Peter M Nilsson

Skåne University Hospital, Malmö, Skåne, Sweden

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Publications (790)3701.3 Total impact

  • International journal of cardiology 09/2015; 194. DOI:10.1016/j.ijcard.2015.05.081 · 6.18 Impact Factor
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    ABSTRACT: Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity.
    Journal of Hypertension 06/2015; DOI:10.1097/HJH.0000000000000645 · 4.22 Impact Factor
  • Peter M Nilsson
    Hypertension 06/2015; DOI:10.1161/HYPERTENSIONAHA.115.05621 · 7.63 Impact Factor
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    ABSTRACT: b>Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI:1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals.
    International Journal of Epidemiology 06/2015; DOI:10.1093/ije/dyv075 · 9.20 Impact Factor
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    ABSTRACT: Cardiac troponins are biomarkers of myocardial injury and serve both diagnostic and prognostic purposes. Even mild elevations represent subclinical myocardial damage in the general population. The objective of this study was to investigate the relationship between glucometabolic status and cardiac troponin T in middle-aged or older apparently healthy subjects. We examined cross-sectional associations between high-sensitivity cardiac troponin T (hsTnT) and FPG categorized as normal fasting glucose (NFG: FPG</=6.0mmol/L), impaired fasting glucose (IFG: FPG 6.1-6.9mmol/L), and diabetes mellitus (DM: FPG>/=7.0mmol/L), in 535 men and 226 women aged 56-79 years without overt cardiovascular disease who received no cardiovascular, antidiabetic or lipid lowering drugs, using multiple linear regression analysis. FPG category (r = 0.159; p < 0.001) was positively correlated with hsTnT. Mean hsTnT levels increased significantly with worsening glucometabolic status (NFG: 7.55 ng/L +/- standard deviation 3.99 ng/L; IFG: 8.09 ng/L +/- 6.81 ng/L; DM: 10.28 ng/L +/- 7.55 ng/L; p < 0.001). Levels were significantly higher in subjects with DM compared to NFG (p < 0.001) and IFG (p = 0.005), but there was no significant difference between subjects with NFG and IFG (p = 0.26). After adjusting for age and sex, FPG category remained significantly predictive of hsTnT (B = 1.08 [95% confidence interval (CI), 0.56-1.59]; p < 0.001). After further adjusting for traditional cardiovascular risk factors, cystatin C levels, and electrocardiographic left ventricular hypertrophy (LVH) defined by the Sokolow-Lyon index and/or Cornell voltage-duration product, FPG category remained significantly associated with hsTnT (B = 0.87 [95% CI, 0.35-1.39]; p = 0.001), independently of age (B = 0.29 [95% CI, 0.22-0.36]; p < 0.001), sex (B = 2.08 [95% CI, 1.20-2.95]; p < 0.001), systolic blood pressure (B = 0.032 [95% CI, 0.012-0.051]; p = 0.001), and cystatin C (B = 3.69 [95% CI, 1.60-5.79]; p = 0.001). There was a significant interaction between FPG category and age (NFG: B = 0.22 [95% CI, 0.16-0.29]; IFG: B = 0.33 [95% CI, 0.18-0.48]; DM: B = 0.41 [95% CI, 0.20-0.62]; p = 0.03). In middle-aged or older apparently healthy subjects, untreated DM was associated with higher levels of hsTnT, independently of traditional cardiovascular risk factors. The importance of age increased with worsening glucometabolic status.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e54-e55. DOI:10.1097/01.hjh.0000467491.14601.38 · 4.22 Impact Factor
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    ABSTRACT: Neurotensin is released from the gut after fat intake and has a role in appetite regulations. Proneurotensin is a stable fragment of the neurotensin precursor hormone and fasting plasma proneurotensin levels have shown to be significantly associated with the development of cardiovascular disease in middle aged participants of the Malmö Diet and Cancer Study. Here, we aimed at replicating the initial findings in an independent second cohort and to extend its validity to an older population. Malmö Preventive Project (MPP) is a Swedish population based prospective study which comprised 18240 subjects for reexamination in 2002-2006. Fasting proneurotensin was measured in plasma from a random sample of 4804 participants (Age 69 SD (6,2), 68% Male). Multivariate Cox proportional hazard models adjusted for age, sex, use of antihypertensive medications, systolic blood pressure, BMI, current smoking, high density lipoprotein cholesterol (HDL-C), LDL-C, history of diabetes were used to relate the log transformed levels of fasting proneurotensin to the risk of first fatal or non-fatal cardiovascular event (myocardial infarction or stroke) in the mean follow up time of up to 6.5 years. There were 456 cardiovascular events observed in the study. Hazard ratios (HR) for CVD were expressed per 1 (SD) increment of log transformed proneurotensin for cardiovascular disease as HR 1,102; 95% CI; 1,006-1,088; P = 0,037. In addition, proneurotensin was divided in to quartiles where quartile 1 defined as (Ref = 1). The risk of CVD was 1,107(0,848-1,444), 1,349 (1,040-1,749), 1,336 (1,016-1,757) in quartile 2-4 when compared with the reference quartile (P for trend = 0.013). Fasting proneurotensin levels are independently associated with the risk of developing cardiovascular disease which replicates the findings in MDC study.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e11. DOI:10.1097/01.hjh.0000467381.67485.4c · 4.22 Impact Factor
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    ABSTRACT: High dietary salt is a leading risk for death and disability largely by causing increased blood pressure. Other associated health risks include gastric and renal cell cancers, osteoporosis, renal stones, and increased disease activity in multiple sclerosis, headache, increased body fat and Meniere's disease. The World Hypertension League (WHL) has prioritized advocacy for salt reduction. WHL resources and actions include a non-governmental organization policy statement, dietary salt fact sheet, development of standardized nomenclature, call for quality research, collaboration in a weekly salt science update, development of a process to set recommended dietary salt research standards and regular literature reviews, development of adoptable power point slide sets to support WHL positions and resources, and critic of weak research studies on dietary salt. The WHL plans to continue to work with multiple governmental and non-governmental organizations to promote dietary salt reduction towards the World Health Organization (WHO) recommendations.
    06/2015; 5(3):238-42. DOI:10.3978/j.issn.2223-3652.2015.04.08
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    ABSTRACT: To explore possible hemodynamic and glucometabolic determinants of left ventricular filling pressures as assessed by the non-invasive surrogate marker, averaged E/é, in otherwise healthy, middle-aged male survivors from a random population sample. Prospective population-based cohort study examining associations between hemodynamic factors [systolic blood pressure (SBP), heart rate (HR)), glucometabolic factors (fasting blood glucose, fasting plasma insulin, Homeostatic Model Assessment (HOMA) derived indices of beta-cell function (HOMA-2B) and insulin sensitivity (HOMA-2S)], other traditional cardiovascular risk factors [age, smoking status, body mass index (BMI), total serum cholesterol, serum creatinine] assessed at baseline, and values of E/é assessed at follow-up examination, using multivariable linear regression analysis (significance level 0.05, p-stay 0.20 on multivariable analysis). Subjects with prevalent cardiovascular disease and/or diabetes mellitus were excluded. E/é was positively skewed and, therefore, naturally log-transformed, as was fasting plasma insulin. HOMA-indices were assessed as continuous variables, both non-transformed and after natural log-transformation, as well as categorically, using quartiles. Study subjects were included 1974-1992, whilst the follow-up with echocardiography was performed 2002-2006. The final study population comprised 246 men with a median (IQR) age of 47 (47-48) years. Median (IQR) follow-up time was 28 (27-28) years, and median (IQR) E/é was 10 (8-12). In univariable analyses, E/é was associated positively with higher age, BMI, and serum creatinine, and negatively with shorter follow-up time. The multivariable model (adjusted r = 0.15) included all of these variables, i.e. age (beta = 0.016 per year [95% confidence interval (CI), 0.006 to 0.027]; p = 0.002), BMI (beta = 0.03 per kg/m [95% CI, 0.02 to 0.04]; p < 0.0001), serum creatinine (beta = 0.002 per micromole/l [95% CI, -0.001 to 0.005]; p = 0.18), and time elapsed between baseline examination and echocardiography (beta = -0.03 per year [-0.06 to -0.01]; p = 0.01). We did not find any significant interactions in the prediction of E/é. In a prospective population-based cohort study including apparently healthy, middle-aged male subjects, higher age, BMI, and creatinine, but not SBP or HR, were significantly associated with higher left ventricular filling pressures as assessed by averaged E/é.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e67. DOI:10.1097/01.hjh.0000467530.97498.73 · 4.22 Impact Factor
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    ABSTRACT: The Large Hadron Collider (LHC), operating at the international CERN Laboratory in Geneva, Switzerland, is leading Big Data driven scientific explorations. Experiments at the LHC explore the fundamental nature of matter and the basic forces that shape our universe, and were recently credited for the discovery of a Higgs boson. ATLAS and ALICE are the largest collaborations ever assembled in the sciences and are at the forefront of research at the LHC. To address an unprecedented multi-petabyte data processing challenge, both experiments rely on a heterogeneous distributed computational infrastructure. The ATLAS experiment uses PanDA (Production and Data Analysis) Workload Management System (WMS) for managing the workflow for all data processing on hundreds of data centers. Through PanDA, ATLAS physicists see a single computing facility that enables rapid scientific breakthroughs for the experiment, even though the data centers are physically scattered all over the world. The scale is demonstrated by the following numbers: PanDA manages O(102) sites, O(105) cores, O(108) jobs per year, O(103) users, and ATLAS data volume is O(1017) bytes. In 2013 we started an ambitious program to expand PanDA to all available computing resources, including opportunistic use of commercial and academic clouds and Leadership Computing Facilities (LCF). The project titled 'Next Generation Workload Management and Analysis System for Big Data' (BigPanDA) is funded by DOE ASCR and HEP. Extending PanDA to clouds and LCF presents new challenges in managing heterogeneity and supporting workflow. The BigPanDA project is underway to setup and tailor PanDA at the Oak Ridge Leadership Computing Facility (OLCF) and at the National Research Center "Kurchatov Institute" together with ALICE distributed computing and ORNL computing professionals. Our approach to integration of HPC platforms at the OLCF and elsewhere is to reuse, as much as possible, existing components of the PanDA system. We will present our current accomplishments with running the PanDA WMS at OLCF and other supercomputers and demonstrate our ability to use PanDA as a portal independent of the computing facilities infrastructure for High Energy and Nuclear Physics as well as other data-intensive science applications.
    Journal of Physics Conference Series 05/2015; 608:012040. DOI:10.1088/1742-6596/608/1/012040
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    ABSTRACT: A high intake of omega-3 polyunsaturated fatty acids (ω-3 PUFAs), has been associated with reduced levels of blood pressure (BP). Their antihypertensive action may be due to the reduction of the ω-6/ω-3 ratio and the resulting competitive effect of ω-3 as compared to arachidonic acid (an ω-6 PUFA) as a substrate of cytochrome P450 (CYP450) enzymes involved in the production of vasoactive mediators. Some functional polymorphisms (SNPs), in genes which encode for the same enzymes, were associated with hypertension and ischemic stroke in the Malmö Diet and Cancer (MDC), a Swedish urban-based longitudinal study. The aim of this study was to evaluate the effect of the intake of different types of PUFAs on BP change over time (Δ-BP; mean follow-up 16.6±1.5 years; n=3,550 with complete phenotypic data), also considering the interaction with SNPs in genes involved in their metabolism via CYP450. PUFA intakes were collected by a modified diet history method, and functional SNPs in CYP4F2, CYP4A11, CYP2J2 and EPHX2 were genotyped by Taqman. We did not find any overall association between ω-6 or ω-3 PUFA intakes, or their ratio, with Δ-BP but observed an interaction between CYP4F2 V433M genotype and total omega-3, α-linolenic acid and linoleic/α-linolenic ratio, so that a higher ω-3 PUFA intake was significantly associated with a more pronounced BP decrease over time in subjects with the 433VV genotype (-0.041±0.018mmHg/year; p=0.024; p-interaction=0.031) CONCLUSIONS: Our data do not support a major role of ω-6 or ω-3 PUFA intakes on BP change over time, but suggest a possible interaction of ω-3 PUFA with the CYP4F2 V433M. Copyright © 2015. Published by Elsevier Inc.
    Prostaglandins & other lipid mediators 05/2015; DOI:10.1016/j.prostaglandins.2015.05.003 · 2.86 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) episodes are thought to be started by an electrical trigger reaching a susceptible atria. Such a trigger could be present long before the occurrence of sustained symptomatic arrhythmia. We sought to determine if supraventricular extrasystoles (SVES) and supraventricular tachycardias (SVT) measured at 24 h Holter ECG were associated with increased incidence of AF. In 1998-2000, 389 individuals (44% men, mean age 65 years) were examined using 24 h Holter ECG. Six individuals with known prevalent AF were excluded. After a mean follow-up of 10.3 years there were 45 cases of incident AF. Hazard ratios (HR) were computed using multivariable Cox regression adjusting for age, gender, systolic blood pressure, height, weight, smoking and HOMA-IR (homeostatic model assessment of insulin resistance). Frequency of SVES as well as SVT episodes per hour were independent predictors of incident AF, HR per log unit 1.38, 95% confidence interval (CI) 1.14-1.68, p= 0.001; and HR 1.95, 95% CI 1.21-3.13, p=0.006, respectively. Further adjustment for education level, alcohol use, use of medication and physical activity did not substantially alter the results, nor did analysis using competing risks regression accounting for a competing risk of death. The maximum duration of SVT or the heart rate at SVT was not significantly associated with incidence of AF. SVES and SVT independently predict AF. The prognostic significance was similar for SVES, SVT and a combination of the two. Repeated efforts to detect AF could be of merit in individuals with frequent supraventricular activity. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 05/2015; DOI:10.1016/j.hrthm.2015.04.042 · 4.92 Impact Factor
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    ABSTRACT: Blood pressure (BP) in patients with sickle cell disease (SCD) has been reported to be lower than in persons in the general population. Data on arterial stiffness, which is an important risk factor for the progression of BP, are inconclusive for this patient population. Forty-five adult patients with SCD and 40 controls matched for sex, age, and body mass index were studied. Brachial systolic BP (SBP) and diastolic BP (DBP) were significantly lower in the patient group (SBP 115.1±13.8 mm Hg vs 121.9±11.3 mm Hg and DBP 68.5±8.0 mm Hg vs 80.6±9.1 mm Hg, P<.05, respectively). Augmentation index (AIx), however, was significantly higher in SCD patients compared with healthy controls (24.9±9.6 for patients vs 12.4±10.8 for controls, P<.001), while carotid femoral pulse wave velocity was comparable between the two groups. The study shows that mechanisms other than arterial elasticity are involved in the low BP phenotype of patients with SCD. ©2015 Wiley Periodicals, Inc.
    Journal of Clinical Hypertension 05/2015; DOI:10.1111/jch.12572 · 2.96 Impact Factor
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    ABSTRACT: To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography. Subjects were selected randomly from groups defined by FPG. Traditional risk markers were assessed. LVH was defined by either Cornell voltage-duration product (CP) or Sokolow-Lyon voltage combination (SL), and univariate and multivariable regressions were performed in search of explanatory factors for the presence of LVH and the values of CP and SL. Of the 1759 subjects included, 1007 had a history of cardiovascular disease and/or medical treatment, while 752 subjects appeared to be healthy. We found an independent association between FPG and LVH (odds ratio 1.152, p = 0.042] as well as continuous CP (beta = 0.126, p = 0.007) in healthy men. As expected, we found an association between systolic blood pressure and LVH (odds ratio 1.020, p < 0.001) among healthy subjects, but only in subjects with FPG < 6 mmol/l (p = 0.04 for interaction). We found an independent association between FPG and LVH in healthy men, and no potentiating effect by FPG on the impact of hypertension.
    Blood pressure 04/2015; 24(3):1-10. DOI:10.3109/08037051.2015.1030892 · 1.61 Impact Factor
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    ABSTRACT: Previous observational studies on the association between brachial blood pressure (BP) and cognition have reported conflicting results. Central BP has been hypothesized to be more strongly related to cognition than brachial BP. The aim of this study was to assess the association between brachial as well as central BP and cognitive function, both cross-sectionally and with brachial BP measured 17 years before cognitive testing. The study population comprised 2548 individuals aged 61-85 years at follow-up (61.4% women). The cognitive tests administered were A Quick Test of cognitive speed and the Mini Mental State Examination. In fully adjusted linear regressions, small but significant cross-sectional associations were found between higher BP (systolic, diastolic and pulse pressure) and worse results on both of the cognitive tests (P-values <0.05). No significant prospective associations were found. Central BP did not show a stronger association than brachial BP did. After stratification, significant results were mainly found in the group taking BP-lowering drugs at follow-up. In summary, these findings add to existing evidence on the relationship between BP and cognition, but they do not support a superior role of central compared with brachial BP in the elderly.Journal of Human Hypertension advance online publication, 16 April 2015; doi:10.1038/jhh.2015.33.
    Journal of human hypertension 04/2015; DOI:10.1038/jhh.2015.33 · 2.69 Impact Factor
  • Journal of Clinical Hypertension 04/2015; 17(5). DOI:10.1111/jch.12557 · 2.96 Impact Factor
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    ABSTRACT: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. Mean PWV value for the entire population was 8.4 m/s (men: 8.6 m/s; women: 8.2 m/s; P < 0.02). The individuals were classified with EVA if their PWV was at least 97.5th percentile of z-score for mean PWV values adjusted for age (using normal European reference values as comparators). The overall prevalence of EVA was 12.5%; 26.1% of individuals below 30 years presented this feature and 40.2% of individuals in that same age strata were placed above the 90th percentile of PWV; and 18.7% of the population exhibited PWV values above 10 m/s, with male predominance (17.2% of men aged 40-49 years had PWV > 10 m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10 m/s 10 years later than men. The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found.
    Journal of Hypertension 03/2015; 33(7). DOI:10.1097/HJH.0000000000000565 · 4.22 Impact Factor
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    ABSTRACT: Obesity is the major modifiable risk factor for diabetes. This study investigated the incidence of diabetes in relation to multiple anthropometric measures. Body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), waist-hip ratio (WHR) and body fat percentage (BF %) were measured among 26 604 subjects (aged 45-73 years) without history of diabetes from the Malmö Diet and Cancer cohort. During 14 years of follow-up, 2935 subjects (1519 men, 1416 women) were diagnosed with diabetes. In men, incidence of diabetes was 24.1 and 4.0 per 1000 person-years comparing the fourth vs. first quartile of WHtR. The multivariate adjusted hazard ratios (HR; fourth vs first quartile) were 6.00 [95% confidence interval (CI): 5.02-7.16) for WHtR, 5.95 (CI: 4.96-7.14) for WC, 5.19 (CI: 4.38-6.15) for BMI, 4.71 (CI: 3.96-5.60) for WHR and 3.21 (CI: 2.75-3.76] for BF%. For women, incidence of diabetes was 15.1 and 1.4 per 1000 person-years for fourth vs first quartile of WHtR (HR: 10.19, CI: 8.10-12.82). HR was 9.16 (CI: 7.40-11.33) for WC, 6.42 (CI: 5.27-7.81) for BMI, 6.75 (CI: 5.52-8.25) for WHR and 5.39 (CI: 4.42-6.57) for BF%. Model discrimination was marginally increased when WC, WHtR or WHR was used in combination with BMI. All measures of obesity were associated with substantially increased incidence of diabetes. Abdominal obesity was associated with higher incidence rates in men than in women, but in terms of relative risks the relationships were stronger in women. The combination of BMI and abdominal obesity measures had stronger association with diabetes than BMI alone. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
    The European Journal of Public Health 03/2015; DOI:10.1093/eurpub/ckv044 · 2.46 Impact Factor
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    ABSTRACT: Experimental studies have suggested possible protective effects of dimethylglycine (DMG) on glucose metabolism. DMG is degraded to glycine through a DMG-dehydrogenase (DMGDH)-catalyzed reaction and this is the only known pathway for the breakdown of DMG in mammals. In this study we aimed to identify the strongest genetic determinant of circulating DMG concentration and to investigate its associations with metabolic traits and incident diabetes. In the cohort with full metabolomics data (n=709), low plasma levels of DMG were significantly associated with higher blood glucose levels (p=3.9E-4). In the genome-wide association study (GWAS) of the discovery cohort (n=5,205) the strongest genetic signal of plasma DMG was conferred by rs2431332 at the DMGDH-locus where the major allele was associated with lower DMG levels (p=2.5E-15). The same genetic variant (major allele of rs2431332), was also significantly associated with higher plasma insulin (p=0.019), increased insulin resistance (HOMA-IR) (p=0.019), as well as increased risk of incident diabetes (p=0.001) in the pooled analysis of the discovery cohort together with the two replication cohorts ((n=20,698) and (N=7,995). These data are consistent with a possible causal role of DMG deficiency in diabetes development and encourages for future studies examining if inhibition of DMG-dehydrogenase, or alternatively supplementation of DMG, might prove useful for the treatment/prevention of diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 03/2015; DOI:10.2337/db14-1863 · 8.47 Impact Factor
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    ABSTRACT: Previous studies of prostate cancer (PCa) risk and anthropometrics (ie, body measurements) were based on single measurements or obtained over limited time spans. To study the association between anthropometrics measured at multiple time points in life and their relation to later diagnosis, metastasis, or death from PCa. This case-control study includes 27 167 Swedish men enrolled in two population-based projects from 1974 to 1996. PCa diagnosis up to December 31, 2006, disease information, gestation time, and anthropometrics at birth, military conscript testing, and adulthood were collected. A total of 1355 PCa cases were matched with 5271 controls. Univariate conditional logistic regression was used to determine whether clinical diagnosis, metastasis, or PCa death was associated with low birth weight (weight <2500g); with small size for gestational age; or with weight, length, or body mass index (BMI) at birth, adolescence (aged 16-22 yr), or early middle age (aged 44-50 yr). Apart from weight at adolescence, which was associated with an increased risk of PCa diagnosis (odds ratio [OR] per 5kg: 1.05; 95% confidence interval [CI], 1.01-1.09; p=0.026), preadulthood measurements were not associated with any PCa end point. Adulthood parameters were not associated with diagnosis. In contrast, weight and BMI at early middle age were significantly associated with metastasis (OR per 5kg: 1.13; 95% CI, 1.06-1.20; p<0.0001, and OR: 1.09; 95% CI, 1.05-1.14; p<0.0001) and death (OR per 5kg: 1.11 (95% CI, 1.03-1.19; p=0.005, and OR: 1.08; 95% CI, 1.03-1.13; p=0.003), respectively. It remains unclear whether these results apply to men of nonwhite origin, to populations with active PCa screening programs, or to countries without socialized health care. The analyses of these large data sets demonstrate that significant effects of body characteristics (with links to metabolic syndrome) measured at early middle age are associated with PCa disease severity, metastatic progression, and outcome. Conversely, measurements at birth and adolescence are not associated with PCa prevalence or outcome. Increased weight and body mass index in adults is associated with a higher risk of prostate cancer metastasis and death. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 03/2015; DOI:10.1016/j.eururo.2015.03.017 · 12.48 Impact Factor
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    ABSTRACT: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:

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  • 2012–2015
    • Skåne University Hospital
      Malmö, Skåne, Sweden
    • University of Oxford
      • Wellcome Trust Centre for Human Genetics
      Oxford, ENG, United Kingdom
    • University Medical Center Utrecht
      • Julius Center for Health Sciences and Primary Care
      Utrecht, Provincie Utrecht, Netherlands
  • 1987–2015
    • Lund University
      • • Department of Clinical Sciences, Malmö
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      • • Department of Diagnostic Radiology
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      • • Department of Health Sciences
      Lund, Skåne, Sweden
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      Örebro, Örebro, Sweden
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      Tukholma, Stockholm, Sweden
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      Londinium, England, United Kingdom
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      Lund, Skåne, Sweden
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      • Department of Physics
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      Uppsala, Uppsala, Sweden
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      Malmö, Skåne, Sweden
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      Lutetia Parisorum, Île-de-France, France
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  • 1995–2010
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      • Department of Public Health and Caring Sciences
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      Valenza, Valencia, Spain
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      Chandigarh, Chandīgarh, India
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      Ames, Iowa, United States
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      • Department of Physics
      Benares, Uttar Pradesh, India