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Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Endokrinologi och diabetes) > Kungliga Tekniska Högskolan

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1.
  • Ritsinger, V., et al. (författare)
  • Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction : A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort
  • 2018
  • Ingår i: Diabetes & Vascular Disease Research. - : SAGE Publications Ltd. - 1479-1641 .- 1752-8984. ; 15:5, s. 387-395
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the long-term prognostic value of insulin-like growth factor-binding protein 1 in patients with acute myocardial infarction. Methods: Patients (n = 180) with admission glucose < 11 mmol/L without previously known diabetes admitted for an acute myocardial infarction in 1998–2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/acute myocardial infarction/stroke/severe heart failure) until the end of 2011 (median 11.6 years). Fasting levels of insulin-like growth factor-binding protein 1 at day 2 were related to outcome in Cox proportional hazard regression analyses. Results: Median age was 64 years, 69% were male and median insulin-like growth factor-binding protein 1 was 20 µg/L. Total mortality was 34% (n = 61) and 44% (n = 80) experienced a cardiovascular event during a median follow-up time of 11.6 years. After age adjustment, insulin-like growth factor-binding protein 1 was associated with all-cause (1.40; 1.02–1.93, p = 0.039) and cancer mortality (2.09; 1.15–3.79, p = 0.015) but not with cardiovascular death (p = 0.29) or cardiovascular events (p = 0.57). After adjustments also for previous myocardial infarction, previous heart failure and body mass index, insulin-like growth factor-binding protein 1 was still associated with all-cause mortality (1.38; 1.01–1.89, p = 0.046). Conclusion: In patients with acute myocardial infarction without previously known diabetes, high insulin-like growth factor-binding protein 1 was associated with long-term all-cause and cancer mortality but not with cardiovascular events.
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2.
  • Darmanis, Spyros, et al. (författare)
  • Identification of Candidate Serum Proteins for Classifying Well-Differentiated Small Intestinal Neuroendocrine Tumors
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e81712-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPatients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NET) are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are required.Materials and methodsSuspension bead arrays targeting 124 unique proteins with antibodies from the Human Protein Atlas were used to profile biotinylated serum samples. Discoveries from a cohort of 77 individuals were followed up in a cohort of 132 individuals both including healthy controls as well as patients with untreated primary WD-SI-NETs, lymph node metastases and liver metastases.Results A set of 20 antibodies suggested promising proteins for further verification based on technically verified statistical significance. Proceeding, we assessed the classification performance in an independent cohort of patient serum, achieving, classification accuracy of up to 85% with different subsets of antibodies in respective pairwise group comparisons. The protein profiles of nine targets, namely IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP were verified as significant contributors to tumor classification.ConclusionsWe propose new potential protein biomarker candidates for classifying WD-SI-NET at different stage of disease. Further evaluation of these proteins in larger sample sets and with alternative approaches is needed in order to further improve our understanding of their functional relation to WD-SI-NET and their eventual use in diagnostics.
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3.
  • Sahebekhtiari, Navid, et al. (författare)
  • Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity—A Study on Rare BMI-Discordant Monozygotic Twin Pairs
  • 2019
  • Ingår i: Proteomics - Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The purpose of this study is to elucidate the effect of excess body weight and liver fat on the plasma proteome without interference from genetic variation. Experimental Design: The effect of excess body weight is assessed in young, healthy monozygotic twins from pairs discordant for body mass index (intrapair difference (Δ) in BMI > 3 kg m −2 , n = 26) with untargeted LC-MS proteomics quantification. The effect of liver fat is interrogated via subgroup analysis of the BMI-discordant twin cohort: liver fat discordant pairs (Δliver fat > 2%, n = 12) and liver fat concordant pairs (Δliver fat < 2%, n = 14), measured by magnetic resonance spectroscopy. Results: Seventy-five proteins are differentially expressed, with significant enrichment for complement and inflammatory response pathways in the heavier co-twins. The complement dysregulation is found in obesity in both the liver fat subgroups. The complement and inflammatory proteins are significantly associated with adiposity measures, insulin resistance and impaired lipids. Conclusions and Clinical Relevance: The early pathophysiological mechanisms in obesity are incompletely understood. It is shown that aberrant complement regulation in plasma is present in very early stages of clinically healthy obese persons, independently of liver fat and in the absence of genetic variation that typically confounds human studies.
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4.
  • Seoane, Fernando, et al. (författare)
  • Slightly superior performance of bioimpedance spectroscopy over single frequency regression equations for assessment of total body water.
  • 2015
  • Ingår i: Engineering in Medicine and Biology Society (EMBC), 2015 37th Annual International Conference of the IEEE. 25-29 Aug. 2015, Milan, Italy.. - : IEEE. - 1094-687X .- 1558-4615. - 9781424492718 - 9781424492701 ; 2015, s. 3707-10
  • Konferensbidrag (refereegranskat)abstract
    • Electrical bioimpedance has been used for several decades to assess body fluid distribution and body composition by using single frequency and bioimpedance spectroscopic (BIS) techniques. It remains uncertain whether BIS methods have better performance compare to single frequency regression equations. In this work the performance of two BIS methods and four different 50 kHz single frequency prediction equations was studied in a data set of wrist-to-ankle tetrapolar BIS measurements (5-1000 kHz) together with reference values of total body water obtained by tritium dilution in 92 patients. Data were compared using regression techniques and Bland-Altman plots. The results of this study showed that all methods produced similarly high correlation and concordance coefficients, indicating good accuracy as a method. Limits of agreement analysis indicated that the population level performance of Sun's prediction equations was very similar to the performance of both BIS methods. However, BIS methods in practice have slightly better predictive performance than the single-frequency equations as judged by higher correlation and the limits of agreement from the Bland-Altman analysis. In any case, the authors believe that an accurate evaluation of performance of the methods cannot be done as long as the evaluation is done using Bland-Altman analysis, the commonly accepted technique for this kind of performance comparisons.
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5.
  • Atabaki Pasdar, Naeimeh, et al. (författare)
  • Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts
  • 2020
  • Ingår i: PLoS Medicine. - San Francisco : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 17:6, s. 1003149-1003149
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. METHODS AND FINDINGS: We utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (
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6.
  • Baboota, Ritesh, et al. (författare)
  • BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH
  • 2022
  • Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:8, s. 1007-21
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of hepatic cell senescence in human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is not well understood. To examine this, we performed liver biopsies and extensive characterization of 58 individuals with or without NAFLD/NASH. Here, we show that hepatic cell senescence is strongly related to NAFLD/NASH severity, and machine learning analysis identified senescence markers, the BMP4 inhibitor Gremlin 1 in liver and visceral fat, and the amount of visceral adipose tissue as strong predictors. Studies in liver cell spheroids made from human stellate and hepatocyte cells show BMP4 to be anti-senescent, anti-steatotic, anti-inflammatory and anti-fibrotic, whereas Gremlin 1, which is particularly highly expressed in visceral fat in humans, is pro-senescent and antagonistic to BMP4. Both senescence and anti-senescence factors target the YAP/TAZ pathway, making this a likely regulator of senescence and its effects. We conclude that senescence is an important driver of human NAFLD/NASH and that BMP4 and Gremlin 1 are novel therapeutic targets. Baboota et al. investigate senescence as a driver of human NAFLD/NASH and show the roles of BMP4 and its antagonist Gremlin 1 as anti-senescent and pro-senescent molecules, respectively.
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7.
  • Fortin, Elena, et al. (författare)
  • Plasma mannose as a novel marker of myocardial infarction across different glycaemic states : A case control study
  • 2022
  • Ingår i: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840 .- 1475-2840. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Plasma mannose, an emerging novel biomarker of insulin resistance, is associated with both diabetes mellitus and coronary atherosclerosis, but the relationship between mannose concentrations and myocardial infarction (MI) across different glycaemic states remains to be elucidated. The aim of this study was to investigate the independent association between mannose and a first MI in a group of subjects characterized according to their glycaemic state. Methods Fasting plasma mannose concentrations were analysed in 777 patients 6-10 weeks after a first myocardial infarction and in 770 matched controls by means of high-performance liquid chromatography coupled to tandem mass spectrometry. Participants without known diabetes mellitus were categorized by an oral glucose tolerance test (OGTT) as having normal glucose tolerance (NGT, n = 1045), impaired glucose tolerance (IGT, n = 246) or newly detected type 2 diabetes (T2DM, n = 112). The association between mannose and MI was investigated across these glycaemic states by logistic regression. Results Mannose levels increased across the glycaemic states (p < 0.0001) and were significantly associated with a first MI in the whole study population (odds ratio, OR: 2.2; 95% CI 1.4 to - 3.5). Considering the different subgroups separately, the association persisted only in subjects with NGT (adjusted OR: 2.0; 95% CI 1.2-3.6), but not in subgroups with glucose perturbations (adjusted OR: 1.8, 95% CI 0.8-3.7). Conclusions Mannose concentrations increased across worsening levels of glucose perturbations but were independently associated with a first MI only in NGT individuals. Thus, mannose might be a novel, independent risk marker for MI, possibly targeted for the early management of previously unidentified patients at high cardiovascular risk.
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8.
  • Govind, Satish C., et al. (författare)
  • Differing myocardial response to a single session of hemodialysis in end-stage renal disease with and without type 2 diabetes mellitus and coronary artery disease
  • 2006
  • Ingår i: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 4:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Though hemodialysis (HD) acutely improves cardiac function, the impact of background diseases like coronary artery disease (CAD) and Type 2 diabetes (DM) in the setting of end-stage renal disease (ESRD) is not known. Tissue velocity echocardiography (TVE) offers a fast choice to follow changes in myocardial function after HD in ESRD with concomitant DM and/or CAD. Methods: 46 subjects (17 with ESRD, Group 1; 15 with DM, Group 2; 14 with DM+CAD, Group 3) underwent standard and TVE prior to and shortly after HD. Besides standard Doppler variables, regional myocardial systolic and diastolic velocities, as well as systolic strain rate were post processed. Results: Compared with pre-HD, post-HD body weight (kg) significantly decreased in all the three groups (51 ± 9 vs. 48 ± 8, 62 ± 10 vs.59 ± 10, and 61 ± 9 vs. 58 ± 9 respectively; all p < 0.01). Left ventricular end diastolic dimensions (mm) also decreased post- HD (46 ± 5 vs. 42 ± 7, 53 ± 7 vs. 50 ± 7, 51 ± 7 vs. 47 ± 8 respectively; all p < 0.01). Regional longitudinal peak systolic velocity in septum (cm/s) significantly increased post-HD in Group 1(5.7 ± 1.6 vs. 7.2 ± 2.3; p < 0.001) while remained unchanged in the other two groups. Similar trends were noted in other left ventricular walls. When the myocardial velocities (cm/s) were computed globally, the improvement was seen only in Group 1 (6.3 ± 1.5 vs. 7.9 ± 2.0; p < 0.001). Global early regional diastolic velocity (cm/s) improved in Group 1, remained unchanged in Group 2, while significantly decreased in Group 3(-5.9 ± 1.3 vs. -4.1 ± 1.8; p < 0.01). Global systolic strain rate (1/sec) increased in the first 2 Groups but remained unchanged (-0.87 ± 0.4 vs. -0.94 ± 0.3; p = ns) in Group 3. Conclusion: A single HD session improves LV function only in ESRD without coexistent DM and/or CAD. The present data suggest that not only dialysis-dependent changes in loading conditions but also co-existent background diseases determine the myocardial response to HD.
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9.
  • Govind, Satish C., et al. (författare)
  • Impaired Myocardial Functional Reserve in Hypertension and Diabetes Mellitus Without Coronary Artery Disease: Searching for the Possible Link With Congestive Heart Failure in the Myocardial Doppler in Diabetes (MYDID) Study II
  • 2006
  • Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 19:8, s. 851-857
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although the impact of type 2 diabetes mellitus (DM) and hypertension (HTN) on myocardial function has recently been studied using tissue Doppler echocardiography (TDE), the independent role of both conditions, and the influence of other risk factors on myocardial function has not been completely defined, particularly in absence of coronary artery disease (CAD). The aim of this study was to assess the myocardial functional reserve in patients with DM or HTN with apparently normal left ventricular (LV) systolic function. Methods: Standard and dobutamine stress echocardiography using TDE was performed in 128 subjects: 59 had DM, 20 had HTN, 27 had both DM and HTN (HTN + DM), and 22 subjects were controls (C). Subjects with known CAD and depressed LV function were excluded. In addition, standard two-dimensional and Doppler measurements, LV regional peak systolic (PSV), early (E') and late (A') diastolic velocities, strain (S%) and strain rate (SR), were assessed at rest and peak stress. Results: The LV mass did not differ, although relative wall thickness was significantly higher in subjects with HTN + DM and HTN. The PSV did not differ at rest but was lowest in subjects with HTN + DM at peak stress. The E' wave velocity was significantly lower in subjects with HTN + DM both at rest and during peak stress, as were S% and SR. Conclusions: The addition of DM to HTN has a negative effect on LV systolic and diastolic functions. A depressed myocardial functional reserve might be postulated as one of the pathophysiologic mechanisms for the excessive occurrence of congestive heart failure in patients with DM or HTN.
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10.
  • Govind, Satish C., et al. (författare)
  • Isolated Type 2 Diabetes mellitus Causes Myocardial Dysfunction That Becomes Worse in the Presence of Cardiovascular Diseases : Results of the Myocardial Doppler in Diabetes (MYDID): Study 1
  • 2005
  • Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 103:4, s. 189-195
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Patients with type 2 diabetes mellitus (DM) often suffer disproportionately and have a worse outcome when burdened with cardiovascular complications compared with those without DM. A specific heart muscle disease reportedly caused by DM per se may explain this. We sought to investigate whether an echo Doppler diagnosis of such a myocardial disease is clinically relevant in DM with or without coexistent coronary artery disease (CAD) and/or hypertension ( HTN). Subjects and Methods: Two hundred subjects (127 males, 73 females, 56 +/- 10 years) including controls (n=23), patients with HTN (n=20), CAD (n=35), uncomplicated DM (n=59), DM+HTN (n=27), DM+ CAD (n=16) and DM+CAD+HTN (n=20) underwent tissue Doppler-enhanced dobutamine stress echocardiography. Myocardial function was assessed by measuring left ventricular myocardial peak systolic velocity (PSV) and early diastolic velocity at rest and during peak stress, besides measurements of standard Doppler variables. Results: Average left ventricular PSV at rest was significantly lower in CAD (4.7 +/- 1.5) compared with controls (5.7 center dot +/- 1.2) and in DM+CAD+HTN (4.6 +/- 1.4) compared with DM (5.6 +/- 1.3; all p < 0.05). During peak stress, lower PSV persisted in CAD (9.5 +/- 3.1) and DM+CAD+HTN (8.1 +/- 2.7), while appearing de novo in DM (11.3 +/- 2.6) and HTN (11.0 +/- 2.3) unlike in the controls (12.5 +/- 2.5; all p < 0.001). When pooled together, DM subjects with CAD and/or HTN or both had significantly lower PSV (9.1 +/- 2.7) than those without (10.0 +/- 2.8; p < 0.001). Early diastolic velocity response was equally lower in both groups compared with the controls. Conclusion: The results suggest that dobutamine stress unmasks myocardial functional disturbances caused by uncomplicated DM. The discrete disturbances become quantitatively more pronounced in the presence of coexistent cardiovascular diseases.
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