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INTRODUCTION: Long-term results from bariatric surgery amongst individuals with obesity is considered good in general, with regard to weight loss, complications of obesity or quality of life. However, risk of nutrient deficiency might be increased. The aim of the study was to assess vitamin D status of patients before and after metabolic and bariatric surgery at Landspitali. METHODS: Data on 25(OH)D concentration and parathyroid hormone (PTH) was retrieved from medical records for patients undergoing metabolic and bariatric surgery at Landspitali from 2001-2018 (n=539). Insufficient vitamin D status was defined as 25(OH)D concentration

Macrosomia and child obesity are growing health-care issues worldwide. The purpose of the study was to evaluate how extremely high or low birth weight affects metabolic markers evaluated in newborn screening. The study was register-based and included full-term singletons born in Iceland from 2009 to 2012 with newborn screening samples taken 72–96 h after birth. Three groups based on birth weight were compared: low birth weight (

AIMS To estimate potential differences in neonatal metabolomic profiles at birth and at the time of newborn screening by delivery mode. METHODS A prospective study at Women's Clinic at Landspitali-The National University Hospital of Iceland. Women having normal vaginal birth or elective caesarean section from November 2013 to April 2014 were offered participation. Blood samples from mothers before birth and umbilical cord at birth were collected and amino acids and acylcarnitines measured by tandem mass spectrometry. Results from the Newborn screening programme in Iceland were collected. Amino acids and acylcarnitines from different samples were compared by delivery mode. RESULTS Eighty three normal vaginal births and 32 elective caesarean sections were included. Mean differences at birth were higher for numerous amino acids, and some acylcarnitines in neonates born vaginally compared to elective caesarean section. Maternal blood samples and newborn screening results showed small differences that lost significance after correction for multiple testing. Many amino acids and some acylcarnitines were numerically higher in cord blood compared to maternal. Many amino acids and most acylcarnitines were numerically higher in newborn screening results compared to cord blood. CONCLUSION We observed transient yet distinct differences in metabolomic profiles between neonates by delivery mode.

International audience; Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together.

Disruption to endothelial cell homeostasis results in an extensive variety of human pathologies that are particularly relevant to major trauma. Circulating catecholamines, such as adrenaline and noradrenaline, activate endothelial adrenergic receptors triggering a potent response in endothelial function. The regulation of the endothelial cell metabolism is distinct and profoundly important to endothelium homeostasis. However, a precise catalogue of the metabolic alterations caused by sustained high catecholamine levels that results in endothelial dysfunction is still underexplored. Here, we uncover a set of up to 46 metabolites that exhibit a dose–response relationship to adrenaline-noradrenaline equimolar treatment. The identified metabolites align with the glutathione-ascorbate cycle and the nitric oxide biosynthesis pathway. Certain key metabolites, such as arginine and reduced glutathione, displayed a differential response to treatment in early (4 h) compared to late (24 h) stages of sustained stimulation, indicative of homeostatic metabolic feedback loops. Furthermore, we quantified an increase in the glucose consumption and aerobic respiration in endothelial cells upon catecholamine stimulation. Our results indicate that oxidative stress and nitric oxide metabolic pathways are downstream consequences of endothelial cell stimulation with sustained high levels of catecholamines. A precise understanding of the metabolic response in endothelial cells to pathological levels of catecholamines will facilitate the identification of more efficient clinical interventions in trauma patients.

Macrosomia and child obesity are growing health-care issues worldwide. The purpose of the study was to evaluate how extremely high or low birth weight affects metabolic markers evaluated in newborn screening.The study was register-based and included full-term singletons born in Iceland from 2009 to 2012 with newborn screening samples taken 72-96 h after birth. Three groups based on birth weight were compared: low birth weight (2500 g), appropriate-for-gestational age, and extreme macrosomia (≥5000 g). The comparison was adjusted for possible confounding factors.Compared to appropriate-for-gestational age neonates, both low birth weight and extreme macrosomia were associated with higher levels of glutamic acid. The amino acids alanine and threonine were increased in low birth weight neonates. Free carnitine and some medium- and long-chain acylcarnitines were higher in low birth weight infants. Hydroxybutyrylcarnitine was lower in low birth weight infants, but higher in extremely macrosomic neonates. Acetylcarnitine was higher in low birth weight and extremely macrosomic neonates. Succinylcarnitine was lower and hexadecenoylcarnitine higher in macrosomic newborns.Low birth weight and extremely macrosomic neonates show distinctive differences in their metabolomic profile compared to appropriate-for-gestational age newborns. The differences are not explained by gestational age.The key message of this article is that both low birth weight and extremely macrosomic newborns show dissimilar metabolomic profiles compared to appropriate-for-gestational age neonates. The article contributes to knowledge on what affects evaluation of results in newborn screening. The impact of this article is to provide information on metabolism at both ends of the birth weight range after accounting for confounding factors including gestational age.

While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA) by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded. In three of these seven the prominent cause was believed to derive from the use of moisturising creams and in another three from antibiotics containing pivalate; one country reported that the cause was mixed. As a result, four of these seven centres routinely perform second tier testing to resolve C5 isobars when an initial C5 result is elevated, and a fifth is considering making this change within their national programme. The use of creams containing neopentanoate by nursing mothers and evolving patterns in the prescription of pivalate-containing antibiotics during pregnancy require those involved in the design and operation of newborn screening programmes used to detect IVA and the doctors who receive clinical referrals from these programmes to maintain an awareness of the potential impact of this form of interference on patient results.

Introduction PKU is a metabolic disorder caused by a mutation in the phenylalanine hydroxylase (PAH) gene. Icelandic neonatal screening for PKU started in 1972. The mutation causes a variable [corrected] dysfunction in PAH, that metabolizes phenylalanine (Phe) to tyrosine (Tyr) with the cofactor tetrahydrobiopterin (BH4). Accumulation of Phe causes mental retardation and seizures. Current therapy focuses on Phe-restrictive diet and newer methods like BH4 in large doses. The primary aim was to collect data about PKU in Iceland and evaluate therapy and screening. Additional focus was on BH4 therapy. Materials and methods Information was gathered from Landspitali medical charts retrospectively. Serum-Phe (S-Phe) measurements, age at initiation of therapy, PAH mutation types and information on current therapy was collected. RESULTS from BH4 loading tests were collected. Results 27 patients have been diagnosed with PKU in Iceland since 1947. Incidence 1972-2008 is 1/8400 living births. Classic PKU is the most common presentation in Iceland. Patients diagnosed after screening started have normal intelligence. Age at initiation of therapy and S-Phe average values lower with time. 12 PAH mutation types have been found in Iceland. A novel Icelandic mutation, Y377fsdelT, did not respond to BH4 loading test. Two patients responded to a BH4 loading test and four other patients are likely to respond to BH4 loading test. Conclusion PKU incidence in Iceland is slightly higher than in neighboring countries. Therapy compliance is adequate and international consensuses regarding therapy are met. PKU patients in Iceland are generally in good health. Screening is efficient and save. BH4 therapy is a an optional alternative therapy in Iceland.

Risk factors for bone loss among the elderly are largely unknown. The objective of the study was to examine longitudinal bone loss in the hip in one-hundred and sixty-two 75-year-old women. Bone mineral density (BMD, g/cm2) was measured with dual X-ray absorptiometry (DXA) at baseline and after 4 years. The relationship between changes in BMD during follow-up and the following factors; baseline BMD, baseline weight, weight change, baseline lean and fat body mass (measured with DXA), serum values of biochemical markers and hormones, nutritional and lifestyle factors according to a questionnaire was assessed. The annual mean (SD) change in femoral neck BMD was −0.31% (1.38) in total trochanter −0.35% (1.15) and total hip −0.34% (1.10) and did not differ significantly between measurement sites. Bisphosphonate users had a 2.9%, 1.7% and 1.9% mean adjusted increase in femoral neck, total trochanter and total hip BMD respectively, different from none-users (p < 0.05). Subjects with more than three weekly physical activity sessions had less femoral neck bone loss than less active women (p < 0.05). The proportion of the variance in BMD changes explained by multivariate models (R2) was 12–13%. Women gaining weight had less loss of BMD than those losing weight in the trochanter and the total hip (p < 0.001), and in the femoral neck (p = 0.055). Elderly women should be advised to maintain their body weight and participate in physical activity. Despite the large number of variables examined in this study, bone loss occurring with increased age is not thoroughly explained.

Objectives. The purpose of this study was to examine factors associated with high or low parathyroid hormone (PTH) levels in relationship to vitamin D insufficiency. Design. This was a cross-sectional study consisting of 516 healthy men and women, aged 30–85, all Caucasians with vitamin D insufficiency [serum 25(OH)D

Risk factors for bone loss among the elderly are largely unknown. The objective of the study was to examine longitudinal bone loss in the hip in two hundred and twenty-five 70-year-old women. The mean time between examinations was 5.6 years. Bone mineral density (BMD, g/cm2) was measured with dual X-ray absorptiometry (DXA). The relationship between changes in BMD during follow-up and the following factors; baseline BMD, baseline weight, weight change, baseline lean and fat body mass (measured with DXA), biochemical markers, hormonal, nutritional and lifestyle factors, according to a questionnaire was assessed. Mean BMD decreased significantly more in the femoral neck (− 1.22%/year) than in the total trochanter (− 0.54%/year) and the total hip (− 0.66%/year), p

We found that age-related decline in bone mineral density (BMD) is more pronounced in women than in men, that lean mass was the most important determinant of BMD in all age groups in both sexes, and that different factors may be important for bone health of men and women and at different ages.Multiple factors may affect bone mineral density (BMD). Our objective was to identify the correlates of age-related differences in BMD among men and women.We performed a cross-sectional study involving 490 men and 517 women between the age of 29 and 87 years that were free of medication and diseases known to affect bone metabolism. BMD was measured at various sites using dual-energy X-ray absorptiometry, and factors possibly associated with skeletal status were assessed by direct measurements and a detailed questionnaire.BMD was lower with advancing age at all BMD measurement sites, the greatest difference being for the femoral neck where in women BMD was 37.5 % lower in the oldest compared to that in the youngest age group, but the difference was 22.9 % in men. Levels of free estradiol were sharply lower after age of 40 among women; free testosterone declined gradually with age among men but was not independently associated with BMD. Factors including lean mass, physical activity, ionized calcium, C-terminal telopeptide (CTX), serum sodium, free estradiol, and smoking explained a large fraction of difference in BMD in different age groups but to a varying degree in men and women. Lean mass was the strongest independent factor associated with BMD at all sites among men and women.Age-related decline in BMD is more pronounced in women than in men, but determinants of BMD are multiple and interrelated. Our study indicates that different factors may be important for bone health of men and women and at different ages.

Quantitative ultrasound (QUS) can be used as a screening tool for low bone mineral density (BMD), but clinical guidelines have not been set. The aim of this population-based, cross-sectional study was to compare age-related changes in bone mass measured by QUS (Lunar, Achilles Plus) and dual-energy X-ray absorptiometry (DXA) in a random sample of 1630 individuals (1041 females, 589 males) 30–85 yr of age. Individuals with DXA T-scores ≤–2.5 at the femoral neck or total hip were identified and receiver operating curves (ROCs) were used to calculate cutoff points for QUS. Sensitivity, specificity, and kappa statistics were calculated. Age-related bone loss was significantly larger with QUS than DXA at all sites in women. For men, the curves were similar for QUS and DXA in the hip. Similar correlations were found between QUS and DXA in different age groups of both sexes (0.36–0.60). For women aged 50–65 yr, a QUS T-score >−1.0 was found to be the most applicable for identifying normal BMD. In the 70–85 yr age group, a T-score

A collaboration among 157 newborn screening programs in 47 countries has lead to the creation of a database of 705,333 discrete analyte concentrations from 11,462 cases affected with 57 metabolic disorders, and from 631 heterozygotes for 12 conditions. This evidence was first applied to establish disease ranges for amino acids and acylcarnitines, and clinically validate 114 cutoff target ranges. Objective: To improve quality and performance with an evidence-based approach, multivariate pattern recognition software has been developed to aid in the interpretation of complex analyte profiles. The software generates tools that convert multiple clinically significant results into a single numerical score based on overlap between normal and disease ranges, penetration within the disease range, differences between specific conditions, and weighted correction factors. Design: Eighty-five on-line tools target either a single condition or the differential diagnosis between two or more conditions. Scores are expressed as a numerical value and as the percentile rank among all cases with the condition chosen as primary target, and are compared to interpretation guidelines. Tools are updated automatically after any new data submission (2009- 2011: 5.2 new cases added per day on average). Main outcome measures: Retrospective evaluation of past cases suggest that these tools could have avoided at least half of 277 false positive outcomes caused by carrier status for fatty acid oxidation disorders, and could have prevented 88% of false negative events caused by cutoff 7 values set inappropriately. In Minnesota, their prospective application has been a major contributing factor to the sustained achievement of a false positive rate below 0.1% and a positive predictive value above 60%. Conclusions: Application of this computational approach to raw data could make cutoff values for single analytes effectively obsolete. This paradigm is not limited to newborn screening and is applicable to the interpretation of diverse multi-analyte profiles utilized in laboratory medicine. Abstract word

Introduction: The purpose of this study was to compare age-related differences in osteoprotegerin (OPG) in relationship with BMD and the serum bone markers osteocalcin (OC), collagen crosslinks (CTX), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Methods: Data were derived from a cross-sectional study on bone health in a random sample of community-dwelling adults aged 30 to 85 years in the Reykjavik area in Iceland. All subjects had whole body, hip, and lumbar spine BMD measured (by DXA), gave blood samples, and answered a thorough questionnaire on medications and medical history. We assessed relationships using the Spearman correlation coefficient, partial correlation, and multivariable linear regression. Men and women were analyzed separately. Results: Of 2,310 subjects invited over 2 years, 1,630 participated. After excluding individuals with diseases and medications affecting bone metabolism, 517 women (age 56.1 ± 16.9 years) and 491 men (age 58.7 ± 14.9 years) remained for analysis. OPG increased steadily with age in both genders without a gender difference. In women, BMD at all sites declined steadily after age 50. In men, BMD remained relatively stable until age 70, after which it declined significantly. After controlling for age, BMI, and other confounding variables, OPG showed only a borderline positive relationship with whole body BMD in men (P=0.10), but the relationship was nonsignificant in women. In multivariable models, OPG was inversely related to TRACP-5b (P=0.002) and positively with OC (P=0.007), the OC/TRACP-5b (P=0.001) and OC/CTX (P=0.02) ratios in women. Among men, multivariable models showed a positive association between OPG and OC (P=0.05) and OC/TRACP-5b (P

Objectives: To examine the effect of raloxifene on bone turnover in elderly women. Design: Clinical intervention. Setting: Long-term care facilities. Participants: Nineteen women completed the study, mean age 85 (range 76–99). Intervention: Raloxifene 60 mg was given daily for 12 weeks. Measurements: Markers of bone turnover were plasma C-telopeptides of type I collagen (CTx), urine cross-linked N-telopeptides of type I collagen (NTx) and serum tartrate–resistant acid phosphatase (TRAP 5b), plasma osteocalcin, and serum bone alkaline phosphatase. Other markers were serum 25-OH vitamin D, parathyroid hormone, ionized calcium, and phosphate. Markers were measured at baseline, after calcium and vitamin D had been taken for 6 weeks, after raloxifene had been taken for 12 weeks, and 6 weeks after raloxifene had been stopped. Paired sample t test was used to examine changes in markers at each time point. Results: Plasma CTx decreased on average by 31%, urinary NTx by 35%, plasma osteocalcin by 25%, serum bone alkaline phosphatase by 15% (P

Hyperphagia was achieved by continuous intracerebroventricular infusion of a melanocortin receptor antagonist (HS024; Neosystem, Strasbourg, France) in rats. The effects of hyperphagia on FA composition and concentration of plasma phospholipids (PL), plasma FFA, and adipose tissue TAG were studied in rats for 8 d [short-term hyperphagia (STH); n = 8], or 28 d [long-term hyperphagia (LTH); n = 9]. The control rats were treated with artificial cerebrospinal fluid for 8 d (n = 8) or 28 d (n = 10). The rats were fed the same regular diet. In STH rats the plasma PL and fasting plasma FFA contained higher concentrations of saturated FA (SFA) and monounsaturated FA (MUFA), and plasma FFA contained lower n-6 PUFA than in the control rats. In LTH rats the plasma PL contained higher concentrations of SFA, MUFA, and n-3 PUFA and higher proportions of 16:1n-7 and 18:1n-9 at the expense of 18:2n-6 than in the control rats. In LTH rats the abundant dietary intake of 18:2n-6 did not enrich 18:2n-6 of the plasma PL or adipose tissue TAG. In LTH rats the fasting plasma FFA contained more than twofold higher concentrations of SFA and MUFA, and higher proportions of 16:1n-7 and 18:1n-9 at the expense of 18:2n-6 than in the control rats. This animal obesity model shows that LTH affects the FA composition and concentration of plasma PL, plasma FFA, and adipose tissue TAG, a result consistent with changes associated with increased risk of various diseases in humans. These results also demonstrate that LTH alters the FA composition of plasma PL and adipose tissue TAG in a way that does not reflect the FA composition of dietary fat.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Inborn errors of metabolism (IEMs) are hereditary metabolic defects, which are encountered in almost all major metabolic pathways occurring in man. Many IEMs are screened for in neonates through metabolomic analysis of dried blood spot samples. To enable the mapping of these metabolomic data onto the published human metabolic reconstruction, we added missing reactions and pathways involved in acylcarnitine (AC) and fatty acid oxidation (FAO) metabolism. Using literary data, we reconstructed an AC/FAO module consisting of 352 reactions and 139 metabolites. When this module was combined with the human metabolic reconstruction, the synthesis of 39 acylcarnitines and 22 amino acids, which are routinely measured, was captured and 235 distinct IEMs could be mapped. We collected phenotypic and clinical features for each IEM enabling comprehensive classification. We found that carbohydrate, amino acid, and lipid metabolism were most affected by the IEMs, while the brain was the most commonly affected organ. Furthermore, we analyzed the IEMs in the context of metabolic network topology to gain insight into common features between metabolically connected IEMs. While many known examples were identified, we discovered some surprising IEM pairs that shared reactions as well as clinical features but not necessarily causal genes. Moreover, we could also re-confirm that acetyl-CoA acts as a central metabolite. This network based analysis leads to further insight of hot spots in human metabolism with respect to IEMs. The presented comprehensive knowledge base of IEMs will provide a valuable tool in studying metabolic changes involved in inherited metabolic diseases. info:eu-repo/grantAgreement/EC/FP7/232816

PKU is a metabolic disorder caused by a mutation in the phenylalanine hydroxylase (PAH) gene. Icelandic neonatal screening for PKU started in 1972. The mutation causes a variable [corrected] dysfunction in PAH, that metabolizes phenylalanine (Phe) to tyrosine (Tyr) with the cofactor tetrahydrobiopterin (BH4). Accumulation of Phe causes mental retardation and seizures. Current therapy focuses on Phe-restrictive diet and newer methods like BH4 in large doses. The primary aim was to collect data about PKU in Iceland and evaluate therapy and screening. Additional focus was on BH4 therapy.Information was gathered from Landspitali medical charts retrospectively. Serum-Phe (S-Phe) measurements, age at initiation of therapy, PAH mutation types and information on current therapy was collected. RESULTS from BH4 loading tests were collected.27 patients have been diagnosed with PKU in Iceland since 1947. Incidence 1972-2008 is 1/8400 living births. Classic PKU is the most common presentation in Iceland. Patients diagnosed after screening started have normal intelligence. Age at initiation of therapy and S-Phe average values lower with time. 12 PAH mutation types have been found in Iceland. A novel Icelandic mutation, Y377fsdelT, did not respond to BH4 loading test. Two patients responded to a BH4 loading test and four other patients are likely to respond to BH4 loading test.PKU incidence in Iceland is slightly higher than in neighboring countries. Therapy compliance is adequate and international consensuses regarding therapy are met. PKU patients in Iceland are generally in good health. Screening is efficient and save. BH4 therapy is a an optional alternative therapy in Iceland.

To elucidate bone mineral density (BMD) and bone turnover in an un-selected group of patients with Systemic Sclerosis (SSc) in national based registry.All patients who have been diagnosed with SSc in Iceland were invited to participate in the study. Participants underwent standardized interview and delivered urine and blood samples for measurements of various bone metabolites (e.g. PTH, osteocalcin, Cross Laps, PINP, IGF-1, Cystatin-C and 25-OH-vitamin-D), before they underwent measurement of BMD with DEXA (QDR 4500 Elite).Twenty-four individuals, 20 female and four male, of 29 diagnosed patients with SSc in Iceland accepted to participate in the study (83%). The mean age was 60 +/- 15 years. Seventeen of 20 females were postmenopausal. Twelve patients had history of fractures. Only four patients were on treatment with bisphosphonate. All measured bone metabolites were in normal ranges, but U-calcium was in the lower ranges. According to DEXA, eight patients had osteopenia (T-value = -1.0 - -2.5) and three osteoporosis (T-value---2.5), while six patients had BMD more than one standard deviation below the mean of age matched controls.Although the majority of patients with SSc have normal bone turnover and BMD, every fourth patient may have low BMD. No single pathogenic factor was observed, however, several individuals are in calcium saving stages reflected in low urinary calcium excretion. This may be result of defects in intestinal absorption of calcium due to gastrointestinal involvement of the disease. This study does not give opportunity to evaluate effects of treatment on BMD in this group of patients. Thus, individual evaluation concerning osteoporosis is recommended in patients with SSc.

The purpose of this study was to examine the effect of vitamin D intake and production in skin on vitamin D homeostasis in adult Icelanders.Participants were 30-85 years old, randomly selected from the registry of the Reykjavik area (64 degrees N) and answered a thorough questionnaire on diet and vitamin supplements. Concentrations of 25(OH)-vitamin D [25(OH)D] in peripheral blood were examined based on season during the study period February 2001-January 2003, vitamin D intake and age (age groups 30-45, 50-65, and 70-85 years old). We defined vitamin D deficiency as either [25(OH)D]25 nmol/l or as [25(OH)D] where the inverse relationship between serum iPTH and [25(OH)D] became statistically significant.Of 2310 invited, 1630 subjects participated (70,6% participation) but 21 individuals were excluded due to primary hyperparathyroidism. Mean [25(OH)D] was 46.5-/+20 nmol/l but varied by season, age and vitamin D intake, highest in June-July, 52.1-/+19.8 and lowest in February-March, 42.0-/+20.5 (p0.001). [25(OH)D] was highest in the oldest age group, 50.8-/+19.7, but lowest in the youngest, 42.5-/+20 as was the intake 16.6-/+10 microg/day compared to 9.9-/+9 microg/day in the youngest. The correlation between vitamin D intake and [25(OH)D] was highest for the oldest group, r=0.41, p0.001 but lowest in the youngest, r=0.24, p0.001. [25(OH)D] was significantly higher among users of vitamin supplements (45.4-/+19.7) or fish oil (53.0-/+18.4) than among non-users (38.0-/+18.9). Vitamin D insufficiency was seen among 14.5% of those participating according to traditional definition, but 50% were below [25(OH)D] of 45 nmol/l where negative correlation between [25(OH)D] and PTH became statistically significant.The serum concentration of 25(OH)D at which vitamin D deficiency becomes biochemically significant is higher than traditionally thought. A daily intake of 15-20 microg/day during wintertime would be required to maintain normal homeostasis in Icelandic adults, which is considerably higher than present recommendations of 7-10 microg/day for adults. Further research is needed to define the limit for vitamin-D sufficiency.

To study physical activity among Icelandic adults and the relationship with anthropometric factors and grip strength.Randomly selected participants, 30-85 years of age, answered questions regarding exercise and diet. Body composition was measured with DXA, which detects the proportions of different body tissues. Height, weight and grip strength were measured and the body mass index (kg/m(2)) was calculated. The prevalence of regular physical activity was studied for men and women in the age groups of 30-45 years, 50-65 years and 70-85 years and the relationship to body mass index, body composition and grip strength examined. The possible preventive effect of exercise on overweight and obesity was also studied.Of 2310 invited, 1630 subjects (70.6%) participated. Mean participation in regular physical activity was 3-4 times a week but 19% of the women and 24% of the men did no exercise at all. In general, swimming, walking and calisthenics of various types and intensities were the most common forms of exercise and in the age group 30-45 year old 16% of the women and 8% of the men did strength training. 50.4% of women 30-45 years of age and 68.2% of 50-65 year old men were overweight or obese. Mean fat mass was highest in 70-85 year old women (38%) and men (27%). Occupational activity was not related to body mass index, body composition or grip strength. Significant negative relationship was found between frequency of exercise and fat mass. The relationship between grip strength and lean mass or exercise was non-significant. The odds ratio of being overweight or obesity was 0.5 (CI was 0.37-0.77 for women and 0.37-0.94 for men) for those who exercised five or more days per week compared to those who exercised less frequently.One of four Icelandic men and one of five women do not participate in regular physical activity despite of strong scientific indications of various positive health effects of exercise. More than half of adult Icelanders are overweight or obese but the risk is halved among those who exercise at least five days per week, compared to those who exercise less frequently. Sedentary lifestyle is more common amongst Icelanders than in the neighboring countries and realistic goals need to be set to increase the participation in regular physical activity.

Current assays measuring intact PTH may not only measure the active form, PTH(1-84), but also some large breakdown products, including PTH(7-84). A new method is believed to measure only PTH(1-84). The purpose of this study was to examine whether increases in intact PTH that accompany age, weight and worsening renal function could be related to breakdown products interfering with traditional assays.We used data from an ongoing cross-sectional study on bone health in 40-85 years old Icelanders. Over a 12 month period, 1096 subjects were invited for a DEXA scan, blood test, height and weight measurements and each subject answered a questionnaire on health and medication. For the current analysis we excluded those who were taking medications affecting bone and mineral metabolism. PTH was measured using PTH elecsys (Roche) and the new PTH cap (Scantibodies). We used kappa statistic to assess agreement with regard to levels above upper reference values for each assay and ANOVA, Pearson's and Spearman's correlation coefficients for other analysis. Women and men were analyzed separately.Of 746 individuals who came for the study, after exclusion, 247 women and 209 men remained for this analysis. PTH was on the average roughly 40% lower with the new PTH cap assay. The correlation between the assays was 0.787 (P0.001) for women and 0.69 (P0.001) for men. Kappa statistic was 0.486 (P0.001) for women and 0.283 (P0.001) for men, indicating fair to good agreement. PTH elecsys increased with age (P=0.03 and P=0.01 for women and men, respectively) but not PTH cap (P=0.7 and P=0.09 for women and men, respectively). PTH elecsys was positively associated with cystatin C (P0.05 for both genders), but the correlation between PTH cap and Cystatin C was not statistically significant. The association with body mass index was similar for the two assays (r=0.16 to 0.24, P0.05) for both genders.There is a significant difference between these two PTH assays. It is likely that increases in intact PTH observed with age and worsening renal function are related to large breakdown products of PTH whereas the PTH increase seen with higher weight seems to be related to PTH(1-84) itself.

SHPT is a consequence of decreased concentration of ionized calcium in blood, which may have many causes. The purpose of this study was to assess the prevalence and contributing factors of SHPT in an adult Icelandic population and explore the relationship between PTH and other variables which might explain age related increase in PTH. Such knowledge might be helpful in evaluating the results of PTH measurements. METHODS AND STUDY GROUP: The study group was a random sample of men and women in the Reykjavik area, 30-85 years of age. Serum PTH was measured by ECLIA (Roche Diagnostics), serum 25(OH)D by RIA (DiaSorin), and body composition by DXA. SHPT was defined as PTH65 ng/l and ionized calcium1.25 mmol/l. Inadequate vitamin D was defined as serum 25(OH)D 25-45 nmol/l and vitamin D deficiency25 nmol/l, inadequate calcium intake800 mg/day (from questionnaire) and reduced kidney function as serum cystatin-C1.55 ng/l. The relationship between PTH and other variables was assessed by Spearman?s correlation coefficient and linear regression.Of 2,310 individuals invited 1,630 attended (70%), 586 men and 1,023 women. Further 21 were excluded because of primary hyperparathyroidism. Of the total group 6.6% did have SHPT, 7.7% of the women and 4.6% of men (p0.01 by gender). Underlying causes were identified in 90% of cases, most commonly inadequate vitamin D (73%). Other important causes were obesity, inadequate calcium intake, reduced kidney function and furosemide intake. Many individuals did have more than one possible underlying cause. The concentration of PTH was found in a multivariate linear regression to be associated with age, ionized calcium, 25(OH)D, cystatin-C, smoking, and BMI, especially fat mass. Testosterone did have a weak negative relationship with PTH in men.Most cases of SHPT could be explained by known causes and far the commonest was inadequate vitamin D. The prevalence of SHPT in Iceland is probably higher than described elsewhere, possibly due to less sunlight exposure. These results would suggest that a greater intake of vitamin D is needed in Iceland. The relationship of PTH with body composition, especially fat mass, sex hormones and smoking, needs further evaluation.

To examine the effect of raloxifene on bone turnover in elderly women.Clinical intervention.Long-term care facilities.Nineteen women completed the study, mean age 85 (range 76-99).Raloxifene 60 mg was given daily for 12 weeks.Markers of bone turnover were plasma C-telopeptides of type I collagen (CTx), urine cross-linked N-telopeptides of type I collagen (NTx) and serum tartrate-resistant acid phosphatase (TRAP 5b), plasma osteocalcin, and serum bone alkaline phosphatase. Other markers were serum 25-OH vitamin D, parathyroid hormone, ionized calcium, and phosphate. Markers were measured at baseline, after calcium and vitamin D had been taken for 6 weeks, after raloxifene had been taken for 12 weeks, and 6 weeks after raloxifene had been stopped. Paired sample t test was used to examine changes in markers at each time point.Plasma CTx decreased on average by 31%, urinary NTx by 35%, plasma osteocalcin by 25%, serum bone alkaline phosphatase by 15% (P.01), and serum TRAP 5b by 10% (P.05) on treatment.Raloxifene reduces bone turnover in elderly women living in long-term care facilities. The effect of raloxifene on bone turnover is comparable with that seen in younger postmenopausal women.

The determination of parathyroid hormone (PTH) is of great clinical relevance in the assessment of calcium metabolic disorders. Although PTH was one of the first hormones measured by immunoassays, there are still many difficulties in its determination due to the low concentration of the hormone in blood and due to the heterogeneity of PTH resulting from different circulating hormone fragments. The aim of our multicenter-study was to evaluate the technical performance and the clinical validity of a new immunoassay for intact PTH measurement on the Elecsys Systems 2010 and 1010.The multicenter evaluation was performed in 11 clinical laboratories. The Elecsys PTH assay is a one step sandwich electrochemiluminescence immunoassay based upon the streptavidin-biotin technology. Two monoclonal antibodies are used in the assay providing detection of intact PTH. The imprecision study yielded within-run and between-days coefficients of variation of 3.1% - 6.6% and 3.4% - 15.6%, respectively using a three level control (PreciControl Bone, Roche Diagnostics) and human pool sera at two different concentrations (HS-low: 20 - 60 pg/ml, HS-high65 pg/ml). The analytical sensitivity calculated as the mean value plus 2 standard deviations of a within-run imprecision was below 2.70 pg/ml using zero calibrator matrix. Dilution linearity was observed up to 4890 pg/ml using zero calibrator matrix or human pool sera. Recoveries ranged between 85% - 115%. Serum, EDTA- and heparin plasma were evaluated for PTH measurement. Due to a better analyte stability (48h at 21 degrees C; 3d at 4 degrees C) EDTA plasma was recommended for PTH measurement. Results of the Elec sys PTH immunoassay correlated well (r = 0.926 - 0.994) with three different immunoradiometric assays (N-tact PTH SP, DiaSorin; Nichols Allegro Intact PTH, Nichols Institute Diagnostics; ELSA-PTH, CISBio International) and two different immunochemiluminometric assays (PTH-Intact-Immulite, DPC Biermann; Nichols Advantage Intact PTH, Nichols Institute Diagnostics) in technical and clinical method comparisons. The Passing/Bablok regression analysis yielded slopes of 0.692 - 1.729 and intercepts of -13.982 - +15.763 pg/ml. Deviations from slope 1.0 and intercept 0.0 were not unexpected due to differences in immunoassay standardization and probably due to the presence of different PTH fragments and a variable affinity of the used antibodies to these PTH fragments. Highly similar PTH concentration pattern of the Elecsys immunoassay and the Quick-Intraoperative Intact PTH immunoassay (Nichols Institute Diagnostics) obtained from specimens taken intraoperatively support the applicability of the Elecsys immunoassay to monitor the success of parathyroid resection. A reference range of 12.3 - 56.0 pg/ml calculated from PTH values of 43 apparently healthy individuals confirms reference limits published in the literature. The partition of collectives according to age showed, that individuals50 years have slightly higher PTH concentrations, independently of gender. This shift could be due to age itself or to an increased prevalence of individuals without obvious calcium metabolic disorders in this collective.The Elecsys PTH assay is a useful and reliable tool for determination of intact PTH. Our data support the intended use of the assay in clinical applications related to disorders of calcium metabolism.

Acute injections of melanocortin (MC) agonist and antagonist are highly effective in reducing or increasing food take, respectively. Much less is known about how injection of MC receptor active substances affects metabolism, in particular during long term administration. Here we investigated the effect of 8 days continuous i.c.v. infusion of either MC receptor agonist MTII or the selective MC4 receptor antagonist HS024 on oxygen consumption, food intake and body weight in rats. We observed significant increase in oxygen consumption 2 days after the start of the MTII infusion. However, this increase had disappeared by day 4 of the study. No difference was observed in the oxygen consumption after injection of HS024. MTII substantially decreased the food intake during the first days, but then the feeding recovered and the body weight stabilised at a new level. The immediate effect of the MC receptor agonist on both food intake and metabolism was thus transient, even though the weight loss was maintained. The HS024 treated rats were hyperphagic throughout the test period, continuously gaining weight, resulting in increased fat pads and high leptin levels. This is the first study that describes long term effects of MC receptor agonist and antagonist on metabolism and energy balance.

Hypovitaminosis D has been shown to be associated with low bone mineral density in middle-aged and elderly women. The aim of this study was to evaluate whether such an association might exist in adolescent and young adult girls, approaching peak bone mass.Cross-sectional study carried out in late winter.Reykjavik area at latitude 64 degrees N.Two-hundred and fifty-nine Icelandic Caucasian girls, aged 16, 18 and 20 years, randomly selected from the registry of Reykjavik.Bone mineral density in lumbar spine, hip, distal forearm and total skeleton was measured with dual-energy X-ray absorptiometry (DEXA) and compared with 25-hydroxyvitamin D levels [25 (OH)D] in serum, measured by radioimmunoassay. Calcium and vitamin-D intake were also assessed by a questionnaire.18.5% of the girls were below 25 nmol L-1 in serum 25 (OH)D which has been recognized as the lower normal limit for adults. No significant association was found between 25 (OH)D levels and bone mineral density.Normal calcium and phosphate concentrations in plasma and normal bone mineral density are maintained in adolescent and young adult girls at lower 25 (OH)D levels than published 'normal' levels for middle-aged and elderly.

Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1×10−10). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3×10−23) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0×10−17) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0×10−6), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7×10−5)., Author Summary Chronic kidney disease (CKD) is a common condition that is associated with substantial morbidity and mortality and has been recognized as a major public health problem worldwide. Common causes of CKD include hypertension, diabetes, and inflammatory disorders. Previous studies have shown a significant genetic contribution to kidney disease and a recent genome-wide association study yielded a variant in the UMOD gene that affects the risk of CKD. Here, we replicate the association between UMOD and CKD in an independent analysis. We also demonstrate for the first time an interaction between the UMOD variant and age that suggests that this variant may adversely affect the aging kidney and its adaptation to age-related risk factors of kidney disease, such as hypertension and diabetes. Furthermore, we show that the UMOD variant that affects risk of CKD also provides protection against kidney stone disease.

ContextAdequate vitamin D status for optimum bone health has received increased recognition in recent years; however, the ideal intake is not known. Serum 25-hydroxyvitamin D is the generally accepted indicator of vitamin D status, but no universal reference level has been reached.ObjectiveTo investigate the relative importance of high calcium intake and serum 25-hydroxyvitamin D for calcium homeostasis, as determined by serum intact parathyroid hormone (PTH).Design, Setting, and ParticipantsCross-sectional study of 2310 healthy Icelandic adults who were divided equally into 3 age groups (30-45 years, 50-65 years, or 70-85 years) and recruited from February 2001 to January 2003. They were administered a semi-quantitative food frequency questionnaire, which assessed vitamin D and calcium intake. Participants were further divided into groups according to calcium intake ( 1200 mg/d) and serum 25-hydroxyvitamin D level ( 18 ng/mL).Main Outcome MeasureSerum intact PTH as determined by calcium intake and vitamin D.ResultsA total of 944 healthy participants completed all parts of the study. After adjusting for relevant factors, serum PTH was lowest in the group with a serum 25-hydroxyvitamin D level of more than 18 ng/mL but highest in the group with a serum 25-hydroxyvitamin D level of less than 10 ng/mL. At the low serum 25-hydroxyvitamin D level (