| 1. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 2. |
- Björck, Niclas, et al.
(författare)
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Keramik : I: UV GAL Rapport 200:14. Snåret.Aspekter på sten-, brons och järnålder i Vendel, Väg E4, sträckan Uppsala-Mehedeby, Uppland, Vendels socken, Fallsboda 1:2, Karby 29:5, RAÄ 291
- 2007
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Rapport (populärvet., debatt m.m.)abstract
- Arkeologisk undersökning av boplats med lämningar från neolitikum, yngre bronsålder och vendeltid. På platsen fanns även sannolika gravar. Analyser görs av hus, keramik, pollen mm. Platsen har under vendeltid utnyttjats för tjärframställning
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| 3. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 4. |
- Ahmad, Shafqat, et al.
(författare)
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Telomere length in blood and skeletal muscle in relation to measures of glycaemia and insulinaemia.
- 2012
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Ingår i: Diabetic Medicine: A journal of the British Diabetic Association. - : Wiley. - 1464-5491 .- 0742-3071. ; 29:10, s. 377-381
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Skeletal muscle is a major metabolic organ and plays important roles in glucose metabolism, insulin sensitivity and insulin action. Muscle telomere length reflects the myocyte's exposure to harmful environmental factors. Leukocyte telomere length is considered a marker of muscle telomere length and is used in epidemiologic studies to assess associations with ageing-related diseases where muscle physiology is important. However, the extent to which leucocyte and muscle telomere length are correlated is unknown, as are their relative correlations with glucose and insulin concentrations. The purpose of this study was to determine the extent of these relationships. Methods: Leucocyte and muscle telomere length were measured by quantitative real-time polymerase chain reaction in participants from the Malmö Exercise Intervention (n = 27) and the Prevalence, Prediction and Prevention of Diabetes-Botnia studies (n = 31). Participants in both studies were free from Type 2 diabetes. We assessed the association between leucocyte telomere length, muscle telomere length and metabolic traits using Spearmen correlations and multivariate linear regression. Bland-Altman analysis was used to assess agreement between leucocyte and muscle telomere length. Results: In age-, study-, diabetes family history- and sex-adjusted models, leucocyte and muscle telomere length were positively correlated (r = 0.39, 95% CI 0.15-0.59). Leucocyte telomere length was inversely associated with 2-h glucose concentrations (r = -0.58, 95% CI -1.0 to -0.16), but there was no correlation between muscle telomere length and 2-h glucose concentrations (r = 0.05, 95% CI -0.35 to 0.46) or between leucocyte or muscle telomere length with other metabolic traits. Conclusions: In summary, the current study supports the use of leucocyte telomere length as a proxy for muscle telomere length in epidemiological studies of Type 2 diabetes aetiology.
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| 5. |
- Alhadad, Alaa, et al.
(författare)
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Erythromelalgia: Incidence and clinical experience in a single centre in Sweden.
- 2012
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Ingår i: Vasa: European Journal of Vascular Medicine. - : Hogrefe Publishing Group. - 0301-1526. ; 41:1, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Background: Erythromelalgia (EM) incidence has not been well studied and there are only two studies published on this subject as far as we know. The aims are to study the incidence of this rare condition in the south of Sweden, to report the clinical experience from a single centre including characterisation of comorbidity and to report on prognosis. Patients and methods: Retrospective study of a population-based analysis of data from the southernmost part of Sweden corresponding to the median age of the patients (Statistics Sweden). The diagnosis of EM is based on the medical record reflecting the triad of redness, burning pain and increased temperature of the feet or hands or both. We evaluated the presence or absence of EM triad by recording the history, physical examination, laboratory analysis, cold provocation test and laser Doppler imaging, and by searching for any confounding disease in cases of suspected EM. Results: During a 10.5 year period we clinically identified 27 patients with EM. Median age was 49 [IQR (34 - 68)] years, 19 (70 %) were women. The mean delay from the onset of the symptoms to the time of diagnosis was 4.5 (SD ± 3.9) years. Gender and age adjusted incidence of EM for our region was calculated to be 0.36 per 100 000 persons per year. Three patients developed intraabdominal cancer during the follow up, but there was no mortality directed related to EM. Conclusions: The overall population-based incidence of erythromelalgia was 0.36 per 100 000 which is identical with a previous report in a Scandinavian population.
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| 6. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 7. |
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| 8. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 9. |
- Cederlund, Ragnhild, et al.
(författare)
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Hand disorders, hand function, and activities of daily living in elderly men with type 2 diabetes.
- 2009
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 23, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: This study aimed to examine hand disorders, symptoms, overall hand function, activities of daily living (ADLs), and life satisfaction in elderly men with type 2 diabetes mellitus (DM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). METHODS: Subjects were interviewed and evaluated with a battery of clinical and laboratory tests, including hand assessment, and a questionnaire. RESULTS: HbA1c differed between groups (highest in DM, especially in long-term DM). Limited joint motion (LJM), for example, prayer sign and Dupuytren's contracture, was most common in individuals with DM, followed by individuals with IGT, as compared to those with NGT. Vibrotactile sense was impaired symmetrically in the index and little fingers in DM. However, there were no differences for sensibility, dexterity, grip strength, and cold intolerance between groups. Individuals with long-term (>15 years) DM were more affected regarding sensibility and ADL than individuals with short-term DM, who had more sleep disturbances. ADL difficulties were less among IGT subjects. Vibrotactile sense showed correlations with Semmes-Weinstein monofilament test and static two-point discrimination. CONCLUSIONS/INTERPRETATION: Dupuytren's contracture and impaired vibrotactile sense in finger pulps occurred in patients with DM but not in those with IGT, although LJM occurred in both IGT and DM patients. A longer duration of DM was associated with more severe neuropathy and ADL difficulties. Life satisfaction was high, and hand disorders did not have a significant impact on ADL.
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| 10. |
- Dahlin, Lars, et al.
(författare)
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Sequelae following sural nerve biopsy in type 1 diabetic subjects.
- 2008
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 118, s. 193-197
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Tidskriftsartikel (refereegranskat)abstract
- Objectives - To detect post-operative sequelae of sural nerve biopsy. Materials and methods-- A questionnaire mailed to type 1 diabetic patients (n = 24; male/female 23/1; reply n = 23) 2 years after biopsy. Results - Type 1 diabetic patients (age 56 [11]; median [interquartile range]) had a long duration of diabetes (DM; 20 [19] years) and all had neuropathy. Three out of 24 patients developed infection (two superficial and one deep) and one had a post-operative bleeding. Less frequent pain among the patients were reported from one centre. About one-third or more of the patients still complained of pain, mostly mild, in the biopsy area and paraesthesia in the foot 2 years after surgery. More than two-thirds of the patients were reluctant for further biopsy; a crucial information in drug trial planning. Conclusions - Sequelae of a sural nerve biopsy occur in type 1 DM. The risk for wound infections should be considered.
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