| 1. |
- Baldimtsi, Evangelia, 1981-, et al.
(författare)
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Systemic biomarkers of microvascular alterations in type 1 diabetes associated neuropathy and nephropathy : A prospective long-term follow-up study
- 2023
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Ingår i: Journal of diabetes and its complications. - : Elsevier. - 1056-8727 .- 1873-460X. ; 37:12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: This study aimed to investigate circulating biomarkers associated with the risk of developing diabetic peripheral neuropathy (DPN) and nephropathy in type 1 diabetes (T1D).MATERIALS AND METHODS: Patients with childhood-onset T1D (n = 49, age 38.3 ± 3.8 yrs.) followed prospectively were evaluated after 30 years of diabetes duration. DPN was defined as an abnormality in nerve conduction tests. Matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1, neutrophil gelatinase-associated lipocalin-2 (NGAL), soluble P-selectin (sP-selectin), estimated GFR (eGFR), micro/macroalbuminuria and routine biochemistry were assessed. For comparison, control subjects were included (n = 30, age 37.9 ± 5.5 yrs.).RESULTS: In all, twenty-five patients (51 %) were diagnosed with DPN, and nine patients (18 %) had nephropathy (five microalbuminuria and four macroalbuminuria). Patients with DPN had higher levels of TIMP-1 (p = 0.036) and sP-selectin (p = 0.005) than controls. Patients with DPN also displayed higher levels of TIMP-1 compared to patients without DPN (p = 0.035). Patients with macroalbuminuria had kidney disease stage 3 with lower eGFR, higher levels of TIMP-1 (p = 0.038), and NGAL (p = 0.002). In all patients, we found only weak negative correlations between eGFR and TIMP-1 (rho = -0.304, p = 0.040) and NGAL (rho = -0.277, p = 0.062, ns), respectively. MMP-9 was higher in patients with microalbuminuria (p = 0.021) compared with normoalbuminuric patients.CONCLUSIONS: Our findings indicate that TIMP-1 and MMP-9, as well as sP-selectin and NGAL, are involved in microvascular complications in T1D. Monitoring and targeting these biomarkers may be a potential strategy for treating diabetic nephropathy and neuropathy.
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| 2. |
- Bilinski, Wojciech J., et al.
(författare)
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Effect of fasting hyperglycemia and insulin resistance on bone turnover markers in children aged 9–11 years
- 2021
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Ingår i: Journal of diabetes and its complications. - : Elsevier. - 1056-8727 .- 1873-460X. ; 35:10
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Impaired regulation of glucose metabolism in childhood adversely affects bone health. We assessed the effect of fasting hyperglycemia and insulin resistance on bone turnover markers in prepubertal children with normal glycemia (<100 mg/dL) and fasting hyperglycemia (100-125 mg/dL).Methods: Glucose, hemoglobin A1c, IGF-I (insulin-like growth factor I), iP1NP (N-terminal propeptide of type I procollagen), CTX-1 (C-terminal telopeptide of type I collagen) and insulin were measured. Bone turnover index (BTI) and HOMA-IR (homeostasis model assessment) were calculated.Results: Bone resorption marker (CTX) levels were decreased by 26.5% in boys with hyperglycemia, though only 7% in girls. Hyperglycemia had no effect on the bone formation marker iP1NP. IGF-1, the best predictor of bone marker variance accounted for 25% of iP1NP and 5% of CTX variance. Girls presented significantly higher BTI indicating the predominance of bone formation over resorption. Insulin resistance significantly decreased CTX. In girls, HOMA-IR and IGF-1 predicted 15% of CTX variance.Conslusions: Fasting hyperglycemia and insulin resistance in children impact bone turnover suppressing bone resorption. Hyperglycemia decreased resorption, particularly in boys, while suppression of resorption by insulin resistance was more pronounced in girls. We suggest that the progression of disturbances accompanying prediabetes, may interfere with bone modelling and be deleterious to bone quality in later life.
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| 3. |
- Lilja, Erika, et al.
(författare)
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The impact of diabetes mellitus on major amputation among patients with chronic limb threatening ischemia undergoing elective endovascular therapy- a nationwide propensity score adjusted analysis.
- 2021
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 35:2
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the risk of major amputation after elective endovascular therapy in patients with chronic limb threatening ischemia (CLTI) comparing patients with and without diabetes mellitus (DM).In this nationwide cohort study, all patients registered in the Swedish Vascular Register after elective endovascular therapy for CLTI caused by infra-inguinal arterial disease from 2010 to 2014 were included. Among 4578 individuals, 2251 had DM and were registered in the National Diabetes Register between 2009 and 2014. A propensity score adjusted Cox regression analysis was conducted to compare outcomes between groups. Median follow-up was 4.0 and 3.6years for patients with DM and without DM, respectively.The incidence rates of major amputation and acute myocardial infarction (AMI) were 43% (95% CI 1.23-1.67) and 37% (95% CI 1.13-1.67) higher, respectively, among patients with DM compared to patients without DM. There was no difference in mortality (HR 1.04, 95% CI 0.95-1.14).Patients with DM had a higher risk of major amputation and AMI compared to those without DM after elective endovascular therapy for CLTI. Prevention of DM with CLTI is of utmost importance to reduce the risk of adverse limb and cardiovascular outcomes.
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| 4. |
- Ritsinger, Viveca, et al.
(författare)
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Design and rationale of the myocardial infarction and new treatment with metformin study (MIMET) - Study protocol for a registry-based randomised clinical trial
- 2023
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Ingår i: Journal of diabetes and its complications. - : Elsevier. - 1056-8727 .- 1873-460X. ; 37:10
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate if addition of metformin to standard care (life-style advice) reduces the occurrence of cardiovascular events and death after myocardial infarction (MI) in patients with newly detected prediabetes.Methods: The Myocardial Infarction and new treatment with Metformin study (MIMET) is a large multicentre registry-based randomised clinical trial (R-RCT) within the SWEDEHEART registry platform expected to include 5160 patients with MI and newly detected prediabetes (identified with fasting blood glucose, HbA1c or 2-h glucose on oral glucose tolerance test) at similar to 20 study sites in Sweden. Patients 18-80 years, without known diabetes and naive to glucose lowering therapy, will be randomised 1:1 to open-label metformin therapy plus standard care or standard care alone.Outcomes: Patients will be followed for 2 years for the primary outcome new cardiovascular event (first of death, non-fatal MI, hospitalisation for heart failure or non-fatal stroke). Secondary endpoints include individual components of the primary endpoint, diabetes diagnosis, initiation of any glucose lowering therapy, cancer, and treatment safety. Events will be collected from national healthcare registries.Conclusions: The MIMET study will investigate if metformin is superior to standard care after myocardial infarction in preventing cardiovascular events in patients with prediabetes (Clinicaltrials.gov identifier: NCT05182970; EudraCT No: 2019-001487-30).
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| 5. |
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| 6. |
- Stefánsson, Bergur V., et al.
(författare)
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Correction of anemia by dapagliflozin in patients with type 2 diabetes
- 2020
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Ingår i: Journal of diabetes and its complications. - : Elsevier. - 1056-8727 .- 1873-460X. ; 34:12
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Anemia is common in type 2 diabetes (T2D), particularly in patients with kidney impairment, and often goes unrecognized. Dapagliflozin treatment increases hemoglobin and serum erythropoietin levels. We investigated the effect of dapagliflozin 10-mg/day on hemoglobin in T2D patients with and without anemia. Methods: Data from 5325 patients from 14 placebo-controlled, dapagliflozin-treatment studies of at least 24-weeks duration were pooled. Dapagliflozin's effects (vs. placebo) on hemoglobin, serum albumin, estimated glomerular filtration rate (eGFR), systolic blood pressure, body weight, and safety in patients with and without anemia were evaluated. Results: At baseline, 13% of all T2D patients and 28% of those with chronic kidney disease (eGFR <60 mL/min/1.73 m2) had anemia. Hemoglobin increased continuously to at least week 8 and was sustained throughout 24-weeks follow-up in dapagliflozin-treated patients. Serum albumin increased in dapagliflozin-treated patients at week 4 and remained stable thereafter. Dapagliflozin was well tolerated and corrected anemia in 52% of patients with anemia at baseline (placebo: 26%). Incidences of new-onset anemia were lower in dapagliflozin-treated (2.3%) versus placebo-treated (6.5%) patients. Conclusions: Treatment with dapagliflozin can correct and prevent anemia in T2D patients. A gradual increase in hemoglobin beyond week 4 may indicate an erythropoiesis-stimulating effect of sodium-glucose cotransporter 2 inhibition.
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| 7. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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A registry-based randomised trial comparing an SGLT2 inhibitor and metformin as standard treatment of early stage type 2 diabetes (SMARTEST): Rationale, design and protocol
- 2021
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Ingår i: Journal of Diabetes and Its Complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 35:10
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Tidskriftsartikel (refereegranskat)abstract
- Aim: SGLT2 inhibitors have been shown to reduce cardiovascular and renal complications in type 2 diabetes (T2D) patients at high cardiovascular risk. Metformin is currently widely used as initial monotherapy in T2D but lacks convincing data to show that it reduces risk of complications. We aim to compare the SGLT2 inhibitor dapagliflozin and metformin as first-line T2D medication with regard to development of complications in a registry-based randomised controlled trial. Methods: The SGLT2 inhibitor or metformin as standard treatment of early stage type 2 diabetes (SMARTEST) trial will enrol 4300 subjects at 30-40 study sites in Sweden who will be randomised 1:1 to either metformin or dapagliflozin. Participants must have T2D duration <4 years, no prior cardiovascular disease, and be either drug-naive or on monotherapy for T2D. Results: The primary endpoint is a composite of all-cause death, major adverse cardiovascular events and occurrence or progression of microvascular complications (retinopathy, nephropathy, diabetic foot lesions). Secondary endpoints include individual components of the primary endpoint, start of insulin therapy, risk factor biomarkers, patient-reported outcome measures, and cost-effectiveness analysis. Outcomes will primarily be assessed using nationwide healthcare registries. Conclusions: The SMARTEST trial will investigate whether dapagliflozin is superior to metformin in preventing complications in early stage T2D. (Clinicaltrials.gov identifier NCT03982381, EudraCT 2019-001046-17).
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| 8. |
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| 9. |
- Wijkman, Magnus, 1978-, et al.
(författare)
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NT-proBNP versus routine clinical risk factors as a predictor of cardiovascular events or death in people with dysglycemia & ndash : A brief report from the ORIGIN trial
- 2021
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Ingår i: Journal of diabetes and its complications. - : ELSEVIER SCIENCE INC. - 1056-8727 .- 1873-460X. ; 35:7
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Tidskriftsartikel (refereegranskat)abstract
- In patients with diabetes and cardiovascular or renal comorbidities, circulating levels of the N-terminal fragment of prohormone B-type natriuretic peptide (NT-proBNP) have similar discriminatory ability as multivariate models for prediction of cardiovascular events or death. We validated this finding in patients with dysglycemia not selected for co-existing cardiorenal diseases. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
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| 10. |
- Butt, Talha, et al.
(författare)
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Amputation-free survival in patients with diabetic foot ulcer and peripheral arterial disease : Endovascular versus open surgery in a propensity score adjusted analysis
- 2020
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1056-8727. ; 34:5
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of the present study was to compare outcomes of endovascular surgery versus open vascular surgery in patients with diabetic foot ulcer (DFU) and peripheral arterial disease (PAD). Methods: Between 1984 and 2006, 1151 patients with DFU were admitted to the diabetic foot care team. Three hundred seventy-six patients with 408 limbs were consecutively included at a multidisciplinary foot center, 289 limbs were treated with endovascular surgery and 119 limbs with open vascular surgery first strategy. A propensity score adjusted analysis was performed to compare outcomes for type of revascularization. Results: Major amputation rates at 3 years were 17.0% and 16.8% (p = 0.97) and mortality at 3 years were 43.1% and 46.5% (p = 0.55) after endovascular surgery and open vascular surgery, respectively. In the propensity score adjusted analysis, patients undergoing endovascular surgery first had similar outcomes in terms of major amputation, mortality, combined major amputation/mortality compared to those undergoing open vascular surgery. Longer time to intervention (p = 0.003) was associated with increased major amputation rate in the multivariable Cox regression analysis. Conclusion: The endovascular surgery first and open vascular surgery first strategies were associated with similar long-term results in a large cohort of patients with DFU and PAD undergoing revascularization. Rapid revascularization reduces the risk of amputation.
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| 11. |
- Handelsman, Yehuda, et al.
(författare)
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Impact of dronedarone on patients with atrial fibrillation and diabetes : A sub-analysis of the ATHENA and EURIDIS/ADONIS studies
- 2022
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1056-8727. ; 36:7
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This post hoc analysis evaluated efficacy and safety of dronedarone in atrial fibrillation (AF) and atrial flutter (AFL) patients with/without diabetes. Methods: Patients were categorized according to baseline diabetes status. Time-to-event analyses were performed using Kaplan-Meier method. Hazard-ratios were assessed using Cox models. Results: 945/4628 (dronedarone = 482; placebo = 463) patients in ATHENA and 215/1237 (dronedarone = 148; placebo = 67) patients in EURIDIS/ADONIS studies had diabetes. In ATHENA, there were higher rates of CV hospitalization/death in patients with diabetes (39.5%) than without diabetes (34.7%). Incidence of first CV hospitalization/death was lower in patients with diabetes treated with dronedarone (35.1%) than placebo (44.1%), and time to this event was longer in those treated with dronedarone than placebo (log-rank p = 0.005). Median AF/AFL recurrence time was longer in patients treated with dronedarone than placebo in patients with diabetes (ATHENA: 722 vs 527 days, log-rank p = 0.004; EURIDIS/ADONIS: 100 vs 23 days, log-rank p = 0.15) or without diabetes (ATHENA: 741 vs 492 days, log-rank p < 0.0001; EURIDIS/ADONIS: 120 vs 59 days, log-rank p = 0.0002). Occurrence of any treatment-related adverse events with dronedarone was similar for patients with/without diabetes and was comparable to placebo. Conclusions: Dronedarone reduced incidence of CV hospitalization/death, AF/AFL recurrence and increased time to these events in AF/AFL patients with/without diabetes. Trial registration: Not applicable, as it was a post hoc analysis. This article is based on previously conducted studies (ATHENA: NCT00174785, EURIDIS: NCT00259428, and ADONIS: NCT00259376).
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| 12. |
- Ousmaal, Mohamed E.F., et al.
(författare)
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Circulating microparticles released during dyslipidemia may exert deleterious effects on blood vessels and endothelial function
- 2020
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1056-8727. ; 34:10
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To compare the bioactivity of circulating microparticles (MPs) isolated from dyslipidemic Psammomys obesus (P. obesus) fed a high-energy diet (HED) with those released from healthy P. obesus fed a normal diet (ND). Methods: Vascular reactivity of aortic rings was evaluated by myography, after 24 h incubation in the absence or in the presence of circulating MPs isolated, by differential centrifugations, from the plasma of animals subjected to HED (MPsHED) or ND (MPsND) for 12 weeks. Human umbilical vein endothelial cells (HUVECs) were treated for 24 h with MPsHED or MPsND animals and subjected to immunofluorescence staining of caveolin-1 (cav-1), intercellular adhesion molecule-1 (ICAM-1), endothelial nitric oxide synthase (eNOS), F-actin and reactive oxygen species (ROS) detection. Results: The HED exerted a distinctly pronounced hyperlipidemic effect marked by plasmatic increase of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and triglyceride (TG). Both MPsND and MPsHED induced a significant reduction of maximal relaxation induced by acetylcholine (ACh). Interestingly, MPsHED significantly decreased eNOS expression up to ~25% and increased ROS production up to ~75% on in vitro treated HUVECs. Moreover, in HUVECs, MPsHED significantly decreased cav-1 expression up to ~50% whereas significant increase of ICAM-1 expression by about 2-fold approximately was observed. Conclusion: Our experimental study demonstrated the dual role of MPs on vascular function by modulating endothelial cell function. Furthermore, MPs may be considered as vectors of a bioactive information contributing to inflammation and vascular damage.
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