bluuebunny/crossref_metadata_2025_split huggingface dataset:
A small reduction in glomerular filtration is accompanied by insulin resistance in type I diabetes patients with diabetic nephrophathy
Authors: Svensson M. , Yu Z‐W. , Eriksson J. W. 
Published: March 2003

Abstract Background Insulin sensitivity and insulin clearance are compromised in end‐stage renal disease but it has not been fully established whether they are altered in earlier stages of diabetic nephropathy.Design We studied three groups of patients with type 1 diabetes; 10 with no sign of nephropathy, 11 with albuminuria (> 20 µg min−1) but normal glomerular filtration rate (GFR) and eight with a small reduction in GFR, (43–73 mL min−1 1·73 m−2). The groups were matched for age (range 36–61 years), body mass index (BMI), diabetes duration and glycaemic control. The euglycaemic hyperinsulinaemic clamp technique was utilized to study insulin sensitivity (M‐value) and metabolic clearance rate for insulin. Needle biopsies from abdominal subcutaneous fat tissue were obtained to study insulin binding, insulin degradation, insulin‐stimulated glucose uptake and anti‐lipolysis in adipocytes in vitro.Results Patients with reduced GFR were more insulin‐resistant (M‐value 5·7 ± 0·7 mg kg LBM−1 min−1) than those without nephropathy (9·6 ± 0·7, P = 0·001) and those with only albuminuria (8·9 ± 1·2, P = 0·044). In all subjects taken together there was a strong association between insulin sensitivity and GFR (r = 0·46, P = 0·012). Patients with reduced GFR displayed no significant difference in insulin clearance (12·2 ± 1·6 mL kg−1 min−1) compared to controls (13·8 ± 1·3) but a slightly lower insulin clearance than patients with only albuminuria (16·6 ± 1·0, P = 0·027). There were no significant differences between patient groups in the adipocyte studies in vitro, i.e. with respect to insulin binding, insulin degradation and the effects of insulin on glucose uptake and lipolysis. This is compatible with humoral factors causing whole‐body insulin resistance and in the group with reduced GFR, we found that serum parathyroid hormone, interleukin‐6 and tumour necrosis factor‐α levels were elevated whereas the morning cortisol was decreased.Conclusions In type 1 diabetes, the appearance of albuminuria does not seem to alter insulin sensitivity and clearance. A marked insulin resistance but no consistent impairment in insulin clearance seems to accompany progression to a stage with a slight reduction in GFR. These alterations are not accompanied by general defects in insulin target cells. Instead, alterations in the regulation of insulin‐antagonistic hormones and cytokines could potentially contribute to the development of insulin resistance in diabetic nephropathy.
Increased TGFβ1 plasma level in patients with lung cancer: potential mechanisms
Authors: Barthelemy‐Brichant N. , David J. L. , Bosquée L. , Bury T. , Seidel L. , Albert A. , Bartsch P. , Baugnet‐Mahieu L. , Deneufbourg J. M. 
Published: March 2003

AbstractBackground Plasma transforming growth factor β1 (TGFβ1) levels are elevated in patients with lung cancer. As TGFβ1 is mainly found in platelets and as nonmalignant pulmonary diseases (NMPD) are frequently associated with lung cancer, we investigated the potential contribution of platelet degranulation and/or of a concomitant NMPD to the increased plasma levels of TGFβ1 reported in patients with lung cancer.Materials and Methods Blood samples were collected in duplicate from 30 healthy subjects, 14 patients suffering from NMPD and 37 patients with lung cancer. The platelet count was determined and the samples were processed to obtain plasma. One sample was collected in EDTA (EDTA plasma) and the other in a mixture inhibiting platelet degranulation (PIM plasma). TGFβ1 concentrations and β‐thromboglobulin (βTG) levels, an index of platelet degranulation, were measured in both plasma samples.Results TGFβ1 and βTG plasma levels measured in PIM plasma were lower than those obtained in EDTA plasma. With respect to PIM plasma, both TGFβ1 and βTG levels were higher in patients with lung cancer than those with NMPD and in healthy individuals. In patients with NMPD, only TGFβ1 levels were increased as compared to healthy controls, βTG levels being similar.Conclusion Methods for collecting and processing blood samples are critical in determining reliable circulating TGFβ1 levels. Increased TGFβ1 plasma levels observed in patients with lung cancer are related, at least partly, to concomitant NMPD and also to platelet degranulation as proved by increased βTG levels.
Endocrine abnormalities in healthy first‐degree relatives of type 2 diabetes patients – potential role of steroid hormones and leptin in the development of insulin resistance
Authors: Jansson P‐A. , Eliasson B. , Lindmark S. , Eriksson J. W. 
Published: March 2003

AbstractBackground First‐degree relatives of type 2 diabetes patients are at risk of developing diabetes and they display several metabolic and hormonal perturbations. The interplay between insulin resistance, steroid hormones and circulating leptin is, however, still not fully explored in this group.Design Thirty‐three healthy first‐degree relatives of type 2 diabetic patients (relatives; M/F 19/14) were compared to 33 healthy subjects without a family history of diabetes (controls) and the groups were matched for gender, age and body mass index (BMI). We performed euglycaemic hyperinsulinaemic clamps and blood was sampled for hormone analyses.Results Relatives exhibited decreased insulin sensitivity (index of metabolic clearance rate of glucose; MCRI) but when genders were analysed separately, this difference was significant only in males (11·3 ± 1·3 vs. 15·0 ± 1·5 units, means ± SEM, P = 0·030). In male relatives morning cortisol and testosterone levels were lower, whereas leptin was higher than in male controls (P = 0·018, 0·008 and 0·063, respectively). In male relatives plasma testosterone levels were significantly associated with insulin sensitivity (r = 0·48, P = 0·040). Circulating leptin levels were inversely correlated with insulin sensitivity in all subject groups (r‐values –0·49 to –0·66; P < 0·05, except in female control subjects P = 0·063). These associations were present also when age and BMI or waist : hip ratio were included in stepwise multiple regression analyses.Conclusion Male subjects genetically predisposed for type 2 diabetes display several endocrine abnormalities including leptin, cortisol and testosterone levels. Dysregulation of these hormones may be important in the development of insulin resistance and type 2 diabetes.
Blood glucose pre‐prandial baseline decreases from morning to evening in type 2 diabetes: role of fasting blood glucose and influence on post‐prandial excursions
Authors: Trovati M. , Ponziani M. C. , Massucco P. , Anfossi G. , Mularoni E. M. , Burzacca S. , Tassone F. , Perna P. , Traversa M. , Cavalot F. 
Published: March 2003

AbstractBackground  To know the relationships between pre‐ and postprandial blood glucose (BG), i.e. BG profile shape, is a requisite for an appropriate therapy for type 2 diabetic patients. In non diabetic subjects, pre‐breakfast, pre‐lunch and pre‐dinner BG are similar, so that BG postprandial excursions are superimposed on a stable BG preprandial baseline. We aimed to clarify: (a) whether BG preprandial baseline is stable also in type 2 diabetes and (b) whether fasting BG (FBG) influences the slope of BG preprandial baseline and the relationships between pre‐ and postprandial BG.Design  We evaluated self‐measured BG profiles of 237 type 2 diabetic patients on diet alone (M/F, 152/85; age 58·6 ± 0·7 years; years from diagnosis 4·8 ± 0·6; BMI 28·0 ± 0·3 kg m−2): 536 profiles containing preprandial BG (corresponding HbA1c 6·8 ± 0·06%) and 208 profiles containing both pre‐ and postprandial BG (corresponding HbA1c 6·8 ± 0·09%). The profiles, measured by nurses, of 866 type 2 diabetic patients on diet alone were also considered (corresponding HbA1c 6·7 ± 0·04%).Results  In self‐measured profiles containing only preprandial BG: (i) FBG (6·77 ± 0·07 mmol L−1) is higher than pre‐lunch BG (6·09 ± 0·07 mmol L−1, P = 0·0001) and pre‐dinner BG (5·84 ± 0·06 mmol L−1, P = 0·0001); (ii) the delta value between FBG and predinner BG is correlated with FBG (r = 0·57, P = 0·0001), the highest FBG, the steepest the fall of BG preprandial baseline throughout the day. This trend is confirmed in profiles measured by nurses. In profiles containing both pre‐ and postprandial BG: (i) there is a trend to preprandial BG fall (P = 0·0001) and to postprandial BG increase (P = 0·0001) from morning to evening; (ii) postprandial excursions are influenced and sometimes masked by the slope of BG preprandial baseline, thus, in profiles with FBG ≤ 6·7 mmol L−1 all postprandial values are higher than FBG (P = 0·0001), whereas in profiles with FBG > 7·8 mmol L−1, postprandial values are not significantly higher than FBG.Conclusion  In type 2 diabetes, the shape of BG profiles changes in relation to FBG, because it deeply influences the slope of BG preprandial baseline on which postprandial excursions are superimposed. Thus, before planning treatment policies, not only the extent of fasting and postprandial hyperglycaemia, but also the shape of profiles should be considered, to safely correct hyperglycaemia without inducing hypoglycaemia.
The effect of the Interleukin‐6–174G > C promoter gene polymorphism on endothelial function in healthy volunteers
Authors: Brull D. J. , Lesson C. P. M. , Montgomery H. E. , Mullen M. , DeDivitiis M. , Humphries S. E. , Deanfield J. E. 
Published: March 2003

AbstractAims  Atherosclerosis is a chronic inflammatory condition, manifest in its early stages by endothelial dysfunction. Interleukin‐6 (IL6) plays a key role in driving this process through stimulation of acute phase protein synthesis. We have examined the effect of the IL6 gene −174G > C promoter polymorphism on endothelial function in a group of healthy subjects.Methods  248 adults aged 20–28 years participated. Polymerase chain reaction was performed for the −174G > C polymorphism. Brachial artery diameter was measured at rest and after forearm cuff occlusion by high‐resolution ultrasound. Responses were represented as absolute flow mediated dilatation (FMDA).Results  Overall there was a trend towards greater FMDA for genotype CC, P = 0·14. No effect was seen in women; however, in men, following multivariate analysis, there was a significant association between genotype and FMDA, P = 0·04. In addition, a significant detrimental effect of smoking on FMDA was only seen in males of genotype CC (P < 0·05) when compared to nonsmokers of the same genotype.Conclusion  IL6–174G > C promoter polymorphism influences endothelial function in healthy male subjects. The detrimental effect of smoking on endothelial function is most clearly seen in men of genotype –174 CC, suggesting a genotype‐specific interaction with smoking.
Elective coronary angioplasty with 60 s balloon inflation does not cause peroxidative injury
Authors: Cedro K. , Marczak E. , Czerwosz L. , Herbaczynska‐Cedro K. , Rużyllo W. 
Published: March 2003

AbstractBackground The aim of this study was to evaluate the ongoing controversial issue of whether ischemia/reperfusion during elective coronary angioplasty evokes myocardial peroxidative injury.Design We measured indicators of free radical damage to lipids (free malondialdehyde) and proteins (sulphydryl groups) in coronary sinus blood in 19 patients with stable angina who were undergoing elective angioplasty for isolated stenosis of the proximal left anterior descending coronary artery. Ischemia induced by 60 s balloon inflations was confirmed by lactate washout into coronary sinus after deflation, with immediate and 1 min samples. Peroxidative injury was assessed from washout of (a) malondialdehyde measured directly by high performance liquid chromatography and (b) reduced sulphydryl groups, inverse marker of protein oxidative stress.Results Mean lactate concentration immediately after each deflation increased by 120–150% of the initial value, confirming ischemia and showing that blood originated largely from the ischemic region. Lack of myocardial production of malondialdehyde was confirmed by (a) no arteriovenous differences in individual basal concentrations (aortic, range 0·33–12·03 nmol mL−1, mean 7·82; coronary sinus blood, range 0·52–15·82 nmol mL−1, mean 8·18), and (b) after deflations, mean concentrations were not significantly different from preocclusion value. There was no decrease in concentration of sulphydryl groups throughout angioplasty.Conclusion Elective coronary angioplasty with 60 s balloon inflations is a safe procedure that does not induce peroxidative myocardial injury as assessed by methods used in the present study.
Tumour cell–dendritic cell fusion for cancer immunotherapy: comparison of therapeutic efficiency of polyethylen‐glycol versus electro‐fusion protocols
Authors: Lindner M. , Schirrmacher V. 
Published: March 2003

AbstractBackground  Fusion of tumour cells with dendritic cells (DC) is a powerful new technology to increase tumour vaccine immunogenicity. The aim of this study was to compare fusion protocols with syngenic DCs with respect to the efficiency of polyethylen‐glycol‐(PEG) and electric pulse‐mediated fusions for induction of protective anti‐tumour immune responses. As a model we chose a low immunogenic and metastatic murine mammary carcinoma cell line, which mimics clinically relevant tumour features.MethodsFACS‐staining, chromium release assay, therapeutic immunization, adoptive transfer.Results  We show that the parental line with low cell surface expression of MHC molecules as well as a lacZ transfectant becomes highly immunogenic upon fusion with DCs. This was true for PEG‐ as well as for electro‐fused cells. Immunization with products of DCs and tumour cells cocultivated for 16 h without the fusing agent PEG also caused induction of profound anti‐tumour immunity, while this was not the case when using parental tumour cells or their lacZ transfectants as vaccines. Immune protection against the parental tumour cells after vaccination with fused cells was long‐lasting and could be transferred via immune spleen cells into immuno‐incompetent nude (nu/nu) mice.Conclusion  Fusion products of DA3hi mammary carcinoma cells and DCs produced by an electric pulse were similar to those produced by PEG fusion with regard to vaccine potency in prophylactic antitumour immunization assays in vivo. Therefore, both techniques seem to be promising for clinical application.
Morning cortisol production in coronary heart disease patients
Authors: Fantidis P. , Perez De Prada T. , Fernandez‐Ortiz A. , Carcia‐Touchard A. , Alfonso F. , Sabaté M. , Hernández R. , Escaned J. , Bauelos C. , Macaya C. 
Published: March 2003

AbstractBackground The circadian cycle of the endogenous anti‐inflammatory system (EAIS) is characterized by a morning increase in cortisol production. Circulating interleukin‐6 (IL‐6) activates the EAIS. A circadian variation in the onset of myocardial infarction, sudden death, stable angina (SA) and unstable angina (UA) has been reported. The aim of this study was to determine morning cortisol production in coronary heart disease (CHD) patients.Materials and methods Serum cortisol and IL‐6 were measured in 129 patients with either SA (n = 65) or UA (n = 64) and 40 healthy volunteers. Blood samples were taken between 9 : 00 h and 12 : 00 h. The upper normal range of cortisol (25 µg dL−1) was used as a reference to classify patients.Results Forty‐eight patients had elevated cortisol levels (ECL) (32·5 ± 5·4 µg dL−1), while 81 patients had normal cortisol levels (NCL) (15·7 ± 5·9 µg dL−1). In NCL patients, IL‐6 levels (26·6 pg mL−1, ranged from 0·2 to 183.7) were significantly higher (P < 0·004) than in ECL patients (9·70 pg mL−1, range 0·07–56·5). Forty‐eight patients with UA belonged to the NCL group of patients, while only 16 UA patients belonged to the ECL group (χ2 = 0·000). Thirty‐two patients with SA belonged to the ECL group, and 33 to the NCL group (χ2 = 0·08).Conclusions Patients with ‘inappropriately’ normal morning cortisol production had high IL‐6 levels. ‘Inappropriately’ normal cortisol, detected in 75% of UA and 50% of SA patients, may be insufficient for limiting inflammation. These findings have novel clinical implications and suggest new therapeutic approaches in the treatment of these patients.
Physical training increases heart rate variability in healthy prepubertal children
Authors: Mandigout S. , Melin A. , Fauchier L. , N’Guyen L. D. , Courteix D. , Obert P. 
Published: March 2003

AbstractBackground The aim of the present study was to evaluate the effect of an endurance training program on heart rate variability (HRV) in prepubertal healthy children and to determine the relationships between HRV components and training‐induced cardiac adaptations.Methods Nineteen prepubertal children (aged 10–11 years old) took part in this study: 12 children were assigned to participate in a 13‐week endurance training program (3 × 1 h week−1; intensity, > 80% HRmax) and 7 children served as a control group. Before and after the 13‐week study period, all the children were tested for maximal oxygen uptake (V O2max), HRV was measured by spectral and time domain analysis of 5 h night ECG recordings, and left ventricular (LV) cardiac morphology and function were assessed by means of Doppler‐Echocardiography.Results V O2max increased significantly (+15·5% ± 12·1; P < 0·01) after the training program. All the frequency domain components (absolute values) increased after training except the low (LF) to high (HF) frequency ratio. Also, LF and HF did not change when expressed relative to total power. For the time domain components, only N–N intervals, the standard deviation of all N–N and the average of all 5 min standard deviations of N–N increased after training. Our training program induced also an increase in LV internal diameter and mass as well as an enhancement in early diastolic passive LV filling with a concomitant reduction in late diastolic active LV filling. These cardiac morphological and functional adaptations did not correlate however, with the autonomous nervous system modifications due to training.Conclusion Our study shows that an endurance training program had a positive effect on aerobic potential, morphological and functional cardiac parameters and on nocturnal global HRV in healthy prepubertal children without inducing sympathetic and parasympathetic modifications.
Rate‐dependency of calcitonin secretion in response to increased plasma Ca2+
Authors: Wang W. , Lewin E. , Olgaard K. 
Published: March 2003

AbstractBackground  Calcitonin (CT) is a polypeptide hormone secreted from C‐cells of the thyroid gland in response to hypercalcemia. The physiological contribution of CT to calcium homeostasis has not been completely clarified. The present study therefore further characterized the sigmoidal relationship between plasma ionized calcium (P‐Ca2+) and CT in normal rats, and examined the possibility of rate‐dependency of CT secretion in response to changes in P‐Ca2+.Design  Hypercalcaemia was induced by an infusion of calcium gluconate at rate of 4·5 × 10−2 mmol h−1rat−1i.v. (n = 8) and hypocalcaemia was induced by an EGTA infusion at a rate of 4·5 × 10−2 mmol h−1rat−1 (n = 7) in one protocol: the ‘slow’ protocol. In another protocol an increased rate of infusion of calcium gluconate or EGTA was used to induce a more rapid change in P‐Ca2+. Calcium gluconate was infused at a rate of 6·0 × 10−2 mmol h−1 rat−1 (n = 6) and EGTA infused at a rate of 7·5 × 10−2 mmol h−1rat−1 (n = 7): the ‘rapid’ protocol.Results  The infusions of both the ‘slow’ and ‘rapid’ protocols resulted in linear changes in P‐Ca2+, but with significantly different slopes (P < 0·01). The Ca2+/CT curves of both protocols were represented by sigmoidal curves. The ‘rapid’ increase of P‐Ca2+ resulted in a higher maximal CT secretion (2032 ± 215 pg mL−1) than the ‘slow’ increase of P‐Ca2+ (1213 ± 85 pg mL−1; P < 0·001), despite similar minimal and maximal levels being obtained in P‐Ca2+ in the two protocols. Thus, a significantly greater CT response was obtained with a more rapid increment in P‐Ca2+.Conclusion  The relationship between P‐Ca2+ and CT is represented by a sigmoidal curve, as previously shown. The CT response depended, however, not only upon the concentration of P‐Ca2+ obtained but also upon the rate of increase in P‐Ca2+, demonstrating rate‐dependency as another significant physiological relation between Ca2+ and CT.
Current and adolescent levels of cardiopulmonary fitness are related to large artery properties at age 36: the Amsterdam Growth and Health Longitudinal Study
Authors: Ferreira I. , Twisk J. W. R. , Van Mechelen W. , Kemper H. C. G. , Stehouwer C. D. A. 
Published: March 2003

AbstractBackground High levels of cardiopulmonary fitness (VO2max) are associated with reduced risk of cardiovascular morbidity and mortality, but little is known to what extent this is related to the effects of cardiopulmonary fitness on atherosclerosis and arterial stiffness. Moreover, the time course of these relationships needs to be elucidated. We sought to investigate (i) the cross‐sectional relationship between VO2max and carotid atherosclerosis and carotid and femoral arterial stiffness at age 36, as well as (ii) the relationship between VO2max during adolescence (13–16 years) and the same arterial properties at age 36 (prospective analyses).Design Cross‐sectional analyses consisted of 351 subjects (183 women) and the prospective analyses of a subpopulation of 154 subjects (79 girls). Arterial properties were assessed noninvasively by ultrasound imaging; VO2max was measured with a maximal running text on a treadmill with direct measurements of oxygen uptake.Results After adjustment for confounding by other known risk factors, current and adolescent levels of VO2max were independently associated with carotid intima‐media thickness (β = −0·288, P = 0·004 and β = −0·381, P = 0·012) in men, and with the diameter of the femoral artery (β = 0·375, P < 0·001 and β = 0·252, P = 0·026, respectively) in both sexes. Current levels of VO2max were positively associated with the compliance of the carotid and the femoral arteries (β = 0·186, P = 0·023 and β = 0·183, P = 0·033, respectively), and with the distensibility of the carotid (β = 0·162, P = 0·047) but not the femoral artery.Conclusion We conclude that cardiopulmonary fitness is associated with large artery properties at age 36, and that the roots of this association may already be present in adolescence.
The hormone‐sensitive lipase i6 gene polymorphism and body fat accumulation
Authors: Lavebratt C. , Rydén M. , Schalling M. , Sengul S. , Ahlberg S. , Hoffstedt J. 
Published: March 2003

AbstractBackground The hormone sensitive lipase (HSL) catalyses the breakdown of adipose tissue triglycerides into free fatty acids. The objective of this study was to determine whether HSLi6 microsatellite allele 5 (A5) and/or homozygosity for this allele is associated with body fat in Swedes.Design A large case–control study on gender‐specific association for several body fat‐related clinical parameters to HSLi6 A5, and to HSLi6 A5 homozygosity, comparing A5 with the other alleles in group. The subjects were 323 obese patients (85 males, 238 females) without other metabolic complication, and 301 nonobese healthy individuals (134 males, 167 females). They were analyzed for various body fat‐related clinical parameters, and HSLi6 genotype.Results Homozygosity for HSLi6 A5 was a risk factor for obesity, BMI ≥ 30 kg m−2 (Odds ratio = 1·75, 95% CI 1·58–1·93) and body fat mass > 39·6% (Odds ratio = 1·89, 95% CI 1·60–2·23) in women. This genotype was also associated with increased diastolic blood pressure and triglyceride level among nonobese women, and with increased body fat mass and waist/hip ratio among nonobese men.Conclusion HSLi6 A5 homozygosity is a risk factor for body fat accumulation.