Serum resistin is reduced by glucose and meal loading in healthy human subjects

Resistin is an adipokine that induces insulin resistance in mice; serum concentrations are decreased by fasting and increased by feeding. Adiponectin, another adipokine, improves insulin sensitivity. The aims of this study were to determine the effects of glucose and meal loading on serum resistin and total and high-molecular weight (HMW) adiponectin in humans and to explore potential determinants of fasting serum resistin and of changes in resistin. Serum resistin and total and HMW adiponectin were measured by enzyme-linked immunosorbent assay in young, lean, nondiabetic subjects during 75-g oral glucose tolerance test (OGTT) and meal tolerance test (MTT). Resistin single nucleotide polymorphism (SNP) -420 was typed. Serum resistin was decreased at 60 and 120 minutes during OGTT compared with baseline (n = 36, 1-way repeated-measures analysis of variance, P < .0001; Scheffe, P = .0457 and P < .0001, respectively). Serum resistin was also reduced at 240 minutes during MTT (n = 33, 1-way repeated measures analysis of variance, P < .0001; Scheffe, P = .0002). Multiple regression analysis adjusted for age, sex, and body mass index revealed that the reductions in serum resistin were dependent on baseline resistin levels. Subjects with greater baseline concentrations of resistin experienced more pronounced declines in resistin (OGTT, unstandardized regression coefficient (beta) = -0.19, P = .0005; MTT, beta = -0.63, P < .0001). Serum total and HMW adiponectin was unchanged. Fasting serum resistin was positively correlated with the G allele number of SNP -420 (beta = 7.70, P = .01) and white blood cell count (beta = 0.007, P = .0001) adjusted for age, sex, and body mass index. Therefore, in young, lean, nondiabetic humans, serum resistin was reduced by glucose and meal loading; the reduction in resistin was greater in subjects with higher fasting resistin. Fasting resistin was correlated with SNP -420 and white blood cell count.     

GIP and insulin responses to a test meal in healthy and obese subjects

Twenty-three obese and 17 control subjects were studied after ingestion of a heavy breakfast. Blood samples were drawn before and at 30, 60, 90, 120, 150, and 180 min after the start of the meal. The m ean serum insulin level was significantly (p less than 0.02) higher in the obese than in the control group throughout the study, whereas the mean blood glucose concentration was significantly (p less than 0.02) higher in the obese group at 30, 60, and 90 min only. No significant differences between the two groups were noted in fasting or in postprandial plasma GIP, and it appears that hypersecretion of GIP is not responsible for the hyperinsulinemia seen in obesity.     

Serum resistin level among healthy subjects: relationship to anthropometric and metabolic parameters

Resistin is a novel adipocyte-secreted hormone that has been proposed to be the link between obesity and diabetes, although little appears to be known regarding the physiological role of resistin in human beings. We aimed to explore the relationship between serum resistin level and certain anthropometric and metabolic parameters. Seventy-one healthy subjects with a mean body mass index of 23 kg/m 2 or greater were recruited in this study. Anthropometric measurements including height, weight, body mass index, waist and hip circumferences, waist-to-hip ratio, and blood pressure were recorded. Insulin resistance was measured by homeostasis model assessment (HOMA). Fasting serum resistin, insulin and plasma glucose, lipid profiles, and uric acid levels were measured. The results revealed that serum resistin level did not correlate with any markers for adiposity, blood pressure, fasting plasma glucose, or uric acid level for either sex. Serum resistin level correlated negatively with fasting insulin level (gamma=-0.455, P=.006) and HOMA (gamma=-0.455, P=.006) in women but not in men. Serum resistin level only correlated negatively with high-density lipoprotein cholesterol (HDL-C) level in men (gamma=-0.347, P=.038); there was no correlation between serum resistin level and lipid profiles in women. Multiple linear regression analysis using the logarithm of resistin as a dependent variable revealed that only HDL-C level (beta=-.058, P=.019) was an independent significant predictor for resistin in men; however, the analysis revealed that HDL-C level (beta=-.044, P=.029) and HOMA (beta=-.719, P=.004) were independent significant predictors for resistin in women. In conclusion, resistin is not related to adiposity, blood pressure, insulin resistance, fasting plasma glucose level, and most lipid profiles. Resistin correlates negatively with HDL-C level for both sexes. The role of resistin in metabolic syndrome warrants further investigation.     

Small particle size of a solid meal increases gastric emptying and late postprandial glycaemic response in diabetic subjects with gastroparesis

Our goal was to investigate if food of small particle size increases the gastric emptying rate and lessens the fall in postprandial blood glucose in seven subjects with Type 1 diabetes and gastroparesis. Two solid meals of identical composition but of different particle size, with 5MBq (99m)Tc added to the meals, were ingested in randomized order in seven subjects with Type 1 Diabetes Mellitus and gastroparesis and seven healthy subjects. During 180min blood glucose and insulin concentrations were measured and gastric emptying of the ingested meals was registered by a gamma camera. The lag phase in the stomach was significantly shorter, the radioactivity remaining in the stomach after 120min (T(120)) was significant less and the postprandial blood glucose dip was less and of shorter duration after a small particle (SP) meal, compared to a large particle (LP) meal in diabetic subjects. Gastric emptying did not differ significantly between groups after an SP meal. Food of small particle size increases the gastric emptying rate and reduces the postprandial blood glucose dip in both magnitude and duration in Type 1 diabetic subjects with gastroparesis, which is likely to be of importance in achieving good metabolic control.     

Colonic myoelectric activity during fasting and postprandial periods in healthy subjects and colonopathic patients

The purpose of this prospective study was to assess colonic myoelectric activity during fasting and after a test meal in patients with the Irritable Bowel Syndrome (IBS) and in control subjects. Colonic electromyographic activity was recorded using an intraluminal probe in 14 patients and in 8 controls. Only rapid electrical activity [i. e. Short Spike Bursts (SSB) and Long Spike Bursts (LSB)] was taken into account. In control subjects the test meal provoked a significant increase in LSB from 46.7 +/- 16.3 to 88.6 +/- 20.3 (p less than 0.001) but not in SSB. In IBS patients rapid myoelectrical activity was not significantly modified by food intake (47.2 +/- 10.3 vs. 62.2 +/- 10.9; NS). The increase of postprandial LSB activity was found to be significantly higher in controls than in IBS patients (41.8 +/- 7.6 vs. 12.9 +/- 8.4; p less than 0.05). These results showed that colonic myoelectrical activity in IBS patients is different from that of controls; such a difference could be useful in classifying IBS patients.     

The postprandial response of adiponectin to a high-fat meal in normal and insulin-resistant subjects

OBJECTIVE: Adiponectin is an adipose-specific protein with short-term effects in vivo on glucose and fatty acid levels. We studied the plasma concentration and the proteolytic activation status of adiponectin following the consumption of a high-fat, low-carbohydrate meal. DESIGN: Analysis of adiponectin concentration and polypeptide structure after consumption of a fat meal. SUBJECTS: Normal subjects (n=24) and first-degree relatives of patients with type II diabetes (n=20). MEASUREMENTS: All subjects had a normal fasting plasma glucose and glucose tolerance. Blood was collected for the determination of plasma insulin, adiponectin, triglyceride, and free fatty acids. Body composition was assessed with dual-energy X-ray absorptiometry and whole-body insulin sensitivity with a euglycaemic, hyperinsulinaemic clamp. Postprandial response over 6 h was determined for plasma adiponectin, glucose, insulin, triglyceride, and free fatty acids. Adiponectin was measured by commercial RIA and its polypeptide structure examined by Western blotting. RESULTS: The relatives were more insulin resistant and had increased adiposity compared with control subjects. There was no significant difference in postprandial response in fatty acids, triglyceride, or insulin between the groups. Postprandial levels of adiponectin measured by radioimmunoassay were not significantly different from fasting levels, and no breakdown products of adiponectin were detectable in postprandial samples by Western blotting. CONCLUSIONS: Levels of circulating adiponectin do not alter in response to a fat meal, despite evidence in mice that acute changes in adiponectin significantly affect postprandial fatty acid flux. Moreover, a fat meal challenge did not lead to significant activation of adiponectin by proteolytic conversion.     

Flow limitation and dyspnoea in healthy supine subjects during methacholine challenge.

The purpose of this study was to assess whether during standard methacholine (Mch) challenge (concentration up to 128 mg x mL(-1)) healthy supine subjects a) develop tidal expiratory flow limitation (FL) and hyperinflation, and b) whether the onset of tidal FL is associated with dyspnoea. Eight healthy subjects were studied. Dyspnoea was assessed using the Borg scale, FL by the negative expiratory pressure (NEP) method and hyperinflation in terms of decrease in inspiratory capacity (IC). Seven patients became flow limited at Mch doses ranging 4-64 mg x mL(-1), with FL encompassing 34-84% of the control tidal volume. In six of them the onset of tidal FL was associated with little or no dyspnoea and a modest degree of hyperinflation (deltaIC <-0.4 L). In one subject, however, onset of FL was associated with a substantial reduction in IC (0.58 L) and moderately severe dyspnoea. In all of these seven subjects FL was transiently reversed after an IC manoeuvre. In conclusion, the results show that a) most healthy subjects may develop flow limitation and hyperinflation during methacholine challenge in supine position, and b) at onset of flow limitation there is little or no dyspnoea, suggesting that onset of dynamic airway compression per se does not elicit significant dyspnoea. Significant dyspnoea probably only occurs with marked dynamic hyperinflation.     

Effects of body position and liquid meal ingestion on esophageal acid exposure time in healthy subjects

We investigated the effect of body position and ingestion of a test liquid meal on esophageal acid exposure time in 20 asymptomatic healthy subjects. Intraesophageal pH monitoring was performed for 1 h before meals and 3 h postprandially with the subject in the supine (n = 10) or sitting position (n = 10). The test meal had a total volume of 800 ml and an energy content of 500 kcal. Esophageal acid exposure time was defined as the percentage of time at pH < 4.0. There was no difference in preprandial or postprandial esophageal acid exposure time between the supine and sitting positions. Esophageal acid exposure time for the 3-h postprandial period was significantly greater than that for the preprandial period in both the supine and the sitting positions. The difference in body position did not influence preprandial or postprandial esophageal acid exposure time, but ingestion of the liquid meal significantly increased the esophageal acid exposure time in both the supine and sitting positions in asymptomatic healthy subjects. (Received Feb. 3, 1997; accepted July 25, 1997)     

Serum bile acid concentration after a test meal.

Total serum bile acid concentrations were studied by an enzymatic-fluorimetric method employing a highly purified 3 alpha-hydroxysteroid dehydrogenase. In 28 control subjects mean total serum bile acid concentration was 2.5 mumoles/1 (S.D. 1.4). In 6 healthy subjects a significant postprandial increase in total serum bile acids occurred with maximal values at 90 and 120 minutes after ingestion of a liquid test meal. The maximal postprandial increase for each subject was 1.5 to 3 times the fasting value. In 7 patients with various hepatobiliary diseases the maximal postprandial elevation of serum bile acids was higher than in the normals, and the duration of serum bile acid elevation was significantly prolonged. In the patients with normal fasting concentration of bile acids the postprandial elevation was also significantly greater than in the controls. A 2-hour postprandial sample seems suitable for the study of the bile acid test meal response for clinical use.     

High-fat meal impairs vascular compliance in a subgroup of young healthy subjects

Postprandial hypertriglyceridemia impairs endothelial function and may possibly worsen vascular compliance by increasing oxidative stress. Large (C1) and small (C2) artery compliance, glucose, insulin, and triglycerides (TGs) were measured hourly for 6 hours in 18 young healthy volunteers after a low-fat meal and a high-fat meal, with and without antioxidant vitamins. C1 and C2 declined significantly for 6 hours after fat ingestion in 8 subjects ("fat reactors") and increased in 10 ("nonreactors"). Fat reactors had higher fasting and peak serum TGs after fat loading and increased baseline glucose and insulin levels and homeostasis model assessment of insulin resistance (HOMA(IR)). Fasting insulin correlated with C1 and C2 only in fat reactors. After fat intake, plasma nitric oxide metabolites decreased more in fat reactors than in nonreactors (17.0% +/- 5.1% vs 4.8% +/- 2.1%; P < .05). In fat reactors, pretreatment with antioxidant vitamins before the high-fat meal blunted the fall in C1 but not in C2. Compliance was unchanged after the low-fat meal. Normal weight young subjects with an insulin resistance phenotype show significantly decreased vascular compliance, increased postprandial TG peaks, and markedly reduced plasma nitric oxide metabolites after a high-fat meal.     

Low-salt diet increases insulin resistance in healthy subjects

Low-salt (LS) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which can increase insulin resistance (IR). We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects. Healthy individuals were studied after 7 days of LS diet (urine sodium <20 mmol/d) and 7 days of high-salt (HS) diet (urine sodium >150 mmol/d) in a random order. Insulin resistance was measured after each diet and compared statistically, unadjusted and adjusted for important covariates. One hundred fifty-two healthy men and women, aged 39.1 ± 12.5 years (range, 18-65) and with body mass index of 25.3 ± 4.0 kg/m², were included in this study. Mean (SD) homeostasis model assessment index was significantly higher on LS compared with HS diet (2.8 ± 1.6 vs 2.4 ± 1.7, P < .01). Serum aldosterone (21.0 ± 14.3 vs 3.4 ± 1.5 ng/dL, P < .001), 24-hour urine aldosterone (63.0 ± 34.0 vs 9.5 ± 6.5 μg/d, P < .001), and 24-hour urine norepinephrine excretion (78.0 ± 36.7 vs 67.9 ± 39.8 μg/d, P < .05) were higher on LS diet compared with HS diet. Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age, sex, blood pressure, body mass index, serum sodium and potassium, serum angiotensin II, plasma renin activity, serum and urine aldosterone, and urine epinephrine and norepinephrine. Low-salt diet is associated with an increase in IR. The impact of our findings on the pathogenesis of diabetes and cardiovascular disease needs further investigation.     

Effect of cisapride on gastric emptying and ileal transit time of balanced liquid meal in healthy subjects

Cisapride is a new prokinetic gastrointestinal agent which has been shown to be able to increase gastric emptying and intestinal transit time in experimental animals and in patients with preexisting motility alterations. Up to now, however, clinical research evaluating the activity of the drug in healthy subjects is very limited. We have therefore undertaken a placebo-controlled study to simultaneously investigate the effect of cisapride (20 mg p.o.) on gastric emptying and intestinal transit time of a balanced liquid meal in 9 healthy volunteers. Median gastric half-time was 60 min after cisapride, as compared to 73 min after placebo (p less than 0.05). Intestinal transit time was similar after cisapride (75 min) or after placebo (105 min). These data confirm that cisapride significantly increases the speed of gastric emptying also in normal subjects. The lack of effect on intestinal transit could be explained by the interindividual variation observed in our experiments.     

Oral clarithromycin enhances gallbladder emptying induced by a mixed meal in healthy subjects

Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5+/-10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7+/-8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student's t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin (P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.     

Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects

During feeding, dietary galactose is a potential source of hepatic glycogen synthesis; but its contribution has not been measured to date. In the presence of deuterated water ((2)H(2)O), uridine diphosphate (UDP)-glucose derived from galactose is not enriched, whereas the remainder derived from glucose-6-phosphate (G6P) is enriched in position 2 to the same level as body water, assuming complete G6P-fructose-6-phosphate (F6P) exchange. Hence, the difference between UDP-glucose position 2 and body water enrichments reflects the contribution of galactose to glycogen synthesis relative to all other sources. In study 1, G6P-F6P exchange in 6 healthy subjects was quantified by supplementing a milk-containing breakfast meal with 10 g of [U-(2)H(7)]glucose and quantifying the depletion of position 2 enrichment in urinary menthol glucuronide. In study 2, another 6 subjects ingested (2)H(2)O and acetaminophen followed by an identical breakfast meal with 10 g of [1-(13)C]glucose to resolve direct/indirect pathways and galactose contributions to glycogen synthesis. Metabolite enrichments were determined by (2)H and (13)C nuclear magnetic resonance. In study 1, G6P-F6P exchange approached completion; therefore, the difference between position 2 and body water enrichments in study 2 (0.20% ± 0.03% vs 0.27% ± 0.03%, P < .005) was attributed to galactose glycogenesis. Dietary galactose contributed 19% ± 3% to glycogen synthesis. Of the remainder, 58% ± 5% was derived from the direct pathway and 22% ± 4% via the indirect pathway. The contribution of galactose to hepatic glycogen synthesis was resolved from that of direct and indirect pathways using a combination of (2)H(2)O and [1-(13)C]glucose tracers.     

Electrogastrography before and after a high-caloric,liquid test meal in healthy volunteers and patients with severe functional dyspepsia

BACKGROUND: The cutaneous recording of gastric electric rhythm, so-called electrogastrography (EGG), has been purported as a non-invasive method for studying patients with functional dyspepsia and unexplained nausea and vomiting. The aims of this study were to determine normal values for EGG characteristics before and after a liquid, high-caloric test meal and to investigate whether EGG could discriminate between patients with functional dyspepsia and normal controls. METHODS: In studying 20 healthy volunteers and 10 patients with functional dyspepsia, we recorded gastric electrical activity during the 30 min before and after a liquid 1.0-1.5 kcal/ml test meal. Satiety before and after the meal was estimated on a 10-point scale. EGG was analysed regarding dominant frequency, instability of the dominant frequency, power ratio and percentage activity in the normal frequency range. RESULTS: The mean (+/-s) caloric intake in patients with functional dyspepsia (286 +/- 160 kcal) was significantly lower (P < 0.001) than in healthy volunteers (610 +/- 211 kcal). The patients reported a more pronounced feeling of satiety before the test meal (5.6 +/- 3.2) compared to healthy volunteers (3.6 +/- 1.2, P < 0.05), but at the end of the test meal there was no difference in satiety (7.9 +/- 2.5 versus 7.7 +/- 1.0). However, none of the EGG parameters showed any difference between patients and healthy volunteers. CONCLUSIONS: EGG before and after a high-caloric test meal showed large variation in healthy subjects and seemed to be of little value for differentiating between healthy individuals and patients with functional dyspepsia.     

Lipase and co-lipase activities of human small intestinal contents after a liquid test meal.

Methods for the determination of pancreatic lipase in small intestinal content have been re-evaluated in the light of the presence of co-lipase therein. A method is described for the determination of co-lipase in intestinal content based on its property to reactivate bile-salt-inhibited lipase. Figures are given for lipase and co-lipase activities in intestinal contents of normal humans aged 1-22. These two components originating in the pancreatic juice vary in a parallel fashion, and no variations with age were apparent. A simple diagnostic criterion is given to detect a possible specific co-lipase deficiency.     

Salt loading increases urinary excretion of linoleic acid diols and triols in healthy human subjects

Increased dietary linoleic acid has been associated with reduced blood pressure in clinical and animal studies possibly mediated by prostaglandins. Urinary linoleate and prostaglandin metabolite excretion were investigated in subjects exposed to a salt-loading/salt-depletion regimen. Twelve healthy subjects were recruited from the New Orleans population (before Hurricaine Katrina) and admitted to the Tulane-Louisiana State University-Charity Hospital General Clinical Research Center after a 5-day outpatient lead-in phase on a 160-mmol sodium diet. On inpatient day 1, the subjects were maintained on the 160-mmol sodium diet, and a 24-hour urine specimen was collected. On day 2, the subjects received 2 L of IV normal saline over 4 hours and continued on a 160-mmol Na(+) diet (total: 460 mmol of sodium). Two 12-hour urine collections were obtained. On day 3, the subjects received three 40-mg oral doses of furosemide, two 12-hour urine collections were obtained, and the subjects were given a 10-mmol sodium diet. Urinary oxidized lipids were measured by high-performance liquid chromatography-tandem quadrupole mass spectroscopy. The excretion of the urinary linoleate metabolites, dihydroxyoctadecamonoenoic acids, and trihydroxyoctadecamonoenoic acids increased significantly during intravenous salt loading as compared with day 1 and the salt-depleted periods. The urinary excretion of 6-keto- prostaglandin F1alpha was unaffected by salt loading but was dramatically increased 7- to 10-fold by salt depletion. Prostaglandin E2 excretion was positively correlated with sodium excretion. The salt-stimulated production of linoleic acid diols and triols may inhibit tubular sodium reabsorption, thereby assisting in the excretion of the sodium load.     

Methacholine inhalation challenge after rapid saline infusion in healthy subjects

Five healthy subjects were challenged with methacholine on 2 different days, 1 week apart, the second day after acute intravenous 30 ml/kg 0.9% saline infusion. After infusion, we observed a significant reduction in vital capacity (VC), maximal expiratory volume in 1 s (FEV1), provocation dose producing a 35% fall in SGaw (PD35SGaw) and in 25% of maximal expiratory flow (MEF25), and an increase in the slopes of log dose-response curves. Our results suggest an increased bronchial reactivity in acute minimal interstitial lung edema.