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- Elhadad, M. A., et al.
(författare)
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Deciphering the plasma proteome of type 2 diabetes
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:12, s. 2766-2778
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Tidskriftsartikel (refereegranskat)abstract
- With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between type 2 diabetes and >1,000 plasma proteins in the Cooperative Health Research in the Region of Augsburg (KORA) F4 cohort (n = 993, 110 cases), with subsequent replication in the third wave of the Nord-Trøndelag Health Study (HUNT3) cohort (n = 940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status, and hypertension. Addition-ally, we investigated associations with incident type 2 diabetes and performed two-sample bidirectional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent type 2 diabetes revealed 24 replicated proteins, of which 8 are novel. Proteins showing association with incident type 2 diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor–binding protein 2. Aminoacylase-1 was associated with both prevalent and incident type 2 diabetes. MR analysis yielded nominally significant causal effects of type 2 diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone–binding globulin on type 2 diabetes. In conclusion, our high-throughput pro-teomics study replicated previously reported type 2 diabetes–protein associations and identified new candidate proteins possibly involved in the pathogenesis of type 2 diabetes. © 2020 by the American Diabetes Association.
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- Khunti, K, et al.
(författare)
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Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:8, s. e034613-
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme.DesignDISCOVER is a 3-year, prospective, observational study programme including data from 38 countries across 6 continents from 2014 to 2019.SettingPrimary and secondary healthcare centres, hospitals and specialist diabetes centres in both urban and rural locations.ParticipantsA total of 15 992 patients with type 2 diabetes initiating second-line glucose-lowering therapy.Primary and secondary outcome measuresThe proportion of patients who discontinued metformin as a second-line therapy and the factors associated with this treatment change.ResultsOf the 14 668 patients (from 37 countries) with valid treatment data, 11 837 (80.7%) received metformin as first-line glucose-lowering therapy; 8488 (71.7%) received metformin monotherapy and 3349 (28.3%) received metformin as part of a combination therapy. Overall, treatment with metformin was discontinued in 15.1% (1782) of patients who received first-line metformin (14.1% (1194) and 17.6% (588) in those who received metformin as monotherapy and as part of a combination, respectively); this proportion varied across regions from 6.9% (54) in Africa to 20.6% (628) in South-East Asia. On metformin discontinuation, 73.6% (1311) of patients received a non-insulin monotherapy at second line. Factors associated with an increased odds of metformin discontinuation were older age (≥75 years) and having a history of chronic kidney disease. The probability of metformin monotherapy discontinuation was lower in patients from Africa than in those from Europe.ConclusionsA substantial number of patients discontinued taking metformin when beginning second-line therapy. Most of these patients subsequently received a non-insulin monotherapy at second line, in contradiction to international guidelines and potentially leaving them at an increased risk of hyperglycaemia and associated adverse outcomes.Trial registration numbersNCT02322762 and NCT02226822.
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- Rathmann, Jens, et al.
(författare)
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Incidence and predictors of severe infections in ANCA-associated vasculitis in a population-based cohort – preliminary results
- 2020
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 58:Suppl 2, s. 69-69
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Infectious complications in ANCA associated vasculitis (AAV) are a major cause of morbidity and mortality. The aim of this study was to determine the incidence rates, predictors and outcome of severe infections in AAV. Methods: We conducted a population-based cohort study in Southern Sweden with 326 incident cases of AAV diagnosed between 1997 and 2016. Diagnosis of vasculitis was confirmed by case record review and patients were classified according to the European Medicines Agency algorithm. Demographics, clinical, andlaboratory data was collected from time of diagnosis and follow-up. All events of severe infection (required hospitalization and treated with intravenous antimicrobials) were identified. Vasculitis disease activity was evaluated using the Birmingham Vasculitis Activity Score (BVAS) and the extent of organ damage was assessed using the vasculitis damage index (VDI). Patients were followed from time of AAV-diagnosis to death or end of study, December 2017Results: Data on 262 patients (122 women) was collated and are presented in this report. Total time of follow-up was 1368 person-year. In total 104 (39.7%) patients experienced at least one severe infection during the follow-up, 33 (12.5%) suffered 2 infections and 14 (5%) suffered 3 severe infections or more. The incidence rate of severe infection was higher during the first year after diagnosis compared to that during the whole follow-up time (24.3/100 year vs. 7.6/100, p<0.001). Patients with severe infection were older at diagnosis, had higher serum creatinine, higher BVAS at diagnosis and higher VDI after 12 months (Table 1). They were also more likely to be MPO-ANCA positive. Age and BVAS at diagnosis were the only factors that independently predicted severe infection. Severe infection was associated with worse prognosis in terms of renal and patient’s survival. Conclusion: In this cohort the incidence rate of severe infection is comparable to earlier published data in AAV. The rate of severe infection is higher early in the disease course. Severe infection is still a major clinical problem and is associated with high age, increased disease activity at diagnosis, renal disease and MPO-ANCA positivity. Severe infection is associated with a worse prognosis.
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