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Biomedical subjects

S W Coppack

Publications and source records attributed to S W Coppack.

At least 37 records · Page 2Linked to original sources
PubMed2000

Leptin production during early starvation in lean and obese women.

We evaluated abdominal adipose tissue leptin production during short-term fasting in nine lean [body mass index (BMI) 21 +/- 1 kg/m(2)] and nine upper body obese (BMI 36 +/- 1 kg/m(2)) women. Leptin kinetics were determined by arteriovenous balance across abdominal subcutaneous adipose tissue at 14 and 22 h of fasting. At 14 h of fasting, net leptin release from abdominal adipose tissue in obese subjects (10.9 +/- 1.9 ng x 100 g tissue x (-1) x min(-1)) was not significantly greater than the values observed in the lean group (7.6 +/- 2.1 ng x 100 g(-1) x min(-1)). Estimated whole body leptin production was approximately fivefold greater in obese (6.97 +/- 1.18 microg/min) than lean subjects (1.25 +/- 0.28 microg/min) (P < 0.005). At 22 h of fasting, leptin production rates decreased in both lean and obese groups (to 3.10 +/- 1.31 and 10.5 +/- 2.3 ng x 100 g adipose tissue(-1) x min(-1), respectively). However, the relative declines in both arterial leptin concentration and local leptin production in obese women (arterial concentration 13.8 +/- 4.4%, local production 10.0 +/- 12.3%) were less (P < 0.05 for both) than the relative decline in lean women (arterial concentration 39.0 +/- 5.5%, local production 56.9 +/- 13.0%). This study demonstrates that decreased leptin production accounts for the decline in plasma leptin concentration observed after fasting. However, compared with lean women, the fasting-induced decline in leptin production is blunted in women with upper body obesity. Differences in leptin production during fasting may be responsible for differences in the neuroendocrine response to fasting previously observed in lean and obese women.

Abdomen↗
PubMed2000

Physiological relationships of uncoupling protein-2 gene expression in human adipose tissue in vivo.

The physiological significance of changes in uncoupling protein-2 (UCP-2) gene expression is controversial. In this study we investigated the biochemical and functional correlates of UCP-2 gene expression in sc abdominal adipose tissue in humans in vivo. UCP-2 messenger ribonucleic acid expression was quantified by nuclease protection in adipose tissue from lean and obese humans in both the fasting and postprandial states. Plasma fatty acids, insulin, and leptin were all determined in paired samples from the superficial epigastric vein and radial artery, and local production rates were calculated from 133Xe washout. In the fasting state UCP-2 expression correlated inversely with body mass index (r = -0.45; P = 0.026), percent body fat (r = -0.41; P = 0.05), plasma insulin (r = -0.47; P = 0.02), epigastric venous fatty acids (r = -0.45; P = 0.04), and leptin (r = -0.50; P = 0.018). UCP-2 expression remained inversely related with plasma leptin after controlling for percent body (r = -0.45; P = 0.038). At 2 or 4 h postprandially, there were no significant relationships between UCP-2 expression and biochemical parameters. In conclusion, 1) UCP-2 messenger ribonucleic acid expression in sc adipose tissue is inversely related to adiposity and independently linked to local plasma leptin levels; and 2) UCP-2 expression is not acutely regulated by food intake, insulin, or fatty acids. Reduced UCP-2 expression may be a maladaptive response to sustained energy surplus and could contribute to the pathogenesis and maintenance of obesity.

Adipose Tissue↗
PubMed1999

Lack of evidence for secretion of plasminogen activator inhibitor-1 by human subcutaneous adipose tissue in vivo.

Circulating plasminogen activator inhibitor-1 (PAI-1) levels are elevated in patients with coronary heart disease and may play an important role in atherothrombosis. Levels are also raised in obese, hypertriglyceridaemic, or insulin-resistant subjects, which predispose people to coronary heart disease. It is unclear, though, which organ is responsible for PAI-1 secretion, either in health or disease. We measured arteriovenous differences across a subcutaneous adipose tissue bed in 25 subjects without coronary heart disease, which, combined with measures of adipose tissue blood flow, provides synthetic rates. There was no net increase in levels of PAI-1 activity (median change 0.23, interquartile range -0.59, 1.21 IU x L(-1), p=0.30) or of PAI-1 antigen (mean change -0.01, SD+/-2.93 ng x mL(-1), p=0.98) in these subjects. Assuming homogeneous production of PAI-1 by all adipose tissue beds, the contribution of adipose tissue to PAI-1 activity is 3.1% (interquartile range, -11.7, +7.0%) and to PAI-1 antigen 1.6% (interquartile range -14.5, +7.3%). Arteriovenous difference of PAI-1 activity and antigen did not relate to measures of obesity, triglyceride, insulin, fatty acids, or circulating concentrations or adipose tissue production of tumour necrosis factor-alpha or interleukin-6. We conclude that, at least in healthy subjects, subcutaneous adipose tissue does not contribute significantly to circulating levels of PAI-1.

Adipose Tissue↗
PubMed1999

An in vivo study of the cortisol-cortisone shuttle in subcutaneous abdominal adipose tissue.

OBJECTIVE: Previous in vitro studies have demonstrated significant 11-beta hydroxysteroid dehydrogenase (11 beta-HSD) oxo-reductase activity in visceral, but not subcutaneous adipose stromal cells. We have conducted an in vivo study of the cortisol-cortisone shuttle in subcutaneous abdominal adipose tissue. DESIGN: We measured arteriovenous (A-V) differences in serum cortisol and cortisone across subcutaneous abdominal adipose tissue and forearm muscle in a heterogeneous group of subjects. PATIENTS: We studied 34 subjects (male:female = 12:22), age median (interquartile range) 45 (19-65) years, body mass index 32.7 (20.4-77.1) kg m-2, total body fat 34.4 (5.6-119.1) kg. MEASUREMENTS: Serum cortisol and cortisone were measured in serum samples from a radial artery, superficial epigastric vein and deep forearm vein. Abdominal adipose and forearm blood flow rates were measured by 133Xenon washout and plethysmography, respectively. RESULTS: For cortisone, there was significant (P < 0.001) clearance by adipose tissue, with an A-V difference of 4 (1-7) nmol/l. For cortisol there was a trend for arterial concentrations (203 (142-292) nmol/l) to be lower than venous (225 (152-263) nmol/l), but this was not significant. The adipose tissue cortisone clearance rate correlated with total body fat (r = 0.35, P = 0.05). CONCLUSIONS: We have demonstrated 11 beta-HSD oxo-reductase activity in subcutaneous abdominal adipose tissue, which may be increased in obesity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Glycerol and nonesterified fatty acid metabolism in human muscle and adipose tissue in vivo.

To determine the relationship between glycerol and nonesterified fatty acid (NEFA) release from adipose tissue, and to test whether forearm muscle and abdominal adipose tissue are capable of extracting these two lipolytic products from the circulation, 13 male subjects were studied after an overnight fast during combined infusion of radiolabeled palmitate and glycerol. Blood samples were taken from a radial artery, a deep forearm vein, and a superficial abdominal vein before and during a 2-h infusion of glucose at approximately 7 mg. kg-1. min-1. The ratio of the appearance rates of total NEFA to glycerol was approximately 3/1 during the baseline period but decreased to 1.3/1 during glucose infusion. There was significant extraction of both glycerol and NEFA by forearm muscle. In contrast, there was no apparent uptake of glycerol by adipose tissue. Adipose tissue NEFA uptake was undetectable during the baseline period but became significant during glucose infusion. These data indicate that there is very little to no in situ reesterification of NEFA in adipose tissue after an overnight fast. During glucose infusion, there was apparently a relative increase in the fraction of glycerol derived from the action of lipoprotein lipase and an increase in reesterification in situ.

Abdomen↗
PubMed1999

Effect of short-term fasting on lipid kinetics in lean and obese women.

We evaluated whole body and regional adipose tissue lipid kinetics and norepinephrine (NE) spillover during brief fasting in six lean [body mass index (BMI) 21 +/- 1 kg/m2] and six upper-body obese (UBO; BMI 36 +/- 1 kg/m2) women. At 14 h of fasting, abdominal adipose tissue glycerol and free fatty acid (FFA) release rates were lower (P = 0.07), but whole body glycerol and FFA rates of appearance (Ra) were greater (P < 0.05) in obese than in lean subjects. At 22 h of fasting, glycerol and FFA Ra increased less in obese (19.8 +/- 7.0 and 87.1 +/- 30.3 micromol/min, respectively) than in lean (44.2 +/- 6.6 and 137.4 +/- 30.4 micromol/min, respectively; P < 0.05) women. The percent increase in glycerol Ra correlated closely with the percent decline in plasma insulin in both groups (r2 = 0.85; P < 0.05). Whole body NE spillover declined in lean (P < 0.05) but not obese subjects with continued fasting, whereas regional adipose tissue NE spillover did not change in either group. We conclude that, compared with lean women, in UBO women 1) basal adipose tissue lipolysis is lower, but whole body lipid kinetics is higher because of their greater fat mass; 2) the increase in lipolysis during fasting is blunted because of an attenuated decline in circulating insulin; and 3) downregulation of whole body sympathetic nervous system activity is impaired during fasting.

Adipose Tissue↗
PubMed1999

Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo.

To investigate in vivo adipose tissue production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their soluble receptors: TNF receptor type I (sTNFR-I), TNF receptor type II (sTNFR-II), and IL-6 receptor (sIL-6R), we determined arteriovenous differences in their levels across abdominal subcutaneous adipose tissue in obese subjects. Subjects had a median (interquartile range) age of 44.5 (27-51.3) yr, body mass index (BMI) of 32.9 (26. 0-46.6) kg/m(2), and %body fat of 42.5 (28.5-51.2) %. Although there was not a significant difference in the arteriovenous concentrations of TNF-alpha (P = 0.073) or sTNFR-II (P = 0.18), the levels of sTNFR-I (P = 0.002) were higher in the vein compared with artery, suggesting adipose tissue production of this soluble receptor. There was a significant arteriovenous difference in IL-6 (P < 0.001) but not in its soluble receptor (P = 0.18). There was no relationship between TNF-alpha levels and adiposity indexes (r(s) = 0.12-0.22, P = not significant); however, levels of both its soluble receptor isomers correlated significantly with BMI and %body fat (sTNFR-I r(s) = 0.42-0.72, P < 0.001; sTNFR-II r(s) = 0.36-0.65, P < 0.05- <0. 001). IL-6 levels correlated significantly with both BMI and %body fat (r(s) = 0.51, P = 0.004, and r(s) = 0.63, P < 0.001), but sIL-6R did not. In conclusion, 1) soluble TNFR-I is produced by adipose tissue, and concentrations of both soluble isoforms correlate with the degree of adiposity, and 2) IL-6, but not its soluble receptor, is produced by adipose tissue and relates to adiposity.

Abdomen↗
PubMed1999

C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?

C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We have also related levels of C-reactive protein and interleukin-6 to markers of the insulin resistance syndrome and of endothelial dysfunction. We performed a cross-sectional study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly related to those of interleukin-6 (r=0.37, P<0.0005) and tumor necrosis factor-alpha (r=0.46, P<0.0001). (2) Concentrations of C-reactive protein were related to insulin resistance as calculated from the homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and to markers of endothelial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin). A mean standard deviation score of levels of acute phase markers correlated closely with a similar score of insulin resistance syndrome variables (r=0.59, P<0.00005), this relationship being weakened only marginally by removing measures of obesity from the insulin resistance score (r=0.53, P<0.00005). These data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not. Moreover, our data support the concept that such a low-level, chronic inflammatory state may induce insulin resistance and endothelial dysfunction and thus link the latter phenomena with obesity and cardiovascular disease.

Adipose Tissue↗
PubMed1999

Sources and physiological significance of plasma dopamine sulfate.

Dopamine in the circulation occurs mainly as dopamine sulfate, the sources and physiological significance of which have been obscure. In this study, plasma concentrations of dopamine sulfate were measured after a meal, after fasting for 4 days, and during i.v. L-DOPA, nitroprusside, or trimethaphan infusion in volunteers; after dopamine infusion in patients with L-aromatic-amino-acid decarboxylase deficiency; in arterial and portal venous plasma of gastrointestinal surgery patients; and in patients with sympathetic neurocirculatory failure. Meal ingestion increased plasma dopamine sulfate by more than 50-fold; however, prolonged fasting decreased plasma dopamine sulfate only slightly. L-DOPA infusion produced much larger increments in dopamine sulfate than in dopamine; the other drugs were without effect. Patients with L-aromatic amino acid decarboxylase deficiency had decreased dopamine sulfate levels, and patients with sympathetic neurocirculatory failure had normal levels. Decarboxylase-deficient patients undergoing dopamine infusion had a dopamine sulfate/dopamine ratio about 25 times less than that at baseline in volunteers. Surgery patients had large arterial-portal venous increments in plasma concentrations of dopamine sulfate, so that mesenteric dopamine sulfate production accounted for most of urinary dopamine sulfate excretion, a finding consistent with the localization of the dopamine sulfoconjugating enzyme to gastrointestinal tissues. The results indicate that plasma dopamine sulfate derives mainly from sulfoconjugation of dopamine synthesized from L-DOPA in the gastrointestinal tract. Both dietary and endogenous determinants affect plasma dopamine sulfate. The findings suggest an enzymatic gut-blood barrier for detoxifying exogenous dopamine and delimiting autocrine/paracrine effects of endogenous dopamine generated in a "third catecholamine system."

Adult↗
PubMed1999

Norepinephrine spillover in forearm and subcutaneous adipose tissue before and after eating.

The sympathetic nervous system regulates lipolysis. There are regional differences in the sensitivity of lipolysis to adrenergic regulation. Little is known about regional sympathetic activity in response to eating in humans. We studied the effect of feeding on systemic and local sympathetic nervous system activity and lipolysis in lean healthy subjects (three women and five men; age, 27.0+/-2.0; body mass index, 23.4+/-1.2 kg/m(-2)) using isotope dilution methodology and arterio-venous sampling. Feeding increased arterial norepinephrine (NE) concentration (mean premeal, 0.96+/-0.12 nmol/L x L; mean postmeal, 1.28+/-0.14 nmol/L x L; P < 0.02) and total body NE spillover (mean premeal, 2.11+/-0.30 nmol/min x L; mean postmeal, 2.76+/-0.31 nmol/min x L; P < 0.02), whereas the arterial epinephrine concentration decreased (mean premeal, 289+/-61 pmol/L; mean postmeal, 170+/-5 pmol/L; P < 0.02). Palmitate concentration and total body systemic rate of appearance of palmitate declined postprandially (mean premeal, 117 +/- 15 micromol/min; mean postmeal, 38+/-4 micromol/min; P < 0.01). NE spillover increased by the same proportion in both forearm and adipose tissue [in forearm, mean premeal and postmeal, 1.02+/-0.11 and 2.41+/-0.44. nmol/100 mL x min, respectively (P < 0.02); in adipose tissue, mean premeal and postmeal, 0.41+/-0.12 and 0.73+/-0.17 nmol/100 g x min, respectively (P < 0.02)]. The results show that a meal caused differential changes in systemic sympatho-adrenal activity and an increase in sympathetic activity in adipose tissue postprandially, However, this increase in postprandial sympathetic activity was not enough to overcome the inhibition of lipolysis by insulin.

Adipose Tissue↗
PubMed1998

Adipose tissue as an endocrine and paracrine organ.

The discovery of leptin has imparted great impetus to adipose tissue research by demonstrating a more active role for the adipocyte in energy regulation. Besides leptin, however, the adipose tissue also secretes a large number other signals. Cytokine signals, TNFalpha and IL-6, and components of the alternative pathway of complement influence peripheral fuel storage, mobilization and combustion, as well as energy homeostasis. In addition to the acute regulation of fuel metabolism, adipose tissue also influences steroid conversion and sexual maturation. In this way, adipose tissue is an active endocrine organ, influencing many aspects of fuel metabolism through a network of local and systemic signals, which interact with the established neuroendocrine regulators of adipose tissue. Thus, insulin, catecholamines and anterior pituitary endocrine axes interact at multiple levels with both cytokines and leptin. It may be proposed that the existence of this network of adipose tissue signalling pathways, arranged in an hierarchical fashion, constitutes a metabolic repertoire which enables the organism to adapt to a range of different metabolic challenges, including starvation, reproduction, times of physical activity, stress and infection, as well as short periods of gross energy excess. However, the occurrence of more prolonged periods of energy surplus, leading to obesity, is an unusual state in evolutionary terms, and the adipose tissue signalling repertoire, although sophisticated, adapts poorly to these conditions. Rather, the responses of the adipose tissue endocrine network to obesity are maladaptive, and lay the foundations of metabolic disease.

Adipose Tissue↗
PubMed1998

Effect of isoprenaline on plasma leptin and lipolysis in humans.

OBJECTIVE: The sympathetic nervous system may play a central role in the regulation of both lipolysis and leptin production. Therefore, we investigated the effect of intravenous infusions of the beta-adrenergic agonist isoprenaline on plasma concentrations of leptin and nonesterified fatty acids. DESIGN AND PATIENTS: Eight lean, healthy human volunteers, (4M:4F; median (interquartile range) age 36.5 (30.8-40.0) years; BMI 22.9 (20.1-29.2) kg.m-2; % body fat 24.5 (17.9-26.3)), were studied following an overnight fast. Intravenous infusion of isoprenaline was carried out for 3 h, followed by a 1 hour recovery phase. The isoprenaline infusion rates (0.5-3.5 micrograms.min-1) were titrated individually for each subject in order to achieve similar biological sympathetic responses based on heart rate (target heart rates were > 100 min-1 but < twice resting heart rate). MEASUREMENTS: Plasma leptin was determined using an in-house radioimmunoassay, nonesterified fatty acids estimated with an enzymatic colourimetric assay and insulin concentrations were assayed using a specific, two-site immunoenzymometric assay. RESULTS: Fasting preinfusion plasma leptin concentrations (6.3 (3.0-12.8) micrograms/l) correlated with percentage body fat measured by bioimpedance (r = 0.95; P < 0.001). Plasma leptin concentrations were rapidly suppressed by isoprenaline, with maximal suppression (20.5 (15.0-25.0)% of preinfusion levels (Wilcoxon rank sum test; P < 0.05)), observed after 2 h. In the recovery period, plasma leptin concentrations rapidly returned to preinfusion levels (postinfusion vs maximally suppressed leptin concentrations P < 0.05; vs preinfusion leptin concentrations P = NS). Plasma nonesterified fatty acids and insulin concentrations showed opposite changes to those observed with leptin. CONCLUSION: Plasma leptin concentrations are rapidly and reversibly suppressed by the infusion of isoprenaline in humans in vivo.

Adrenergic beta-Agonists↗
PubMed1998

Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects.

OBJECTIVE: To study interactions between leptin and the pituitary-thyroid axis, both in euthyroid and dysthyroid states. SUBJECTS AND MEASUREMENTS: We investigated the relationships of plasma leptin to levels of free thyroid hormones and TSH in 18 patients with newly diagnosed hyperthyroidism, 22 with newly diagnosed primary hypothyroidism, and 32 lean (body mass index [BMI] < 30) and 37 obese (BMI > 30 kg/m2) euthyroid subjects. Hypothyroid patients were restudied during thyroxine replacement treatment. RESULTS: Median [interquartile range] plasma leptin concentrations were highest in obese euthyroid subjects (31.5 [19.0-48.0] and in untreated hypothyroid patients (19.2 [11.5-31.5]), and lowest levels in untreated hyperthyroid patients (8.9 [5.5-11.1]) and lean euthyroid control subjects (6.6 [3.9-14.4] micrograms/l (Kruskall-Wallis one-way analysis of variance; P < 0.0001). In euthyroid subjects, plasma leptin levels were higher in obese than in lean subjects (P < 0.00001). In obese subjects plasma levels of TSH correlated with percentage body fat (r = 0.67; P < 0.001) and plasma leptin (r = 0.61; P < 0.001). In untreated hyperthyroid subjects plasma leptin was unrelated to free T3, and in untreated hypothyroidism plasma leptin was unrelated to either free T3 or TSH concentrations (all P = NS). In untreated hyperthyroid, but not hypothyroid, patients plasma leptin concentrations correlated with BMI (r = 0.57; P = 0.02). Treatment of hypothyroidism with thyroxine resulted in a significant reduction in plasma leptin concentrations from 20.8 (11.8 to 31.6) to 12.9 (4.6-21.2) micrograms/l (P = 0.005), but BMI did not change significantly in the hypothyroid subjects being studied prospectively. CONCLUSIONS: (i) In euthyroid subjects, plasma leptin and TSH levels correlate, and both are positively correlated with adiposity. (ii) Plasma leptin was significantly elevated in hypothyroid subjects, to levels similar to those seen in obese euthyroid subjects. (iii) Treatment of hypothyroidism resulted in a reduction in the raised plasma leptin levels. The data are consistent with the hypothesis that leptin and the pituitary-thyroid axis interact in the euthyroid state, and that hypothyroidism reversibly increases leptin concentrations.

Adult↗
PubMed1998

Whole body, adipose tissue, and forearm norepinephrine kinetics in lean and obese women.

We evaluated whole body and regional (subcutaneous abdominal adipose tissue and forearm) norepinephrine (NE) kinetics in seven lean (body mass index 21.3 +/- 0.5 kg/m2) and six upper body obese (body mass index 36.4 +/- 0.4 kg/m2) women who were matched on fat-free mass. NE kinetics were determined by infusing [3H]NE and obtaining blood samples from a radial artery, a deep forearm vein draining mostly skeletal muscle, and an abdominal vein draining subcutaneous abdominal fat. Mean systemic NE spillover tended to be higher in obese (2.82 +/- 0.49 nmol/min) than in lean (2.53 +/- 0.40 nmol/min) subjects, but the differences were not statistically significant. Adipose tissue and forearm NE spillover rates into plasma were greater in lean (0.91 +/- 0.08 pmol. 100 g tissue-1. min-1 and 1.01 +/- 0.09 pmol. 100 ml tissue-1. min-1, respectively) than in obese (0.26 +/- 0.05 pmol. 100 g tissue-1. min-1 and 0.58 +/- 0.11 pmol. 100 ml tissue-1. min-1, respectively) subjects (P < 0.01). These results demonstrate that adipose tissue is an active site for NE metabolism in humans. Adipose tissue NE spillover is considerably lower in obese than in lean women, which may contribute to the lower rate of lipolysis per kilogram of fat mass observed in obesity.

Adipose Tissue↗
PubMed1998

Relation between number of cardiovascular risk factors/events and noninvasive Doppler ultrasound assessments of aortic compliance.

The aim of this study was to establish the relation between noninvasive Doppler ultrasound assessments of aortic compliance, based on "foot-to-foot" aortic pulse wave velocity measurements, and presumed atherosclerotic load in patients with vascular disease and/or diabetes mellitus. One hundred ten patients with vascular disease and/or diabetes mellitus (arteriopaths) underwent measurement of in vivo aortic compliance using Doppler ultrasound. Demographic data on these subjects were recorded along with details of cardiovascular risk factors and events. Aortic compliance values were compared with data from 51 age-matched healthy, asymptomatic subjects putatively free of vascular disease (controls). Data are expressed as mean+/-SD. Arteriopaths were aged 64.1+/-8.4 years and had total cholesterol levels of 5.9+/-1.1 mmol/L and aortic compliance of 0.78+/-0.42%/10 mm Hg [1.33 kPa]. Most arteriopaths had 2 or more cardiovascular risk factors and events: diabetes (n=41), hypertension (n=45), smoking (n=86), cerebrovascular/transient ischemic event (n=13), myocardial infarction (n=44), angina (n=51), and/or peripheral vascular disease (n=33). Controls were aged 64.3+/-12.1 years with total cholesterol of 6.1+/-1.1 mmol/L and aortic compliance of 1.14+/-0.46%/10 mm Hg [1.33 kPa] (P<0.002 versus arteriopaths). Subset analysis revealed that patients with the greatest number of cardiovascular risk factors and events (n=5) had the stiffest aortas (aortic compliance, 0.58+/-0.15%/10 mm Hg [1.33 kPa]) compared with those patients with the median and mean (n=2) number of risk factors and events (aortic compliance, 0.80+/-0.50%/10 mm Hg [1.33 kPa]; P<0.02). The data suggest that a significant inverse relation exists between presumed atherosclerotic load (as assessed by the number of cardiovascular risk factors and events) and aortic compliance determined noninvasively based on aortic pulse wave velocity measurements. If these findings are confirmed by prospective, longitudinal follow-up studies, such measurements may prove useful as a noninvasive marker of vascular risk.

Adult↗
PubMed1998

Effect of salt-loading on blood pressure, insulin sensitivity and limb blood flow in normal subjects.

1. The aim of this study was to determine the effects of high (220 mmol/day) and low (40 mmol/day) salt intake for 6 days on blood pressure, leg blood flow and insulin sensitivity in 18 healthy normotensive subjects. 2. Twenty-four-hour ambulatory blood pressure was measured at baseline, during salt-loading and salt-depletion. Insulin sensitivity was determined by a two-step euglycaemic-hyperinsulinaemic clamp (low and high insulin infusion rates: 40 and 600 m-unit.min-1.m-2 respectively) and leg blood flow by plethysmography. 3. Salt-loading resulted in changes in weight [change between salt-loading and salt-restriction: delta=+0.45 (S.D. +/-0.69) kg, P=0.015], plasma renin [delta=-11.5 (S.D.+/-12.9) micro-units/l, P=0.001] and urinary noradrenaline [delta=-8.6 (S.D. +/-18.7) nmol/mmol creatinine, P=0.05]. There were borderline significant increases in 24-h systolic blood pressure [delta=+5.8 (S. D.+/-14.2) mmHg, P=0.06] and plasma volume [delta=+0.29 (S.D.+/-0. 67) litres, P=0.08]. 4. Insulin sensitivity was similar in both salt states. Geometric mean metabolic clearance rate of low-dose insulin: low salt, 5.13 (S.D.x//1.35) dl/min; high salt, 4.94 (S.D.x//1.37) dl/min, P=1.0. Geometric mean metabolic clearance rate of high-dose insulin: low salt, 9.68 dl/min (S.D.x//1.30); high salt, 9.68 (S.D. x//1.27) dl/min, P=0.69. 5. Leg blood flow response to high-dose insulin on high salt increased significantly compared with low salt. Percentage change of blood flow on low salt, delta=+36.6 (S.D.+/-22. 9)% versus high salt, delta=+66.8 (S.D.+/-52.2)%, P=0.03. 6. There were no significant relationships between salt-related changes in limb blood flow and changes in insulin sensitivity at either insulin infusion rate. 7. We conclude that salt-loading, despite changing body weight, the renin-angiotensin-aldosterone system, urinary noradrenaline and the leg blood flow response to insulin, has no significant effect on insulin sensitivity. Salt-loading causes dissociated effects on insulin-induced vasodilatation and glucose disposal.

Aldosterone↗
PubMed1997

Relationships between plasma leptin and insulin concentrations, but not insulin resistance, in non-insulin-dependent (type 2) diabetes mellitus.

In non-diabetic subjects, insulin concentrations and insulin resistance are clearly connected, and both correlate with leptin levels, making interpretations about mechanisms difficult. In non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), however, insulin concentrations and insulin resistance are less closely associated. Therefore, we examined the relationship of plasma leptin concentrations within insulin resistance and insulin levels in 32 subjects with NIDDM, who underwent measurement of insulin resistance with an insulin sensitivity test. Plasma leptin was measured with an in-house monoclonal immunoradiometric assay. Fasting leptin level correlated with BMI (r = 0.78; p < 0.001), metabolic clearance rate of glucose (= -0.44; p = 0.015), and fasting specific insulin (r = 0.58; p = 0.001), but not with age, cholesterol, triglycerides or blood pressure (r = -0.26 to 0.21; p = NS). In linear regression analysis, after adjustment for BMI and gender, leptin concentrations correlated with those of insulin (partial r = 0.42; p = 0.025), but not insulin resistance (partial r = -0.10; p = NS). We conclude that in NIDDM, concentrations of plasma leptin are closely related to those of insulin per se and to obesity, but not to insulin resistance. Insulin may be an important regulator of leptin concentration in NIDDM.

Blood Glucose↗