| 1. |
- Zhang, C., et al.
(författare)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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| 2. |
- Isaksson, Johan, et al.
(författare)
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Early psychosocial adversity and cortisol levels in children with attention-deficit/hyperactivity disorder
- 2013
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Ingår i: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 22:7, s. 425-432
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggest a different regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis) with lower diurnal cortisol levels, especially in the morning, in children with attention-deficit/hyperactivity disorder (ADHD) compared with controls. Since exposure to foetal and childhood psychosocial adversity has been associated with both ADHD and HPA-axis functioning, such exposures may explain these low cortisol levels in ADHD via early programming of the HPA-axis. Thus, our main aim was to retrospectively study foetal and early childhood exposures to psychosocial adversity in children with ADHD and to relate these exposures to cortisol levels. Saliva samples were collected during a regular weekday in children, 6-17 years old, with clinically confirmed ADHD (n = 197) and non-affected comparisons (n = 221) for radioimmunoassay analysis of cortisol. Parental rating scales were used for categorising subtypes of ADHD and degree of exposure to adversity. Children with ADHD had more reports of at least one rated foetal adversity (p = 0.041) and childhood adversity (p < 0.001) than comparisons. The association between low morning cortisol levels and ADHD-symptoms remained when analyses were adjusted for adversities, age, sex, sampling time and symptoms of oppositional defiant disorder. No relation was found between exposures to foetal/childhood adversity and cortisol levels except for a positive relation between childhood adversity and cortisol morning increase in children with ADHD. The hypothesis that early adversity may influence the HPA-axis, leading to lower cortisol levels in children with ADHD, was not supported by our findings.
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| 3. |
- Lennartsson, Anna-Karin, et al.
(författare)
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Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 38:9, s. 1650-1657
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Method: Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Results: Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. Conclusions: This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may Lead to higher risk for adverse effects on psychological and physiological health, particularly if stress exposure continues. (C) 2013 Elsevier Ltd. All rights reserved.
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| 4. |
- Marseglia, Anna, et al.
(författare)
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Cognitive Trajectories of Older Adults With Prediabetes and Diabetes : A Population-Based Cohort Study
- 2018
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 73:3, s. 400-406
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been linked to dementia risk; however, the cognitive trajectories in older adults with diabetes remain unclear. We aimed to investigate the effect of prediabetes and diabetes on cognitive trajectories among cognitively intact older adults in a long-term follow-up study.Methods Within the Swedish Adoption/Twin Study of Aging, 793 cognitively intact older adults aged ≥50 were identified at baseline and followed for up to 23 years. Based on standardized scores from 11 cognitive tests, administered at baseline and up to seven follow-ups, four cognitive domains (verbal abilities, spatial/fluid, memory, perceptual speed) were identified by principal-component analysis. Prediabetes was defined according to blood glucose levels in diabetes-free participants. Diabetes was ascertained based on self-report, hypoglycemic medication use and blood glucose levels. Data were analyzed with linear mixed-effect models adjusting for potential confounders.Results At baseline, 68 participants (8.6%) had prediabetes and 45 (5.7%) had diabetes. Compared to diabetes-free individuals, people with diabetes had a steeper decline over time in perceptual speed and verbal abilities. The annual declines in these domains were greater than the annual decline in memory. Prediabetes was associated with lower performance in memory in middle-age, but also associated with a less steep memory decline over the follow-up.Conclusions Diabetes is associated with a faster decline in perceptual speed and verbal abilities, while prediabetes is associated with lower memory performance in middle-age. However, the detrimental effects of hyperglycemia seem to not affect memory over time.
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| 5. |
- Brandao, Luiz Eduardo M., et al.
(författare)
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Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial
- 2022
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:2
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Tidskriftsartikel (refereegranskat)abstract
- The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (similar to 27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.
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| 6. |
- El-Garawani, Islam M., et al.
(författare)
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Angiotensinogen Gene Missense Polymorphisms (rs699 and rs4762) : The Association of End-Stage Renal Failure Risk with Type 2 Diabetes and Hypertension in Egyptians
- 2021
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Ingår i: Genes. - : MDPI. - 2073-4425 .- 2073-4425. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) and hypertension are common chronic diseases mainly associated with the development and progression of end-stage renal disease (ESRD) leading to morbidity and mortality. Gene polymorphisms linked to the renin–angiotensin (AGT)–aldosterone system (RAAS) were broadly inspected in patients with diabetic nephropathy (DN) and hypertension. This study aimed to investigate the association of AGT gene polymorphisms (rs699 and rs4762) with ESRD in T2DM hypertensive Egyptian patients. Genotyping of rs699 and rs4762 was conducted using the tetra-primers amplification refractory mutation system (ARMS-PCR). The allelic distribution analysis was performed on 103 healthy control subjects, 97 non-ESRD patients, and 104 patients with ESRD. The allelic frequencies of AGT gene polymorphisms (rs4762 and rs699) in all study participants were assessed. For the non-ESRD group, the frequencies of the alleles of AGT-rs4762 (χ2 = 31.88, p < 0.001, OR = 5.17, CI 95%: 2.81–9.51) and AGT-rs699 (χ2 = 4.85, p = 0.027, OR = 1.56, CI 95%: 1.05–2.33) were significantly associated with the non-ESRD group. However, for the ESRD group, the T allele was significantly higher than that in the controls (χ2 = 24.97, p < 0.001, odds ratio (OR) = 4.35, CI 95%: 2.36–8.02). Moreover, AGT (rs699) genotypes showed no significant difference between the ESRD group and controls. In conclusion, AGT gene polymorphisms rs699 and rs4762 were associated with non-ESRD versus controls, without any significant risk observed in all patient groups. However, the AGT (rs4762) variant showed a significant risk in the ESRD group in comparison to controls in Egyptians.
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| 7. |
- Lowe, Adrian J, et al.
(författare)
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Impact of Maternal Obesity on Inhaled Corticosteroid Use in Childhood : A Registry Based Analysis of First Born Children and a Sibling Pair Analysis
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt has been proposed that maternal obesity during pregnancy may increase the risk that the child develops allergic disease and asthma, although the mechanisms underpinning this relationship are currently unclear. We sought to assess if this association may be due to confounding by genetic or environmental risk factors that are common to maternal obesity and childhood asthma, using a sibling pair analysis.MethodsThe study population comprised a Swedish national cohort of term children born between 1992 and 2008 to native Swedish parents. Maternal body mass index (BMI) was measured at 8-10 weeks gestation. Unconditional logistic regression models were used to determine if maternal obesity was associated with increased risk of inhaled corticosteroid (ICS) in 431,718 first-born children, while adjusting for potential confounders. An age-matched discordant sib-pair analysis was performed, taking into account shared genetic and environmental risk factors.ResultsMaternal over-weight and obesity were associated with increased risk that the child would require ICS (for BMI >= 35 kg/m(2), aOR = 1.30, 95% CI = 1.10-1.52 compared with normal weight mothers) in children aged 6-12 years. Similar effects were seen in younger children, but in children aged 13-16 years, maternal obesity (BMI >= 30) was related to increased risk of ICS use in girls (aOR = 1.28, 95% CI = 1.07-1.53) but not boys (OR = 1.05, 95% CI = 0.87-1.26). The sib-pair analysis, which included 2,034 sib-pairs older than six years who were discordant for both ICS use and maternal BMI category, failed to find any evidence that increasing maternal weight was related to increased risk of ICS use.ConclusionMaternal obesity is associated with increased risk of childhood ICS use up to approximately 12 years of age, but only in girls after this age. These effects could not be confirmed in a sib pair analysis, suggesting either limited statistical power, or the effects of maternal BMI may be due to shared genetic or environmental risk factors.
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| 8. |
- Song, Fei, et al.
(författare)
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The prevalence and determinants of hypothyroidism in hospitalized patients with type 2 diabetes mellitus
- 2017
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 55:1, s. 188-194
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the prevalence of hypothyroidism among hospitalized patients with type 2 diabetes mellitus and its related factors, and to assess the prevalence of macrovascular and microvascular diseases among type 2 diabetes mellitus inpatients with hypothyroidism and euthyroidism. A total of 1662 type 2 diabetes mellitus inpatients hospitalized at the Metabolic Diseases Hospital, Tianjin Medical University from 1 January 2008 to 1 March 2013 were included in this study. Information on demographic and anthropometric factors and additional variables related to hypothyroidism were collected from medical records. Prevalence rates were calculated and standardized using direct method based on the age-specific and sex-specific structure of all participants. Data were analyzed using binary logistic regression with adjustment for potential confounders. The prevalence of hypothyroidism among type 2 diabetes mellitus inpatients was 6.8 %, and 77.0% of the patients with hypothyroidism had subclinical hypothyroidism. The prevalence of hypothyroidism increased with age, and was higher in women (10.8 %) than in men (3.4 %). Older age (odds ratio, 1.74; 95% confidence interval, 1. 05 to 2.89), female gender (odds ratio, 2.02; 95% confidence interval, 1.05 to 3.87), and positive thyroid peroxidase antibody (odds ratio, 4.99; 95% confidence interval, 2.83 to 8.79) were associated with higher odds of hypothyroidism among type 2 diabetes mellitus inpatients. The type 2 diabetes mellitus inpatients with hypothyroidism had higher prevalence of cerebrovascular diseases than those with euthyroidism after adjustment for age and gender. The prevalence of hypothyroidism among type 2 diabetes mellitus inpatients was 6.8 %, and most patients had subclinical hypothyroidism. Older age, female gender, and positive thyroid peroxidase antibody could be indicators for detecting hypothyroidism in type 2 diabetes mellitus inpatients.
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| 9. |
- Anderbro, Therese, et al.
(författare)
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Fear of hypoglycemia : relationship to hypoglycemic risk and psychological factors
- 2014
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The major aims of this study were to examine (1) the association between fear of hypoglycemia (FOH) in adults with type 1 diabetes with demographic, psychological (anxiety and depression), and disease-specific clinical factors (hypoglycemia history and unawareness, A1c), including severe hypoglycemia (SH), and (2) differences in patient subgroups categorized by level of FOH and risk of SH.RESEARCH DESIGN AND METHODS: Questionnaires were mailed to 764 patients with type 1 diabetes including the Swedish translation of the Hypoglycemia Fear Survey (HFS) and other psychological measures including the Perceived Stress Scale, Hospital Anxiety and Depression Scale, Anxiety Sensitivity Index, Social Phobia Scale, and Fear of Complications Scale. A questionnaire to assess hypoglycemia history was also included and A1c measures were obtained from medical records. Statistical analyses included univariate approaches, multiple stepwise linear regressions, Chi-square t tests, and ANOVAs.RESULTS: Regressions showed that several clinical factors (SH history, frequency of nocturnal hypoglycemia, self-monitoring) were significantly associated with FOH but R (2) increased from 16.25 to 39.2 % when anxiety measures were added to the model. When patients were categorized by level of FOH (low, high) and SH risk (low, high), subgroups showed significant differences in non-diabetes-related anxiety, hypoglycemia history, self-monitoring, and glycemic control.CONCLUSION: There is a strong link between FOH and non-diabetes-related anxiety, as well as hypoglycemia history. Comparison of patient subgroups categorized according to level of FOH and SH risk demonstrated the complexity of FOH and identified important differences in psychological and clinical variables, which have implications for clinical interventions.
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| 10. |
- Backeström, Anna, et al.
(författare)
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Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women : a cross sectional study
- 2015
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Ingår i: Diabetology & Metabolic Syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. Methods: We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 +/- 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. Results: A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. Conclusions: This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.
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