| 1. |
- Chisalita, Simona Ioana, 1972-, et al.
(author)
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Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells
- 2004
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In: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 286, s. E896-E901
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Journal article (peer-reviewed)abstract
- Micro- and macroangiopathy are major causes of morbidity and mortality in patients with diabetes. Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. Cultured human dermal microvascular endothelial cells (HMVEC) and human aortic endothelial cells (HAEC) were used. Gene expression was measured by quantitative real-time RT-PCR and receptor protein by ligand-binding assay. Phosphorylation of IGF-IR ß-subunit was analyzed by immunoprecipitation and Western blot. Glucose metabolism and DNA synthesis was assessed using [3H]glucose and [3H]thymidine incorporation, respectively. We detected gene expression of IGF-IR and IR in HAEC and HMVEC. IGF-IR gene expression was severalfold higher than that of IR. The specific binding of 125I-IGF-I was higher than that of 125I-insulin in HAEC and HMVEC. Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. Phosphorylation of the IGF-IR ß-subunit was shown in HAEC for IGF-I (10-8 M) and insulin (10-6 M) and in HMVEC for IGF-I and glargine (10-8 M, 10-6 M). IGF-I 10-7 M stimulated incorporation of [3H]thymidine into DNA, and 10-9–10-7 M also the incorporation of [3H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10-9–10-7 M. Human micro- and macrovascular endothelial cells express more IGF-IR than IR. IGF-I and high concentrations of glargine and insulin ctivates the IGF-IR. Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo.
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| 2. |
- Davidson, Lee Ti, et al.
(author)
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Association of physiological stress markers at the emergency department to readmission and death within 90 days: a prospective observational study
- 2023
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 128:1
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Journal article (peer-reviewed)abstract
- Background: Predicting the risk of readmission or death in patients at the emergency department (ED) is essential in identifying patients who would benefit the most from interventions. We aimed to explore the prognostic value of mid-regional proadrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, and high-sensitivity troponin T (hs-TnT) to identify patients with a higher risk of readmission and death among patients presenting with chest pain (CP) and/or shortness of breath (SOB) in the ED.Methods: This single-center prospective observational study included non-critically ill adult patients with a chief complaint of CP and/or SOB who visited the ED at Linköping University Hospital. Baseline data and blood samples were collected, and patients were followed up for 90 days after inclusion. The primary outcome was a composite of readmission and/or death from non-traumatic causes within 90 days of inclusion. Binary logistic regression was used and receiver operating characteristics (ROC) curves were constructed to determine the prognostic performance for predicting readmission and/or death within 90 days.Results: A total of 313 patients were included and 64 (20.4%) met the primary endpoint. MR-proADM > 0.75 pmol/L (odds ratio [OR]: 2.361 [95% confidence interval [CI]: 1.031 – 5.407], P = 0.042) and multimorbidity (OR: 2.647 [95% CI: 1.282 – 5.469], P = 0.009) were significantly associated with readmission and/or death within 90 days. MR-proADM increased predictive value in the ROC analysis to age, sex, and multimorbidity (P = 0.006).Conclusions: In non-critically ill patients with CP and/or SOB in the ED, MR-proADM and multimorbidity may be helpful for the prediction of the risk of readmission and/or death within 90 days.
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| 3. |
- Davidson, Lee Ti, et al.
(author)
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Copeptin and asymptomatic arterial disorder in patients with type 2 diabetes, a cross-sectional study
- 2024
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Conference paper (other academic/artistic)abstract
- Background: Individuals with diabetes are at higher risk for developing arterial disorders. The toe-brachial index (TBI) is associated with peripheral vascular disease, and aortic pulse-wave velocity (aPWV) is currently the gold standard for assessing arterial stiffness. High concentrations of plasma arginine vasopressin (AVP) preferentially stimulate V1a receptors, which affect the vascular bed and may contribute to cardiovascular (CV) complications. Copeptin, a more stable peptide of AVP, is co-secreted from the pituitary gland in equimolar amounts to AVP upon hemodynamic, osmotic, and other stress-related stimuli. Elevated levels of copeptin are potentially linked to vascular dysfunction.Objective: To analyze the association of copeptin to TBI and aPWV as a marker of arterial disorder in patients with type 2 diabetes mellitus (T2D).Methods: A cross-sectional analysis was conducted on 681 patients from the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes – a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) with data on copeptin, TBI, and aPWV. The relationship between the conventional cardiovascular risk factors and copeptin with TBI and aPWV were examined, respectively. Pearson correlation analysis and linear regression analyses were used.Results: Copeptin correlated to TBI (r=-0.086, P=0.027) and aPWV (r=0.143, P<0,001). Copeptin was also negatively associated with TBI (β=-0.093, P=0.027) and aPWV (β=0.121, P=0.004) independently of age, sex, diabetes duration, BMI, smoking, previous cardiovascular diseases, HbA1c, HDL cholesterol, and estimated glomerular filtration rate.Conclusion: Copeptin is independently associated with TBI and aPWV. Copeptin may play an important role in the development of arterial disorders. Measuring copeptin levels may be a simpler method and more efficient way to identify individuals at risk for arterial disorders compared to current methods such as TBI and aPWV.
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| 4. |
- Davidson, Lee Ti, et al.
(author)
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Plasma copeptin and markers of arterial disorder in patients with type 2 diabetes, a cross-sectional study
- 2024
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In: Cardiovascular Diabetology. - : Springer. - 1475-2840. ; 23:1
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Journal article (peer-reviewed)abstract
- Objectives There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD).Methods In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55–65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV.Results Copeptin was associated with TBI (β–0.0020, CI–0.0035– (–0.0005), p = 0.010) and aPWV (β 0.023, CI 0.002–0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking.Conclusions Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders.
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| 5. |
- Simona Chisalita, Ioana, 1972-, et al.
(author)
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Association of Insulin-like Growth Factor-1, Bone Mass and Inflammation to Low-energy Distal Radius Fractures and Fracture Healing in Elderly Women Attending Emergency Care
- 2017
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In: ORTHOPAEDIC SURGERY. - : Wiley-Blackwell. - 1757-7853. ; 9:4, s. 380-385
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Journal article (peer-reviewed)abstract
- ObjectiveElderly patients suffer fractures through low-energy mechanisms. The distal radius is the most frequent fracture localization. Insulin-like growth factor-1 (IGF1) plays an important role in the maintenance of bone mass and its levels decline with advancing age and in states of malnutrition. Our aim was to investigate the association of IGF1 levels, bone mass, nutritional status, and inflammation to low-energy distal radius fractures and also study if fracture healing is influenced by IGF1, nutritional status, and inflammation.MethodsPostmenopausal women, 55 years or older, with low-energy distal radius fractures occurring due to falling on slippery ground, indoors or outdoors, were recruited in the emergency department (ED) and followed 1 and 5 weeks after the initial trauma with biomarkers for nutritional status and inflammation. Fractures were diagnosed according to standard procedure by physical examination and X-ray. All patients were conservatively treated with plaster casts in the ED. Patients who needed interventions were excluded from our study. Fracture healing was evaluated from radiographs. Fracture healing assessment was made with a five-point scale where the radiological assessment included callus formation, fracture line, and stage of union. Blood samples were taken within 24 h after fracture and analyzed in the routine laboratory. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA).ResultsThirty-eight Caucasian women, aged 70.5 8.9 years (mean +/- SD) old, were recruited. Nutritional status, as evaluated by albumin (40.3 +/- 3.1 g/L), IGF1 (125.3 +/- 39.9 g/L), body mass index (26.9 +/- 3.6 kg/m(2)), arm diameter (28.9 +/- 8.9 cm), and arm skinfold (2.5 +/- 0.7 cm), was normal. A positive correlation was found between IGF1 at visit 1 and the lowest BMD for hip, spine, or radius (r = 0.39, P = 0.04). High sensitive C-reactive protein (hsCRP) and leukocytes were higher at the fracture event compared to 5 weeks later (P = 0.07 and P amp;lt; 0.001, respectively). Fracture healing parameters (i.e. callus formation, fracture line, and stage of union) were positively correlated with the initial leukocyte count and to difference in thrombocyte count between visit 1 and 3.ConclusionsIn elderly women with low-energy distal radius fractures, an association between IGF1 and lowest measures of BMD was found, indicating that low IGF1 could be an indirect risk factor for fractures. Fracture healing was associated with initial leukocytosis and a lower thrombocyte count, suggesting that inflammation and thrombocytes are important components in fracture healing.
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| 6. |
- Simona Chisalita, Ioana, 1972-, et al.
(author)
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Insulin-Like Growth Factor-1 at Diagnosis and during Subsequent Years in Adolescents with Type 1 Diabetes
- 2018
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In: Journal of Diabetes Research. - : Hindawi Publishing Corporation. - 2314-6745 .- 2314-6753.
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Journal article (peer-reviewed)abstract
- Background. Type 1 diabetes (T1D) in adolescents is associated with alterations in the insulin-like factor system probably caused both by a deranged metabolism and insulinopenia in the portal vein.Objective. To study how the circulating IGF-1 is affected at diagnosis and during subsequent years in adolescents with T1D.Methods. Ten girls and ten boys with type 1 diabetes (T1D), aged 13.0 +/- 1.4 (mean +/- SD) years at diagnosis, took part in the study. Blood samples were drawn at diagnosis and after 3, 9, 18, and 48 months. HbA1c, total IGF-1, and C-peptide were measured.Results. At diagnosis, the patients had high HbA1c, low IGF-1, and measurable C-peptide. After the start of insulin treatment, maximal improvement in glycemic control and IGF-1 occurred within 3 months and then both tended to deteriorate, that is, HbA1c to increase and IGF-1 to decrease. C-peptide decreased with time, and after 4 years, half of the patients were C-peptide negative. At diagnosis, C-peptide correlated positively to IGF-1 (r = 0 50; p amp;lt; 0 03). C-peptide correlated negatively with insulin dose (U/kg) after 18 and 48 months from diagnosis (r = -0 48; p amp;lt; 0 03 and r = -0 72; p amp;lt; 0 001, resp.).Conclusions. In conclusion, our results show that in newly diagnosed adolescents with type 1 diabetes and deranged metabolism, the IGF-1 level is low and rapidly improves with insulin treatment but later tends to decrease concomitantly with declining endogenous insulin secretion.
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| 7. |
- Simona Chisalita, Ioana, 1972-, et al.
(author)
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Toe brachial index predicts major acute cardiovascular events in patients with type 2 diabetes independently of arterial stiffness
- 2020
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In: Diabetes Research and Clinical Practice. - : ELSEVIER IRELAND LTD. - 0168-8227 .- 1872-8227. ; 161
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Journal article (peer-reviewed)abstract
- Objective: Our aim was to analyze the predictive value of toe brachial index (TBI) as a risk marker for future major adverse cardiovascular events (MACE) and all-cause mortality in patients with type 2 diabetes (T2D). Methods: TBI was measured in 741 patients with T2D in 2005-2008. Conventional risk factors for vascular disease as well as non-invasive measurements such as pulse-wave velocity (PWV) and intima-media thickness (IMT) of the carotid arteries were estimated. MACE was defined as cardiovascular death or hospitalization for non fatal myocardial infarction or non fatal stroke. Patients were followed for incidence of MACE using the national Swedish Cause of Death Registry and the Inpatient Register. Results: During the follow-up for a period of 9 years MACE occurred in 97 patients and 85 patients died. TBI tertile, 1 versus 3, was significantly related to MACE (HR 2.67, 95%CI 1.60-4.50; p < 0.001) and to all-cause mortality (HR 1.98, 95%CI 1.16-3.83; p = 0.01). TBI tertile 1 as compared to TBI tertile 3 predicted MACE, but not all-cause mortality, independently of age, sex, diabetes duration and treatment, antihypertensive treatment, previous cardiovascular diseases, office systolic blood pressure, HbA1c, LDL cholesterol, estimated glomerular filtration rate, body mass index, current smoking PWV, IMT and carotid plaque presence (HR 3.39, 95%CI 1.53-7.51; p = 0.003 and HR 1.81, 95%CI 0.87-3.76; p = 0.1, respectively). Conclusions: Low TBI predicts an increased risk for MACE independently of arterial stiffness in patients with type 2 diabetes. Trial registration: Clinical Trials.gov number NCT 01049737. Registered January 14, 2010. (C) 2020 Elsevier B.V. All rights reserved.
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| 8. |
- Söderlund, Gustav, et al.
(author)
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Inhibition of puromycin-induced apoptosis in breast cancer cells by IGF-I occurs simultaneously with increased protein synthesis
- 2004
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In: Neoplasma (Bratislava). - 0028-2685 .- 1338-4317. ; 51:1
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Journal article (peer-reviewed)abstract
- The objective of the following work was to study the apoptosis inducing effect of puromycin in MCF-7 breast cancer cells and compare this effect with cycloheximide and emetine, 2 other inhibitors of protein synthesis. We also wished to investigate if the apoptosis modulating effect of insulin-like growth factor-1 (IGF-I) was similar for the 3 inhibitors. An immunological assay, quantifying mono- and oligonucleosome fragments and morphological criteria after nuclear staining, were used to study apoptosis. Protein synthesis was measured by incorporation of 3H-leucine in the cells, and solution hybridization and Western blot were performed to estimate IGF-I receptor m-RNA and IGF-I receptor protein respectively. Puromycin at 0.5 μg/ml induced a high level of apoptosis in MCF-7 breast cancer cells, although there was still a non-negligible amount of synthesized protein. In the case of cycloheximide and emetine, apoptosis occured when protein synthesis was almost completely blocked. IGF-I at a concentration of 10 ng/ml significantly reduced the level of apoptosis induced by puromycin, emetine, or cycloheximide. We also noticed a parallel increase in 3H-leucine incorporation when apoptosis induced by puromycin was lowered as an effect of IGF-I, in contrast to cycloheximide and emetine where IGF-I reduced the apoptosis level without increasing the 3H-leucine incorporation. At a higher concentration of puromycin (5. 7 μg/ml), which blocked protein synthesis, IGF-I at 10 ng/ml did not reduce apoptosis. The level of IGF-I receptor m-RNA was not influenced by the use of a concentration of puromycin (0.5 μg/ml) inducing a high degree of apoptosis. These results suggest, that reduction of puromycin-induced apoptosis by IGF-I occurs simultaneously with increased protein synthesis, in contrast to emetine and cycloheximide. Furthermore it would appear that puromycin-induced apoptosis is not caused by reduced levels of IGF-I receptors.
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| 9. |
- Woisetschläger, Mischa, 1974-, et al.
(author)
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Selection of risk assessment methods for osteoporosis screening in postmenopausal women with low-energy fractures : A comparison of fracture risk assessment tool, digital X-ray radiogrammetry, and dual-energy X-ray absorptiometry
- 2022
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In: SAGE Open Medicine. - : SAGE PUBLICATIONS INC. - 2050-3121. ; 10
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Journal article (peer-reviewed)abstract
- Objectives:Fracture liaison services are designed to identify patients needing osteoporosis treatment after a fracture. Some fracture liaison service designs involve a prescreening step, for example, fracture risk assessment tool (FRAX®). Another possible prescreening tools are bone mass density assessment in the acute setting. The aim of this study was to assess the effectiveness of prescreening tools.Methods:In the present prospective cohort study, women aged >55 years with a radius fracture were included. Patients were recruited at the emergency department after experiencing their fracture. All patients performed fracture risk assessment by fracture risk assessment tool, and bone mass density assessment by digital X-ray radiogrammetry and dual-energy X-ray absorptiometry (prescreening steps) as well as full routine evaluation at the osteoporosis unit (endpoint). The main outcome measures were sensitivity, specificity, predictive values, and area under the curve.Results:Forty-one women were recruited (mean age: 70 ± 8 years). Of these, 54% fulfilled the treatment indication criteria of osteoporosis after a full examination. Fracture risk assessment tool without bone mass density (cutoff ⩾ 15%) for prescreening patients had a high sensitivity (90%) but a low area under the curve (0.50) and specificity (16%). The highest area under the curve (0.73) was found prescreening with bone mass density assessment (dual-energy X-ray absorptiometry or digital X-ray radiogrammetry) having a sensitivity of 59%–86% and specificity of 61%–90%.Conclusion:This study, though small, raises questions regarding the effectiveness of using a prescreening step in fracture liaison services for high-risk individuals. In this cohort, FRAX® without bone mass density had a low precision, with a risk of both underestimating and overestimating patients requiring treatment. Bone mass density assessment in the acute setting could improve the precision of prescreening. Further investigations on the effectiveness and health economics of prescreening steps in fracture liaison services are needed.
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