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Lars Hellgren

Bio: Lars Hellgren is an academic researcher from Technical University of Denmark. The author has contributed to research in topics: Insulin resistance & Ceramide. The author has an hindex of 33, co-authored 144 publications receiving 5316 citations. Previous affiliations of Lars Hellgren include University of Copenhagen & Ferring Pharmaceuticals.


Papers
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Journal ArticleDOI
21 Jul 2016-Nature
TL;DR: It is shown how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals and suggested that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
Abstract: Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.

1,309 citations

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TL;DR: The results lend support for the notion that autism sometimes has a hereditary component and that perinatal stress is involved in some cases.
Abstract: The Nordic countries were screened for the occurrence of cases of autism with a same-sexed twin under age 25 years. Twenty-one pairs (11 monozygotic and 10 dizygotic) of twins and one set of identical triplets were found and extensively examined. The concordance for autism by pair was 91% in the monoygotic and 0% in the dizygotic pairs. The corresponding concordances for cognitive disorder were 91% and 30%, respectively. In most of the pairs discordant for autism, the autistic twin had more perinatal stress. The results lend support for the notion that autism sometimes has a hereditary component and that perinatal stress is involved in some cases.

792 citations

Journal ArticleDOI
TL;DR: It is concluded that short-term feeding of diets resembling human diets (Mediterranean diet high in monounsaturated fat, diethigh in saturated fat, or dietHigh in polyunsaturated fat) can affect tissue levels of endocannabinoids and N-acylethanolamines.

305 citations

Journal ArticleDOI
01 Jul 2010-Allergy
TL;DR: Stratatum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema are studied to determine the role of these lipids in protecting the skin from scrotal injury.
Abstract: Background Prior to the discovery of filaggrin (FLG) mutations, evidence for an impaired skin barrier in atopic dermatitis (AD) has been documented, and changes in ceramide profile, altered skin pH and increased trans-epidermal water loss (TEWL) in patients with AD have been reported. Until now, no studies have analysed stratum corneum (SC) lipids combined with skin barrier parameters in subjects of known FLG genotype. Methods A cohort of 49 German individuals genotyped for the most common FLG mutations (R501X, 2282del4) had SC samples taken for lipid analysis by high-performance thin layer chromatography. In addition, TEWL, erythema, skin hydration and pH were measured. In 27 of the 49 individuals, a 24-h irritation patch test with sodium lauryl sulphate was performed. For the analysis, both the AD group and the control group were stratified by FLG mutation status (FLGmut/FLGwt). Results In the FLGmut AD group, significantly lower levels of ceramide 4 and significantly higher levels of ceramide 7 were observed when compared to both healthy control groups. However, ceramide 7 levels also significantly differed between FLGwt AD and FLGwt controls, as did ceramide 1 levels. No significant differences were observed for ceramide 2, 3, 5 and 6. FLGmut individuals had significantly higher skin pH values than individuals not carrying FLG mutations. Patients with AD with FLG mutations had significantly higher erythema compared to patients with AD without FLG mutations. Conclusion Our results confirm previous observations of altered ceramide levels in AD, which however appear to show no clear relationship with FLG mutations.

295 citations

Journal ArticleDOI
TL;DR: Children with childhood onset deficits in attention, motor control and perception (DAMP) were followed-up at age 16 years and compared with children without DAMP, finding discrepancies between teenagers with and without a prior history of DAMP.
Abstract: Fifty-six cases with childhood onset deficits in attention, motor control and perception (DAMP) were followed-up at age 16 years and compared with 45 children without DAMP. Both groups had originally been recruited from the general population at the age of 6 years. Psychiatric disorders (affective disorders in particular) were more common in the DAMP group. Personality disorders were common in both groups, but the DAMP group much more often had a combination of several different personality disorders. The reasons for the discrepancies between teenagers with and without a prior history of DAMP are discussed.

167 citations


Cited by
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Journal ArticleDOI
TL;DR: In this article, a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation is described and validated, which addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities.
Abstract: This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

3,060 citations

Journal ArticleDOI
TL;DR: The remarkable range of discoveriesGWASs has facilitated in population and complex-trait genetics, the biology of diseases, and translation toward new therapeutics are reviewed.
Abstract: Application of the experimental design of genome-wide association studies (GWASs) is now 10 years old (young), and here we review the remarkable range of discoveries it has facilitated in population and complex-trait genetics, the biology of diseases, and translation toward new therapeutics. We predict the likely discoveries in the next 10 years, when GWASs will be based on millions of samples with array data imputed to a large fully sequenced reference panel and on hundreds of thousands of samples with whole-genome sequencing data.

2,669 citations

Journal ArticleDOI
TL;DR: Given the limitations of the data on which they are based, this report provides the best available prevalence estimates for arthritis and other rheumatic conditions overall, and for selected musculoskeletal disorders, in the US population.
Abstract: Objective To provide a single source for the best available estimates of the national prevalence of arthritis in general and of selected musculoskeletal disorders (osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, the spondylarthropathies, systemic lupus erythematosus, scleroderma, polymyalgia rheumatica/giant cell arteritis, gout, fibromyalgia, and low back pain). Methods The National Arthritis Data Workgroup reviewed data from available surveys, such as the National Health and Nutrition Examination Survey series. For overall national estimates, we used surveys based on representative samples. Because data based on national population samples are unavailable for most specific musculoskeletal conditions, we derived data from various smaller survey samples from defined populations. Prevalence estimates from these surveys were linked to 1990 US Bureau of the Census population data to calculate national estimates. We also estimated the expected frequency of arthritis in the year 2020. Results Current national estimates are provided, with important caveats regarding their interpretation, for self-reported arthritis and selected conditions. An estimated 15% (40 million) of Americans had some form or arthritis in 1995. By the year 2020, an estimated 18.2% (59.4 million) will be affected. Conclusion Given the limitations of the data on which they are based, this report provides the best available prevalence estimates for arthritis and other rheumatic conditions overall, and for selected musculoskeletal disorders, in the US population.

2,667 citations

Journal ArticleDOI
TL;DR: The findings indicate that autism is under a high degree of genetic control and suggest the involvement of multiple genetic loci.
Abstract: Two previous epidemiological studies of autistic twins suggested that autism was predominantly genetically determined, although the findings with regard to a broader phenotype of cognitive, and possibly social, abnormalities were contradictory. Obstetric and perinatal hazards were also invoked as environmentally determined aetiological factors. The first British twin sample has been re-examined and a second total population sample of autistic twins recruited. In the combined sample 60% of monozygotic (MZ) pairs were concordant for autism versus no dizygotic (DZ) pairs; 92% of MZ pairs were concordant for a broader spectrum of related cognitive or social abnormalities versus 10% of DZ pairs. The findings indicate that autism is under a high degree of genetic control and suggest the involvement of multiple genetic loci. Obstetric hazards usually appear to be consequences of genetically influenced abnormal development, rather than independent aetiological factors. Few new cases had possible medical aetiologies, refuting claims that recognized disorders are common aetiological influences.

2,378 citations

Journal ArticleDOI
TL;DR: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.
Abstract: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.

2,083 citations