| 51. |
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| 52. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Established and emerging factors affecting the progression of nonalcoholic fatty liver disease
- 2020
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 111
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease affecting approximately 25% of the global population. Although a majority of NAFLD patients will never experience liver-related symptoms it is estimated that 5-10% will develop cirrhosis-related complications with risk of death or need for liver transplantation. NAFLD is closely associated with cardiovascular disease and components of the metabolic syndrome. However, NAFLD is not uncommon in lean individuals and may in these subjects represent a different entity with separate pathophysiological mechanisms involved implying a higher risk for development of end-stage liver disease. There is considerable fluctuation in the histopathological course of NAFLD that may partly be attributed to lifestyle factors and dietary composition. Nutrients such as fructose, monounsaturated fatty acids, and trans-fatty acids may aggravate NAFLD. Presence of type 2 diabetes mellitus seems to be the most important clinical predictor of liver-related morbidity and mortality in NAFLD. Apart from severity of the metabolic syndrome, genetic polymorphisms and environmental factors, such as moderate alcohol consumption, may explain the variation in histopathological and clinical outcome among NAFLD patients. (c) 2020 Elsevier Inc. All rights reserved.
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| 53. |
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| 54. |
- Kurko, Johanna, et al.
(författare)
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Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI)
- 2016
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Ingår i: Metabolism. - : Saunders Elsevier. - 0026-0495 .- 1532-8600. ; 65:9, s. 1361-1375
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lysinuric protein intolerance (LPI [MIM 222700]) is an aminoaciduria with defective transport of cationic amino acids in epithelial cells in the small intestine and proximal kidney tubules due to mutations in the SLC7A7 gene. LPI is characterized by protein malnutrition, failure to thrive and hyperammonemia. Many patients also suffer from combined hyperlipidemia and chronic kidney disease (CKD) with an unknown etiology.METHODS: Here, we studied the plasma metabolomes of the Finnish LPI patients (n=26) and healthy control individuals (n=19) using a targeted platform for analysis of amino acids as well as two analytical platforms with comprehensive coverage of molecular lipids and polar metabolites.RESULTS: Our results demonstrated that LPI patients have a dichotomy of amino acid profiles, with both decreased essential and increased non-essential amino acids. Altered levels of metabolites participating in pathways such as sugar, energy, amino acid and lipid metabolism were observed. Furthermore, of these metabolites, myo-inositol, threonic acid, 2,5-furandicarboxylic acid, galactaric acid, 4-hydroxyphenylacetic acid, indole-3-acetic acid and beta-aminoisobutyric acid associated significantly (P<0.001) with the CKD status. Lipid analysis showed reduced levels of phosphatidylcholines and elevated levels of triacylglycerols, of which long-chain triacylglycerols associated (P<0.01) with CKD.CONCLUSIONS: This study revealed an amino acid imbalance affecting the basic cellular metabolism, disturbances in plasma lipid composition suggesting hepatic steatosis and fibrosis and novel metabolites correlating with CKD in LPI. In addition, the CKD-associated metabolite profile along with increased nitrite plasma levels suggests that LPI may be characterized by increased oxidative stress and apoptosis, altered microbial metabolism in the intestine and uremic toxicity.
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| 55. |
- Larsen, Filip J, et al.
(författare)
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Cardiorespiratory fitness predicts insulin action and secretion in healthy individuals.
- 2012
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 61:1, s. 12-6
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Tidskriftsartikel (refereegranskat)abstract
- Long-term cardiorespiratory fitness (CRF) and the development of type 2 diabetes mellitus are inversely correlated. Here, we examined the relationships between peak oxygen uptake (VO(2)peak), on the one hand, and glucose infusion rate at rest (GIR(rest)) and during exercise (GIR(exercise)), as well as insulin secretion (both the early and late phases of response [area under the curve {AUC}(insulin)]), on the other. Eight male and 4 female healthy, lean, nonsmoking volunteers were recruited. The VO(2)peak was measured during graded exercise on a cycle ergometer until exhaustion was reached. The GIR(rest) and GIR(exercise) were determined using a euglycemic-hyperinsulinemic clamp, and insulin secretion at rest was evaluated with an intravenous glucose tolerance test. The VO(2)peak correlated positively to GIR(rest) (r = 0.81, P = .001) and GIR(exercise) (r = 0.87, P < .001) and negatively to AUC(insulin) (r = -0.64, P = .03). The respiratory exchange ratio (RER) during insulin infusion was positively correlated to GIR(rest) (r = 0.83, P < .001) and GIR(exercise) (r = 0.86, P < .01) and negatively correlated to both the early insulin response (r = -0.86, P < .0001) and AUC(insulin) (r = -0.87, P = .001). The VO(2)peak accounted for 45% of the variability in RER (R(2) = 0.45, P = .035). In this healthy population, CRF and RER were highly correlated to insulin sensitivity and secretion, as well as to the ability to alter the substrate being oxidized during exercise. These findings highlight the importance of good CRF to maintaining normal insulin action.
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| 56. |
- Larsson, Charlotte A, et al.
(författare)
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Leisure time and occupational physical activity in relation to obesity and insulin resistance: a population-based study from the Skaraborg Project in Sweden.L
- 2012
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495. ; 61:4, s. 590-598
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to study obesity and insulin resistance in relation to leisure time physical activity (LTPA) and occupational physical activity (OPA) in a Swedish population, with particular focus on sex differences. Using a cross-sectional design, waist circumference, body mass index (BMI), glucose/insulin metabolism, blood pressure, heart rate, self-reported education, smoking, alcohol consumption, LTPA, and OPA were assessed in 1745 men and women (30-74 years) randomly chosen from 2 municipalities in southwestern Sweden. In both men and women, LTPA was inversely associated with BMI, waist circumference, and the homeostasis model assessment of insulin resistance (HOMA-IR), respectively. These associations remained statistically significant after adjustments for age, OPA, education, alcohol consumption, smoking, and study area, and also for BMI in the analyses concerning waist circumference and HOMA-IR. A statistically significant interaction term (P = .030), adjusted for multiple confounders, revealed a stronger association between LTPA and HOMA-IR in women compared with men. Occupational physical activity was positively associated with BMI (P < .001), waist circumference (P < .001), and HOMA-IR (P = .001), however, only in women. These associations remained when adjusting for multiple confounders. The sex differences were confirmed by statistically significant interaction terms between sex and OPA in association with BMI, waist circumference, and HOMA-IR, respectively. The observed sex differences regarding the strength of the association between LTPA and insulin resistance, and the positive association between OPA and obesity and insulin resistance found solely in women, warrant further investigation. Although exploration of the metabolic effects of OPA appears to be needed, thorough measurement of potential confounders is also vital to understand contextual effects.
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| 57. |
- Larsson, Susanna C., et al.
(författare)
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Body fatness associations with cancer : evidence from recent epidemiological studies and future directions
- 2022
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 137
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Forskningsöversikt (refereegranskat)abstract
- This narrative review highlights current evidence linking greater body fatness to risk of various cancers, with focus on evidence from recent large cohort studies and pooled analyses of cohort studies as well as Mendelian randomization studies (which utilized genetic variants associated with body mass index to debrief the causal effect of higher body fatness on cancer risk). This review also provides insights into the biological mechanisms underpinning the associations. Data from both observational and Mendelian randomization studies support the associations of higher body mass index with increased risk of many cancers with the strongest evidence for digestive system cancers, including esophageal, stomach, colorectal, liver, gallbladder, and pancreatic cancer, as well as kidney, endometrial, and ovarian (weak association) cancer. Evidence from observational studies sug-gests that greater body fatness has contrasting effects on breast cancer risk depending on menopausal status and on prostate cancer risk depending on disease stage. Experimental and Mendelian randomization studies indicate that adiponectin, insulin, and sex hormone pathways play an important role in mediating the link between body fatness and cancer risk. The possible role of specific factors and pathways, such as other adipocytokines and hormones and the gut microbiome in mediating the associations between greater body fatness and cancer risk is yet uncertain and needs investigation in future studies. With rising prevalence of overweight and obesity worldwide, the proportion of cancer caused by excess body fatness is expected to increase. There is thus an urgent need to identify efficient ways at the individual and societal level to improve diet and physical activity patterns to reduce the burden of obesity and accompanying comorbidities, including cancer.
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| 58. |
- Larsson, Susanna C., et al.
(författare)
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Circulating lipoprotein(a) levels and health outcomes : Phenome-wide Mendelian randomization and disease-trajectory analyses
- 2022
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerotic and valvular diseases, but its possible role in other diseases has not yet been established. We conducted phenome-wide Mendelian randomization and disease-trajectory analyses to assess any associations of circulating Lp(a) levels with a broad range of diseases.METHODS: A weighted polygenic risk score was constructed using independent genetic variants in the LPA gene and with an established effect on Lp(a) levels. The PheWAS analysis included 1081 phenotype outcomes ascertained among 385,917 White participants of the UK Biobank. Novel findings were investigated in MR analysis using data from the FinnGen consortium. Disease-trajectory and comorbidity analyses were further conducted to explore the sequential patterns of multiple morbidities related to high circulating Lp(a) levels.RESULTS: PheWAS revealed statistically significant associations of higher circulating Lp(a) levels with increased risk of a large number of circulatory system diseases (including various cardiac diseases, peripheral vascular disease, hypertension, and valvular and cerebrovascular diseases) as well as some endocrine/metabolic diseases (including hyperlipidemia, hypercholesterolemia, disorders of lipoid metabolism, and type 2 diabetes), genitourinary system diseases (renal failure), and hematologic diseases (including different types of anemia). Two-sample MR analysis supported the association between Lp(a) and risk of anemia, showed a suggestive association with type 2 diabetes, but found no association with renal failure. Disease-trajectory and comorbidity analyses identified 3 major sequential patterns of multiple morbidities, mainly in the cardiovascular, metabolic, and mental disorders, related to high circulating Lp(a) levels.CONCLUSIONS: Genetically predicted higher circulating Lp(a) levels were associated with increased risk of many circulatory system diseases and anemia. Additionally, this study identified three major sequential patterns of multiple morbidities related to high Lp(a).
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