| 1. |
- Ekström, Nils, et al.
(författare)
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Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register
- 2016
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 18:10, s. 990-998
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. Research design and methods: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. Results: Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was similar to 60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. Conclusions: This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.
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| 2. |
- Eriksson, Mats, et al.
(författare)
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Blood lipids in 75,048 type 2 diabetic patients: a population-based survey from the Swedish National diabetes register.
- 2011
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Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - 1741-8275 .- 1741-8267. ; 18:1, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes and diabetic dyslipidemia are high-risk conditions for cardiovascular disease. However, the description of the distribution of blood lipids in diabetic patients has not been based on population-based surveys. The aim of this study was to describe diabetic dyslipidemia in a large unselected sample of patients from the Swedish National Diabetes Register.
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| 3. |
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| 4. |
- Jain, Ruchi, et al.
(författare)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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| 5. |
- Kalani, Majid, et al.
(författare)
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Beneficial effects of dalteparin on haemostatic function and local tissue oxygenation in patients with diabetes, severe vascular disease and foot ulcers.
- 2007
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Ingår i: Thrombosis research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 120:5, s. 653-61
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A state of hypercoagulation and fibrinolytic dysfunction is present in individuals with diabetes, which may contribute to disturbed skin microcirculation and impaired ulcer healing. We have previously reported an improved outcome of chronic diabetic foot ulcers during treatment with dalteparin. In the present study we investigated the effects of dalteparin on skin microcirculation and haemostatic function. MATERIALS AND METHODS: 87 patients with diabetes, peripheral arterial obliterative disease and chronic foot ulcers were investigated in a prospective, randomised, double-blind and placebo-controlled study. They were randomised to treatment with subcutaneous injections of 5000 U dalteparin (n=44) or placebo (n=43), once daily until ulcer healing or for a maximum of six months. Plasma fibrinogen, fibrin gel structure [permeability coefficient (Ks) and fiber mass/length ratio (mu)], prothrombin fragment 1+2 (F1+2) antigen, plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator (tPA) antigen were analysed before randomization (baseline value), and at the end of the treatment period. The skin microcirculation of the foot was investigated by transcutaneous oxygen tension (TcPO(2)) and laser Doppler fluxmetry (LDF). RESULTS: The changes (Delta-values) of Ks, mu, tPA and TcPO(2) were higher (p<0.05) during treatment with dalteparin, as compared to the changes during treatment with placebo. At baseline, plasma fibrinogen and Ks were significantly correlated to TcPO(2). CONCLUSIONS: Local skin oxygenation improved and a less thrombogenic fibrin gel structure was formed in patients treated with dalteparin. Beneficial effects on haemostatic function are likely to contribute to the improved skin oxygenation observed during treatment with dalteparin.
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| 6. |
- Kalani, Majid, et al.
(författare)
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Effect of dalteparin on healing of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease: a prospective, randomized, double-blind, placebo-controlled study.
- 2003
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Ingår i: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:9, s. 2575-80
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers. RESEARCH DESIGN AND METHODS: A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1). who healed with intact skin; 2). in whom the study ulcer was improved, unchanged, or impaired; or 3). who were amputated above or below the ankle level, as compared with control subjects. RESULTS: Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided chi(2) test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area >or=50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased >or=50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 +/- 8 weeks in the dalteparin group compared with 16 +/- 7 weeks in placebo group (NS). CONCLUSIONS: The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.
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| 7. |
- Keindl, Magdalena, et al.
(författare)
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Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphisms
- 2020
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic beta cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naive to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care.
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| 8. |
- Ozgumus, T., et al.
(författare)
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Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.
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| 9. |
- Svanström, Henrik, et al.
(författare)
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Use of liraglutide and risk of major cardiovascular events: a register-based cohort study in Denmark and Sweden.
- 2019
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595. ; 7:2, s. 106-114
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Tidskriftsartikel (refereegranskat)abstract
- Trial evidence shows that the glucagon-like peptide-1 receptor agonist liraglutide significantly reduces the risk of major cardiovascular events among patients with type 2 diabetes who have established cardiovascular disease or are at high cardiovascular risk. We aimed to assess the cardiovascular effectiveness of liraglutide in routine clinical practice.We used data from nationwide registers in Denmark and Sweden for the period from Jan 1, 2010, to Dec 31, 2016, to investigate the risk of major cardiovascular events associated with use of liraglutide, compared with an active comparator drug class, dipeptidyl peptidase-4 (DPP-4) inhibitors, in patients with type 2 diabetes. The cohort included incident users of liraglutide or DPP-4 inhibitors, who were also using metformin at baseline, matched 1:1 on age, sex, and propensity score. The main outcome was major cardiovascular events, a composite outcome consisting of myocardial infarction, stroke, and cardiovascular death. Other outcomes assessed were the individual components of the main composite outcome, heart failure, death from any cause, and an expanded composite major cardiovascular events outcome that also included other ischaemic heart disease, coronary revascularisation, and peripheral arterial disease.The study population consisted of 23402 users of liraglutide and 23402 matched users of DPP-4 inhibitors; patients were followed up for a mean of 3·3 years (SD 2·0). A major cardiovascular event occurred in 1132 users of liraglutide (incidence rate 14·0 per 1000 person-years) and in 1141 users of DPP-4 inhibitors (15·4 per 1000 person-years; hazard ratio [HR] 0·90, 95% CI 0·83-0·98). The HRs were 0·81 (0·71-0·92) for patients with a history of major cardiovascular disease and 0·96 (0·86-1·06) for patients without such a history (p=0·057 [test of homogeneity], suggesting no statistical evidence of heterogeneity). Compared with use of DPP-4 inhibitors, use of liraglutide was associated with a significantly lower risk of cardiovascular death (HR 0·78, 95% CI 0·68-0·91), but no significant differences were identified for risk of myocardial infarction (0·94, 0·84-1·06) or stroke (0·88, 0·77-1·01). Furthermore, use of liraglutide was associated with a significantly lower risk of death from any cause (HR 0·83, 95% CI 0·77-0·90), but no significant differences were identified for risk of heart failure (0·90, 0·80-1·03) or for the expanded major cardiovascular events outcome (0·95, 0·89-1·01).In this large Scandinavian cohort, use of liraglutide, as compared with use of DPP-4 inhibitors, was associated with significantly reduced risk of major cardiovascular events. Patients with history of cardiovascular disease seemed to derive the largest benefit from treatment with liraglutide. These data provide support for the cardiovascular effectiveness of liraglutide in routine clinical practice.Swedish Heart-Lung Foundation, Novo Nordisk Foundation, and Swedish Society for Medical Research.
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