| 1. |
- Gadd, Gustaf, et al.
(författare)
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A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.
- 2024
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Ingår i: International journal of molecular sciences. - 1661-6596 .- 1422-0067. ; 25:9
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Tidskriftsartikel (refereegranskat)abstract
- Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.
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| 2. |
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| 3. |
- Åberg, Daniel, 1973, et al.
(författare)
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Increased Cerebrospinal Fluid Level of Insulin-like Growth Factor-II in Male Patients with Alzheimer's Disease
- 2015
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 48:3, s. 637-646
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer's disease (AD). Objective and methods: This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 32), stable MCI (SMCI, n = 13), or other dementias (n = 15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF). Results: Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (n = 40), CSF IGF-II level was higher in AD compared to SMCI and controls (p < 0.01 and p < 0.05, respectively). Furthermore, CSF IGFBP-2 levelwas increased inADmen versus SMCI men (p < 0.01) and tended to be increased versus control men (p = 0.09). There were no between-group differences in women (n = 40). In the total study population (n = 80) as well as in men (n = 40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein. Conclusion: In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.
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| 4. |
- Åberg, Daniel, 1973, et al.
(författare)
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Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke—A Prospective Observational Study
- 2023
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Ingår i: International Journal of Molecular Sciences. - 1422-0067. ; 24:11
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor- I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4–8.5 and OR 5.7, 95% CI: 2.5–12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1–3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.
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| 5. |
- Åberg, N David, 1970, et al.
(författare)
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Association Between Levels of Serum Insulin-like Growth Factor I and Functional Recovery, Mortality, and Recurrent Stroke at a 7-year Follow-up.
- 2020
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Ingår i: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. - : Georg Thieme Verlag KG. - 1439-3646. ; 128:5, s. 303-310
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Tidskriftsartikel (refereegranskat)abstract
- The association of serum insulin-like growth factor I (s-IGF-I) with favorable outcome after ischemic stroke (IS) beyond 2 years is unknown. We investigated whether the levels of s-IGF-I 3 months post-stroke were associated with functional recovery up to 7 years after IS, considering also mortality and recurrent strokes.Patients (N=324; 65% males; mean age, 55 years) with s-IGF-I levels assessed 3 months after the index IS were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The modified Rankin Scale (mRS) was used to evaluate outcomes at 3 months, 2 and 7 years after IS, and recovery was defined as an improvement, no change, or deterioration in the shifts of mRS score. Baseline stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS).The mRS score distributions were better in the above-median s-IGF-I group (>146.7ng/ml). The s-IGF-I level was not associated with recurrent stroke (N=79) or death (N=44), although it correlated with recovery (r=0.12, P=0.035). In the regression analysis, s-IGF-I associated with recovery between 3 months and 7 years (but not between 2 and 7 years). The associations did not withstand adjustment for age and sex. For comparison, the corresponding associations between 3 months and 2 years withstood all adjustments.The association for s-IGF-I with long-term post-stroke recovery persists after 7 years, which is also reflected in the mRS score distributions at all time-points. The effects are however modest, and not driven by mortality or recurrent stroke.
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| 6. |
- Åberg, Daniel, 1973, et al.
(författare)
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Homeostasis model assessment of insulin resistance and outcome of ischemic stroke in non-diabetic patients - a prospective observational study
- 2019
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundInsulin resistance (IR) in relation to diabetes is a risk factor for ischemic stroke (IS), whereas less is known about non-diabetic IR and outcome after IS.MethodsIn non-diabetic IS (n=441) and controls (n=560) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), IR was investigated in relation to IS severity and functional outcome. IR was evaluated acutely and after 3months using the Homeostasis model assessment of IR (HOMA-IR). Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS). Functional outcome was evaluated using the modified Rankin Scale (mRS) after 3months, 2 and 7years. Associations were evaluated by logistic regression.ResultsHigher acute and 3-month HOMA-IR was observed in IS compared to the controls (both p<0.001) and in severe compared to mild IS (both p<0.05). High acute HOMA-IR was associated with poor outcome (mRS 3-6) after 3months and 7years [crude Odds ratios (ORs), 95% confidence intervals (CIs) 1.50, 1.07-2.11 and 1.59, 1.11-2.30, respectively], but not after 2years. These associations lost significance after adjustment for all covariates including initial stroke severity. In the largest IS subtype (cryptogenic stroke), acute HOMA-IR was associated with poor outcome after 2years also after adjustment for age and stroke severity (OR 2.86, 95% CI 1.01-8.12).ConclusionsIn non-diabetic IS patients, HOMA-IR was elevated and related to stroke severity, but after adjustment for IS severity, the associations between HOMR-IR and poor outcome lost significance. This could suggest that elevated IR mostly is a part of the acute IS morbidity. However, in the subgroup of cryptogenic stroke, the associations with poor outcome withstood correction for stroke severity.
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| 7. |
- Åberg, Daniel, 1973, et al.
(författare)
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Insulin-Like Growth Factor-II and Ischemic Stroke-A Prospective Observational Study
- 2021
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Ingår i: Life-Basel. - : MDPI AG. - 2075-1729. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised ischemic stroke cases (n = 492) and controls (n = 514) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months and 2 years using the modified Rankin Scale (mRS), and additionally, survival was followed at a minimum of 7 years or until death. S-IGF-II levels were higher in IS cases both in the acute phase and at 3-month follow-up compared to controls (p < 0.05 and p < 0.01, respectively). The lowest quintile of acute s-IGF-II was, compared to the four higher quintiles, associated with an increased risk of post-stroke mortality (median follow-up 10.6 years, crude hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.56-3.49, and fully adjusted HR 1.64, 95% CI 1.02-2.61). In contrast, crude associations with poor functional outcome (mRS 3-6) lost significance after full adjustment for covariates. In conclusion, s-IGF-II was higher in IS cases than in controls, and low acute s-IGF-II was an independent risk marker of increased mortality.
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| 8. |
- Åberg, Daniel, 1973, et al.
(författare)
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Serum IGF-I levels correlate to improvement of functional outcome after ischemic stroke.
- 2011
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:7
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Tidskriftsartikel (refereegranskat)abstract
- GH has positive cognitive effects when given to GH-IGF-I-deficient patients. GH and IGF-I exert both neuroprotective and regenerative effects on experimental stroke. We investigated whether the endogenous serum IGF-I (s-IGF-I) levels correlated with recovery of functional independence in patients who had suffered an ischemic stroke.
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| 9. |
- Åberg, N David, 1970, et al.
(författare)
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Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study
- 2018
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like growth factor I (IGF-I) has neuroprotective effects in experimental ischemic stroke (IS). However, in patients who have suffered IS, various associations between the levels of serum IGF-I (s-IGF-I) and clinical outcome have been reported, probably reflecting differences in sampling time-points and follow-up periods. Since changes in the levels of post-stroke s-IGF-I have not been extensively explored, we investigated whether decreases in the levels of s-IGF-I between the acute time-point (median, 4 days) and 3 months (Delta IGF-I, further transformed into Delta IGF-I-quintiles, Delta IGF-I-q) are associated with IS severity and outcome. Methods: In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) conducted in Gothenburg, Sweden, patients with IS who had s-IGF-I measurements available were included (N = 354; 65% males; mean age, 55 years). Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and converted into NIHSS-quintiles (NIHSS-q). Outcomes were assessed using the modified Rankin Scale (mRS) at 3 months and 2 years. Results: In general, the levels of s-IGF-I decreased (positive Delta IGF-I), except for those patients with the most severe NIHSS-q. After correction for sex and age, the 3rd Delta IGF-I-q showed the strongest association to mRS 0-2 [Odds Ratio (OR) 5.11, 95% confidence interval (CI) 2.18-11.9], and after 2 years, the 5th Delta IGF-I-q (OR 3.63, 95% CI 1.40-9.38) showed the strongest association to mRS 0-2. The associations remained significant after multivariate correction for diabetes, smoking, hypertension, and hyperlipidemia after 3 months, but were not significant (p = 0.057) after 2 years. The 3-month associations withstood additional correction for baseline stroke severity (p = 0.035), whereas the 2-year associations were further attenuated (p = 031). Conclusions: Changes in the levels of s-IGF-I are associated primarily with temporally near 3-month outcomes, while associations with long-term 2-year outcomes are weakened and attenuated by other factors. The significance of the change in post-stroke s-IGF-I is compatible with a positive role for IGF-I in IS recovery. However, the exact mechanisms are unknown and probably reflects combinations of multiple peripheral and central actions.
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| 10. |
- Åberg, N David, 1970, et al.
(författare)
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Genetic variation at the IGF1 locus shows association with post-stroke outcome and to circulating IGF1.
- 2013
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 169:6, s. 759-65
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Tidskriftsartikel (refereegranskat)abstract
- In humans, serum IGF1 (s-IGF1) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF1. We investigated whether genetic variation at the IGF1 locus is associated with i) s-IGF1, ii) IS occurrence, iii) IS severity, and iv) post-stroke outcome.
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| 11. |
- Åberg, N David, 1970, et al.
(författare)
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Relationship between Levels of Pre-Stroke Physical Activity and Post-Stroke Serum Insulin-Like Growth Factor I
- 2020
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) and insulin-like growth factor I (IGF-I) have beneficial effects for patients who have suffered an ischemic stroke (stroke). However, the relationship between the levels of PA and IGF-I after stroke has not been explored in detail. We investigated the pre-stroke PA level in relation to the post-stroke serum IGF-I (s-IGF-I) level, at baseline and at 3 months after the index stroke, and calculated the change that occurred between these two time-points (Delta IGF-I). Patients (N = 380; 63.4% males; mean age, 54.7 years) with data on 1-year leisure-time pre-stroke PA and post-stroke s-IGF-I levels were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Pre-stroke, leisure-time PA was self-reported as PA1-4, with PA1 representing sedentary and PA2-4 indicating progressively higher PA levels. Associations between s-IGF-I and PA were evaluated by multiple linear regressions with PA1 as the reference and adjustments being made for sex, age, history of previous stroke or myocardial infarctions, cardiovascular risk factors, and stroke severity. PA correlated with baseline s-IGF-I and Delta IGF-I, but not with the 3-month s-IGF-I. In the linear regressions, there were corresponding associations that remained as a tendency (baseline s-IGF-I, p = 0.06) or as a significant effect (Delta IGF-I, p = 0.03) after all the adjustments. Specifically, for each unit of PA, Delta IGF-I increased by 9.7 (95% CI 1,1-18.4) ng/mL after full adjustment. This supports the notion that pre-stroke PA is independently related to Delta IGF-I.
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| 12. |
- Seymour, M. L., et al.
(författare)
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Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics
- 2001
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Ingår i: Am J Respir Crit Care Med. - 1073-449X. ; 164:11, s. 2051-6
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Tidskriftsartikel (refereegranskat)abstract
- Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen. Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p < or = 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged. Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.
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| 13. |
- Vikström, Linnea, et al.
(författare)
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Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern : an observational study
- 2023
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal COVID-19 among nursing homes residents.METHODS: We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort of nursing home residents in Sweden. We analyzed immunological and registry data from 16 September 2021 to 31 August 2022 with follow-up of deaths to 30 September 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves.FINDINGS: A total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG in blood and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the associated 30-day mortality was 9.1%. We found no indication that levels of vaccine-induced antibodies protected against infection with Omicron VOCs. In contrast, the risk of death was inversely correlated to levels of S-directed IgG below the 20th percentile. The death risk plateaued at population average above the lower 35th percentile of S-binding IgG.INTERPRETATION: In the absence of neutralizing antibodies that protect from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal COVID-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern.FUNDING: Swedish Research Council, SciLifeLab via Knut and Alice Wallenberg Foundation, VINNOVA. Swedish Healthcare Regions, and Erling Persson Foundation.
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