Increased B-cell activating factor, interleukin-6, and interleukin-8 in induced sputum from primary Sjögren's syndrome patients.

OBJECTIVE: Small airway disease and chronic obstructive pulmonary disease are common in primary Sjögren's syndrome (pSS). However, the underlying inflammatory mechanisms behind pSS-associated airway disease have not been studied in detail. We therefore wanted to study cytokine and leucocyte levels in induced sputum in never-smoking patients with pSS. METHOD: Induced sputum cytokines and leucocytes were assessed in 20 never-smoking patients with pSS and 19 age- and gender-matched population-based controls. In addition, pulmonary function, disease activity, respiratory symptoms, and inflammatory and serological features of pSS were assessed. RESULTS: B-cell activating factor (BAFF), interleukin-6 (IL-6) and IL-8 were significantly increased in induced sputum in pSS patients compared to population-based controls, while IL-1ß, interferon-α, and tumour necrosis factor-α levels and leucocytes were not. The proportion of lymphocytes and BAFF levels in induced sputum correlated significantly in pSS patients. However, cytokine levels in induced sputum were not associated with pulmonary function tests, disease activity, respiratory symptoms, or serological features of pSS. CONCLUSION: The increase in BAFF, IL-6, and IL-8 in induced sputum suggests a specific ongoing inflammatory disease process in the airways in pSS patients. Its association with pSS-associated airway disease needs to be further examined in future larger studies.

Raynaud's phenomenon and its impact on activities in daily life during one year of follow-up in early systemic sclerosis.

OBJECTIVE: To investigate Raynaud's phenomenon (RP) and its impact on daily life activities during 1 year of follow-up in early systemic sclerosis (SSc). METHOD: Fourteen SSc patients with a median disease duration of 2 years were enrolled in the study. Every 7 weeks the patients completed a 7 day diary documenting the frequency and duration of RP attacks, the activity causing the attack, and how they handled the attack. The patients also recorded in the diary daily self-assessments of the difficulties with RP, using a 0-10 ordinal scale according to the Raynaud's Condition Score. RESULTS: Ninety-eight RP weekly diaries were analysed. The median number of RP attacks varied between six and nine per week, and the median score reflecting the difficulty associated with the attacks varied between 2.0 and 2.9. No difference was found in the number of attacks or the difficulties associated with them between winter, spring, and autumn. Fewer attacks and less difficulty were reported in August than in any of the other documented weeks (p < 0.05). In all diaries, all patients reported RP attacks associated with domestic activities. The use of heating devices varied during the follow-up. In February, all patients except one used such devices, while about half of the group used devices during the rest of the year. CONCLUSIONS: Difficulties resulting from RP are present and disabling all year round, which underscore the importance of intense vasoactive therapy and non-pharmacological strategies throughout the year.

The forced oscillation technique is a sensitive method for detecting obstructive airway disease in patients with primary Sjögren's syndrome.

OBJECTIVES: To study signs of obstructive airway disease (OAD) in patients with primary Sjögren's syndrome (pSS) using the forced oscillation technique (FOT). METHOD: Thirty-seven female pSS patients (median age 64, range 38-77 years) without previous physician-diagnosed OAD, participating in a longitudinal follow-up study of pulmonary function, and 74 female population-based controls (median age 64, range 47-77 years), also without physician-diagnosed OAD, and matched with regard to age, height, weight, and tobacco consumption, were included in the study. The pSS patients and controls were studied by the FOT, evaluating resistance and reactance of the respiratory system. RESULTS: pSS patients had significantly increased resistances at 5-25 Hz, decreased reactance at 10-35 Hz, and an increased resonant frequency (Fres) in comparison with controls. Resistance was correlated negatively and reactance positively to the vital capacity (VC), the forced expiratory volume in 1 s (FEV1), and the diffusing capacity for carbon monoxide (DLCO). Compared with controls, pSS patients with (n = 14) and without OAD (n = 21), as determined by spirometry, had significantly increased resistances at 5-25 Hz and decreased reactances at 10-35 Hz. In never-smoking subjects, identical FOT signs were found. CONCLUSIONS: pSS patients showed FOT signs of obstruction affecting both peripheral and central airways. pSS patients without spirometric signs of OAD and never-smoking pSS patients also showed clear FOT signs of obstruction. FOT therefore seems to be a sensitive method for detecting obstruction in pSS patients.

Aerobic capacity related to cardiac size in young children.

AIM: Aerobic capacity, defined as peak oxygen uptake (VO2PEAK), is generally considered to be the best single marker for aerobic fitness. We assessed if VO2PEAK is related to different cardiac dimensions in healthy young children on a population base. METHODS: In a cross-sectional study, 245 children (137 boys and 108 girls) aged 8-11 years, were recruited from a population based cohort. VO2PEAK (ml/min-1/kg-1) was assessed by indirect calorimetry during a maximal exercise test. DXA-scan was used to measure lean body mass (LBM) and total fat mass (TBF). Echocardiography, with 2-dimensional guided M-mode, was performed in accordance with current guidelines. Left ventricular end-diastolic diameter (LVDD) and left atrial end-systolic diameter (LA) were measured, and left ventricular mass (LVM) was calculated. RESULTS: Univariate correlations were found between VO2PEAK versus LVDD r=0.44 and LA r=0.27 (both P<0.05) and LVM r=-0.06 (NS) in boys. Corresponding values for girls were; 0.55, 0.34 (both P<0.05) and 0.11 (NS). Multiple regression analysis with VO2PEAK as dependent variable and inclusion of LBM, TBF, sex, age, Tanner stage, and maximal heart rate as independent variables showed that 67% of the total variance of VO2PEAK could be explained by these variables. Including LVDD or LA in the model, added 1% additional explained variance. CONCLUSION: Findings from this population based cohort of young healthy children show that multiple cardiac dimensions at rest are related to VO2PEAK. However, the different cardiac dimensions contributed very little to the added explained variance of VO2PEAK.

Fibroblast growth factor 23 is an independent marker of COPD and is associated with impairment of pulmonary function and diffusing capacity.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that in recent years has been reported to have significant effects on numerous tissues. Chronic obstructive pulmonary disease (COPD) is associated with hypophosphatemia but the evidence for elevated plasma levels of FGF23 in COPD subjects is ambiguous. Recently, FGF23 has even been shown to be involved in the inflammatory pathways activated in COPD, so FGF23 could be a novel biomarker for COPD and impairment of pulmonary function. The purpose was thus to explore the association of FGF23 with COPD and measures of pulmonary function. This was a cross sectional study of 450 subjects who underwent spirometry, body plethysmography, determination of diffusing capacity (DL,CO) and biomarker analysis of FGF23, interleukin (IL)-1 receptor antagonist, IL-6 and IL-8. Forty-four participants were excluded due to missing data or renal impairment (eGFR <45 mL/min/m2). Spirometry identified 123 subjects with COPD. FGF23 levels were elevated in COPD subjects compared to non COPD subjects, and this remained significant after adjustment for age, sex and smoking habits (OR = 1.6, p = 0.02). Linear regression showed significant relationships between FGF23 and FEV1 (ß = -0.15, p = 0.003), RV/TLC (ß = 0.09, p = 0.05) and DL, CO (ß = -0.24, p < 0.001). In conclusion we found that plasma levels of FGF23 are elevated in COPD subjects even when adjusting for traditional risk factors. Furthermore, FGF23 is associated with impairment in lung function as measured by FEV1 and DL,CO. Further studies are needed to establish whether FGF23 could serve as a novel biomarker of COPD and emphysema development.

Safety and efficacy of inhaled insulin (AERx iDMS) compared with subcutaneous insulin therapy in patients with Type 1 diabetes: 1-year data from a randomized, parallel group trial.

AIMS: Assessment of the long-term safety and efficacy of liquid inhaled insulin via AERx insulin Diabetes Management System (iDMS) in a basal/bolus treatment regimen of adults with Type 1 diabetes. METHODS: Patients were randomized 2 : 1 to prandial inhaled (n = 205) or subcutaneous (s.c.) (n = 99) insulin, plus one/two daily injections of neutral protamine Hagedorn (NPH) insulin for 12 months. The primary endpoints were pulmonary function tests (PFT) and baseline changes in chest X-rays at 12 months. Safety and efficacy assessments were measured at regular intervals. RESULTS: PFTs after 12 months were comparable between the groups, except for reduced per cent of predicted carbon monoxide lung diffusing capacity with inhaled insulin (difference: -2.03%, P = 0.04) occurring after the first 3 months and then stabilizing. There were no apparent treatment differences in chest X-rays. Overall risk of hypoglycaemia [risk ratio (RR) 1.02, P = 0.83] and adverse events were comparable between groups. Risk of nocturnal hypoglycaemia was higher in the inhaled group (RR 1.58, P = 0.001). Cough [10% (inhaled); 3% (s.c.)] tended to be mild in nature. Inhaled insulin was non-inferior to s.c. insulin for change in glycated haemoglobin (HbA(1c)) after 12 months [difference 0.18% (CI 95%-0.04; 0.39)]. At trial end, mean laboratory measured fasting plasma glucose was lower in the inhaled group (inhaled 9.2 mmol/l; s.c. 11.7 mmol/l; difference: -2.53 mmol/l, P < 0.001). CONCLUSIONS: The safety and efficacy results in this trial were similar to those reported with other inhaled insulins; however, inhaled insulin using AERx iDMS requires further optimization to reduce nocturnal hypoglycaemia before it has comparable safety and efficacy to s.c. insulin aspart.

Objectively measured daily physical activity related to cardiac size in young children.

Training studies in children have suggested that endurance training can give enlargement of cardiac dimensions. This relationship has not been studied on a population-based level in young children with objective methods. A cross-sectional study was made of 248 children (140 boys and 108 girls), aged 8-11 years, from a population-based cohort. Left ventricular end-diastolic diameter (LVDD) and left atrial end-systolic diameter (LA) were measured with echocardiography and indexed for body surface area (BSA). Physical activity was assessed by accelerometry, and the duration of vigorous physical activity per day (VPA) was calculated. Acceptable accelerometer and echocardiography measurements were obtained in 228 children (boys=127, girls=101). Univariate correlations between VPA and LVDD were indexed for BSA in boys (r=0.27, P<0.05) and in girls (r=0.10, NS). Multiple regression analysis showed that independent factors for LVDD, indexed for BSA for boys, were age and VPA. LA indexed for BSA was not related to physical activity variables in either gender. No clear relationship exists between cardiac size and daily physical activity in children aged 8-11 years. This suggests that significant cardiac remodelling due to volume exposure secondary to a high amount of physical activity begins later in life.

Forces applied at the footrest during ergometer kayaking among female athletes at different competing levels - a pilot study.

BACKGROUND: Power output and force development during exercise are thought to be important indices of performance in elite athletes. The aim of this preliminary study was to determine the forces applied at the footrest during ergometric kayaking in individual kayakers at different competitive levels. METHODS: Three elite female kayakers participated voluntarily in the study. Oxygen consumption (VO2) and mean power were measured during paddling at three different work levels (15 W below onset of blood lactate accumulation (OBLA), at OBLA, 15 W above OBLA and all-out paddling) on a modified kayak ergometer. External force sensors were attached to the wires on right and left side connecting the paddle to the flywheel of the kayak ergometer. Individual footrests were built to enable measurements of pushing and pulling forces and to distinguish between the left and right foot. RESULT: The relative differences between the three athletes were similar for power, VO2peak and forces at the paddle. There were, however, differences in the forces applied at the footrest, where the most accomplished paddler generated forces 3 to 26 times as high as the least accomplished paddler. CONCLUSION: The relative differences between the three athletes were similar for power, VO2 and forces at the paddle. There were, however, dramatic differences in the forces applied at the footrest.

Matrix Metalloproteinases in COPD and atherosclerosis with emphasis on the effects of smoking.

BACKGROUND: Matrix metalloproteinases (MMP´s) are known biomarkers of atherosclerosis. MMP´s are also involved in the pathophysiological processes underlying chronic obstructive pulmonary disease (COPD). Cigarette smoking plays an important role in both disease states and is also known to affect the concentration and activity of MMP´s systemically. Unfortunately, the epidemiological data concerning the value of MMP´s as biomarkers of COPD and atherosclerosis with special regards to smoking habits are limited. METHODS: 450 middle-aged subjects with records of smoking habits and tobacco consumption were examined with comprehensive spirometry, carotid ultrasound examination and biomarker analysis of MMP-1, -3, -7, -10 and -12. Due to missing data 33 subjects were excluded. RESULTS: The remaining 417 participants were divided into 4 different groups. Group I (n = 157, no plaque and no COPD), group II (n = 136, plaque but no COPD), group III (n = 43, COPD but no plaque) and group IV (n = 81, plaque and COPD). Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque. This remained statistically significant for MMP-1 and-12 after adjusting for traditional risk factors. CONCLUSION: COPD and concomitant plaque in the carotid artery were associated with elevated levels of MMP-1 and -MMP-12 even when adjusting for risk factors. Further studies are needed to elucidate if these two MMP´s could be useful as biomarkers in a clinical setting. Smoking was associated with increased serum levels of MMP´s (except for MMP-3) and should be taken into account when interpreting serum MMP results.

Autonomic nervous symptoms in primary Sjogren's syndrome.

OBJECTIVES: Objective signs of autonomic dysfunction (AD) have been reported in patients with primary SS (pSS) while the presence of associated symptoms has not been systematically studied. Therefore, the aims of this study were (i) to assess the presence and severity of various AD symptoms in pSS patients and (ii) to relate AD symptoms to other clinical features of pSS. METHODS: Thirty-eight pSS patients and 200 population-based controls were studied for presence and severity of AD symptoms using the Autonomic Symptom Profile (ASP), a validated self-completed questionnaire evaluating various AD symptoms. In addition, patients were investigated by three different objective autonomic nervous function tests. RESULTS: pSS patients scored significantly higher in the parasympathetic [secretomotor disorder, urinary disorder, gastroparesis (females only) and pupillomotor disorder] as well as sympathetic (orthostatic intolerance and vasomotor disorder) ASP domains compared with controls. Consequently, the standardized ASP total score was significantly increased in pSS patients [1.77 (0.57, 3.15) vs - 0.21 (-0.82, 0.72); P = 0.00] and 45% of pSS patients had an ASP total score >/=2 s.d. Furthermore, the autonomic nervous function tests showed signs of objective parasympathetic and sympathetic dysfunction as well. However, the ASP domain and total scores showed limited associations with the objective autonomic nervous function test parameters as well as clinical and serological factors of pSS. CONCLUSIONS: pSS patients showed subjective and objective signs of both a parasympathetic and a sympathetic dysfunction. However, AD symptoms showed limited associations with objective autonomic nervous function as well as other clinical features of the disease.

Daily physical activity related to aerobic fitness and body fat in an urban sample of children.

This study evaluates associations between objectively measured daily physical activity vs aerobic fitness and body fat in children aged 8-11 years. A cross-sectional study of 225 children aged 7.9-11.1 years was performed. Abdominal fat mass (AFM) and total body fat (TBF) were quantified by dual-energy x-ray absorptiometry. TBF was calculated as percentage of total body mass (BF%). Body fat distribution was calculated as AFM/TBF. Aerobic fitness was measured by indirect calorimetry during a maximal cycle ergometer exercise test. Daily physical activity was assessed by accelerometers for 4 days and daily accumulation of moderate-to-vigorous and vigorous activity was calculated. Significant relationships (P<0.05) existed for vigorous activity vs ln BF% (r=-0.40), ln AFM (r=-0.35), TBF/AFM (r=-0.22) and aerobic fitness (r=0.38), whereas moderate-to-vigorous activity displayed weaker relationships (-0.22, -0.18, -0.12 NS, and 0.25). Multiple regression analyses with inclusion of possible confounders concluded that vigorous activity was independently related to aerobic fitness and ln BF% or ln AFM. Moderate-to-vigorous activity was only independently related to aerobic fitness. In this population, low daily accumulation of vigorous activity was, already in children aged 8-11 years, associated with more body fat and lower aerobic fitness. A similar relation was not found for daily accumulation of moderate-to-vigorous activity.

Deposition of inhaled nanoparticles is reduced in subjects with COPD and correlates with the extent of emphysema: proof of concept for a novel diagnostic technique.

BACKGROUND: The diagnosis of chronic obstructive pulmonary disease (COPD) is often based on spirometry, which is not sensitive to early emphysema. We have recently described a method for assessing distal airspace dimensions by measuring recovery of nanoparticles in exhaled air after a single-breath inhalation followed by breath-hold. Recovery refers to the non-deposited particle fraction. The aim of this study was to explore differences in the recovery of exhaled nanoparticles in subjects with COPD and never-smoking controls. A secondary aim was to determine whether recovery correlates with the extent of emphysema. METHOD: A total of 19 patients with COPD and 19 controls underwent three repeats of single-breath nanoparticle inhalation followed by breath-hold. Particle concentrations in the inhaled aerosol, and in an alveolar sample exhaled after breath-hold, were measured to obtain recovery. FINDINGS: The patients with COPD had a significantly higher mean recovery than controls, 0·128 ± 0·063 versus 0·074 ± 0·058; P = 0·010. Also, recovery correlated significantly with computed tomography (CT) densitometry variables (P<0·01) and diffusing capacity for carbon monoxide (DL,CO ; P = 0·002). INTERPRETATION: Higher recovery for emphysema patients, relative to controls, is explained by larger diffusion distances in enlarged distal airspaces. The nanoparticle inhalation method shows potential to be developed towards a tool to diagnose emphysema.

Reference values for respiratory system impedance by using impulse oscillometry in children aged 2-11 years.

The forced oscillation technique makes it possible to evaluate the mechanical properties of the respiratory system with a minimum of cooperation. The method is therefore especially useful in children. Impulse oscillometry (IOS) is a commercially available version of this technique. There is, as yet, limited information on reference values for IOS in children. The aim of this study was to extend the reference values for IOS variables and to study their correlation with height, weight and age in healthy children. A sample (n = 360) of children (age 2.1-11.1 years) was measured by using impulse oscillometry (IOS; Jaeger, Würzburg, Germany). The sample was based on children attending kindergarten in Finland and children attending primary school in Sweden. Measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs) and the resonance frequency (Fr) were made. All variables were related to body height. Most of them were also weakly related to weight. Reference equations for children (height 90-160 cm) are presented.

Occurrence and prognostic significance of ventricular arrhythmia is related to pulmonary function: a study from "men born in 1914," Malmö, Sweden.

BACKGROUND: Reduced lung function has been associated with increased rates of myocardial infarction. Whether the occurrence and prognostic significance of ventricular arrhythmia is related to lung function is largely unknown. METHODS AND RESULTS: We performed a population-based study of 68-year-old men without a history of stroke or myocardial infarction; 402 men participated. Mortality and coronary events (fatal or nonfatal) were studied in relation to ventricular arrhythmia during 24 hours, percentage of the predicted forced expiratory volume (FEV1(%pred)), vital capacity (VC(%pred)), and the FEV/VC ratio. During 14 years of follow-up, 181 men died and 87 experienced a coronary event. Occurrence of frequent or complex ventricular arrhythmia (Lown class 2 to 5) was significantly and inversely associated with FEV1(%pred). Men with Lown class 2 to 5 and a low FEV1(%pred) (below median) had significantly higher mortality (71.5 versus 26.8 per 1000 person-years; P<0.0001) and coronary event rates (37.7 versus 18.0; P=0.02) than men with Lown class 2 to 5 and a high FEV1(%pred). These associations remained significant after adjustments for potential confounders (mortality: relative risk [RR], 2.91; 95% CI,1.68 to 5.04; coronary events: RR, 2.16; 95% CI, 1.07 to 4.37). In men without frequent or complex arrhythmia (Lown 0 to 1), a low FEV1(%pred) was not significantly associated with mortality (RR, 1.37; 95% CI, 0.92 to 2.05) or coronary events (RR, 1.24; 95% CI, 0.67 to 2.27) after adjustments for confounders. The FEV/VC ratio showed similar associations with arrhythmia, mortality, and coronary events. CONCLUSIONS: Lung function is inversely associated with the occurrence of ventricular arrhythmia. The increased incidence of myocardial infarction and death associated with arrhythmia was mainly limited to men with a low FEV1(%pred) or FEV/VC. We suggest that lung function should be considered when assessing the prognostic significance of ventricular arrhythmia.

Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins.

BACKGROUND: The inverse relationship between pulmonary function and incidence of cardiovascular disease remains largely unexplained. This prospective study explored the hypothesis of a relationship with inflammation-sensitive plasma proteins. METHODS AND RESULTS: Forced vital capacity (FVC) and plasma levels of fibrinogen, alpha(1)-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 5064 healthy men aged 28 to 61 years. All-cause mortality, cardiovascular mortality, and incidence of myocardial infarction were monitored over a mean follow-up period of 18.4 years. Low FVC (fourth quartile) was associated with higher protein levels and with increased incidences of myocardial infarction and cardiovascular death. Adjustments for protein levels reduced the age-adjusted relative risks (RRs) for myocardial infarction (from 1.99, 95% CI 1.5 to 2.6, to 1.70, 95% CI 1.3 to 2.2) and cardiovascular death (from 2.71, 95% CI 1.9 to 3.9, to 2.28, 95% CI 1.6 to 3.3) among men with low FVC, corresponding to approximately 25% of the excess risk. The risk factor-adjusted RRs were reduced from 1.45 (95% CI 1.1 to 1.9) to 1.38 (95% CI 1.1 to 1.8) and from 1.96 (95% CI 1.4 to 2.8) to 1.85 (95% CI 1.3 to 2.7) for myocardial infarction and cardiovascular death, respectively, corresponding to approximately 10% to 15% of the excess risk. Among men with low FVC, the risk factor-adjusted RR for myocardial infarction was 2.5 (95% CI 1.7 to 3.6) for those with high protein levels (> or =2 proteins in top quartile) and 1.7 (95% CI 1.1 to 2.4) for those with low protein levels (< or =1 protein in top quartile; reference, top quartile of FVC and low protein levels). CONCLUSIONS: FVC is significantly and inversely associated with plasma levels of inflammation-sensitive plasma proteins. This relationship contributes to but cannot fully explain the increased cardiovascular risk among men with low FVC.

Comparison between fundamental and second-harmonic imaging echocardiography for calculation of left ventricular mass in children.

In adults, calculation of left ventricular mass (LVM) has been shown to give higher values when based on M-mode measurements obtained by the second-harmonic imaging (SHI) technique than with the older fundamental imaging (FI) technique. No information is available in paediatric subjects. This study, therefore, compares LVM calculated from measurements obtained with SHI and FI in 14 children, aged 6.9-13.0 years. M-mode tracings were obtained in accordance with American Society of Echocardiography (ASE) recommendations. Three experienced sonographers performed measurements on each subject with both SHI and FI. The mean value was used in all calculations. LVM was calculated according to ASE convention and indexed by body surface area. LVM mean values were 58.9 +/- 9.7 g m(-2) for SHI and 57.8 +/- 8.2 g m(-2) for FI (P = 0.45). This preliminary study in a small group of paediatric subjects demonstrates no systematic differences between FI and SHI modalities in the calculation of LVM. The likely explanation is that the left ventricular endocardial border is usually well visualized with SHI as well as with FI in children.

Detection of autonomic sympathetic dysfunction in diabetic patients. A study using laser Doppler imaging.

OBJECTIVE: To study signs of the disturbed reflex autonomic sympathetic nerve function in type 1 and type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Measurements were made on 15 type 1 (duration 13-32 years) and on 50 recently diagnosed type 2 diabetic patients (duration 3-4 years). The vasoconstrictor responses in the distal phalanx of the middle finger (locally heated to 40 degrees C) to the cooling of the contralateral arm were measured using Laser Doppler Imaging (LDI). A vasoconstriction index (VAC) was calculated taking age into account and was compared with reference values obtained in 80 control subjects. The diabetic patients were also studied with deep-breathing tests (i.e., the heart-rate variation expressed as the expiration-to-inspiration [E/I] ratio, a test of parasympathetic nerve function). RESULTS: The vasoconstrictor responses to indirect cooling (VAC) were significantly reduced in the fingers of the diabetic patients, both type 2 (0.77 +/- 0.02 V; P < 0.01) and type 1 (0.83 +/- 0.04 V; P < 0.001), compared with the healthy control subjects (0.65 +/- 0.01); the age-corrected VAC (VACz) was slightly more impaired in type 1 than in type 2 diabetic patients. The frequency of an abnormal VACz corresponded well to the frequency of an abnormal E/I ratio in type 1 diabetic patients (approximately 50%), whereas the frequency of an abnormal VACz was significantly higher than an abnormal E/I ratio among type 2 diabetic patients (11/50 vs. 4/50; P < 0.05). CONCLUSIONS: Both type 1 and type 2 diabetic patients have impaired cutaneous blood flow regulation. The VAC index seems to be a promising tool for detection of subclinical changes in autonomic sympathetic function.

Less pronounced response to exercise in healthy relatives to type 2 diabetic subjects compared with controls.

Healthy first-degree relatives with heredity of type 2 diabetes (FH+) are known to have metabolic inflexibility compared with subjects without heredity for diabetes (FH-). In this study, we aimed to test the hypothesis that FH+ individuals have an impaired response to exercise compared with FH-. Sixteen FH+ and 19 FH- insulin-sensitive men similar in age, peak oxygen consumption (V̇o2 peak), and body mass index completed an exercise intervention with heart rate monitored during exercise for 7 mo. Before and after the exercise intervention, the participants underwent a physical examination and tests for glucose tolerance and exercise capacity, and muscle biopsies were taken for expression analysis. The participants attended, on average, 39 training sessions during the intervention and spent 18.8 MJ on exercise. V̇o2 peak/kg increased by 14%, and the participants lost 1.2 kg of weight and 3 cm waist circumference. Given that the FH+ group expended 61% more energy during the intervention, we used regression analysis to analyze the response in the FH+ and FH- groups separately. Exercise volume had a significant effect on V̇o2 peak, weight, and waist circumference in the FH- group, but not in the FH+ group. After exercise, expression of genes involved in metabolism, oxidative phosphorylation, and cellular respiration increased more in the FH- compared with the FH+ group. This suggests that healthy, insulin-sensitive FH+ and FH- participants with similar age, V̇o2 peak, and body mass index may respond differently to an exercise intervention. The FH+ background might limit muscle adaptation to exercise, which may contribute to the increased susceptibility to type 2 diabetes in FH+ individuals.

Plethysmographic pulse wave amplitude and future leg arteriosclerosis.

A low pulse wave amplitude during calf plethysmography at 55 years of age was previously found to be associated with an increased mortality and incidence of myocardial infarction. In order to test the hypothesis that a low pulse wave amplitude is associated with an increased risk of future leg atherosclerosis as well, we have studied the relationship between a low ankle-brachial pressure index (ABPI; < 0.9) at 68 years of age and the pulse wave amplitude at 55 years of age in that same cohort. The prevalence of a low pulse wave amplitude (< or = 5 mm; lowest quintile) among men with a low ABPI (42%) was more than twice as high as it was among men who had a normal ABPI (19%) (P < 0.001). No association was found between a low ABPI and the plethysmographically recorded leg blood flow at 55 years of age. A low pulse wave amplitude might reflect early symptom-free arteriosclerosis, or age-dependent non-arteriosclerotic loss of vessel wall elasticity. The relationship between a low pulse wave amplitude and a low ABPI remained when controlling for smoking, hypertension and hyperlipidaemia. It is concluded that pulse wave measurement by plethysmography contributes information to improve leg atherosclerotic risk assessment in individuals exposed to known risk factors.

Blood pressure increase between 55 and 68 years of age is inversely related to lung function: longitudinal results from the cohort study 'Men born in 1914'.

BACKGROUND: Although age is associated with increasing blood pressure, there is a substantial heterogeneity within a certain birth cohort. Whether increase in systolic and diastolic blood pressure is related to pulmonary function is largely unknown. OBJECTIVE: To study blood pressure elevation between 55 and 68 years of age in relation to vital capacity (VC) and forced expiratory volume (FEV1.0) at 55. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 375 men without antihypertensive medication at baseline. MAIN OUTCOME MEASURE: Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) over 13 years. RESULTS: Blood pressure increase between 55 and 68 years was highest among men who at 55 years had low vital capacity. Average increase in systolic blood pressure for men with vital capacity in the first, second, third and fourth quartile was 20.4, 18.7, 16.5 and 11.1 mmHg, respectively (P for trend = 0.005). Average increase in diastolic blood pressure was 10.6, 9.9, 9.0 and 6.3 mmHg, respectively (P= 0.02). The trends remained statistically significant after adjustments for baseline blood pressure, tobacco consumption, smoking cessation between 55 and 68, weight change between 55 and 68, physical activity and diabetes. Further analysis showed that the relationships could be found among men with blood pressures < or = 140/ 90 mmHg at baseline, whereas no significant association was found for men whose baseline SBP or DBP exceeded 140/90 mmHg. FEV1.0 showed similar associations with change in blood pressure. CONCLUSION: Lung function is inversely associated with future blood pressure increase. It is suggested that this association could contribute to the relationships between lung function and incidence of cardiovascular disease.