Moira Strand Hutchinson

University Hospital of North Norway, Tromsø, Troms, Norway

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Publications (15)44.84 Total impact

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    ABSTRACT: Objective: High serum thyroid stimulating hormone (TSH) levels predict cardiovascular disease (CVD). Recently several single nucleotide polymorphisms (SNPs) associated with TSH levels have been identified, one of them being the rs4704397 SNP in the phosphodiesterase 8B (PDE8B) gene. If the relation between thyroid function and CVD is causal, one could also expect rs4704397 genotypes to predict CVD and possibly health in general. Methods: DNA was prepared and genotyping performed for rs4704397 in subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer or death as well as a randomly selected control group. Similarly, genotyping was performed in subjects who had participated in clinical trials where serum TSH, free T4 (FT4) and free T3 (FT3) were measured. Results: From the Tromsø Study a total of 8938 subjects without thyroid disease or thyroid medication were successfully genotyped for rs4704397. Among these, 2098 were registered with MI, 1025 with T2DM, 2748 with cancer and 3592 had died. The minor homozygote genotype (A:A) had a median serum TSH level 0.29 mIU/l higher than the major homozygote genotype (G:G). The A:A genotype had a significantly increased risk of MI as compared to the G:G genotype (1.14 (1.00 - 1.29), hazard ratio (95 % confidence interval), Cox regression with adjustment for age, gender and body mass index). No significant associations were seen with the other endpoints or CVD risk factors. Furthermore, subjects with the G:G genotype were significantly taller than subjects with the A:A genotype (mean difference 1.5 cm). In 584 subjects with serum TSH, FT4 and FT3 measurements, the subjects with the A:A genotype had significantly higher serum TSH and non-significantly lower serum FT3 (mean difference 0.15 pmol/l) than subjects with the G:G genotype. Conclusion: rs4704397 is associated with thyroid function, risk of MI and body height. However, confirmation in other cohorts is needed before firm conclusions can be drawn.
    Thyroid: official journal of the American Thyroid Association 08/2013; · 2.60 Impact Factor
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    ABSTRACT: The serum 25-hydroxyvitamin D (25(OH)D) level is not only dependent upon vitamin D intake and production in the skin, but also on genetic factors. Thus, in large genome-wide association studies it has been shown that single nucleotide polymorphisms (SNPs) in the vitamin D binding protein (DBP), as well as in enzymes related to activation or degradation of vitamin D and its metabolites, are as important for the serum 25(OH)D level as the effect of season. How these SNPs affect the serum 25(OH)D response to vitamin D supplementation is uncertain. Data were pooled from three randomized controlled trials where 40 000 IU vitamin D per week was given for six months. Serum 25(OH)D was measured before and at the end of the intervention, and the subjects were genotyped for SNPs related to the serum 25(OH)D level. Baseline 25(OH)D levels were significantly related to SNPs in the DBP and CYP2RI genes. Those with SNPs associated with the lowest baseline 25(OH)D levels also had the smallest increase (delta) after supplementation. Those with the lowest baseline serum 25(OH)D (without regard to genotypes) had the highest increase (delta) after supplementation. Subjects with high body mass index (BMI) had the lowest baseline 25(OH)D levels and also the smallest increase (delta) after supplementation. The serum 25(OH)D response to supplementation depends on genes, baseline level and BMI. However, whether this is clinically important or not depends on the therapeutic window of vitamin D, an issue that is still not settled.
    European Journal of Endocrinology 08/2013; · 3.14 Impact Factor
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    ABSTRACT: Cross-sectional studies indicate a positive relation between serum 25-hydroxyvitamin D [25(OH)D] and testosterone. It is not known if this relation is causal, which in theory could be in both directions. A cross-sectional population based study was designed with pooled data from 3 vitamin D randomized clinical trials (RCTs) performed in Tromsø with weight reduction, insulin sensitivity, and depression scores as endpoints, and one testosterone RCT in subjects with low serum testosterone (<11.0 nmol/l) and with body composition as endpoint. Serum 25(OH)D and androgens were measured in 893 males in the cross-sectional part, at baseline and after 6-12 months of supplementation with vitamin D 20 000 IU-40 000 IU per week vs. placebo in the vitamin D RCTs (n=282), and at baseline and after one year treatment with testosterone undecanoate 1 000 mg or placebo injections (at baseline and after 6, 16, 28, and 40 weeks) in the testosterone RCT (n=37). In the cross-sectional study, serum 25(OH)D was found to be a significant and positive predictor of serum testosterone. In the vitamin D RCTs, no significant effect on serum total or free testosterone levels was seen, and in the testosterone RCT no significant effect on serum 25(OH)D was seen. This was unchanged in sub-analyses in subjects with low serum 25(OH)D (or testosterone) levels. In conclusion, in subjects without significant vitamin D deficiency, there is no increase in serum testosterone after high dose vitamin D supplementation. Similarly, in subjects with moderately low serum testosterone levels, substitution with testosterone does not increase serum 25(OH)D.
    Hormone and Metabolic Research 05/2013; · 2.15 Impact Factor
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    ABSTRACT: HbA(1c) 6.5% has recently been recommended as an alternative diagnostic criterion for diabetes. The aims of the study were to evaluate the effects of age, sex, and other factors on prevalence of diabetes and to compare risk profiles of subjects with diabetes when defined by HbA(1c) and glucose criteria. Subjects were recruited among participants in the longitudinal population-based Tromsø Study. HbA(1c), fasting plasma glucose, and 2-hour plasma glucose were measured in 3,476 subjects. In total, 294 subjects met one or more of the diagnostic criteria for diabetes; 95 met the HbA(1c) criterion only, 130 met the glucose criteria only, and 69 met both. Among subjects with diabetes detected by glucose criteria (regardless of HbA(1c)), isolated raised 2-hour plasma glucose was more common in subjects aged ≥ 60 years as compared to younger subjects and in elderly women as compared to elderly men. Subjects with diabetes detected by glucose criteria only had worse cardiometabolic risk profiles than those detected by HbA(1c) only. In conclusion, the current HbA(1c) and glucose criteria defined different subjects with diabetes with only modest overlap. Among a substantial proportion of elderly subjects, and especially elderly women, the 2-hour plasma glucose was the only abnormal value.
    International Journal of Endocrinology 01/2013; 2013:613475. · 2.52 Impact Factor
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    ABSTRACT: Data were pooled from four randomized clinical trials with vitamin D performed in Tromsø with weight reduction, insulin sensitivity, bone density, and depression scores as endpoints. Serum lipids, glycated hemoglobin (HbA1c), and high sensitivity C-Reactive Protein, (HS-CRP) were measured at baseline and after 6-12 months of supplementation with vitamin D 20 000 IU-40 000 IU per week versus placebo. A total of 928 subjects who completed the interventions were included. At baseline the mean serum 25-hydroxyvitamin D (25(OH)D) level in those given vitamin D was 55.9 (20.9) nmol/L and the mean increase was 82.4 (40.1) nmol/L. Compared with the placebo group there was in the vitamin D group at the end of the studies a slight, but significant, increase in HbA1c of 0.04%, an increase in HS-CRP of 0.07 mg/L in those with serum 25(OH)D < 50 nmol/L, and in those with low baseline HDL-C and serum 25(OH)D < 50 nmol/L a slight decrease serum HDL-C of 0.08 mmol/L (P < 0.05). No serious side-effects were seen. In conclusion, in subjects without vitamin D deficiency, there is no improvement in serum lipids, HbA1c, or HS-CRP with high dose vitamin D supplementation. If anything, the effect is negative.
    ISRN endocrinology. 01/2013; 2013:348705.
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    ABSTRACT: AIMS: To compare depressive symptoms in participants with low and high serum 25-hydroxyvitamin D (25(OH)D) levels and to examine whether supplementation with vitamin D(3) would improve symptoms in those with low serum 25(OH)D levels. METHOD: Participants with low 25(OH)D levels were randomised to either placebo or 40 000 IU vitamin D(3) per week for 6 months. Individuals with high serum 25(OH)D levels were used as nested controls. Depressive symptoms were evaluated with the Beck Depression Inventory, Hospital Anxiety and Depression Scale, Seasonal Pattern Assessment Scale and Montgomery-Åsberg Depression Rating Scale. The study was registered at ClinicalTrials.gov (NCT00960232). RESULTS: Participants with low 25(OH)D levels (n = 230) at baseline were more depressed (P<0.05) than participants with high 25(OH)D levels (n = 114). In the intervention study no significant effect of high-dose vitamin D was found on depressive symptom scores when compared with placebo. CONCLUSIONS: Low levels of serum 25(OH)D are associated with depressive symptoms, but no effect was found with vitamin D supplementation.
    The British journal of psychiatry: the journal of mental science 07/2012; · 6.62 Impact Factor
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    ABSTRACT: Vitamin D deficiency has been associated with a number of diseases, including influenza. Whether or not this reflects a causal relationship is unknown. We therefore wanted to examine if supplementation with vitamin D would affect the incidence and severity of influenza-like disease. Questionnaires on influenza were sent to subjects participating in ongoing placebo-controlled intervention studies with vitamin D supplementation, up until the end of April 2010. Five hundred and sixty-nine subjects from 10 different clinical trials were included in the study, of whom 289 were randomized to receive vitamin D (1111-6800 IU/day) and 280 to receive placebo. Influenza-like disease during the previous fall/winter was reported in 38 subjects in the vitamin D group and 42 in the placebo group (non-significant), of whom 25 and 26 subjects, respectively, fulfilled our clinical criteria for influenza. In these latter subjects, the duration of illness was significantly longer among those in the vitamin D group than among those in the placebo group (median 7 (range 2-60) days vs median 4 (range 2-18) days; p = 0.007). However, this difference was not statistically significant if all 38 (vitamin D) and 42 (placebo) subjects who reported symptoms were included. Our results do not support the hypothesis that high doses of vitamin D supplementation will have a pronounced effect on influenza-like disease in populations not targeted for high influenza risk.
    Scandinavian Journal of Infectious Diseases 02/2012; 44(2):126-32. · 1.71 Impact Factor
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    ABSTRACT: Background Haemoglobin A1c 6.5 % has recently been recommended by the World Health Organization (WHO) and the American Diabetes Association (ADA) as an alternative diagnostic criterion for diabetes mellitus (DM). Aim To evaluate HbA1c as an alternative to oral glucose tolerance test (OGTT) for diagnosis of DM and pre-diabetes and to find the optimal HbA1c cut off points for DM and pre-diabetes in our population. Subjects and Methods The subjects were recruited from the Tromsø Study, performed for the sixth time in 2007-2008 with 12 984 participants. All subjects with HbA1c in the range 5.8 - 6.9 % and a random sample of subjects with levels 5.3 - 5.7 % were invited to an OGTT. Results Among 3476 subjects who completed the OGTT, 199 were diagnosed with DM. The best sensitivity (69.8 %) and specificity (81.8 %) were found at HbA1c 6.2 %. For HbA1c 6.5 % we found a sensitivity of 34.7 % and specificity 97.1 %. The best cut off points for impaired fasting glucose (n=314) and impaired glucose tolerance (n=404) were found at HbA1c 5.9 % and 6.0 %, respectively. Pre-diabetes detected only by OGTT was associated with worse metabolic characteristics than pre-diabetes detected only by HbA1c. Conclusions The optimum HbA1c cut off point for DM in our population was lower than that proposed by WHO and ADA. To establish more precisely the HbA1c levels predictive of micro and macro-vascular complications long term prospective studies are needed. Population specific optimum cut off points may be necessary.
    Journal of endocrinological investigation 12/2011; · 1.65 Impact Factor
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    ABSTRACT: The relationships between vitamin D concentrations, hyperglycemia, and insulin resistance remain uncertain. During 2008 - 2010, an oral glucose tolerance test was performed in 3520 subjects from Tromsø, Norway. Serum 25-hydroxyvitamin D [25(OH)D] was measured in 1193 subjects with normal glucose tolerance, in 304 with isolated impaired fasting glucose, in 254 with isolated impaired glucose tolerance, in 139 with a combination of the two, and in 194 subjects with type 2 diabetes. Serum 25(OH)D did not differ between subjects with isolated impaired fasting glucose or impaired glucose tolerance, but was lower in all groups of deranged glucose metabolism as compared with normal subjects. These differences could not be explained by differences in intakes of vitamin D from cod liver oil or other supplements and remained statistically significant after adjustment for gender, age, body mass index, physical activity score, and month of examination. When the cohort was divided according to serum 25(OH)D quartiles, there was an improvement in all measures of glucose metabolism (fasting and 2-hour plasma glucose, serum insulin, HbA(1c)) and estimates of insulin resistance (QUICKI , HOMA-IR, ISI(0.120)) with increasing serum 25(OH)D quartile. However, interventional studies are needed to prove a causal relationship between vitamin D and glucose metabolism.
    International Journal for Vitamin and Nutrition Research 09/2011; 81(5):317-27. · 1.27 Impact Factor
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    ABSTRACT: Animal and human studies have shown an association between serum 25-hydroxyvitamin D (25(OH)D) level and insulin secretion and sensitivity. Accordingly, an association between 25(OH)D and glycated haemoglobin (HbA(1c)) is to be expected, and this was tested for in the present study. The Tromsø Study is a longitudinal population-based study initiated in 1974. In the sixth Tromsø Study conducted in 2007-2008, 12,984 subjects aged 30-87 years attended. After exclusion of current smokers and subjects with diabetes, the dataset consisted of 8643 subjects available for the present analyses. The correlation between serum 25(OH)D and HbA(1c) was -0.07 (p < 0.001). This association remained significant in a multiple linear regression model after adjustment for covariates gender, age, month of blood sampling, body mass index (BMI), physical activity score, serum triglycerides (TG), serum calcium and haemoglobin, and persisted across categories of gender, age, BMI and TG. The association appears to be most pronounced in the oldest, the obese and in those with the highest TG levels. Seasonal variation was found both for serum 25(OH)D and HbA(1c) with highest serum 25(OH)D levels and lowest HbA(1c) levels during summer months. In conclusion, there is a significant inverse association between serum 25(OH)D and HbA(1c) after adjustment for known confounders. The association is most pronounced in subjects with risk factors for glucose intolerance/type 2 diabetes. In a sub-analysis on subjects with diabetes the association between serum 25(OH)D and HbA(1c) appeared even stronger with a difference in HbA(1c) of 0.48 % between the highest and lowest serum 25(OH)D quartiles.
    Scandinavian journal of clinical and laboratory investigation 04/2011; 71(5):399-406. · 1.38 Impact Factor
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    ABSTRACT: Low serum 25-hydroxyvitamin D (25(OH)D) concentrations are related to increased mortality. One possible explanation could be an association between serum 25(OH)D and serum lipids. The study was performed at the University of Tromsø, Northern Norway. In total, 8018 nonsmoking and 2087 smoking subjects were included in a cross-sectional study performed in 2008, and 1762 nonsmoking and 397 smoking subjects in a longitudinal study from 1994/1995 to 2008. Nonfasting serum 25(OH)D, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio and triacylglycerol (TAG) were measured. After adjustment for gender, age, sample month and body mass index in the cross-sectional study, there was a significant increase in serum TC, HDL-C and LDL-C, and a significant decrease in serum LDL-C/HDL-C ratio and TAG across increasing serum 25(OH)D quartiles. For serum HDL-C and TAG in nonsmokers the differences between the means for the highest and lowest serum 25(OH)D quartiles were 6.0 and 18.5%, respectively. In the longitudinal study, an increase in serum 25(OH)D was associated with a significant decrease in serum TAG. There is a cross-sectional association between serum 25(OH)D and serum lipids, and a longitudinal association over 14 years between serum 25(OH)D and TAG, which may contribute to explain the relation between low serum 25(OH)D concentrations and mortality.
    European journal of clinical nutrition 12/2010; 64(12):1457-64. · 3.07 Impact Factor
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    ABSTRACT: Because we found higher serum 25-hydroxyvitamin D (25(OH)D) levels among smokers than among non-smokers with analyses using an electrochemiluminescence immunoassay (ECLIA) from Roche, the purpose of the present study was to examine whether this difference between smokers and non-smokers was maintained using other serum 25(OH)D assays. A cross-sectional population-based study on 6932 participants from the Tromsø study, 1994-1995, and one validation study comparing six different serum 25(OH)D assays in 53 non-smokers and 54 smokers were performed. The association between smoking, season and serum 25(OH)D as measured by ECLIA (Roche) was assessed in the population-based study using general linear models with multivariate adjustments. In the validation study, serum levels of 25(OH)D were analysed with liquid chromatography coupled with mass spectrometry assay from two different laboratories, RIA (DiaSorin), HPLC, RIA (IDS) and ECLIA (Roche). T-tests and linear mixed model analyses were performed to compare the serum 25(OH)D levels in smokers and non-smokers within and between the methods. In the population-based study, the serum levels of 25(OH)D using the ECLIA method were 51.9, 53.2 and 72.0 nmol/l in never, former and current smokers (P<0.01). In the validation study, the serum concentration of 25(OH)D was 10.3 nmol/l higher in smokers than in non-smokers (P<0.01) using the ECLIA (Roche), while non-significantly lower serum levels of 25(OH)D were found in smokers using the other five methods. These two studies indicate that the ECLIA (Roche) overestimates serum 25(OH)D levels in smokers by unknown mechanisms. If confirmed, this might have clinical consequences, and the issue needs further exploration.
    European Journal of Endocrinology 08/2010; 163(2):339-48. · 3.14 Impact Factor
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    ABSTRACT: Low serum 25-hydroxyvitamin D (25(OH)D) levels are associated with risk factors for cardiovascular disease, and they also appear to predict later development of type 2 diabetes, cancer, and an increased mortality rate. These predictions are all based on a single 25(OH)D measurement, but so far there are no known reports on tracking of serum 25(OH)D levels. In the present Norwegian study, serum 25(OH)D levels were measured 1) in 2,668 subjects in the 1994 and 2008 Tromsø surveys and 2) every third month for 1 year in 94 subjects randomly assigned to placebo in a vitamin D intervention study. There was a marked seasonal variation in 25(OH)D, and, depending on the method of adjusting for season, the correlation coefficient between serum 25(OH)D measurements from 1994 and 2008 ranged from 0.42 to 0.52. In the 1-year intervention study, the correlation between baseline and 12-month values was 0.80. Apart from the effect of season, changes in weight, intake of vitamin D, and physical activity were related to change in serum 25(OH)D levels. Tracking of serum 25(OH)D appears similar to that for blood pressure and serum lipids, and it provides some support for the use of a single 25(OH)D measurement to predict future health outcomes.
    American journal of epidemiology 03/2010; 171(8):903-8. · 5.59 Impact Factor
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    ABSTRACT: Vitamin D receptors have been detected in vascular smooth muscle cells, and 1,25-dihydroxyvitamin D inhibits the renin mRNA expression. Epidemiological studies show an inverse relation between serum 25-hydoxyvitamin D levels and blood pressure, and low serum 25-hydoxyvitamin D levels are reported to be predictors of future development of hypertension. This may indicate an important role for vitamin D in blood pressure regulation. In the present study, 25-hydoxyvitamin D was measured in sera collected in 1994 from 4125 subjects who did not use blood pressure medication, and thereafter measurement was repeated in 2008 for 2385 of these subjects. In sera from 1994 there was a significant decrease in age, body mass index, and systolic blood pressure and a significant increase in physical activity score across increasing 25-hydoxyvitamin D quartiles. After adjusting for sex, age, body mass index, and physical activity, the difference in systolic blood pressure between the lowest and highest serum 25-hydoxyvitamin D quartiles was 3.6 mm Hg. After adjustment for confounders, serum 25-hydoxyvitamin D from 1994 did not predict future hypertension or increase in blood pressure, nor was there any significant association between change in serum 25-hydoxyvitamin D from 1994 to 2008 and change in blood pressure. Our results do not support a causal role for vitamin D in blood pressure regulation, and large randomized clinical trials, preferably including subjects with hypertension and/or low serum 25-hydoxyvitamin D levels, are greatly needed to clarify whether vitamin D supplementation affects the blood pressure.
    Hypertension 03/2010; 55(3):792-8. · 6.87 Impact Factor
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    ABSTRACT: Ecologic and observational studies have suggested an association between serum 25-hydroxyvitamin D (25(OH)D) levels and cardiovascular disease (CVD) risk factors, CVD mortality, and cancer mortality. Based on this, low serum 25(OH)D levels should be associated with higher all-cause mortality in a general population. This hypothesis was tested in the present study. The Tromsø study is a longitudinal population-based multipurpose study initiated in 1974 with focus on lifestyle-related diseases. Our data are based on the fourth Tromsø study carried out in 1994-1995. Information about death and cause of death was registered by obtaining information from the National Directory of Residents and the Death Cause Registry. Serum 25(OH)D was measured in 7161 participants in the fourth Tromsø study. Results are presented for smokers (n=2410) and non-smokers (n=4751) separately as our immunoassay seems to overestimate 25(OH)D levels for smokers. During a mean 11.7 years of follow-up, 1359 (19.0%) participants died. In multivariate regression models, there was a significantly increased risk of all-cause mortality (hazard ratio (HR) 1.32, confidence interval (CI) 1.07-1.62) among non-smoking participants in the lowest 25(OH)D quartile when compared with participants in the highest quartile. Equivalent results for smokers were not significant (HR 1.06, CI 0.83-1.35). Low serum 25(OH)D levels were associated with increased all-cause mortality for non-smokers, but the results did not reach statistical significance for smokers. However, low 25(OH)D levels are known to be associated with impaired general health, and randomized controlled studies are needed to address the question of causality.
    European Journal of Endocrinology 02/2010; 162(5):935-42. · 3.14 Impact Factor