Evaluation of pulmonary function and polysomnography in obese children and adolescents

Obese adults have an increased prevalence of pulmonary disorders. Although childhood obesity is a common problem, few studies have evaluated the pulmonary complications of obesity in the pediatric population. We, therefore, performed pulmonary function tests (PFTs), polysomnography, and multiple sleep latency tests (MSLTs) in 22 obese children and adolescents [mean age, 10 ± 5 (SD) years; 73% female; 184 ± 36% ideal body weight], none of whom presented because of sleep or respiratory complaints. PFTs were normal in all but two subjects. Ten (46%) subjects had abnormal polysomnograms. There was a positive correlation between the degree of obesity and the apnea index (r = 0.47, P < 0.05), and an inverse correlation between the degree of obesity and the S₂O₂ nadir (r = −0.60, P < 0.01). The degree of sleepiness on MSLT correlated with the degree of obesity (r = −0.50, P < 0.05). We conclude that obese children and adolescents have a high prevalence of sleep-disordered breathing, although in many cases it is mild. Obstructive sleep apnea syndrome (OSAS) improved following tonsillectomy and adenoidectomy. We recommend that pediatricians have a high index of suspicion for OSAS when evaluating obese patients, and that polysomnography be considered for these patients. Pediatr Pulmonol. 1996; 21:176–183. © 1996 Wiley-Liss, Inc.     

Serum anti—SS-B/La and IgA rheumatoid factor are markers of salivary gland disease activity in primary sjögren's syndrome

Objective. To identify serologic markers of salivary gland disease activity in 43 patients with primary Sjögren's syndrome. Methods. Comparison of salivary gland biopsies (focus scores) and flow rates with serum concentrations of IgA and IgM rheumatoid factor (RF), total serum IgG, serum anti—SS-B/La antibodies, and the erythrocyte sedimentation rate. Results. Serum anti—SS-B/La antibody levels correlated with focus scores (r_s = 0.477, P < 0.0025). Serum IgA-RF concentrations correlated inversely with stimulated parotid gland salivary flow rates (r_s = −0.394, P < 0.01). Conclusion. Measuring serum levels of anti—SS-B/La and IgA-RF would be useful when monitoring salivary responses in therapeutic trials, especially in patients with minimal salivary function.     

Serum sex-hormone-binding globulin is related to hepatic and peripheral insulin sensitivity but not to beta-cell function in men and women with Type 2 diabetes mellitus

This study examined the relationship of hepatic and peripheral insulin sensitivity and β-cell secretory function with serum sex hormone-binding globulin (SHBG) in men and women with Type 2 diabetes mellitus (DM). Fasting insulin, glucose and SHBG were measured in 58 Type 2 diabetic patients of both sexes (36 men) who were on diet treatment only and terms for insulin sensitivity and β-cell secretion obtained by modelling. There was no significant difference in SHBG between men and women despite similar degree of obesity. SHBG was positively correlated (r = 0.41, p < 0.01) to hepatic insulin sensitivity derived from mathematical modelling of fasting glucose and insulin data using the homeostasis assessment model (HOMA). This relationship was independent of gender (men, r = 0.48, p < 0.01; women, r = 0.45, p < 0.05). Fasting insulin correlated negatively with SHBG in men (r = −0.34, p < 0.05). There were also significant negative correlations between SHBG and either plasma glucose (r = −0.29, p < 0.05) or body mass index (r = −0.34, p < 0.05). SHBG did not correlate with HOMA-modelled beta-cell function. In a multiple regression analysis, SHBG was independently correlated only with insulin sensitivity (p < 0.05). Further studies in 15 of the diabetic patients (11 men), showed a significant positive correlation (r = 0.52, p < 0.05) between SHBG and peripheral insulin sensitivity derived by continuous infusion of glucose with model assessment (CIGMA) but not between SHBG and CIGMA-modelled β-cell function. These results indicate that both hepatic and peripheral insulin sensitivity are similarly related to serum SHBG in Type 2 diabetes of both sexes. The sex-difference in SHBG was abolished in the patients. © 1998 John Wiley & Sons, Ltd.     

Acute phase proteins activation in subjects with coronary atherosclerosis and micro-vessel coronary circulation impairment

Aim To investigate possible correlations between acute phase proteins (APPs) activation and coronary flow in subjects with coronary artery disease (CAD) undergoing coronary angiography. Methods Fifty-nine consecutive patients with CAD who underwent coronary angiography were enrolled in the study: blood samples were taken in order to evaluate plasmatic concentrations of C-reactive protein (CRP) and APPs such as alpha-1-anti-trypsin (A1AT), alpha-1-glyco-protein (A1GP) and haptoglobin (HG). Coronary flow on left anterior descending (LAD) was assessed with TIMI frame count (TFC). Patients with TIMI flow 0–1 were excluded from the study. Results Coronary atherosclerosis expressed in terms of number of coronary vessels with severe (>70%) lumen narrowing was related to serum concentrations of all considered APPs (A1GP: r 0.282, P < 0.05; A1AT: r 0.256, P 0.055; HG: r 0.335, P < 0.01). TFC on LAD was related to all considered APPs (A1GP: r 0.24, P 0.06; A1AT: r 0.28, P < 0.05; HG: r 0.43, P < 0.01; log CRP: r 0.57, P < 0.001); correlations remained significant even after correction for age, gender, risk factors, diagnosis and treatment. Among 12 patients who were previously treated with coronary angioplasty, those implanted with a drug eluting stent showed a significantly slower coronary flow on LAD (19.6 ± 2.07 vs. 16.71 ± 2.06, P < 0.05) if compared with those implanted with a bare metal stent. Conclusions An increased inflammatory systemic activation featured by plasmatic concentrations of CRP and APPs might be associated with both coronary atherosclerosis and an impaired coronary micro-circulation.     

Metabolic changes of anterior cingulate cortex in patients with hepatic cirrhosis: A magnetic resonance spectroscopy study

Aim: The anterior cingulate cortex (ACC) plays an important role in cognitive functions. The purpose of this study is to compare metabolite concentrations in the ACC of cirrhotic patients with normal controls, and to correlate metabolite changes with Child–Pugh class and with severity of hepatic encephalopathy (HE). Methods: Fifty‐two cirrhotic patients and 30 healthy volunteers were included in this study. All subjects performed the number connection test type A (NCT‐A) and digital symbol test (DST) before multiple resonance (MR) examinations. Single‐voxel proton MR spectroscopy (MRS) data in the ACC were acquired on a 1.5‐T scanner. The ratios of all metabolites to creatine and phosphocreatine (Cr) were obtained. Statistical analysis was performed to evaluate the difference between control and cirrhotic patients, with respect to metabolite ratios. The correlation between metabolite ratios and Child–Pugh scale, severity of HE, venous ammonia and neuropsychiatric test results was analyzed. Results: The ratios of choline (Cho)/Cr and myo‐inositol (mIns)/Cr were significantly lower, and the ratio of glutamine– glutamate (Glx)/Cr was significantly higher in cirrhotic patients than those in controls (P < 0.001). mIns/Cr correlated negatively with Child–Pugh scale (r = −0.496, P < 0.001) and HE degree (r = −0.313, P < 0.05). Venous ammonia had a significant correlation with Cho/Cr (r = −0.329, P < 0.05) and mIns/Cr (r = −0.347, P < 0.05). No statistical correlation between metabolite ratios and neuropsychological tests was found for cirrhotic patients, but mIns/Cr did have a statistical correlation with NCT‐A (r = −0.270, P < 0.05) and DST (r = 0.463, P < 0.001) when all subjects were included in the analysis. Conclusion: Significant metabolite changes were seen in the ACC in cirrhotic patients. Of the metabolites examined, the mIns/Cr level in the ACC was most closely associated with the severity of HE and hepatic functional reserve reflected by Child–Pugh scale.     

Relationship between interleukin-6 and ammonia in patients with minimal hepatic encephalopathy due to liver cirrhosis

Aim: Previous studies have shown significantly elevated levels of interleukin (IL)-6 in cirrhotic patients with minimal hepatic encephalopathy (MHE), but the relationship between circulating levels of IL-6 and ammonia is unclear. The aim of this study is to investigate the relationship between both variables in cirrhotic patients with MHE. Methods: Psychometric tests including number connection test part A (NCT-A) and digit symbol test (DST) were performed to diagnose MHE in 85 cirrhotic patients. Simultaneously, circulating levels of IL-6 and ammonia were measured. Results: Thirty-two (37.6%) cirrhotic patients were diagnosed with MHE. IL-6 and ammonia were the independent predictors of the presence of MHE (P < 0.05 for both variables). Circulating levels of IL-6 and ammonia correlated with the severity of MHE represented by results of NCT-A (r = 0.56, P < 0.05 and r = 0.39, P < 0.05, respectively) and DST (r = −0.48, P < 0.05 and r = −0.47, P < 0.05, respectively). Moreover, there was a significant correlation between circulating levels of IL-6 and those of ammonia in patients with MHE (r = 0.61, P < 0.05), and a positive additive interaction was found between IL-6 and ammonia on the presence of MHE, with a significant synergy index of 1.51 (95% confidence interval = 1.12–3.46). Conclusion: The present study demonstrates a significant correlation and a positive additive interaction between IL-6 and ammonia in cirrhotic patients with MHE, suggesting that IL-6 may have a potential synergistic relationship with ammonia in the induction of MHE.     

An overview of the pharmacokinetics and pharmacodynamics of amlodipine in elderly persons with systemic hypertension

Pharmacokinetic and pharmacodynamic data were compared between elderly and young patients with hypertension who received single intravenous doses of amlodipine, a dihydropyridine calcium antagonist, followed by oral administration of amlodipine up to 10 mg once daily for 12 weeks. After intravenous administration, elderly patients had prolonged elimination half-life values (58 ± 11 vs 42 ± 8 hr; p < 0.05) caused by decreased clearance (19 ± 5 vs 7 liters/hr; p < 0.05). Systolic and diastolic blood pressures were significantly decreased from baseline throughout the 3-month treatment period in both groups. After long-term oral administration, elderly and young patients had comparable decreases in mean blood pressure at a given drug plasma concentration. The antihypertensive effect of amlodipine is well correlated with plasma concentration and, at a given concentration, is similar in both elderly and young patients.     

Determinants of the tension-time index of inspiratory muscles in children with cystic fibrosis

Nutritional status and chronic pulmonary hyperinflation can alter respiratory muscle function in cystic fibrosis (CF). This study investigated: 1) whether inspiratory muscle function is reduced in children with stable CF in comparison with healthy controls; and 2) the mechanisms leading to inspiratory muscle weakness, which probably predispose to respiratory muscle fatigue. We determined the tension-time index of the inspiratory muscles (T_TMUS) noninvasively at rest in 16 children with mild to moderate CF (mean age, 11 ± 2 years) and 10 healthy controls (mean age, 11 ± 2 years). The T_TMUS was determined as follows: T_TMUS = T_I/T_TOT · P_I/P_IMAX, where P_I is the mean inspiratory pressure estimated from the measure of mouth occlusion pressure (P0.1), P_IMAX is the maximal inspiratory pressure, and T_I/T_TOT is the duty cycle. The results showed similar nutritional status in both groups, as well as mild to moderate airway obstruction, hyperinflation, and trapped gas in the CF group. In this group only, a significant inverse relationship was found between T₁/T_TOT and P₁/P_IMAX[T_IT_TOT = 0.482 - (0.388P_I/P_IMAX), r = −0.53; p < 0.05]. The patients also had a greater T_TMUS (T_TMUS = 0.087 ± 0.030 in CF vs. 0.056 ± 0.014 in controls, P < 0.01) that increased with decreasing lean body mass (r = −0.70, P < 0.005), with increasing percent predicted functional residual capacity (r = 0.70, P < 0.05). and increasing volumes of trapped gas (r = 0.77, P < 0.01). The multiple linear regression analysis for these factors was significant (R² = 0.84, P < 0.01); however, the partial regression coefficient was significant only for lean body mass (r² = 0.60, P < 0.05). Therefore, muscle mass appeared as the strongest determinant of T_TMUS in CF. This study used a noninvasive method to assess the inspiratory muscle performance in children with CF. The results suggest impairment in inspiratory muscle function in these children despite good nutritional status and only mild to moderate alteration in pulmonary function tests. In addition, we were able to investigate some of the determinants of inspiratory muscle weakness, namely, muscle mass, hyperinflation, and trapped gas, and found that muscle mass played a predominant role. Pediatr. Pulmonol. 1997; 23:336–343. © 1997 Wiley-Liss, Inc.     

Intracoronary ultrasound before coronary interventions: A prospective comparison of two different catheters

Intravascular ultrasound (IVUS) provides unique information about the coronary arterial wall that can be used to guide transcatheter therapy. In this prospective study, two different IVUS systems were compared with respect to feasibility of imaging before intervention and angiographic changes induced by the simple advancement of the catheter across the lesion. Eighty-five patients (mean age 59 ± 10 yr, 11 female) were studied with IVUS before intervention. In 34 patients, a 4.8F (1.6-mm) IVUS catheter was used (Group I), whereas in the remaining 51 patients a 3.5F (1.2-mm) IVUS catheter was used (Group II). Quantitative angiography was performed before and after the IVUS study to determine potential changes in lumen diameter. Clinical and angiographic characteristics were similar in the two groups. A successful IVUS interrogation of the target lesion was obtained more frequently in Group II (45/51 (88%) vs. 19/34 (56%) patients, P < 0.01). After the IVUS study, a change in minimal lumen diameter was seen in Group I (baseline 0.84 ± 0.2 vs. Final 1.17 ± 0.2 mm, P < 0.001) and Group II patients (baseline 0.80 ± 0.3 vs. final 1.03 ± 0.4 mm, P < 0.01). In the 64 lesions successfully crossed, the absolute gain in lumen diameter was significantly higher in Group I (0.40 + 0.2 vs. 0.23 ± 0.2 mm, P < 0.05). In addition, an inverse correlation was found between baseline minimal lumen diameter and the absolute lumen gain induced by the IVUS study in Group I (r = −0.47, P < 0.05) but not in Group II patients (r = −0.16, NS). Neither angiographic nor echogenic lesion characteristics were associated with the change in lumen diameter. When multivariate analysis was applied, catheter size was the only independent predictor of lumen gain induced by IVUS after adjustment. Thus, the advancement of IVUS catheters across severe coronary lesions induces significant angiographic changes consistent with plaque remodeling and a Dotter effect. The use of smaller catheters not only allows a higher number of lesions to be studied before intervention, but also lessens the mechanical disruption of the plaque, yielding a more accurate and veracious picture of baseline plaque characteristics. Cathet Cardiovasc Diagn 40:33–39, 1997. © 1997 Wiley-Liss, Inc.     

Improved carotid intima-media thickness-induced high-intensity interval training associated with decreased serum levels of Dkk-1 and sclerostin in type 2 diabetes

AimsCarotid intima-media thickness (cIMT) is a validated surrogate marker of atherosclerosis. Dickkopf-1 (Dkk-1) and sclerostin modulate wingless signaling, which is involved in atherosclerosis. The purpose of this study was to investigate whether 12 weeks of high-intensity interval training (HIIT) would improve cIMT and serum Dkk-1 and sclerostin levels in patients with type 2 diabetes.MethodsSeventy-four sedentary patients with type 2 diabetes were randomly divided into HIIT and control groups. The HIIT group intervention was 6 intervals (4 min) at 85%–90% HR_max separated by 3 min at 45%–50% HR_max in 3 sessions/week for 12 weeks. Before and after the intervention, cIMT, artery diameter and wall/lm ratio were recorded with high-resolution ultrasound. Serum sclerostin and Dkk-1 were measured by enzyme-linked immunosorbent assay (ELISA).ResultscIMT decreased significantly in the HIIT group (0.83 ± 0.17 baseline, 0.71 ± 0.14 follow-up) compared to the control group (0.84 ± 0.20 baseline, 0.85 ± 0.19 follow-up) (P < .05). Dkk-1 and sclerostin decreased significantly after 12 weeks of HIIT (P < .01). In addition, VO_2peak was increased in the HIIT group than the control group (by 6.2 mL/kg/min) (P < .05). There was a positive correlation between percent changes in cIMT and percent changes in Dkk-1 and sclerostin (both P < .01). Additionally, there were a negative correlation between percent changes VO2peak and cIMT (r = − 0.740, P = .003), Dkk-1 (r = − 0.844, P < .001) and sclerostin (r = − 0.575, P = .001) in HIIT group.ConclusionOur results indicate that HIIT decreases cIMT, serum levels of Dkk-1 and sclerostin and improves VO_2peak in patients with type 2 diabetes.     

Effect of Theophylline on Serum Uric Acid Levels in Children with Asthma

This study was undertaken to investigate the effect of theophylline on serum uric acid levels in children with asthma. Twenty-seven asthmatic children, including 21 patients who were treated with slow-release theophylline and 6 patients not receiving any type of theophylline preparation, were enrolled in this study. Serum uric acid levels were increased in the asthmatic children treated with theophylline compared to those not receiving this agent (6.28 ± 0.29 mg/dl, mean ± SEM, vs. 4.82 ± 0.52 mg/dl, p < 0.05). A significant positive correlation between the serum levels of uric acid and theophylline was demonstrated in the patients of this study (r_s = 0.5%, p < 0.01). All the patients in whom theophylline administration was stopped showed significant decreases in serum uric acid levels (p < 0.05). From these results, we conclude that theophylline increases serum uric acid levels in children with asthma, just as it does in adult asthmatics.     

Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes

Aims/hypothesis Activation of the receptor for advanced glycation end products (RAGE, also known as AGE-specific receptor [AGER]) has been implicated in the development of diabetic vascular complications. Blockade of RAGE using a soluble form of the receptor (sRAGE) suppressed vascular hyperpermeability and atherosclerosis in animal models. Since little is known about the regulation of endogenous sRAGE levels, we determined whether serum sRAGE is influenced by circulating AGEs and the severity of nephropathy in type 2 diabetic patients.Materials and methods We recruited 150 healthy control and 318 diabetic subjects. Diabetic subjects were subdivided into those with proteinuria, microalbuminuria or normoalbuminuria. Serum sRAGE was assayed by ELISA and serum AGEs by competitive ELISA using a polyclonal rabbit antiserum raised against AGE-RNase.Results Diabetic subjects had higher sRAGE (1,029.5 pg/ml [766.1–1,423.0] interquartile range vs 1,002.6 [726.5–1,345.3], p<0.05) and AGEs (4.07±1.13, SD, unit/ml vs 3.39±1.05, p<0.01) than controls. Proteinuric subjects had the highest sRAGE levels and there was a significant trend between the severity of nephropathy and sRAGE (p=0.01). In diabetic subjects, serum log(sRAGE) correlated with AGEs (r=0.27, p<0.001), log(plasma creatinine) (r=0.31, p<0.001), log(urine AER) (r=0.24, p<0.01) and log(triglycerides) (r=0.15, p<0.01). On stepwise linear regression analysis, AGEs and creatinine levels were the main independent determinants of sRAGE concentration.Conclusions/interpretation Serum sRAGE levels and circulating AGEs are associated with the severity of nephropathy in type 2 diabetic patients. Prospective studies are required to determine whether endogenous sRAGE potentially influences the development of diabetic vascular complications.     

Regional myocardial metabolism and electrolyte balance during acute ischemia in dogs

The relationships among regional (ischemic and non-ischemic) myocardial extracellular (coronary venous) potassium concentration, potassium-sodium concentration ratio, acid-base balance, and metabolism of glucose and lactate were evaluated in 14 anesthetized dogs in which ischemia was produced by transitory left anterior descending coronary artery (LAD) occlusion. Coronary blood samples were obtained from the specific regions by using coronary arterial and venous catheters placed directly into the vessel supplying (or draining) that region. During ischemia, in coronary venous blood sampled from the ischemic area, pH decreased, and PCO2, base deficit, potassium concentration, and the potassium-sodium ratio increased. In LAD venous blood samples obtained during LAD occlusion, the percentage change in potassium concentration was inversely related to the percentage change in PCO₂ (r = −0.634, P < 0.05), but not to the percentage change in hydrogen ion concentration (r = −0.339, P > 0.05). During ischemia, arteriovenous O₂ content difference in the LAD region increased from 8.54 ± 0.73 vol % to 10.71 ± 0.73 vol %; lactate extraction became negative (indicating net production), values decreasing from 27.76 ± 4.49% to −138.10 ± 16.81 % (P < 0.05); and glucose extraction increased from 14.57 ± 2.88% to 19.01 ± 6.06% (0.05 < P < 0.1). These observations indicate that efflux of potassium from the myocardium during ischemia is linked to tissue hypoxia, increased glucose extraction, lactate production, and extracellular acidosis. A further contributor to potassium release, failure of the normal membrane-bound, energy-requiring ion pump, cannot be excluded by these data. With the model used in this study, blood can be sampled from discrete regions of the heart, which enables the study of interactions between pharmacologic agents, such as anesthetics, and the metabolic abnormalities produced by acute ischemia.     

Blood ketone bodies in congestive heart failure

Objectives. The present study was designed to assess whether blood ketone bodies are elevated in congestive heart failure (CHF) and whether ketonemia is related to the hemodynamic and neurohumoral abnormalities of CHF.Background. In CHF, consumption of the body's fat stores may become abnormally high, contributing to the development of cardiac cachexia. Increased mobilization of free fatty acids could, in theory, augment ketogenesis, but whether patients with CHF are prone to ketosis remains unknown.Methods. Forty-five patients with chronic CHF (mean age [±SD] 57 ± 13 years) and 14 control subjects free of CHF (mean age 53 ± 13 years) underwent invasive and noninvasive cardiac studies and determination of blood ketone bodies (acetoacetate plus beta-hydroxybutyrate), circulating free fatty acids, glucose, lactate, insulin, glucagon, growth hormone, cortisol, norepinephrine, N-terminal proatrial natriuretic peptide, tumor necrosis factor-alpha and interleukin-6 after an overnight fast.Results. Patients with CHF had elevated blood ketone bodies (median 267 μmol/liter, range 44 to 952) compared with control subjects (median 150 μmol/liter, range 31 to 299, p < 0.05). In the total study group, blood ketone bodies were related to pulmonary artery wedge pressure (r_s = 0.45, p < 0.001), left ventricular ejection fraction (r_s = −0.37, p < 0.01), right atrial pressure (r_s = 0.36, p < 0.01) and circulating concentrations of free fatty acids (r_s = 0.52, p < 0.001), glucose (r_s = −0.39, p < 0.01), norepinephrine (r_s = 0.45, p < 0.001), growth hormone (r_s = 0.30, p < 0.05) and interleukin-6 (r_s = 0.27, p < 0.05). In multivariate analysis, left ventricular ejection fraction, serum free fatty acids and serum glucose were independent predictors of ketonemia.Conclusions. Blood ketone bodies are elevated in CHF in proportion to the severity of cardiac dysfunction and neurohormonal activation. This may be at least partly attributable to increased free fatty acid mobilization in response to augmented neurohormonal stimulation. Additional studies are needed to identify the detailed mechanisms and clinical implications of CHF ketosis.     

Electronegative low density lipoprotein subform (LDL–) is increased in type 2 (non-insulin-dependent) microalbuminuric diabetic patients and is closely associated with LDL susceptibility to oxidation

There is increasing evidence that diabetes mellitus is characterized by an enhanced lipoprotein oxidation. We have therefore investigated whether a relationship exists between LDL oxidation and microalbuminuria, which is considered an early marker of vascular involvement in type 2 diabetic patients. We selected 12 microalbuminuric and 12 normoalbuminuric type 2 diabetic patients, and 12 control subjects comparable for age, sex and blood pressure values. Oxidatively modified plasma LDL, referred as LDL^–, were measured by ion-exchange HPLC. In vitro susceptibility to oxidation of LDL was evaluated by following the kinetics of conjugated diene formation in the presence of Cu⁺⁺ ions (lag-phase time). Microalbuminuric diabetic patients had a less satisfactory metabolic control and showed a higher plasma triglyceride concentration than both normoalbuminuric diabetic patients (2.21±1.01 vs 1.15±0.39 mmol/l, P<0.01) and controls (1.18±0.61 mmol/l, P<0.01). The percentage of LDL^– in plasma was significantly increased in microalbuminuric diabetic patients in comparison with both normoalbuminuric diabetic patients (5.24±1.67 vs 3.13±1.22%, P<0.01) and controls (2.34±1.03%, P<0.001). LDL isolated from microalbuminuric diabetic patients had a significantly shorter lag-phase time in comparison with normoalbuminuric diabetic patients (79±11 vs 97±10 min, P<0.05) and controls (120±24 min, P<0.001). In diabetic patients a significant linear correlation was observed between the percentage of LDL^– and amount of fructosamine (r=0.45, P<0.05), HbA_1c (r=0.41, P<0.05), and triglycerides (r=0.65, P<0.001). An inverse correlation was found between lag-phase time and fructosamine (r=–0.5, P<0.01) and triglycerides (r=–0.59, P<0.001). This study shows that microalbuminuric type 2 diabetic patients had evidence of increased LDL oxidation, which seems to be mainly due to a poor metabolic control and a more atherogenic lipid profile. Received: 9 March 1998 / Accepted in revised form: 24 June 1998     

Relationship between non-enzymatic glycosylation and changes in serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in patients with type 2 diabetes mellitus

The possible occurrence of increased non-enzymatic glycosylation of serum insulin-like growth factor binding protein-3 (IGFBP-3) in vivo and the changes that would simultaneously occur in serum levels of IGFBP-3 and insulin-like growth factor-1 (IGF-I) were investigated. We measured levels of IGF-I and IGFBP-3 and the degree of glycation of total serum protein and IGFBP-3, in serum samples obtained from patients with poorly controlled non-insulin-dependent diabetes (type 2) and from age-matched non-diabetic controls. Type 2 diabetic patients had significantly higher glycated serum protein (GlyP) levels. GlyP significantly correlated with age in the control (r = 0.315, P<0.05) but not in the type 2 diabetes group. Control and diabetic subjects had comparable serum IGF-I levels and in both groups IGF-I levels tended to decrease with age (r = –0.567, P<0.001 and r = –0.465, P<0.05 for control and type 2 diabetic subjects, respectively). In the type 2 diabetes group, IGF-I levels showed a negative correlation with serum GlyP values (r = –0.476, P<0.05). Type 2 diabetic and control patients had comparable serum IGFBP-3 levels, which were significantly higher in diabetic patients in the older age subgroups. A negative correlation was found between IGFBP-3 levels and age in the control (r = –0.705, P<0.001) and in the type 2 diabetes groups (r = –0.463, P<0.05). A significant negative correlation was found between IGFBP-3 levels and GlyP in control (r = –0.449, P<0.002) but not in type 2 diabetic subjects. The mean glycated IGFBP-3 (GlyIGFBP-3) levels were higher in the oldest type 2 diabetic patients. In these patients, GlyIGFBP-3 was negatively associated with IGF-I levels (r = –0.447, P<0.05). The IGF-I/IGFBP-3 molar ratio was significantly reduced in the 46–60-year-old type 2 diabetic group, whereas the IGF-I/IGFBP-3 ratio was positively and significantly correlated with GlyP levels only in the control group (r = 0.489, P<0.01). Our results show that: a) increased non-enzymatic glycosylation of IGFBP-3 occurs in vivo; and b) this effect is accompanied by an increase in IGFBP-3 levels. These results suggest that the IGF-I/IGFBP-3 system is another target for the metabolic derangements of type 2 diabetes. Its alterations might play a role in diabetic complications. Received: 22 September 1997 / Accepted in revised form: 30 April 1998     

Labile Plasma Iron Generation After Intravenous Iron is Time-dependent and Transitory in Patients Undergoing Chronic Hemodialysis

Iron supplementation in hemodialysis patients is fundamental to erythropoiesis, but may cause harmful effects. We measured oxidative stress using labile plasma iron (LPI) after parenteral iron replacement in chronic hemodialysis patients. Intravenous iron saccharate (100 mg) was administered in patients undergoing chronic hemodialysis (N = 20). LPI was measured by an oxidant-sensitive fluorescent probe at the beginning of dialysis session (T0), at 10 min (T1), 20 min (T2), and 30 min (T3) after the infusion of iron and at the subsequent session; P < 0.05 was significant. The LPI values were significantly raised according to the time of administration and were transitory: −0.02 ± 0.20 µmol/L at the beginning of the first session, 0.01 ± 0.26 µmol/L at T0, 0.03 ± 0.23 µmol/L at T1, 0.09 ± 0.28 µmol/L at T2, 0.18 ± 0.52 µmol/L at T3, and −0.02 ± 0.16 µmol/L (P = 0.001 to 0.041) at the beginning of the second session. The LPI level in patients without iron supplementation was −0.06 ± 0.16 µmol/L. Correlations of LPI according to time were T1, T2, and T3 vs. serum iron (P = 0.01, P = 0.007, and P = 0.0025, respectively), and T2 and T3 vs. transferrin saturation (P = 0.001 and P = 0.0003, respectively). LPI generation after intravenous saccharate administration is time-dependent and transitorily detected during hemodialysis. The LPI increment had a positive correlation to iron and transferrin saturation.     

Renal growth during pregnancy in insulin-dependent diabetic women

Kidney volume was measured during pregnancy in insulin-dependent diabetic women by an ultrasound technique and prognostic value of these measurements evaluated. A prospective study was performed on 87 pregnant women with insulin-dependent diabetes attending the maternity clinic of Aarhus Kommunehospital. Patients with proliferative retinopathy alone, hydronephrosis, or nephrotic syndrome were excluded. The patients were grouped according to onset and duration of diabetes and to vascular lesions; group I (n=35, White class B+C), group II (n=11, White class D⁰), groun III (n=26, White class D⁺, and group IV (n=15, White class F+F/R). The patients visited the hospital every 2 weeks during pregnancy for general obstetric and glycaemic control and blood sampling. The volume of both kidneys was measured by a computerized nephrosonograph during the three terms of pregnancy, the puerperium and 4 months postpartum. The kidney volume increased significantly in all four groups from first to third trimester. In the third trimester the kidney volumes were 375±68 ml (I), 341±50 ml (II), 362±63 ml (III), and 343±54 ml (IV). The kidney volume in the third trimester was positively correlated with creatinine clearance (r=0.33,P<0.01) and inversely correlated with creatinine in serum (r=−0.27,P=<0.02). Total kidney volume decrease (in percent) defined as the difference of maximal volume and value at 4 months postpartum was inversely correlated to albuminuria in the third trimester (r=−0.25,P<0.05) and vascular lesions of the patients: (mean±SEM) 37±4% (I), 25±7% (II), 19±5% (III), and 11±7% (IV),P<0.01. In the puerperium, kidney volume decreased significantly from third trimester in groups I, II, and III, whereas we observed no change in group IV. Six of 15 women in groups II and III with kidney volume <300 ml and normoalbuminuria in the first trimester developed persistent microalbuminuria after pregnancy (P<0.02). The renal volume in insulin-dependent diabetic women increases significantly during pregnancy and is inversely related to the vascular lesions of the patients. The decrease in renal volume after pregnancy is related to the albuminuria at the end of pregnancy. Women with long-standing diabetes, White class D (=groups II+III), and kidney volume <300 ml in the first trimester have a high risk of developing permanent microalbuminuria after pregnancy.     

D-Xylose hydrogen breath tests compared to absorption kinetics in human patients with and without malabsorption

Thed-xylose breath H₂ test may be useful in characterizing intestinal absorptive function. Our aim was to determine whether breath H₂ followingd-xylose administration reflects the extent to which thed-xylose is absorbed by comparing it to a kinetic model ofd-xylose absorption. Twenty-five subjects were studied. They ingested 15 gd-xylose on the first day and 25 gd-xylose on the third day. On the second day they received 10 g intravenousd-xylose along with 15 g oral lactulose. Multiple serum and urine samples were obtained ford-xylose content to calculate its rate constants and extent of absorption by multicompartmental analysis. Breath H₂ determinations were obtained every 15 min for 3 hr following the 15 gd-xylose and lactulose ingestion. Peak breath H₂ concentration correlated with extent of absorption (r=–0.787,P<0.001),K ₀, the rate constant for nonabsorptive loss (r=0.744,P<0.001), and 5-hr urine content (r=–0.705,P<0.001). Area under the breath H₂ curve also correlated with these parameters: extent of absorption (r=–0.770,P<0.001),K ₀ (r=0.662,P<0.001), 5-hr urine content (r=–0.629,P<0.012). Peakd-xylose breath H₂ to peak lactulose breath H₂ showed no correlation with extent of absorption. The extent of absorption was higher with the 15-g dose than the 25-g dose in all patients tested (P<0.01). This was the result of decreased nonabsorptive loss (lowerK ₀), as the rate constant for absorption,K _a , was not statistically different (P>0.05). Peakd-xylose breath H₂ can be used as an inverse estimate ofd-xylose absorption. Lactulose breath H₂ cannot be used as a standard for comparison ford-xylose. The three compartment kinetic model ford-xylose absorption with passive absorption of this carbohydrate is supported by similar rate constants for absorption for the twod-xylose doses used.d-xylose at 15 g may be a more appropriate dose than 25 g for H₂ breath testing as it does not lead to increased nonabsorptive losses.Supported in part by grant RR0048, National Institutes of Health, National Center for Research Resources.     

Atrial natriuretic peptide in Type 2 diabetes mellitus: response to a physiological mixed meal and relationship to renal function

Relatively few data exist on atrial natriuretic peptide (ANP) characteristics in Type 2 diabetes mellitus (DM). Therefore, plasma immunoreactive ANP concentrations were measured before and for 4 h following the ingestion of a physiological mixed meal in 8 newly diagnosed, normotensive, normoalbuminuric, patients with Type 2 DM and 6 normotensive, non-diabetic controls. In patients with Type 2 DM, basal plasma ANP concentrations were 4.0 ± 2.0 and not significantly changed following ingestion of the meal, with peak levels of 4.9 ± 2.8 pmol l⁻¹. Non-diabetic controls had higher basal plasma ANP concentrations, 8.7 ± 3.4 pmol l⁻¹ (p < 0.05), significantly increasing to a peak of 11.9 ± 6.3 pmol l⁻¹ at 30 min post meal. Extracellular fluid volume (ECV) was not different between diabetic patients and controls (15877 ± 2679 vs 13668 ± 1792 ml³). Glomerular filtration rate (GFR) (isotopic clearance corrected for body surface area) was elevated in diabetic patients (mean ± SD) 130 ± 39 vs 98 ± 10 ml min⁻¹, p < 0.05). For the DM subjects, basal ANP levels were negatively correlated with GFR (r_s − 0.74, p < 0.05) and effective renal plasma flow (ERPF) (r_s − 0.8, p < 0.05). We conclude that patients with Type 2 DM demonstrate reduced basal plasma ANP concentrations which are inversely correlated to renal function. In contrast to non-diabetic controls, ANP in Type 2 DM does not rise in response to feeding. © 1998 John Wiley & Sons, Ltd.