Exposure to Persistent Organic Pollutants Reduces Testosterone Concentrations and Affects Sperm Viability and Morphology during the Mating Peak Period in a Controlled Experiment on Farmed Arctic Foxes (Vulpes lagopus).

We investigated testosterone production and semen parameters in farmed Arctic foxes by dietary exposure to persistent organic pollutants (POPs) for 22 months. Eight male foxes were given a diet of POP-contaminated minke whale blubber, whereas their eight male siblings were fed a control diet containing pig fat as the main fat source. The minke whale-based feed contained a ∑POPs concentration of 802 ng/g ww, whereas the pig-based feed contained ∑POPs of 24 ng/g ww. At the end of the experiment, ∑POP concentrations in adipose tissue were 8856 ± 2535 ng/g ww in the exposed foxes and 1264 ± 539 ng/g ww in the control foxes. The exposed group had 45-64% significantly lower testosterone concentrations during their peak mating season compared to the controls (p ≤ 0.05), while the number of dead and defect sperm cells was 27% (p = 0.07) and 15% (p = 0.33) higher in the exposed group. Similar effects during the mating season in wild Arctic foxes may affect mating behavior and reproductive success. On the basis of these results, we recommend testosterone as a sensitive biomarker of POP exposure and that seasonal patterns are investigated when interpreting putative endocrine disruption in Arctic wildlife with potential population-level effects.

N-Glycoprofiling Analysis for Carbohydrate Composition and Site-Occupancy Determination in a Poly-Glycosylated Protein: Human Thyrotropin of Different Origins.

Human thyrotropin (hTSH) is a glycoprotein with three potential glycosylation sites: two in the α-subunit and one in the ß-subunit. These sites are not always occupied and occupancy is frequently neglected in glycoprotein characterization, even though it is related to folding, trafficking, initiation of inflammation and host defense, as well as congenital disorders of glycosylation (CDG). For the first time N-glycoprofiling analysis was applied to the site-occupancy determination of two native pituitary hTSH, in comparison with three recombinant preparations of hTSH, a widely used biopharmaceutical. A single methodology provided the: (i) average N-glycan mass; (ii) mass fraction of each monosaccharide and of sulfate; and (iii) percent carbohydrate. The results indicate that the occupancy (65%-87%) and carbohydrate mass (12%-19%) can be up to 34%-57% higher in recombinant hormones. The average glycan mass is 24% lower in pituitary hTSH and contains ~3-fold fewer moles of galactose (p < 0.005) and sialic acid (p < 0.01). One of the two native preparations, which had the smallest glycan mass together with the lowest occupancy and GalNAc, sulfate, Gal and sialic acid contents, also presented the lowest in vivo bioactivity and circulatory half-life. The methodology described, comparing a recombinant biopharmaceutical to its native equivalent, can be applied to any physiologically or clinical relevant glycoprotein.

Vitamin D-binding protein and 25-hydroxyvitamin D during pregnancy in mothers whose children later developed type 1 diabetes.

BACKGROUND: Levels of 25-hydroxyvitamin D (25-OH D) during late pregnancy have been linked to type 1 diabetes risk in the offspring. Vitamin D-binding protein increases in concentration during pregnancy. We aimed to test whether concentrations of vitamin D-binding protein and 25-OH D throughout pregnancy differed between women whose offspring later developed type 1 diabetes (cases) and controls. METHODS: A nested case-control study was conducted within a cohort of pregnant women from all over Norway in 1992-1994. Offspring registered in The Norwegian Childhood Diabetes Registry, diagnosed with type 1 diabetes before age 15, defined the case women, giving 113 cases in the study. Two hundred twenty controls were randomly selected within the same cohort. One to four serum samples from each participant drawn at different time points during pregnancy were analysed for vitamin D-binding protein and 25-OH D by radioimmunoassay. RESULTS: Vitamin D-binding protein and 25-OH D significantly increased by gestational week (p < 0.001) and tended to be lower in cases than in controls, -0.27 µmol/L (95% CI -0.57, 0.03) and -5.01 nmol/L (95% CI -8.03, -0.73), respectively. While first and second trimester concentrations of vitamin D-binding protein and 25-OH D alone were not significantly different, lower third trimester concentrations tended to be associated with higher risk of type 1 diabetes in the offspring, albeit at borderline significance after mutual adjustment. CONCLUSIONS: In this first study of maternal vitamin D-binding protein measured throughout pregnancy and risk of type 1 diabetes in offspring, lower concentration, particularly in the third trimester, tended to be associated with type 1 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

Saffold Virus, a Human Cardiovirus, and Risk of Persistent Islet Autoantibodies in the Longitudinal Birth Cohort Study MIDIA.

The aim of this study was to describe the frequency and distribution of Saffold virus in longitudinal stool samples from children, and test for association with development of persistent autoantibodies predictive of type 1 diabetes. A cohort of Norwegian children carrying the HLA genotype associated with highest risk of type 1 diabetes ("DR4-DQ8/DR3-DQ2") was followed with monthly stool samples from 3 to 35 months of age. Blood samples were tested for autoantibodies to insulin, glutamic acid decarboxylase65 and Islet Antigen-2. 2077 stool samples from 27 children with ≥ 2 repeatedly positive islet autoantibodies (cases), and 53 matched controls were analysed for Saffold virus genomic RNA by semi-quantitative real-time reverse transcriptase PCR. Saffold virus was found in 53 of 2077 (2.6%) samples, with similar proportions between cases (2.5%) and controls (2.6%). The probability of being infected by 3 years of age was 28% (95% CI 0.18-0.40). Viral quantities ranged from <1 to almost 105 copies/µl. Estimated odds ratio between islet autoimmunity and infection episodes prior to seroconversion was 1.98 (95% CI: 0.57-6.91, p = 0.29). Saffold virus had no statistically significant association with islet autoimmunity.

Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study.

BACKGROUND: It is well known that anti-GAD (glutamic acid decarboxylase) serves as a marker for development of autoimmune diabetes in adults. On the other hand, the clinical implications of anti-GAD positivity in persistently non-diabetic (PND) adults are poorly elucidated. Our aim was to establish the frequency of anti-GAD in PNDs in an all-population-based cohort from the Nord-Trøndelag health study (HUNT) and to prospectively test for associations with glucose tolerance and thyroid autoimmunity. METHODS: We formed a primary study population (4496 individuals), selected randomly from the age group 20-90 years (50% men/women), who were non-diabetic both at HUNT2 (1995-1997) and HUNT3 (2006-2008). Anti-GAD-positive individuals at HUNT2, together with anti-GAD-negative individuals aged 20-29 years, were retested for anti-GAD positivity at HUNT3. A secondary study population consisted of individuals with type 2 diabetes (T2D, n=349) at HUNT3 who developed diabetes between HUNT2 and HUNT3. RESULTS: The frequency of anti-GAD positivity in PND was 1.7% (n=76) at HUNT2. Positivity did not associate with gender, family history of diabetes, or glucose levels, but was associated with thyroid-associated autoimmunity (increased frequency of positivity for anti-TPO (thyroid peroxidase), p<0.002). HLA-DQA1/DQB1, a risk haplotype for autoimmunity, was also associated with anti-GAD positivity in PND. The incidence of anti-GAD positivity was low (0.4%) in the subsample of individuals who were anti-GAD negative in HUNT2. Anti-GAD positivity in PNDs was frequently evanescent, with 54% losing, usually low-grade, positivity between HUNT2 and HUNT3. An evanescent state of autoimmunity as assessed by anti-GAD positivity during "pre-diabetes" in individuals later diagnosed with T2D could, however, not be affirmed. CONCLUSIONS: Anti-GAD positivity in PND is associated with HLA risk haplotypes and thyroid autoimmunity but not with clinical parameters of diabetes. Fleeting anti-GAD positivity is common; however, results do not support the notion of a history of autoimmunity in T2D in the present cohort.

Infant feeding in relation to islet autoimmunity and type 1 diabetes in genetically susceptible children: the MIDIA Study.

OBJECTIVE: We aimed to study the association of breast-feeding duration and age at the introduction of solid foods with the risk of islet autoimmunity and type 1 diabetes in genetically susceptible children. RESEARCH DESIGN AND METHODS: Newborns were recruited from the Norwegian general population during 2001-2007. After genetic screening of nearly 50,000 newborns, 908 children with the high-risk HLA genotype were followed up with blood samples and questionnaires at age 3, 6, 9, and 12 months and then annually. Complete infant diet data were available for 726 children. RESULTS: Any breast-feeding for 12 months or longer predicted a decreased risk of developing type 1 diabetes compared with any breast-feeding for less than 12 months before and after adjusting for having a first-degree relative with type 1 diabetes, vitamin D supplementation, maternal education, sex, and delivery type (hazard ratio 0.37 [95% CI 0.15-0.93]). Any breast-feeding for 12 months or longer was not associated with islet autoimmunity but predicted a lower risk of progression from islet autoimmunity to type 1 diabetes (hazard ratio 0.35 [95% CI 0.13-0.94]). Duration of full breast-feeding was not significantly associated with the risk of islet autoimmunity or type 1 diabetes nor was age at introduction of solid foods or breast-feeding at the time of introduction of any solid foods. CONCLUSIONS: These results suggest that breast-feeding for 12 months or longer predict a lower risk of progression from islet autoimmunity to type 1 diabetes among genetically predisposed children.

Adipose tissue distribution in relation to insulin sensitivity and inflammation in Pakistani and Norwegian subjects with type 2 diabetes.

Immigrants from South Asia to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM) associated with obesity. We investigated the relationship between diabetes and adipose tissue distribution in a group of younger T2DM subjects from Norway and Pakistan. Eighteen immigrant Pakistani and 21 Norwegian T2DM subjects (age 29-45, 49% men) were included. They underwent anthropometrical measurements including bioelectrical impedance analysis, CT scans measuring fatty infiltration in liver and adipose and muscle tissue compartments in mid-abdomen and thigh, a euglycemic clamp, and blood samples for serum insulin and plasma glucose, adipokines and inflammation markers. Adipose tissue distribution was similar in Norwegians and Pakistanis. Pakistanis, but not Norwegians, showed a negative correlation between insulin sensitivity and visceral adipose tissue (VAT, rs = - 0.704, p = 0.003). Subcutaneous adipose tissue (SAT) correlated to leptin in both Pakistanis and Norwegians (rs = 0.88, p < 0.001 and 0.67, p = 0.001). SAT also correlated to C-reactive protein (CRP) in the Pakistanis only (rs = 0.55, p = 0.03), and superficial SAT to Interleukin-1 receptor antagonist (IL-1RA) in Norwegians only (rs = 0.47, p = 0.04). In conclusion, despite similar adipose tissue distribution in the two groups Pakistanis were more insulin resistant, with a negative correlation of VAT to insulin sensitivity, not present in Norwegians. The correlation of adipose tissue to Leptin, CRP and IL-1RA showed ethnic differences.

Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study.

AIMS/HYPOTHESIS: Only a few longitudinal molecular studies of enterovirus and islet autoimmunity have been reported, and positive results seem to be limited to Finland. We aimed to investigate an association between enterovirus RNA in blood and islet autoimmunity in the MIDIA study from Norway, a country which largely shares environmental and economic features with Finland. METHODS: We analysed serial blood samples collected at ages 3, 6, and 9 months and then annually from 45 children who developed confirmed positivity for at least two autoantibodies (against insulin, GAD65 and IA-2) and 92 matched controls, all from a cohort of children with a single high-risk HLA-DQ-DR genotype. Enterovirus was tested in RNA extracted from frozen blood cell pellets, using real-time RT-PCR with stringent performance control. RESULTS: Out of 807 blood samples, 72 (8.9%) were positive for enterovirus. There was no association between enterovirus RNA and islet autoimmunity in samples obtained strictly before (7.6% cases, 10.0% controls, OR 0.75 [95% CI 0.36, 1.57]), or strictly after the first detection of islet autoantibodies (10.5% case, 5.8% controls, OR 2.00 [95% CI 0.64, 6.27]). However, there was a tendency towards a higher frequency of enterovirus detection in the first islet autoantibody-positive sample (15.8%) compared with the corresponding time point in matched controls (3.2%, OR 8.7 [95% CI 0.97, 77]). Neither of these results was changed by adjusting for potential confounders, restricting to various time intervals or employing various definitions of enterovirus positivity. CONCLUSIONS/INTERPRETATION: Positivity for enterovirus RNA in blood did not predict the later induction of islet autoantibodies, but enterovirus tended to be detected more often at the islet autoantibody seroconversion stage.

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women.

BACKGROUND: Mammographic density represents epithelial and stromal proliferation, while insulin-like growth factor (IGF)-1, insulin-like growth factor-binding protein-3, growth hormone (GH), and estrogen may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear. MATERIALS AND METHODS: Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast Cancer Aspects-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7-12 of the menstrual cycle). Associations between growth factors, estrogen, and mammographic density were studied in regression models. RESULTS: Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8%. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17ß-estradiol was associated with a higher odds for having higher percent mammographic density (>28.5%). The odds ratios (ORs) per standard deviation increase in 17ß-estradiol were 1.81 [95% confidence interval (CI) 1.08-3.03] in the high IGF-1 stratum and 2.08 (95% CI 1.10-3.94) in the high GH stratum. Furthermore, women in these strata of growth factors (above median) who had an overall average 17ß-estradiol above median (>16.8 pmol/l) had higher ORs for having higher percent mammographic density (>28.5%): IGF-1 4.13 (95 % CI 1.33-12.83) and GH 4.17 (95 % CI 1.41-12.28). CONCLUSION: Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, and may be of potential clinical relevance.

The post-prandial pattern of gut hormones is related to magnitude of weight-loss following gastric bypass surgery: a case-control study.

BACKGROUND: The mechanisms of weight loss after gastric bypass, including the role of gastric hormones, are still not completely understood. While postprandial releases of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) increase post-surgery and ghrelin usually is reduced, their relationship to the magnitude of the weight loss is still obscure. We explored if differing weight loss after Roux Y gastric bypass (RYGB) in morbidly obese were associated with differing postprandial hormonal release. METHODS: We compared patients with large (> 40%) or moderate (< 25%) weight loss three years following RYGP surgery, and an obese control group scheduled for RYGB (six in each group). A 300 kcal mixed meal test was given with blood sampling before and thereafter at 30-min intervals in 180 min. Peak and incremental area under the curve (iAUC) were calculated to characterize postprandial responses. RESULTS: Early postprandial GLP-1 response were significantly higher in the RYGB groups than in the controls, and highest in those with largest weight loss. Postprandial PYY response were also greater for the two RYGB groups vs. controls, but interestingly the controls had higher baseline values. Ghrelin, from similar baseline, was only suppressed in those with the largest weight loss, with close to no reduction in those with modest weight loss or controls. CONCLUSIONS: These results support the hypothesis that the magnitude of weight loss after RYGB surgery might be associated with differing patterns of postprandial responses in GLP-1 and ghrelin, but not PYY. Larger studies are warranted.

Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D.

In the circulation 25-hydroxyvitamin D (25(OH)D) is bound to vitamin D-binding protein (DBP) and albumin. Only a small fraction is in the unbound, free form. According to the 'free-hormone-hypothesis' only the free form is biologically active. Genetic differences in DBP may affect the binding to 25(OH)D and thereby the amount of free 25(OH)D. In the present study sera were obtained from 265 postmenopausal women with low bone mass density (BMD). Serum 25(OH)D, DBP and albumin were measured and the free and bio-available (free + albumin-bound) 25(OH)D calculated. Based on genotyping of the polymorphisms rs7041 and rs4588, the six common DBP phenotypes were identified and the free and bio-available 25(OH)D calculated according to the corresponding binding coefficients. Relations between measures of 25(OH)D and PTH and BMD were evaluated with linear regression adjusted for age and BMI. The calculated amount of free and bio-available 25(OH)D was 0.03% and 13.1%, respectively, of the measured total serum 25(OH)D. Adjusting for DBP phenotype affected the calculated free and bio-available 25(OH)D levels up to 37.5%. All measures of 25(OH)D correlated significantly with PTH, whereas a significant association with BMD was only seen for the free and bio-available 25(OH)D measures. Adjusting for the DBP phenotypes improved the associations. These relations were almost exclusively seen in subjects not using vitamin D and/or calcium supplements. In conclusion, the free and bio-available forms of 25(OH)D may be a more informative measure of vitamin D status than total 25(OH)D. Adjustment for DBP phenotype may improve this further.

Impaired left ventricular function and myocardial blood flow reserve in patients with long-term type 1 diabetes and no significant coronary artery disease: associations with protein glycation.

Our aims were to study left ventricular (LV) function and myocardial blood flow reserve (MBFR) in long-term type 1 diabetes and associations with advanced glycation end products (AGEs). A total of 20 type 1 diabetes patients from the Oslo Study without significant stenosis on coronary angiography were compared with 26 controls. LV systolic and diastolic functions were assessed by two-dimensional strain and the ratio between pulsed Doppler transmitral early (E) velocity and tissue Doppler velocity (E'), respectively. MBFR was evaluated by contrast echocardiography. The AGE methylglyoxal-derived hydroimidazolone was analysed in serum. Glyoxal hydroimidazolone in skin collagen was determined by liquid chromatography-mass spectrometry. Strain was significantly reduced (-19.5% ± 1.9% vs -21.4% ± 3.5%, p < 0.05), and E/E' increased in the diabetes patients compared to controls, 7.3 ± 2 versus 6.0 ± 1.5, p < 0.05. Significant lower MBFR was present in the diabetes patients, 3.4 (2.1, 5.3) versus 5.9 (3.9, 9.6), p < 0.01. Both AGEs correlated significantly with E/E'. The impaired LV function with correlation to AGEs in concert with reduced MBFR in diabetics without coronary artery disease may indicate possible mechanisms for diabetic cardiomyopathy.

Differences in insulin sensitivity, lipid metabolism and inflammation between young adult Pakistani and Norwegian patients with type 2 diabetes: a cross sectional study.

BACKGROUND: Immigrants from South Asia to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM). We explored pathogenic factors that might contribute to the high risk of T2DM in Pakistani immigrants to Norway. METHODS: A cross-sectional study was performed in 18 Pakistani and 21 Norwegian men and women with T2DM (age 29 - 45 years), recruited from two hospital out-patient clinics. Anthropometrics and a two-step euglycemic, hyperinsulinemic clamp with measurements of non-esterified fatty acids (NEFA) during clamp, was performed in all patients. Insulin sensitivity, given as the Glucose Infusion Rate (GIR) and Insulin Sensitivity Index (ISI), was calculated from the two euglycemic clamp steps. Fasting adipokines and inflammatory mediators were measured. Continuous variables between groups were compared using Student's t test or Mann-Whitney U test as appropriate. Spearman's correlation coefficient and multiple linear regression analyses were used. RESULTS: Despite having a lower BMI, Pakistani patients were more insulin resistant than Norwegian patients, during both low and high insulin infusion rates, after adjustment for sex and % body fat: median (interquartile range) GIR(low insulin): 339.8(468.0) vs 468.4(587.3) µmol/m2/min (p = 0.060), ISI(low insulin): 57.1(74.1) vs 79.7(137.9) µmol/m2/min (p = 0.012), GIR(high insulin): 1661.1(672.3) vs 2055.6(907.0) µmol/m2/min (p = 0.042), ISI(high insulin): 14.2(7.3) vs 20.7(17.2) µmol/m2/min (p = 0.014). Pakistani patients had lower percentage NEFA suppression 30 minutes into clamp hyperinsulinemia than Norwegians: 41.9(90.6)% vs 71.2(42.1)%, (p = 0.042). The relationship of ISI to BMI, leptin and interleukin-1 receptor antagonist also differed between Norwegians and Pakistanis. CONCLUSIONS: Compared with Norwegian patients, Pakistani patients with T2DM had lower insulin sensitivity, affecting both glucose and lipid metabolism. The relation of insulin sensitivity to BMI and some adipokines also differed between the groups.

No effects of MRI scan on male reproduction hormones.

Magnetic resonance imaging (MRI) is increasing around the world and the possible adverse effects on reproductive health of electromagnetic fields (EMFs) in MRI are not previously studied. A prospective randomized balanced cross-over study using a head scan in real MRI with whole-body transmitting coil and sham MRI among 24 healthy male volunteers was conducted. Serum-blood samples of inhibin B, testosterone, prolactine, thyreotropine, luteinizing hormone, follicle stimulating hormone, sex-hormone binding globuline and estradiol were taken before and after the different scans. Neither immediately after, nor after 11 days were there seen any differences in the hormone levels comparing real and sham MRI. The lack of effects of EMF on male reproductive hormones should be reassuring to the public and especially for men examined in MRI. Adverse effects on other endpoints than male reproduction or possible chronic effect of multiple MRI scans have not been investigated in this study.

Association between the serum levels of relaxin and responses to the active straight leg raise test in pregnancy.

There is a common belief that the laxity of pelvic joints increases in pregnancy. The hormone relaxin is suggested to be one of the most influential factors implementing this effect. Furthermore, increased laxity is assumed to induce pelvic girdle pain (PGP). The objectives were to examine the serum relaxin levels in pregnancy and to investigate whether relaxin levels relate to symptoms and clinical tests for PGP. Data from questionnaires, clinical tests and blood samples were collected once in pregnancy (gestation week 5-24) from 212 women. Serum from blood samples were analyzed by ELIZA to determine the concentration of relaxin. Self reported symptoms were assessed by Disability Rating Index (DRI) and pain intensity (VAS). Clinical examinations included Active Straight Leg Raise (ASLR) test and pain provocation tests. ANOVA was used to assess the effect of gestation age and multivariable statistics to examine the association between relaxin levels and the symptoms or responses to clinical tests. The serum levels of relaxin varied widely between individuals and were only marginally influenced by the gestation age. There was no association between gestation age and responses to clinical tests or pain intensity, but DRI increased with gestation age. Serum concentration of relaxin showed a significant association to positive score on the ASLR test, but no significant associations to responses to pain provocation tests, pain intensity or DRI. The results indicate that relaxin contributes to laxity of pelvic joints in pregnancy. Yet, no evidence of relaxin having an impact on symptoms or perceived disability was found.

Insulin sensitivity after maximal and endurance resistance training.

The purpose of the study was to compare the effects of maximal resistance training (MRT) vs. endurance resistance training (ERT) on improvements in insulin levels and glucose tolerance in overweight individuals at risk of developing type 2 diabetes. Eighteen participants with baseline values suggesting impaired glucose tolerance were randomly assigned to 1 of 2 groups. Group 1 engaged in supervised MRT (Bernstein inverted pyramid system: 5 × 3-4, 60-85% 1 repetition maximum [1RM]), 3 d·wk(-1) over 4 months, whereas members of group 2 acted as controls. Later, group 2 engaged in supervised ERT (3 × 12-15, 45-65% 1RM), 3 d·wk(-1) over a 4 month period with the 2 prebaselines as controls. Both interventions consisted of 8 exercises that included the entire body. Glucose (fasting and 2-hour test), insulin and C-peptide measures were assessed from pre to post in both groups. The MRT led to reduced blood levels of 2-hour glucose (p = 0.044) and fasting C-peptide (p = 0.023) and decreased insulin resistance (p = 0.040). The ERT caused a significant reduction in the blood levels of insulin (p = 0.023) and concomitant positive effects on % insulin sensitivity (p = 0.054) and beta-cell function (p = 0.020). The findings indicate that both MRT and ERT lead to decreased insulin resistance in people with a risk of developing type 2 diabetes; MRT led to a greater increase in glucose uptake capacity (in muscles), whereas ERT led to greater insulin sensitivity, supporting the recommendation of both MRT and ERT as primary intervention approaches for individuals at a risk of developing type 2 diabetes.

Maternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspring.

Previous studies indicate reduced risk of type 1 diabetes after intake of vitamin D supplements during pregnancy or early childhood. We aimed to test whether lower maternal serum concentrations of 25-hydroxy-vitamin D (25-OH D) during pregnancy were associated with an increased risk of childhood-onset type 1 diabetes. In this case-control study nested within a cohort of 29,072 women in Norway, 25-OH D levels were measured using a radioimmunoassay on samples from late pregnancy in 109 women delivering a child who developed type 1 diabetes before 15 years of age (case subjects) and from 219 control women. Dividing the levels of maternal 25-OH D into quartiles, there was a trend toward a higher risk of type 1 diabetes with lower levels of vitamin D during pregnancy. The odds of type 1 diabetes was more than twofold higher for the offspring of women with the lowest levels of 25-OH D compared with the offspring of those with levels above the upper quartile. Given future replication in independent cohorts, our findings provide support for the initiation of a randomized intervention trial to prevent type 1 diabetes in children by enhancing maternal 25-OH D status during pregnancy.

Bimodal distribution of polyunsaturated fatty acids in schizophrenia suggests two endophenotypes of the disorder.

BACKGROUND: There is conflicting evidence of whether polyunsaturated fatty acids (PUFA) in red blood cells are bimodally distributed in schizophrenia. The purpose of this study was to examine the distribution of PUFA, as well as its links to plausible causal factors. METHODS: A 16-week cohort study and a case-control study as part of a randomized controlled trial. Ninety-nine patients with DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder, aged 18 to 39, were consecutively included at admission to psychiatric departments of nine Norwegian hospitals. Fatty acids were measured in 97 of these patients and in 20 healthy control subjects. The primary outcome measure was the bimodality test statistic T, assessed by a χ(2) test of the likelihood of one or two normal distributions of PUFA. RESULTS: At baseline, levels of polyunsaturated fatty acids were highly significantly bimodally distributed among patients. One third of patients constituted a group (low PUFA) who had PUFA levels at one fifth (p < .001) of those in high PUFA patients and healthy control subjects, which did not differ. Bimodality was mainly accounted for by docosahexaenoic acid and arachidonic acid. Bimodality was confirmed after 16 weeks. α-tocopherol was a robust predictor of PUFA at both occasions. Desaturase and elongase indexes differed between PUFA groups. Smoking, gender, antipsychotic medication, and dietary factors did not explain the bimodal distribution. CONCLUSIONS: Red blood cell PUFA were bimodally distributed among acutely ill patients with schizophrenia and schizoaffective disorder. Endogenous deficiencies of redox regulation or synthesis of long-chain PUFA in the low PUFA group may explain our findings.

A cross-sectional study of vitamin D deficiency among immigrants and Norwegians with psychosis compared to the general population.

OBJECTIVE: Vitamin D deficiency is common among immigrants, who, as a group, have heightened risk of psychosis. This study aimed to determine vitamin D levels among immigrants and Norwegians with psychosis compared to the general population and their association to clinical characteristics. METHOD: This study compared vitamin D levels between immigrants and Norwegians within and between samples of patients with psychosis from a catchment area-based cross-sectional study (2002-2007) with a sample from a population-based health study from the same catchment area (2000-2001). The psychosis sample included patients with a Structured Clinical Interview for DSM-IV Axis I Disorders diagnosis of psychotic disorder (67 immigrants, 66 Norwegians). The reference sample consisted of 1,046 subjects (177 immigrants, 869 Norwegians). Serum levels of vitamin D were measured by radioimmunoassay, and results were presented as 25-hydroxyvitamin D levels. RESULTS: Over 80% (n = 55) of immigrant patients with psychosis had insufficient/deficient serum levels of 25-hydroxyvitamin D (< 50 nmol/L). Immigrants had higher rates of 25-hydroxyvitamin D deficiency than Norwegians (P < .001). Norwegians with psychosis had lower serum levels of 25-hydroxyvitamin D than Norwegians in the reference sample from the general public (P < .001). 25-hydroxyvitamin D levels correlated with certain negative/depressive symptoms among patients with psychosis. CONCLUSIONS: An alarmingly high percentage of immigrants and Norwegians with psychotic disorders have 25-hydroxyvitamin D deficiency. This has important clinical implications as it suggests possible beneficial effects of vitamin D medication/heliotherapy within this group.