Search PubMed⌕ Search

Biomedical subjects

W Ricart

Publications and source records attributed to W Ricart.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Diabetes mellitus associated with the A3243G mutation of mitochondrial DNA. Apropos a case].

The mitochondrial A3243G mutation of the tRNA(Leu) has been described in pedigrees with maternally inherited diabetes mellitus and deafness. Ten diabetic patients with sensorineural deafness were studied. Polymerase chain reaction and enzyme restriction analysis with Apa I were performed. The mutation was found in heteroplasmy in only one patient (1/10). She was a 43-years-old woman with maternally inherited diabetes and deafness since she was 29. The association of sensorineural deafness and maternal inherited diabetes are the clues to suspect this subtype of diabetes.

Adult↗
PubMed1999

Insulin resistance and inflammation in an evolutionary perspective: the contribution of cytokine genotype/phenotype to thriftiness.

AIMS/HYPOTHESIS: To describe a unifying hypothesis of the relation between insulin resistance and inflammatory response in the development of diabetes. METHODS: Review of the literature and authors' research. RESULTS: Infection and injury activate the immune system and bring about widespread metabolic changes which disadvantage and destroy the invading organism and facilitate repair of damaged tissue. Tumour necrosis factor-alpha is involved in inflammatory events and fight against infection. No study has extensively investigated its numerous metabolic effects. From induction of hyperlipidaemia to regulation of intracellular insulin signalling, TNF-alpha has been even associated with nutrient-sensing pathways. Certain TNF-alpha gene polymorphisms (linked to a high transcription rate of TNF-alpha), and the plasma concentrations of the TNF-alpha soluble receptor are simultaneously associated with insulin resistance, body fat, and with mortality after chronic infections. Thus, the TNF system seems to be designed for an effective fight against infection and for providing survival advantages during periods of food shortage. By inducing muscle insulin resistance, the energetic substrates are safeguarded for brain metabolism. CONCLUSION/INTERPRETATION: In the presence of an insulin resistance genotype and westernization (high carbohydrate diet, increased saturated fat, low fibre and sedentary habit), a high cytokine responder genotype would be prone to deterioration of insulin resistance and, finally, to Type II (non-insulin-dependent) diabetes mellitus and atherosclerosis. For our ancestors, the advantages of a high cytokine responder (eradication of injury) or moderate insulin resistance (protection against starvation) overcame the possible inconveniences of atherosclerosis. We propose that the latter are good adaptations to the environment or "maladaptations" of actual lifestyle to our genome. [Diabetologia (1999) 42: 1367-1374]

Biological Evolution↗
PubMed1999

Plasma levels of the soluble fraction of tumor necrosis factor receptors 1 and 2 are independent determinants of plasma cholesterol and LDL-cholesterol concentrations in healthy subjects.

In the last few years, it has been demonstrated that tumor necrosis alpha (TNF-alpha) has important effects on whole-body lipid metabolism. TNF-alpha administration has been found to produce an increase in serum cholesterol levels and increased hepatic hydro-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase activity in mice. The purpose of this study was to test whether plasma levels of the soluble forms of the TNF-alpha receptors 1 and 2 (sTNFR1, sTNFR2) are associated with lipid abnormalities. A total of 36 healthy subjects (19 males, mean age 36.2 +/- 1.9, and 17 females, mean age 34.9 +/- 1.4) were studied. Plasma sTNFR1 levels correlated with total (r = 0.43, P = 0.01) and LDL-cholesterol (r = 0.52, P = 0.002) levels, but not with total or HDL2-HDL3 subfractions of HDL-cholesterol, total plasma triglycerides, VLDL-cholesterol or VLDL-triglycerides (all r < 0.11, P = NS). Plasma sTNFR2 levels also correlated with total (r = 0.44, P = 0.009) and LDL-cholesterol (r = 0.57, P < 0.0001) levels, and negatively with HDL2-cholesterol (r = -0.37, P = 0.029). A stepwise multiple linear regression was constructed to predict total cholesterol levels, with BMI, sex, age, sTNFR1 or sTNFR2 as independent variables. Both sTNFR1 and sTNFR2 were significantly associated with total cholesterol (P = 0.031 and 0.009), contributing to 26 and 19%, respectively, of its variance. In another model in which LDL-cholesterol was substituted for total cholesterol, sTNFR1 or sTNFR2 (P = 0.0084 and 0.0005) were significantly associated with LDL-cholesterol, contributing to 39 and 32% of its variance. In summary, plasma levels of sTNFR1 and sTNFR2 circulate in proportion to total and LDL-cholesterol in healthy subjects.

Adolescent↗
PubMed1999

Plasma oestrone-fatty acid ester levels are correlated with body fat mass in humans.

OBJECTIVE: The metabolites of steroidal hormones, including sulphate, glucuronide, and fatty acid (FA) ester derivatives, have received little attention, although these steroid derivatives are essential components in the global assessment of steroid metabolism. The study of FA-derivatives could, in obesity, contribute some insights into factors modulating steroid metabolism and their plasma levels. In a recent study we found that, in rats, an oestrone-fatty acid ester (E1-FA) was produced by white adipose tissue and released into lipoproteins in the blood-stream. We have examined whether E1-FA levels correlate with body fat and insulin sensitivity in humans. SUBJECTS: A sample of 20 men and 22 women with varying levels of total body fat (mean body mass index (BMI) 29.2 +/- 4.7, range 22.2-35.8 in men; mean BMI 27.6 +/- 6.3, range 16.8-37.9 in women). All participants were healthy. MEASUREMENTS: We measured oestrone fatty acid esters (E1-FA), body fatness, and body fat distribution variables, as well as insulin sensitivity through a frequently sampled intravenous glucose tolerance test. Plasma E1-FA and serum leptin levels were measured by radioimmunoassay. RESULTS: E1-FA levels strongly correlated with BMI (r = 0.69, P = 0.001 in men; r = 0.75, P < 0.0001, in women) percent body fat (PBF, r = 0.52. P = 0.018 in men; and r = 0.69, P < 0.0001, in women) and with the sum of 4 fat skinfolds (sigma skinfolds). E1-FA level was significantly and positively associated with fasting insulin (r = 0.62, P = 0.003 in men, and r = 0.48, P = 0.023 in women) but not with fasting glucose levels. E1-FA correlated with insulin sensitivity (SI, r = -0.72 in men; and -0.76, in women, both P < 0.0001). In men, E1-FA levels also correlated with systolic blood pressure (r = 0.59, P = 0.01), total triglycerides (r = 0.63, P = 0.003), VLDL-triglycerides (r = 0.62, P = 0.004) and VLDL-cholesterol (r = 0.48, P = 0.03), but not with diastolic blood pressure, serum total or LDL-cholesterol, or total and HDL2 and HDL3 subfractions of HDL cholesterol. After controlling for fat mass, only the correlation between VLDL-triglycerides and E1-FA levels remained significant. In women, E1-FA levels correlated with total triglycerides (r = 0.66, P = 0.001), VLDL-triglycerides (r = 0.65, P = 0.001), VLDL-cholesterol (r = 0.63, P = 0.002), LDL-cholesterol (r = 0.57, P = 0.005) and total and HDL2 and HDL3 subfractions of HDL cholesterol (r = -0.58, -0.48, -0.61, P = 0.004, 0.02 and 0.002, respectively), but not with systolic or diastolic blood pressure or total cholesterol. However, covariance analysis revealed that controlling for the concomitant variation in body fat mass eliminated all these associations. Fasting plasma E1-FA concentration correlated with serum leptin (r = 0.60, P = 0.005 in men; r = 0.75, P = 0.0001, in women). However, these correlations no longer persisted after controlling for fat mass (r = 0.33 and 0.36, P = NS). Stepwise regression analysis models were tested, with E1-FA as the dependent variable, and sigma skinfolds and SI as independent covariables. Both the sigma skinfolds (P = 0.03) and SI (P = 0.01) entered the equation at a statistically significant level in men. Therefore, insulin sensitivity was related to E1-FA independently of fat in men. In women only sigma skinfolds (P = 0.04) entered the regression model at a statistically significantly level. Fifty-seven percent of the variance in plasma E1-FA levels in men, and 50% in women, was accounted for using a regression model that combined these variables. CONCLUSIONS: Oestrone-fatty acid esters circulate in human blood in proportion to body fat, independently of gender. Plasma oestrone-fatty acid ester levels are associated with insulin sensitivity in men, independently of body fat. These findings may widen our perspective on the regulation of insulin action and control of body weight.

Adipose Tissue↗
PubMed1999

Plasma total and glycosylated corticosteroid-binding globulin levels are associated with insulin secretion.

In humans, steroid hormones circulate in the blood mainly bound to specific steroid transport proteins, namely corticosteroid-binding globulin (CBG) for cortisol and sex hormone-binding globulin (SHBG) for testosterone and estradiol. The binding activities of these proteins are believed to modulate the biodisposal of steroids to target cells. It has been shown in vitro that insulin is a potent inhibitor of both CBG and SHBG secretion by a human hepatoblastoma cell (HepG2) line. To further investigate this potential effect of insulin in vivo, we prospectively studied three groups of lean subjects, obese subjects, and obese subjects with glucose intolerance, all of whom were otherwise healthy. The three groups were comparable in sex and age, and in the two obese groups, body mass index, waist to hip ratio, and blood pressure were similar. Plasma total CBG concentrations (38.2 +/- 5.4 vs. 31.7 +/- 4.05 mg/L; P = 0.016) and glycosylated CBG levels (37.3 +/- 5.2 vs. 31 +/- 3.9 mg/L; P = 0.018) were significantly increased in obese subjects with glucose intolerance. Plasma CBG correlated positively with fasting glucose levels (r = 0.49; P = 0.002), hemoglobin A1c levels (r = 0.35; P = 0.03), and area under the curve of glucose after an oral glucose tolerance test (r = 0.45; P = 0.005) and correlated negatively with the insulin response to i.v. glucose (AIRg; -0.38, P = 0.02) as well as to oral glucose (r = -0.40; P = 0.01) challenge tests. CBG levels did not covariate with insulin sensitivity. Multiple linear regression analysis showed that only AIRg contributed to the variability of the CBG concentration (P = 0.03), explaining 41% of its variance. Morning cortisol levels did not differ between the groups and did not correlate to any of the glucose or insulin metabolism parameters. Because carbohydrate chains influence the biological activity and half-life of glycoproteins, we analyzed the migration profile of CBG by Western blot and the interaction of CBG with lectin, Con A. The results indicated that the CBG mol wt and interaction with Con A did not differ between lean and obese patients. These data favor the hypothesis that the inhibitory effect of insulin on CBG liver secretion might be relevant in vivo and therefore contribute to decrease CBG levels in obese patients with enhanced insulin secretion. In both men and women, SHBG levels correlated negatively with fasting glucose (r = -0.55; P < 0.0001) and hemoglobin A1c (r = -0.38; P = 0.02) and positively with insulin sensitivity (S(I); r = 0.65; P = 0.003 and r = 0.63; P = 0.007 in men and women, respectively), but not with insulin secretion. The disposition index (S(I) x AIRg) was significantly decreased in the obese, glucose-intolerant subjects, suggesting that AIRg was inadequate for their degree of insulin resistance. The disposition index correlated positively with plasma SHBG levels (r = 0.52; P = 0.001) and negatively with plasma CBG levels (r = -0.54; P = 0.001). Our data suggest that CBG is a marker of insulin secretion in a similar way as SHBG is a marker of insulin sensitivity. As high plasma CBG levels have been associated with increased incidence of type 2 diabetes, this important issue merits further investigations.

Adult↗
PubMed1999

Tumor necrosis factor system activity is associated with insulin resistance and dyslipidemia in myotonic dystrophy.

Myotonic dystrophy (MyD) is a multisystem autosomal dominant disorder associated with progressive muscle wasting and weakness. The striking metabolic abnormality in MyD is insulin resistance. The mechanism by which target tissues are insensitive to insulin action remains uncertain. In a recent study, plasma soluble tumor necrosis factor receptor (sTNFR)2 levels were found to be associated with muscle tissue mass and insulin resistance. Given these associations, we speculated that disorders of the muscle cell membrane could lead simultaneously to insulin insensitivity and sTNFR2 leakage in MyD. To test this hypothesis, we measured the levels of circulating sTNFR1 and sTNFR2 and insulin resistance in MyD patients. We studied 22 MyD patients and 24 age-, BMI-, and fat mass-matched control subjects. Both MyD men and women showed higher plasma insulin levels in the presence of comparable glucose concentrations than did control subjects. sTNFR2, but not sTNFR1, levels were approximately 1.5-fold higher in MyD patients. In parallel with these findings, the fasting insulin resistance index (FIRI) was also higher in MyD patients. In fact, in the whole population, fasting insulin and FIRI strongly correlated with sTNFR2 in both men (r = 0.77 and r = 0.81, P<0.0001, respectively) and women (r = 0.67 and r = 0.64, P = 0.001, respectively). sTNFR2 levels were also associated with the insulin sensitivity index (S(I)), calculated from an oral glucose tolerance test (OGTT) according to the method by Cederholm and Wibell (r = -0.43, P = 0.006). We constructed a multiple linear regression to predict FIRI, with BMI, waist-to-hip ratio, and sTNFR2 as independent variables. In this model, both BMI (P = 0.0014) and sTNFR2 (P = 0.0048) levels contributed independently to 46% of the variance of FIRI. In another model, in which FIRI was substituted for S(I) from the OGTT, both BMI (P = 0.0001) and sTNFR2 (P = 0.04) levels contributed independently to 48% of the variance of S(I) from the OGTT. Plasma cholesterol and triglyceride concentrations were significantly increased in MyD patients. sTNFR1 and sTNFR2 levels were found to be strongly associated with plasma cholesterol, LDL cholesterol, and triglycerides. sTNFR1 and sTNFR2 also correlated with serum creatine kinase activity in MyD patients (r = 0.57, P = 0.006; r = 0.75, P<0.0001, respectively). In conclusion, here we describe, for the first time to our knowledge, a relationship between insulin action and plasma sTNFR2 concentration in MyD patients. We have also found increased concentrations of plasma triglycerides and cholesterol levels in parallel with sTNFR1 and sTNFR2 concentrations in MyD patients. We speculate that the latter associations are dependent on, and secondary to, increased tumor necrosis factor (TNF)-alpha action. Whether TNF action is implicated in the pathogenesis of MyD or is a simple marker of disease activity awaits further studies.

Adult↗
PubMed1998

Plasma levels of the soluble fraction of tumor necrosis factor receptor 2 and insulin resistance.

Recent studies have shown that the tumor necrosis factor (TNF) system is implicated in the insulin resistance of human obesity. Plasma concentrations of the soluble fraction of the TNF receptors 1 and 2 (sTNFR1 and sTNFR2) are thought to reflect the degree of activation of the TNF system. The purpose of this study was to explore whether this activation, as measured by the levels of circulating sTNFR1 and sTNFR2, is associated with insulin resistance. A total of 19 men (mean age 36.2 +/- 1.9; BMI 28.8 +/- 1.2, range 22.2-35.7) and 17 premenopausal women (age 34.9 +/- 1.4; BMI 28.1 +/- 0.8, range 19-37.9) were studied. Men showed higher levels of plasma sTNFR1 and sTNFR2 than women. However, obese men showed increased levels of sTNFR2 but similar levels of sTNFR1 in comparison with obese women. In fact, sTNFR2 levels correlated with BMI (r = 0.50, P = 0.002), fat-free mass (FFM) (r = 0.61, P < 0.0001), and waist-to-hip ratio (WHR) (r = 0.39, P = 0.02), but not with fat mass or percent fat mass. sTNFR2 levels correlated with basal glucose levels (r = 0.45, P = 0.007), area under the curve (AUC) for glucose during an oral glucose tolerance test (r = 0.42, P = 0.013), and with the quotient AUC glucose/log AUC insulin (r = 0.41, P = 0.015). sTNFR2 also correlated negatively with insulin sensitivity (S(I)), evaluated using the frequently sampled intravenous glucose tolerance test with minimal model analysis (r = -0.38, P = 0.02). Plasma sTNFR1 levels were not associated with any of these variables. Because WHR influenced both S(I) and sTNFR2 levels, we constructed a multiple linear regression to predict S(I), with WHR and sTNFR2 as independent variables. In this model, both WHR (P = 0.0078) and sTNFR2 levels (P = 0.025) contributed to 47% of the variance in S(I). In parallel with higher FFM, lean and obese men showed a lower S(I) (2.9 +/- 0.9 vs. 5.2 +/- 1.3 min(-1) x mU x l(-1), P = 0.001; and 1.15 +/- 1.1 vs. 1.8 +/- 0.8 min(-1) x mU x l(-1), P = 0.035, respectively) and higher sTNFR2 levels in comparison with lean and obese women, respectively. After controlling for FFM, the correlation between S(I) and sTNFR2 levels disappeared, indicating that FFM was significantly influencing these associations. In summary, plasma sTNFR2 levels, but not sTNFR1, were proportional to BMI, WHR, FFM (a well-known confounder in the evaluation of insulin sensitivity), basal and postload glucose levels, and insulin resistance. These findings support TNF-alpha as a system regulating insulin action in human obesity.

Adult↗
PubMed1998

[Reversible hypophyseal disfunction and hyperplasia in two cases of primary hypothyroidism].

BACKGROUND: Some patients with primary hypothyroidism (HP) develop massive thyrotrope cell hyperplasia determining pituitary hyperplasia with suprasellar enlargement and pituitary dysfunction. Although TRH secretion undoubtedly has some influence, the intervention of other possible factors determining this hyperplasia and dysfunction has been little assessed. PATIENTS AND METHODS: Two patients with primary hypothyroidism with a serum TSH > 1,000 mU/I were studied. By means of CT and MR a pituitary hyperplasia was ascertained in the two patients. The pituitary functional reserve was investigated by the serum response of TSH and prolactin to the administration of TRH (400 micrograms, i.v.), bromocriptine (BRC, 5 mg, oral route), somatostatine (ST, 50 micrograms/kg/min, i.v. perfusion), and gonadotropin releasing hormone (GnRH, 100 micrograms, i.v.). RESULTS: The TRH induced increment of TSH was 145% and 193%, respectively, compared with basal values. After the administration of BRC, TSH decreased to 57% and 84% of basal values, and PRL to 46% and 43%, respectively. TSH and PRL concentrations did not change after the administration of ST or GnRH. In both cases, hyperplasia and pituitary dysfunction returned to normality after substitutive therapy with levothyroxine. CONCLUSIONS: Basal hyperprolactinemia and TSH and PRL responses to BRC administration suggest that central dopaminergic activity is decreased or abolished in patients with HP and pituitary hyperplasia. The massive thryrotrope cell hyperplasia and hypothyroidism itself determine pituitary dysfunction, which reverts after therapy with levothyroxine, a fact which is scarcely documented in literature.

Adolescent↗
PubMed1997

The TNF-beta gene Nco I polymorphism is not associated with hypertriglyceridemia or insulin resistance in lean and obese subjects.

Interindividual differences in TNF-alpha monocyte responses can be accounted for by genetic polymorphisms at the TNF-beta locus defined by the Nco I restriction enzyme. Higher triglyceride levels in non-insulin-dependent diabetic patients homozygous at the 10.5-kb fragment of the TNF-beta gene have been described. The aim of this study was to investigate whether the Ncol polymorphism of the TNF-beta gene influences the relationship between insulin resistance and triglyceride levels. Thirty-eight healthy volunteers were divided into two groups according to the absence [homozygous for class 1 allele (1/1), n=16] or presence of the class 2 allele [n=22; 19 heterozygous (1/2), and 3 homozygous (2/2)]. Both groups were comparable in sex, age, BMI, waist/hip ratio, fat mass and percentage of body fat as measured by bioelectric impedance, skinfold measurements, and blood pressure (all p>0.05). There were no differences in serum cholesterol (total, or HDL and VLDL fractions) or in total or VLDL triglycerides between the groups (all p>0.05). The insulin sensitivity index (Minimal Model method) was comparable for the two groups. In summary, the 10.5-kb homozygous genotype of the TNF-beta locus does not contribute to differences in triglyceride levels or insulin sensitivity among nondiabetic subjects.

Adult↗
PubMed1997

Lower cortisol levels after oral glucose in subjects with insulin resistance and abdominal obesity.

BACKGROUND: It has been shown previously that morning cortisol levels decline after oral glucose, but no report has been published regarding the changes in serum cortisol in relation to insulin sensitivity or degree of obesity. SUBJECTS AND DESIGN: We studied the effects of oral glucose during a standard oral glucose tolerance test on cortisol levels in 7 obese subjects (body mass index (BMI) 29.7 +/- 3.3 kg/m2) and in 8 control subjects (BMI 24.9 +/- 3.2 kg/m2). Cortisol concentrations were normalized to time 0 because of wide between subject variation. On another day, a frequently sampled intravenous glucose tolerance test with minimal model analysis was performed, obtaining the insulin sensitivity index (SI). Anthropometric measurements included different skinfolds and bioelectric impedance. RESULTS: The waist-to-hip ratio (WHR) was similar between the 2 groups, but abdominal skinfold was significantly higher in the obese group (OG) (158.8 +/- 42.9 vs. 113.6 +/- 27.7, P = 0.03). Fat mass, percentage of fat mass, triceps and subscapular skinfolds, systolic and diastolic blood pressure, VLDL-cholesterol, total triglycerides and VLDL-triglycerides were slightly higher in the obese group (OG). Area under the curve for glucose (AUCg) after OGTT was also significantly higher in OG (9.9 +/- 2.4 vs. 7.1 +/- 0.5 mmol/l, P = 0.02) in contrast to area under the curve for insulin (102 +/- 60 vs. 73.8 +/- 26.7 mU/l, P = NS), or glucose effectiveness (0.015 +/- 0.004 vs. 0.015 +/- 0.009 min-1, P = NS). Subjects with the highest WHR of both groups exhibited a greater cortisol suppression (56 +/- 0.09 vs. 41 +/- 0.17, P = 0.05). Normalized serum cortisol after OGTT was significantly lower from minute 60 to 120 in the OG (P = 0.001, 0.003 and 0.01 at 60, 90 and 120 minutes, respectively). The maximal cortisol suppression was 59.2% in the OG in comparison with 43% in the control group (P = 0.027). This maximal cortisol suppression correlated weakly with the maximal insulin response after oral glucose (r = 0.49, P = 0.07). In a multiple linear regression analysis, with maximal cortisol suppression as dependent variable, both BMI (P = 0.03) and SI (0.02) contributed to the variance of maximal cortisol suppression (R2 = 0.40). CONCLUSION: We show that differences in cortisol decline are at least partially attributed to differences in insulin sensitivity and to differences in abdominal fat. This abdominal-related decrease of cortisol might support the concept that the increased visceral adipose tissue mass with a high density of glucocorticoid receptors enhances the metabolism of cortisol. Perhaps the subjects with higher abdominal fat or insulin resistance are prone to lower cortisol levels after carbohydrate-rich intakes in the morning. These lower cortisol levels, behaving as a positive feed-back signal, might generate higher ACTH and cortisol responses after protein-rich meals at mid-day.

Administration, Oral↗
PubMed1997

The TNF-alpha gene Nco I polymorphism influences the relationship among insulin resistance, percent body fat, and increased serum leptin levels.

Tumor necrosis factor-alpha (TNF-alpha), acting as a modulator of gene expression in adipocytes, is implicated in the development of insulin resistance and obesity. The aim of this study was to investigate whether the Nco I polymorphism of the TNF-alpha gene influences the relationship among insulin resistance, percent body fat, and serum leptin levels. A sample of 38 subjects (19 men, mean age 36.2 +/- 1.9 years, BMI 28.8 +/- 1.2 kg/m2, range 22.2-35.7; and 19 women, age 34.9 +/- 1.4 years, BMI 28.1 +/- 0.8 kg/m2, range 19-37.9) was divided into two groups on the basis of the Nco I genotype. Twenty-three subjects were (+/+) homozygotes for the presence of the Nco I restriction site that is associated with a guanine at position -308 of the TNF-alpha promoter. Of the other subjects, 12 were (+/-) heterozygotes and 3 (-/-) homozygotes for the absence of the restriction site, resulting from a guanine-to-adenine substitution at position -308 of the TNF-alpha promoter. This substitution (termed TNF-2) leads to higher rate of transcription of TNF-alpha than the wild-type allele TNF-1 in vitro. TNF-1 (+/+) and TNF-2 (+/- and -/-) groups of subjects were comparable in sex, age, BMI, waist-to-hip ratio, and several skinfold measurements. Basal serum insulin was greater (14.2 +/- 2 vs. 9.2 +/- 0.9 mU/l, P = 0.041) in the TNF-2 group in the presence of comparable serum glucose concentration. The integrated area under the curve of serum insulin concentrations, measured in response to a 75-g oral glucose challenge, and the percent body fat, measured by bioelectric impedance, were significantly increased in TNF-2 subjects (226.8 +/- 33 vs. 139.4 +/- 17.8 mU/l, P = 0.032; 33.6 +/- 2.8 vs. 24.9 +/- 2%, P = 0.01). TNF-2 subjects also showed a decreased insulin sensitivity index, as determined by the frequently sampled intravenous glucose tolerance test with minimal model analysis (1.9 +/- 0.4 vs. 3.05 +/- 0.3 min(-1) x mU(-1) x l(-1), P = 0.03). These differences were more marked among women. Paralleling the known relationship between insulin and leptin levels, serum leptin concentration was clearly increased in the TNF-2 group (19.6 +/- 3.4 vs. 11.1 +/- 1.5 ng/ml, P = 0.03). Therefore, (+/-) heterozygotes and (-/-) homozygotes may be more susceptible to developing insulin resistance and increased percent body fat. Results of the present study suggest that TNF-alphaNco I polymorphism may exacerbate the alterations in leptin levels normally found among insulin-resistant subjects.

Adult↗
PubMed1996

Effect of malnutrition after acute stroke on clinical outcome.

BACKGROUND AND PURPOSE: Malnutrition has received little attention in acute stroke, although it represents a risk of decreased immunity and nosocomial infections. Our objectives were to determine the prevalence of malnutrition after 1 week of hospitalization in acute stroke and to establish its relation to the stress response and neurological outcome. METHODS: The study included 104 patients with an acute stroke of less than 24 hours' duration. Nutritional parameters (triceps skinfold thickness, midarm muscle circumference, serum albumin, and calorimetry) were evaluated at admission and after 1 week. Stress response (free urinary cortisol) was measured daily during the first week. Neurological deficit was evaluated by the Canadian Stroke Scale. Clinical outcome was estimated by the Barthel Index 1 month after the acute stroke. Patients received an oral standard diet or polymeric enteral nutrition when they had swallowing difficulties. RESULTS: Protein-energy malnutrition was observed in 16.3% of patients at inclusion and in 26.4% after the first week, with a significant decrease in fat (P = .002) and visceral protein compartments (P = .049). Malnourished patients showed higher stress reaction and increased frequency of infections and bedsores in comparison with the appropriately nourished group. Multiple logistic regression analysis showed that malnutrition after 1 week (odds ratio, 3.5; 95% confidence interval, 1.2 to 10.2) and elevated free urinary cortisol (odds ratio, 3.3; confidence interval, 1.05 to 10.2) increased the risk of poor outcome (death or Barthel Index < or = 50 on the 30th day of follow-up) independently of age and nutritional status at admission. CONCLUSIONS: Our findings suggest that protein-energy malnutrition after acute stroke is a risk factor for poor outcome. Early appropriate enteral caloric feeding did not prevent malnutrition during the first week of hospitalization.

Acute Disease↗