Albumin-to-alkaline phosphatase ratio may be a better predictor of survival than sclerostin, dickkopf-1, osteopontin, osteoprotegerin and osteocalcin.

Objectives: The value of biochemical markers of bone turnover (BTMs) in predicting survival and disease remains unclear. In a prospective study we evaluated the novel biomarkers for bone turnover sclerostin, dickkopf-1 (DKK-1), osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC), as well as a traditional biomarker, alkaline phosphatase (ALP) in relation to risk of mortality, cardiovascular events and fractures. Participants: and Methods:Routine blood tests and serum BTMs, including ALP, were analyzed in patients with hip fracture n = 97, stroke n = 71 and healthy volunteers n = 83 (mean age 86, 83 and 77, respectively), followed for 7 years. Hazard Ratios (HR) were calculated for mortality, cardiovascular events and fractures in relation to these biomarkers. After adding the albumin-to-ALP ratio (AAPR) a post hoc analysis was performed. Results: 120 participants died during the study. In the entire group of patients and volunteers (n = 251) higher AAPR (HR 0.28, 95 % CI 0.14-0.59, p < 0.001) was associated with decreased mortality. OPN and OPG were associated with mortality risk only in the univariate statistical analysis. HR for high AAPR in relation to new cardiovascular events was borderline significant (HR 0.29, 95 % CI 0.08-1.06, p = 0.061). None of the examined biomarkers were associated with new fractures, nor with an increased risk of a new cardiovascular event. Conclusions: AAPR may be a better predictor of mortality than the more novel BTMs, and higher AAPR could be associated with longer life expectancy. Further studies should determine the clinical usefulness of AAPR as a biomarker of mortality and cardiovascular disease.

Plasma oxylipin levels associated with preterm birth in preterm labor✰.

INTRODUCTION: Preterm labor is a common clinical problem in obstetrics. Since the majority of women with preterm labor eventually deliver at full term, biomarkers are needed to more accurately predict who will deliver preterm. Oxylipins, given their importance in inflammation regulation, are highly interesting in this respect since labor is an inflammatory process. METHODS: Eighty women with preterm labor before 34 weeks of gestation were enrolled in a prospective observational multi-center cohort study. Oxylipin levels of 67 analytes in plasma samples were analyzed by liquid chromatography coupled to tandem mass spectrometry. RESULTS: Twenty-one (26%) of the women delivered before 34 weeks of gestation, and of those women, fourteen delivered within 48 h of admission. Logistic multivariate regression showed that lower levels of 9,10-DiHODE were associated with delivery before 34 weeks of gestation (aOR 0.12 (0.024-0.62)) and within 48 h ((aOR 0.13 (0.019-0.93)). Furthermore, higher levels of 11,12-DiHETrE were associated with delivery before 34 weeks of gestation ((aOR 6.19 (1.17-32.7)) and higher levels of 8-HETE were associated with delivery within 48 h ((aOR 5.01 (1.13-22.14)). CONCLUSIONS: The oxylipin 9,10-DiHODE may be protective in preterm labor, both for delivery after 34 weeks of gestation and for delivery later than 48 h of admission, whereas 11,12-DiHETrE and 8-HETE display the opposite effect. Larger studies are needed to validate these mediators as biomarkers for prediction of preterm birth following preterm labor.

Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis.

OBJECTIVE: To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB).DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded.RESULTS: In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, P < 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore >6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality.CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies.

Alterations in bone turnover markers in patients with noncardio-embolic ischemic stroke.

BACKGROUND: The major cause of ischemic stroke is unstable or thrombogenic atherosclerotic plaques. Vascular calcification, a process that appears crucial for plaque stability, shares common features with bone formation. Many bone turnover proteins exhibit metabolic properties, but the evidence is conflicting regarding their possible involvement in vascular disease. Antibodies against sclerostin and dickkopf-1 are currently being evaluated as potential therapy for treating bone disorders. It is important to carefully assess the cardiovascular and metabolic effects of these proteins. The aim of the present study was to explore serum levels of bone turnover markers in patients with acute noncardio-embolic ischemic stroke in comparison with healthy controls. METHODS: In a cross-sectional study, we compared 48 patients aged ≥75 years with noncardio-embolic ischemic stroke and 46 healthy controls. Serum levels of dickkopf-1, sclerostin, osteoprotegerin, osteopontin and osteocalcin were determined by Luminex technique. RESULTS: We found clearly increased serum levels of osteoprotegerin, sclerostin, dickkopf-1 and osteopontin in patients with stroke compared with healthy controls. No difference was seen in serum levels of osteocalcin between the two groups. CONCLUSION: Our findings strengthen the hypothesis of bone turnover markers being involved in vascular disease. Whether these proteins can be used as candidate markers for increased stroke risk or prognostic biomarkers remains to be further elucidated.

High target attainment for ß-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.

Patients in the intensive care unit (ICU) are at risk for suboptimal levels of ß-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum ß-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT>MIC). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m2. The rate of patients reaching 100% fT > MICACTUAL was higher (89%, 31/35) compared to the same patients using MICECOFF (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MICECOFF. Increased renal clearance was independently associated to not reaching 100% fT > MICECOFF. On repeated sampling, >77% of patients had stable serum drug levels around the MICECOFF. Serum concentrations of ß-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.

Serum levels of the bone turnover markers dickkopf-1, sclerostin, osteoprotegerin, osteopontin, osteocalcin and 25-hydroxyvitamin D in Swedish geriatric patients aged 75 years or older with a fresh hip fracture and in healthy controls.

BACKGROUND: Bone turnover markers have a potential clinical use in describing bone remodeling and in predicting fractures. AIMS: In an elderly population ≥75 years with a fresh hip fracture, and in healthy controls, investigate bone turnover markers and their relation to each other, to vitamin D status and to bone mineral density (BMD). METHODS: In a cross-sectional study serum levels of dickkopf-1 (DKK-1), sclerostin (SOST), osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, 25-hydroxyvitamin D (25(OH)D) were analyzed in 89 Swedish patients with a fresh hip fracture and in 82 healthy volunteers. Serum levels of bone markers were determined by Luminex technique. RESULTS: S-25-hydroxyvitamin D (S-25(OH)D) was decreased in patients compared to controls (48 ± 21 vs. 76 ± 25 nmol/L, p < 0.001). SOST, but none of the other bone turnover markers correlated with BMD (r = 0.50, p < 0.001). Compared with controls, higher levels of OPG (488 ± 1.4 vs. 191 ± 1.4 ng/L, p < 0.001), OPN (69 ± 1.7 vs. 19 ± 1.4 µg/L, p < 0.001), DKK-1 (273 ± 1.7 vs. 168 ± 1.7 ng/L, p < 0.001), and lower levels of osteocalcin (5.8 ± 3.5 vs. 9.5 ± 3.6 µg/L, p < 0.001), were found in the fracture group. Levels of OPG, DKK-1 and SOST in both groups were positively associated. S-25(OH)D concentration was not found to be strongly associated with any of the bone markers. CONCLUSIONS: In contrast to findings in other studies, we found no strong correlation between 25(OH)D and the investigated bone markers. Both in patients with a fresh hip fracture and in healthy elderly, DKK-1, SOST and OPG appear to be associated. This suggests a relevance in these relationships meriting further investigation.

Increased ferritin levels in patients with anorexia nervosa: impact of weight gain.

PURPOSE: A few recent studies have found elevated ferritin levels in patients with anorexia nervosa (AN), indicating ferritin as a potential biomarker of disease severity. The purpose of this study was to study how body mass index (BMI) and changes in BMI affect plasma ferritin concentrations in Swedish patients with eating disorders. MATERIALS AND METHODS: In a retrospective computer search from 2009 to 2014, 662 patients with an eating disorder were identified from more than 200,000 individuals with electronic medical records. Three hundred and eighty-nine patients (374 females and 15 males) were found to have at least one p-ferritin value with a corresponding BMI value. Patients with AN were compared to a combined group consisting of patients with bulimia nervosa (BN) and patients with an eating disorder not otherwise specified (EDNOS). RESULTS: Patients with AN had lower BMI compared to the combined group of patients with other eating disorders (BMI = 16.5 ± 1.5, n = 77 vs. 21.0 ± 4.7, n = 312, p < 0.001). Patients with AN also had higher plasma ferritin levels (median 42 µg/L (range 3.3-310) vs. 31 µg/L (range 2.8-280); p < 0.001). As BMI increased in patients with AN, ferritin levels decreased (from a median of 40 µg/L (7-400) to 26 (4-170), n = 47; p < 0.001). DISCUSSION: Measuring ferritin in patients with AN could be valuable in monitoring improvements of nutritional status, but the full clinical value of following ferritin in individual patients has yet to be determined. The study also shows how research can benefit from electronically captured clinical data using electronic health records.

Sclerostin, TNF-alpha and Interleukin-18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients.

Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNF-alpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.

Female athlete's heart: Systolic and diastolic function related to circulatory dimensions.

There are relatively few studies on female athletes examining cardiac size and function and how these measures relate to maximal oxygen uptake (VO2max). When determining sports eligibility, it is important to know what physiological adaptations and characteristics may be expected in female athletes, taking body and cardiac size into account. The purposes of this study were (a) to compare right and left heart dimensions and function in female endurance athletes (ATH) and in non-athletic female controls of similar age (CON); and (b) to explore how these measures related to VO2max. Forty-six ATH and 48 CON underwent a maximal bicycle exercise test and an echocardiographic examination at rest, including standard and color tissue Doppler investigation. All heart dimensions indexed for body size were larger in ATH (all P < 0.01). The diastolic mitral E/A ratio was 27% higher in ATH (P < 0.001) while systolic left and right atrio-ventricular longitudinal displacement was 7% (P = 0.002) and 15% (P < 0.001) larger in ATH, respectively. Half (50.3%) of the variability in VO2max could be explained by left ventricular end-diastolic volume. Our results could be useful in evaluating female endurance athletes with suspected cardiac disease and contribute to understanding differences between female athletes and non-athletes.

Bone mass and anthropometry in patients with osteoarthritis of the foot and ankle.

BACKGROUND: Patients with hip and knee osteoarthritis (OA) have high bone mineral density (BMD) and high BMI. If the same accounts for patients with foot or ankle OA is unknown. METHODS: We measured BMD and femoral neck (FN) width by dual-energy X-ray absorptiometry in 42 women and 19 men with idiopathic OA in the foot or ankle, and in 99 women and 82 men as controls. RESULTS: Women with OA had significant higher BMI than controls. Women with OA had higher BMI-adjusted BMD (p<0.01) and smaller BMI-adjusted FN width (p<0.01) than controls. Men with OA had higher BMI adjusted-BMD (p<0.05) and smaller BMI-adjusted FN width (p<0.01) than controls. CONCLUSION: Patients with OA in the foot or ankle have higher BMD and smaller bone size than being expected by their BMI. This phenotype may provide unfavourable forces across the joint and is hypothetically important for development of OA.

Comparison of two commonly used reference materials for exercise bicycle tests with a Swedish clinical database of patients with normal outcome.

BACKGROUND: Reference values for working capacity, blood pressure, heart rate, perceived exertion, etc. during bicycle exercise tests have been sought after for many years. This is because earlier commonly used reference values for physical work capacity have been either too low or too high when compared to the clinical experience of several Swedish departments of clinical physiology. The aim of the study was to compare two commonly used reference materials with normal outcomes from a clinical database. METHODS: Data from a clinical database of standardized exercise tests in Kalmar, Sweden, between 2004 and 2012, and having been judged as normal, were divided into 5-year categories of 5-10 to 75-80 years of age covering people from 7 to 80 years of age. RESULTS: Maximal working capacity (Wmax ), maximal heart rate, maximal systolic blood pressure and maximal perceived exertion are presented for each of the 15 age categories. Regression equations are also presented for each sex with age and height as independent predictors. Quantitative comparisons of Wmax are calculated for the three materials and possible explanations discussed. CONCLUSIONS: Values of Wmax lie between the two reference materials most commonly used in Sweden. In addition, the present material covers subjects aged 7-19 years.

Fibroblast growth factor 23, hepatocyte growth factor, interleukin-6, high-sensitivity C-reactive protein and soluble urokinase plasminogen activator receptor. Inflammation markers in chronic haemodialysis patients?

Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), high-sensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R = 0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r = -0.25) in controls. Ln HGF correlated with ln suPAR (r = 0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

A novel blood-based biomarker for detection of autism spectrum disorders.

Autism spectrum disorders (ASD) are classified as neurological developmental disorders. Several studies have been carried out to find a candidate biomarker linked to the development of these disorders, but up to date no reliable biomarker is available. Mass spectrometry techniques have been used for protein profiling of blood plasma of children with such disorders in order to identify proteins/peptides that may be used as biomarkers for detection of the disorders. Three differentially expressed peptides with mass-charge (m/z) values of 2020 ± 1, 1864 ± 1 and 1978 ± 1 Da in the heparin plasma of children with ASD that were significantly changed as compared with the peptide pattern of the non-ASD control group are reported here. This novel set of biomarkers allows for a reliable blood-based diagnostic tool that may be used in diagnosis and potentially, in prognosis of ASD.

Heat production, nerve function, and morphology following nerve close dissection with surgical instruments.

BACKGROUND: The aim of the present study was to compare an ultrasonically activated instrument (US), monopolar electrosurgery, and bipolar electrosurgery (ES) with respect to heat production, nerve function, and nerve morphology following in vivo application. MATERIALS AND METHODS: The biceps femoris muscle of anesthetized rats was cut in a standardized manner longitudinally 1 mm adjacent to the sciatic nerve using US shears, a monopolar ES knife, or a bipolar ES scissors. Activation time and temperature were recorded continuously within 1-4 mm of the activation site ipsilateral and contralateral to the nerve with two thermoelectric microsensors. Temperature rise and time delay of reaching the temperature maximum, as an expression of heat spread within tissue, maximum temperature, and thermal dose (equivalent time of exposure at 43°C) were measured and calculated. A total of 49 functional experiments were conducted. The electromyographic (EMG) potential was recorded distally. Nerve dysfunction was defined as more than 10% loss of the evoked EMG amplitude. Forty-eight nerves were coded and submitted to blind histopathological examination, and morphological damage was graded on a 4-grade scale. RESULTS: The maximum temperature elevation and the thermal dose were significantly higher for the bipolar ES compared with the US instrument (p = 0.024, p = 0.049), and with much less variation of results for the US instrument. The monopolar ES maximum temperature and thermal dose were lower, but a very large variation occurred, probably as a result of more random electrical spread to the ground electrode and muscle motion artifacts. Functional loss was least common in the US group-without being significant-compared to bipolar and monopolar ES. Moderate and severe morphological damage was significantly less common in the US group than in the monopolar ES group (p = 0.041). We found no statistically significant correlation between the highest temperatures and the degree of morphological damage or functional loss. CONCLUSIONS: The temperature elevation depends strongly on the distance to the activated instrument. The bipolar ES scissors generates a higher maximum temperature and thermal dose with a greater variation in than the US. Functional loss and severe morphological damage were uncommon in all groups.

Previously unknown thyroid dysfunction in patients with acute ischemic stroke.

OBJECTIVES: Opinions differ regarding the clinical significance of subclinical thyroid disorders. The aim of the present study was to evaluate the prevalence and influence of previously unknown overt or subclinical thyroid dysfunction in patients with acute ischemic stroke and to look for differences between cardio-embolic and non-embolic ischemic stroke. MATERIAL AND METHODS: A total of 153 Swedish patients diagnosed with first-time acute ischemic stroke were included in the study and categorized for suspected cardio-embolic (n = 30) or non-embolic (n = 123) ischemic stroke depending on the presence of atrial fibrillation (AF). Blood samples were taken 48 h or earlier after onset of stroke symptoms. RESULTS: Previously, unknown overt or subclinical thyroid dysfunction was found in 12%. Previously, unknown overt or subclinical hyperthyroidism was more common in the AF group (13%) compared to the non-AF group (3%), P = 0.048. Patients with AF had slightly higher concentrations of free T4 (15 vs 14 pm; P < 0.001), but there was no significant difference in concentrations of S-TSH or prevalence of thyroperoxidase (TPO) antibodies between the groups. CONCLUSIONS: In patients with first-time acute ischemic stroke, unknown thyroid dysfunction is common, and unknown overt or subclinical hyperthyroidism is associated with cardio-embolic stroke.

Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition.

Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.

Reimbursement for drugs -- a register study comparing economic outcome for five healthcare centres in areas with different socioeconomic conditions.

AIMS: Previous studies have indicated the negative effects of socioeconomic deprivation on health status and morbidity. Nevertheless, the economic assignment systems for pharmaceutical benefits in Sweden do not take socioeconomic status (SES) into account. The aim of the study was, therefore, to compare reimbursement for subsidized drugs at primary healthcare centres (HCCs) with differing socioeconomic conditions in relation to real costs. The word reimbursement is used to denote economic compensation to the HCCs from the county council for drug benefit costs. METHODS: The numbers of individuals dispensed drugs, total costs and reimbursement at five HCCs with different socioeconomic conditions were compared. A socioeconomic index was calculated for each HCC on the basis of information from the municipality registries on income (with negative sign), assistance allowance, education, foreign background, and unemployment. Register data on drug benefit costs were retrieved from the National Corporation of Pharmacies (Apoteket AB) and the Swedish Prescribed Drug Register at the National Board of Health and Welfare. Data on listed and unlisted citizens at the Kalmar County Council and on public statistics from registers at the HCC municipalities where the HCCs were situated were retrieved. RESULTS: There was an almost inverse linear relationship between total cost compensation and the socioeconomic index (n = 5; r =-0.99; p = 0.001). The HCCs with the lowest SES received lower cost compensation. CONCLUSIONS: HCCs responsible for citizens with lower SES appeared to be disadvantaged by the prevalent reimbursement system in Sweden, thereby increasing differences in the state of health of the citizens. This, in turn, hampers health preventing programmes and lifestyle interventions. An HCC-specific standardized summary of socioeconomic burden is presented.

Low levels of insulin-like growth-factor-binding protein-1 (IGFBP-1) are prospectively associated with the incidence of type 2 diabetes and impaired glucose tolerance (IGT): the Söderåkra Cardiovascular Risk Factor Study.

AIM: To explore the association between baseline levels of insulin-like growth-factor-binding protein-1 (IGFBP-1), a marker of insulin sensitivity, and the development of type 2 diabetes or impaired glucose tolerance (IGT) in a specifically defined middle-aged population. METHODS: This cross-sectional population-based screening study was conducted in 1989-1990 and included baseline data for 664 non-diabetic subjects aged 40-59 years. Clinical data were collected and blood samples analyzed for blood glucose, serum lipids and insulin. Blood specimens were frozen at baseline and later analyzed for IGF-I, IGFBP-1 and C-reactive protein (CRP). At the follow-up in 2006, the incidence of type 2 diabetes and IGT was reported based on primary-care medical records. RESULTS: During the 17-year observation period, 42 subjects (6.3%) developed type 2 diabetes/IGT. Those in the lowest quintile of IGFBP-1 (< or =24 microg/L) at baseline had a diabetes incidence of 12.6% while, in the highest quintile of IGFBP-1 (> or =59 microg/L), the incidence was 1.5%. Cox's proportional-hazards model regression analyses were used to determine the incidence of type 2 diabetes/IGT, corrected for age and gender, in relation to IGFBP-1, CRP and waist circumference. Subjects in the lowest IGFBP-1 quintile showed an independently increased risk of type 2 diabetes/IGT [hazards ratio (HR): 3.54; 95% CI 1.18-10.6; P=0.024]. For CRP and waist circumference, the corresponding figures were HR: 6.81; 95% CI 2.50-18.6; P<0.001 and HR: 3.33; 95% CI 1.47-7.6; P=0.004, respectively. CONCLUSION: Low levels of IGFBP-1 predicted the long-term development of type 2 diabetes or IGT in a middle-aged population. The association was independent of CRP and abdominal obesity.

Hyponatremia complicating labour--rare or unrecognised? A prospective observational study.

OBJECTIVE: The aim of this study was to investigate the occurrence of hyponatraemia following delivery, with a hypothesis that hyponatraemia has a high prevalence in labouring women. DESIGN: Prospective observational study. SETTING: Consultant-led delivery suite in County Hospital, Kalmar, Sweden. SAMPLE: A total of 287 pregnant women at term (37 full gestational weeks). METHODS: Oral fluids were allowed during labour. Blood samples were collected on admission, after delivery, and from the umbilical artery and vein. MAIN OUTCOME MEASURE: Hyponatraemia defined as plasma sodium < or =130 mmol/l after delivery. RESULTS: Hyponatraemia was found in 16 (26%) of the 61 mothers who received more than 2500 ml of fluid during labour. Two-thirds of fluids were orally ingested. Decrease in plasma sodium concentration during labour correlated with duration of labour and the total fluid volume administered. Analysis by multivariate logistic regression showed that hyponatraemia was significantly correlated with fluid volume (P < 0.001) but not with oxytocin administration or epidural analgesia. Hyponatraemia correlated significantly with prolonged second stage of labour, instrumental delivery, and emergency caesarean section for failure to progress (P = 0.002). CONCLUSIONS: Hyponatraemia is not uncommon following labour. Tolerance to a water load is diminished during labour; therefore, even moderate fluid volumes may cause hyponatraemia. Women should not be encouraged to drink excessively during labour. Oral fluids, when permitted, should be recorded, and intravenous administration of hypotonic fluids should be avoided. When abundant drinking is unrecognised or intravenous fluid administration liberal, life-threatening hyponatraemia may develop. The possibility that hyponatraemia may influence uterine contractility merits further investigation.