult↗

PubMed1995

Altered insulin resistance is associated with increased dietary weight loss in obese children.

To determine the relationship between insulin resistance and weight loss in early obesity, we used the euglycemic, hyperinsulinemic clamp to study the effect of a 14-day weight reduction diet in 10 prepubertal and early pubertal obese children (age, 10.1 +/- 1.6 years) on insulin sensitivity. Body weight decreased from 73.7 +/- 6.0 kg to 69.1 +/- 5.8 kg (p < 0.01). Insulin sensitivity before weight reduction negatively correlated with the amount of weight loss during diet (r = -0.8, p < 0.005). Weight loss also positively correlated with height standard deviation score (r = 0.9, p < 0.005). Mean insulin sensitivity increased from 0.068 +/- 0.01 (nmol kg-1 min-1)/(pmol l-1) to 0.096 +/- 0.030 (nmol kg-1 min-1)/(pmol l-1) (p < 0.05, one-tailed test). These results indicate that weight reduction decreases insulin resistance in childhood obesity. The inverse relationship between insulin sensitivity and weight loss during calorie, restriction in these subjects suggests that insulin resistance may enhance weight loss during calorie restriction.

Blood Glucose↗

PubMed1995

Insulin antagonistic effects of growth hormone in short children.

Growth hormone has several insulin antagonistic effects. To determine the time course of these effects in growth-hormone-treated children, the frequently samples intravenous glucose tolerance test was used to measure insulin sensitivity (SI) and glucose effectiveness (Sg) before, and 1 week, 1 month and 6 months after beginning growth hormone therapy in 3 patients with growth hormone deficiency (GHD), 3 patients with non-growth-hormone-deficient short stature (NGHD) and 3 with Turner syndrome (TS). Pretreatment SI was lower in TS than in the other two groups (p < 0.05), but Sg did not differ between groups. Mean SI levels 1 week and 1 month after starting growth hormone therapy were not different from before growth hormone [1.67 +/- 0.26 x 10(-4) (pmol/l)-1 min-1]. SI after 6 months of growth hormone [0.67 +/- 0.15 x 10(-4) (pmol/l)-1 min-1] was lower than before and 1 week after growth hormone (p < 0.005). SI responses did not differ between groups. Sg, glucose tolerance, blood pressure, triglyceride, and cholesterol levels did not change, but the incremental insulin response increased with growth hormone therapy. Thus, in this small study 6 months of growth hormone therapy decreased SI, but did not affect other cardiovascular risk factors.

Blood Glucose↗

PubMed1995

Muscle sympathetic nerve activity is higher in intensively versus conventionally treated IDDM subjects.

OBJECTIVE: To determine whether poor long-term glycemic control may play a role in the lower muscle sympathetic nerve activity (MSNA) levels in insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Intraneural electrodes were used to record MSNA from the peroneal nerve at baseline and during euglycemic insulin infusion (120 mU.m-2.min-1) in 16 IDDM subjects enrolled in the Diabetes Control and Complications Trial (DCCT), 8 intensively treated (HbA1c 7.1 +/- 1.2%) and 8 conventionally treated (HbA1c 9.0 +/- 1.5%; P < 0.05). RESULTS: Fasting plasma glucose levels tended to be higher at baseline in the conventionally treated group (11.3 +/- 1.7 mmol/l) than in the intensively treated group (7.4 +/- 1.1 mmol/l, P < 0.1), but did not differ during insulin infusion (conventional, 5.0 +/- 0.3 mmol/l; intensive, 5.1 +/- 0.4 mmol/l). Plasma free insulin levels did not differ between groups either before or during insulin infusion. The intensively treated group had significantly high MSNA levels than the conventionally treated group both in the fasting state (16.2 +/-2.7 vs 10.5 +/- 4.4 bursts/min, P < 0.05 and during insulin infusion with euglycemia (27.8 +/- 2.1 vs 17.5 +/- 5.2 bursts/min. CONCLUSIONS: MSNA levels in intensively treated IDDM subject are higher than in conventionally treated subjects. These results suggest that improved long-term glycemic control is associated with increased sympathetic neural outflow to muscle. The mechanism for this effect remains unclear.

Adult↗

PubMed1994

Hypoglycemia increases muscle sympathetic nerve activity in IDDM and control subjects.

OBJECTIVE: The relationship between the increase in adrenomedullary catecholamine secretion and the sympathetic response to hypoglycemia is not well understood in humans. To explore this relationship more closely, we directly muscle sympathetic nerve activity (MSNA) in control subjects and in insulin-dependent diabetes mellitus (IDDM) subjects without clinically evident diabetic complications. RESEARCH DESIGN AND METHODS: Twelve IDDM subjects (22.5 +/- 3.9 years of age, diabetes duration of 9.8 +/- 8.3 years) and 12 age-matched control subjects were studied. MSNA was measured during insulin infusion (720 pM.m-2.min-1) with 30-min periods of 1) euglycemia, 2) hypoglycemia (target plasma glucose, 2.8 mM), and 3) recovery. The effect of increased insulin dose (1,440 pM.m-2.min-1) was studied in six subjects in each group, and the effect of prolonged hypoglycemia (1 h) was studied in five IDDM subjects and four control subjects. RESULTS: MSNA levels increased in IDDM and control subjects, 31 +/- 8 and 29 +/- 6%, respectively, above euglycemia during hypoglycemia and returned to euglycemic levels during recovery. MSNA levels during hypoglycemia were lower in IDDM subjects than in control subjects (26 +/- 3 vs. 35 +/- 2 bursts/min, P < 0.01). Importantly, no relationships were found between the MSNA and epinephrine responses to hypoglycemia in either group. Increasing the insulin infusion rate did not alter the MSNA response to hypoglycemia. During prolonged hypoglycemia, MSNA remained elevated above euglycemic levels throughout hypoglycemia. CONCLUSIONS: These results demonstrate that insulin-induced hypoglycemia increases muscle sympathetic neural outflow in IDDM and control subjects. The lack of correlation between the MSNA and epinephrine responses to hypoglycemia indicates that the adrenomedullary and peripheral sympathetic responses to hypoglycemia are independently mediated.

Adult↗

PubMed1993

Effects of maturational stage on insulin sensitivity during puberty.

During puberty, plasma insulin levels increase, and insulin sensitivity decreases along with multiple other physical and hormonal changes. To determine 1) the time course of the decrease in insulin sensitivity in relationship to Tanner stage of genital development, and 2) how this change relates to changes in GH secretion, insulin-like growth factor-I (IGF-I), IGF-binding protein-3, and gonadal steroid secretion, we studied 58 healthy children and adolescents (34 males and 24 females; age 7-15 yr) using overnight GH sampling and frequently sampled iv glucose tolerance tests. The insulin sensitivity index (ISI) was calculated using the program MINMOD. ISI differed significantly by Tanner stage (P < 0.05, by analysis of variance) with a decrease from Tanner stage 1 to 2 (P < 0.05). IGF-I and IGF-binding protein-3 followed opposite patterns to ISI, with lower levels in Tanner stage 1 than in stages 2-5 (P < 0.05). Mean GH levels did not increase until Tanner stage 4 (P < 0.05) and then fell during Tanner stage 5. Multiple linear regression analysis revealed negative relationships among ISI, IGF-I, and body mass index. No relationship was found with GH. We conclude that the pubertal change in ISI is not necessarily associated with increased GH secretion, but is associated with increased GH peripheral effect, as indicated by the relationship between ISI and IGF-I.

Adolescent↗

PubMed1993

Muscle sympathetic nerve activity is reduced in IDDM before overt autonomic neuropathy.

Studies of heart-rate variability have demonstrated that abnormal cardiac parasympathetic activity in individuals with IDDM precedes the development of other signs or symptoms of diabetic autonomic neuropathy. To determine whether IDDM patients have impaired sympathetic activity compared with normal control subjects before the onset of overt neuropathy, we directly recorded MSNA. We also examined the effects of changes in plasma glucose and insulin on sympathetic function in each group. MSNA was recorded by using microneurographic techniques in 10 IDDM patients without clinically evident diabetic complications and 10 control subjects. MSNA was compared during a 15-min fasting baseline period and during insulin infusion (120 mU.m-2.min-1) with 30 min of euglycemia. A cold pressor test was performed at the end of euglycemia. Power spectral analysis of 24-h RR variability was used to assess cardiac autonomic function. IDDM patients had lower MSNA than control subjects at baseline (8 +/- 1 vs. 18 +/- 3 burst/min, P < 0.02). MSNA increased in both groups with insulin infusion (P < 0.01) but remained lower in IDDM patients (20 +/- 3 vs. 28 +/- 3 burst/min, P < 0.01). In the IDDM group, we found no relationships between MSNA and plasma glucose, insulin, or HbA1c concentrations. BP levels did not differ at rest or during insulin. Heart-rate variability and the MSNA response to cold pressor testing in IDDM patients did not differ from those in healthy control subjects. IDDM patients had reduced MSNA at rest and in response to insulin. The lower MSNA is not attributable to differences in plasma glucose or insulin, but, rather, is most likely an early manifestation of diabetic autonomic neuropathy that precedes impaired cardiac parasympathetic control.

Adolescent↗

PubMed1992

Insulin increases sympathetic activity but not blood pressure in borderline hypertensive humans.

We have previously demonstrated that physiological hyperinsulinemia in normotensive humans increases sympathetic nerve activity but not arterial pressure since it also causes skeletal muscle vasodilation. However, in the presence of insulin resistance and/or hypertension, insulin may cause exaggerated sympathetic activation or impaired vasodilation and thus elevate arterial pressure. This study sought to determine if insulin causes a pressor response in borderline hypertensive humans by producing exaggerated increases in sympathetic neural outflow or impaired vasodilation. We recorded muscle sympathetic nerve activity (microneurography, peroneal nerve), forearm blood flow, heart rate, and blood pressure in 13 borderline hypertensive subjects during a 1-hour insulin infusion (38 microunits/m2/min) while holding blood glucose constant. Plasma insulin rose from 12 +/- 3 microunits/ml (mean +/- SEM) during control to 73 +/- 7 microunits/ml during insulin infusion and fell to 9 +/- 2 microunits/ml 2 hours after insulin infusion was stopped. Muscle sympathetic nerve activity, which averaged 25 +/- 2 bursts per minute in control, increased significantly during insulin infusion (+9 bursts per minute) and remained elevated 1.5 hours into recovery (+7 bursts per minute, p less than 0.001). Despite increased muscle sympathetic nerve activity, there were significant (p less than 0.001) increases in forearm blood flow and decreases in forearm vascular resistance during insulin infusion. Further, systolic and diastolic pressures fell approximately 3 and 6 mm Hg, respectively, during insulin infusion (p less than 0.01). This study suggests that acute physiological increases in plasma insulin elevate sympathetic neural outflow in borderline hypertensive humans but produce vasodilation and do not elevate arterial pressure.

Adult↗

PubMed1991

A review of Klinefelter's syndrome in children and adolescents.

Klinefelter's syndrome (XXY syndrome) has been defined as the spectrum of phenotypic features resulting from a sex chromosome complement that includes two or more X chromosomes and one or more Y chromosomes. Cytogenetic surveys conducted across the world have identified a sizable population of XXY males, who have been studied extensively from the newborn period through adolescence. The longitudinal studies of these boys have produced an accurate and reliable account of the growth and development of the XXY male. There now exists a growing body of knowledge that suggests that XXY boys often experience language deficits, neuromaturational lag, academic difficulties, and psychological distress, which may be reduced or ameliorated by early identification, anticipatory guidance, and proper medical management.

Adolescent↗

PubMed1991

Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.

Hyperinsulinemia may contribute to hypertension by increasing sympathetic activity and vascular resistance. We sought to determine if insulin increases central sympathetic neural outflow and vascular resistance in humans. We recorded muscle sympathetic nerve activity (MSNA; microneurography, peroneal nerve), forearm blood flow (plethysmography), heart rate, and blood pressure in 14 normotensive males during 1-h infusions of low (38 mU/m2/min) and high (76 mU/m2/min) doses of insulin while holding blood glucose constant. Plasma insulin rose from 8 +/- 1 microU/ml during control, to 72 +/- 8 and 144 +/- 13 microU/ml during the low and high insulin doses, respectively, and fell to 15 +/- 6 microU/ml 1 h after insulin infusion was stopped. MSNA, which averaged 21.5 +/- 1.5 bursts/min in control, increased significantly (P less than 0.001) during both the low and high doses of insulin (+/- 5.4 and +/- 9.3 bursts/min, respectively) and further increased during 1-h recovery (+15.2 bursts/min). Plasma norepinephrine levels (119 +/- 19 pg/ml during control) rose during both low (258 +/- 25; P less than 0.02) and high (285 +/- 95; P less than 0.01) doses of insulin and recovery (316 +/- 23; P less than 0.01). Plasma epinephrine levels did not change during insulin infusion. Despite the increased MSNA and plasma norepinephrine, there were significant (P less than 0.001) increases in forearm blood flow and decreases in forearm vascular resistance during both doses of insulin. Systolic pressure did not change significantly during infusion of insulin and diastolic pressure fell approximately 4-5 mmHg (P less than 0.01). This study suggests that acute increases in plasma insulin within the physiological range elevate sympathetic neural outflow but produce forearm vasodilation and do not elevate arterial pressure in normal humans.

Adult↗