| 1. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 2. |
- Karlsson, Mathias, et al.
(författare)
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Digitalization Drivers, Barriers, and Effects in Maritime Ports
- 2023
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Ingår i: 29th Annual Americas Conference on Information Systems, AMCIS 2023. - : Americas Conference on Information Systems (AMCIS).
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Konferensbidrag (refereegranskat)abstract
- Maritime transports play a vital role for several industries in enabling efficient and sustainable transportation of goods. Ports are central hubs in the transport chain since they connect the maritime and land-based transport systems. The central position of ports makes them critical enablers of efficiency through digital connectivity but also implies that they need to consider many types of participating agents with whom they form episodic tight couplings. However, the industry's digitalization level remains relatively low, and we know little of the challenges facing ports in increasing it. Through a case study of digitalization in Swedish small- and medium-sized ports handling different types of cargo and serving different types of transport modes, we identify key objectives and critical challenges underlying digitalization processes in ports.
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| 3. |
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| 4. |
- Ahmadi, Shilan Seyed, et al.
(författare)
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Risk factors for nephropathy in persons with type 1 diabetes: a population-based study
- 2022
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 59, s. 761-772
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Tidskriftsartikel (refereegranskat)abstract
- Aims Albuminuria is strongly associated with risk of renal dysfunction, cardiovascular disease and mortality. However, clinical guidelines diverge, and evidence is sparse on what risk factor levels regarding blood pressure, blood lipids and BMI are needed to prevent albuminuria in adolescents and young adults with type 1 diabetes. Methods A total of 9347 children and adults with type 1 diabetes [mean age 15.3 years and mean diabetes duration 1.4 years at start of follow-up] from The Swedish National Diabetes Registry were followed from first registration until end of 2017. Levels for risk factors for a risk increase in nephropathy were evaluated, and the gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. Results During the follow-up period, 8610 (92.1%) remained normoalbuminuric, 737 (7.9%) individuals developed micro- or macroalbuminuria at any time period of whom 132 (17.9% of 737) individuals developed macroalbuminuria. Blood pressure >= 140/80 mmHg was associated with increased risk of albuminuria (p <= 0.0001), as were triglycerides >= 1.0 mmol/L (p = 0.039), total cholesterol >= 5.0 mmol/L (p = 0.0003), HDL < 1.0 mmol/L (p = 0.013), LDL 3.5- < 4.0 mmol/L (p = 0.020), and BMI >= 30 kg/m(2) (p = 0.033). HbA1c was the strongest risk factor for any albuminuria estimated by the measure gradient of risk per 1 SD, followed by diastolic blood pressure, triglycerides, systolic blood pressure, cholesterol and LDL. In patients with HbA1c > 65 mmol/mol (> 8.1%), blood pressure > 140/70 mmHg was associated with increased risk of albuminuria. Conclusions Preventing renal complications in adolescents and young adults with type 1 diabetes need avoidance at relatively high levels of blood pressure, blood lipids and BMI, whereas very tight control is not associated with further risk reduction. For patients with long-term poor glycaemic control, stricter blood pressure control is advocated.
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| 5. |
- Ahmadi, Shilan Seyed, et al.
(författare)
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Risk of atrial fibrillation in persons with type 2 diabetes and the excess risk in relation to glycaemic control and renal function: a Swedish cohort study
- 2020
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background To examine the incidence of atrial fibrillation in individuals with type 2 diabetes compared with age- and sex-matched controls from the general population and its variation in relation to glycaemic control and renal function. Methods A total of 421,855 patients with type 2 diabetes from the Swedish National Diabetes Registry and 2,131,223 controls from the Swedish Population Registry, matched for age, sex and county, were included and followed from January 1, 2001 to December 31, 2013. Results Overall, 8.9% of individuals with type 2 diabetes and 7.0% of controls were diagnosed with atrial fibrillation during follow-up, unadjusted incidence risk ratio (IRR) 1.35 (95% 1.33-1.36). Women < 55 years old with type 2 diabetes had an IRR of 2.36 (95% CI 2.10-2.66), in relation to controls, whereas the corresponding value for men < 55 years old with type 2 diabetes was IRR 1.78 (95% CI 1.67-1.90). In the fully adjusted Cox regression, the risk of type 2 diabetes on incident atrial fibrillation was 28% greater vs controls, hazard ratio (HR) 1.28 (95% CI 1.26-1.30), p < 0.0001. The excess risk of atrial fibrillation in individuals with type 2 diabetes increased with worsening glycaemic control and renal complications. For individuals with HbA1c <= 6.9% (<= 52 mmol/mol) and normoalbuminuria the excess risk vs controls was still increased, adjusted HR 1.16 (95% CI 1.14-1.19); p < 0.0001. Conclusions Individuals with type 2 diabetes had an overall 35% higher risk of atrial fibrillation compared to age- and sex-matched controls from the general population. The excess risk for atrial fibrillation increased with renal complications or with poor glycaemic control. Individuals with type 2 diabetes with good glycaemic control and normoalbuminuria had slightly increased risk.
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| 6. |
- Andréasson, Karin, et al.
(författare)
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Body mass index in adolescence, risk of type 2 diabetes and associated complications: A nationwide cohort study of men
- 2022
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Ingår i: EClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Background Obesity is a predominant factor in development of type 2 diabetes but to which extent adolescent obesity influences adult diabetes is unclear. We investigated the association between body mass index (BMI) in young men and subsequent type 2 diabetes and how, in diagnosed diabetes, adolescent BMI relates to glycemic control and diabetes complications. Methods Baseline data from the Swedish Conscript Register for men drafted 1968-2005 was combined with data from the National Diabetes and Patient registries. Diabetes risk was estimated through Cox regression and Kaplan-Meier survival estimates. Relationships between BMI, glycemic control and diabetes complications were assessed through multiple linear and logistic regression. Findings Among 1,647,826 men, 63,957 (3.88%) developed type 2 diabetes over a median follow-up of 29.0 years (IQR[21.0-37.0]). The risk of diabetes within 40 years after conscription was nearly 40% in individuals with adolescent BMI >= 35 kg/m(2). Compared to BMI 18.5-<20 kg/m(2) (reference), diabetes risk increased in a linear fashion from HR 1.18(95%CI 1.15-1.21) for BMI 20-<22.5 kg/m(2) to HR 15.93(95%CI 14.88-17.05) for BMI >= 35 kg/m(2), and a difference in age at onset of 11.4 years was seen. Among men who developed diabetes, higher adolescent BMI was associated with higher HbA1c levels and albuminuria rates. Interpretation Rising adolescent BMI was associated with increased risk of type 2 diabetes diagnosed at a younger age, with poorer metabolic control, and a greater prevalence of albuminuria, all suggestive of worse prognosis. Copyright (C) 2022 The Authors. Published by Elsevier Ltd.
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| 7. |
- Balintescu, A., et al.
(författare)
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Glycaemic control and sepsis risk in adults with type 1 diabetes
- 2023
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 25:7, s. 1942-1949
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study the association between glycated haemoglobin (HbA1c) and sepsis in adults with type 1 diabetes, and to explore the relationship between HbA1c and mortality among individuals who developed sepsis.Materials and Methods: We included 33 549 adult individuals with type 1 diabetes recorded in the Swedish National Diabetes Register between January 2005 and December 2015. We used multivariable Cox regression and restricted cubic spline analyses to study the relationship between HbA1c values and sepsis occurrence and association between HbA1c and mortality among those with sepsis.Results: In total, 713 (2.1%) individuals developed sepsis during the study period. Com-pared with the HbA1c reference interval of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was: 2.50 [95% confidence interval (CI) 1.18-5.29] for HbA1c <43 mmol/mol; 1.88 (95% CI 0.96-3.67) for HbA1c 43-47 mmol/mol; 1.78 (95% CI 1.09-2.89) for HbA1c 53-62 mmol/mol; 1.86 (95% CI 1.14-3.03) for HbA1c 63-72 mmol/mol; 3.15 (95% CI 1.91-5.19) for HbA1c 73-82 mmol/mol; and 4.26 (95% CI 2.53-7.16) for HbA1c >82 mmol/mol. On multivariable restricted cubic spline analy-sis, we found a J-shaped association between HbA1c and sepsis risk, with the lowest risk observed at HbA1c of approximately 53 mmol/mol. We found no association between HbA1c and mortality among those individuals who developed sepsis.Conclusions: In our nationwide observational study of adult individuals with type 1 diabetes we found a J-shaped relationship between HbA1c and risk of sepsis, with the lowest risk at HbA1c levels about 53 mmol/mol (7.0%). HbA1c was not associ-ated with mortality in individuals affected by sepsis.
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| 8. |
- Balintescu, A., et al.
(författare)
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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:1, s. 127-133
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes, and to assess the association between sepsis and all-cause mortality in such patients. RESEARCH DESIGN AND METHODS We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between 1 January 2005 and 31 December 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. RESULTS Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48–52 mmol/mol (6.5–6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07–1.24) for HbA1c <43 mmol/mol (6.1%), 0.93 (0.87–0.99) for HbA1c 53–62 mmol/mol (7.0–7.8%), 1.05 (0.97–1.13) for HbA1c 63–72 mmol/mol (7.9–8.7%), 1.14 (1.04–1.25) for HbA1c 73–82 mmol/mol (8.8–9.7%), and 1.52 (1.37–1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73–0.82) per SD; it increased thereafter (P for nonlinearity <0.001). As compared with patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03–4.30). CONCLUSIONS In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a fourfold increased risk of death among those developing sepsis. © 2021 by the American Diabetes Association.
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| 9. |
- Balintescu, A., et al.
(författare)
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Prevalence and impact of chronic dysglycemia in intensive care unit patients-A retrospective cohort study
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 65:1, s. 82-91
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Tidskriftsartikel (refereegranskat)abstract
- Background The prevalence of chronic dysglycemia (diabetes and prediabetes) in patients admitted to Swedish intensive care units (ICUs) is unknown. We aimed to determine the prevalence of such chronic dysglycemia and asses its impact on blood glucose control and patient-centered outcomes in critically ill patients. Methods In this retrospective observational cohort study, we obtained glycated hemoglobin A1c (HbA1c) in patients admitted to four tertiary ICUs in Sweden between March and August 2016. Based on previous diabetes history and HbA1c we determined the prevalence of chronic dysglycemia. We used multivariable regression analyses to study the association of chronic dysglycemia with the time-weighted average blood glucose concentration, glycemic lability index (GLI), and development of hypoglycemia (co-primary outcomes), and with ICU length of stay, mechanical ventilation duration, renal replacement therapy (RRT) use, vasopressor use, ICU-acquired infections, and mortality (exploratory clinical outcomes). Results Of 943 patients, 312 (33%) had chronic dysglycemia. Of these 312 patients, 84 (27%) had prediabetes, 43 (14%) had undiagnosed diabetes and 185 (59%) had known diabetes. Chronic dysglycemia was independently associated with higher time-weighted average blood glucose concentration (P < .001), higher GLI (P < .001), and hypoglycemia (P < .001). Chronic dysglycemia was independently associated with RRT use (adjusted odds ratio 1.97, 95% CI 1.24-3.13,P = .004) but not with other exploratory clinical outcomes. Conclusions In four tertiary Swedish ICUs, measurement of HbA1c showed that one-third of patients had chronic dysglycemia. Chronic dysglycemia was associated with marked derangements in glycemic control, and a greater need for renal replacement therapy.
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| 10. |
- Borenäs, Marcus, et al.
(författare)
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ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation
- 2021
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Ingår i: EMBO Journal. - : John Wiley & Sons. - 0261-4189 .- 1460-2075. ; 40:3
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Tidskriftsartikel (refereegranskat)abstract
- High‐risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high‐risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8–10% of primary NB patients are ALK‐positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the “2p‐gain” region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v‐sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI‐sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p‐gain, may benefit from ALK TKI‐based therapeutic intervention.
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| 11. |
- Borenäs, Marcus, et al.
(författare)
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ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition
- 2024
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 121:1
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Tidskriftsartikel (refereegranskat)abstract
- High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.
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| 12. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 13. |
- Dena, Mary, et al.
(författare)
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Renal Complications and Duration of Diabetes: An International Comparison in Persons with Type 1 Diabetes
- 2021
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Ingår i: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; :12, s. 3093-3105
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Renal complications are both a marker of previous suboptimal glycaemic control and a major risk factor for cardiovascular disease in persons with type 1 diabetes (T1D). The aim of the study was to evaluate the prevalence of renal complications in persons with T1D in four geographical regions. Methods Nationwide registry data from Austria/Germany, Sweden and the US were used to estimate the prevalence of renal complications from January 2016 until September 2018. Chronic kidney disease (CKD) and albuminuria in the study population and each registry were analysed by diabetes duration. Risk factors for renal complications were described by registry. Results In the total cohort of 78.926 adults with T1D, mean age was 44.4 +/- 18.43 years and mean diabetes duration was 21.6 +/- 22 years. Mean estimated glomerular filtration rate (eGFR) was 94.0 +/- 31.45 ml/min, 13.0% had microalbuminuria and 3.9% had macroalbuminuria. Mean age, diabetes duration, use of insulin pumps and continuous glucose monitoring, as well as presence of albuminuria, varied between registries. Albuminuria was present in approximately 10% of persons with diabetes duration < 20 years and impaired renal function (eGFR < 60 ml/min) was present in 17%. In persons with diabetes duration > 40 years, approximately one-third had albuminuria and 25% had impaired renal function. Conclusions This analysis used three nationwide registries of persons with T1D. Despite recent use of more effective diabetes therapies, a substantial proportion of persons with T1D have renal complications at < 20 years after diagnosis. Efficient glucose-lowering and renal-protective strategies are needed in persons with T1D.
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| 14. |
- Edqvist, Jon, 1988, et al.
(författare)
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Severe COVID-19 Infection in Type 1 and Type 2 Diabetes During the First Three Waves in Sweden.
- 2023
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:3, s. 570-578
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is an established risk factor for hospitalization and death in COVID-19 infection, while findings with respect to type 1 diabetes have been diverging.Using nationwide health registries, we identified all patients aged ≥18 years with type 1 and type 2 diabetes in Sweden. Odds ratios (ORs) describe the general and age-specific risk of being hospitalized, need for intensive care, or dying, adjusted for age, socioeconomic factors, and coexisting conditions, compared with individuals without diabetes. Machine learning models were used to find predictors of outcomes among individuals with diabetes positive for COVID-19.Until 30 June 2021, we identified 365 (0.71%) and 11,684 (2.31%) hospitalizations in 51,402 and 504,337 patients with type 1 and 2 diabetes, respectively, with 67 (0.13%) and 2,848 (0.56%) requiring intensive care unit (ICU) care and 68 (0.13%) and 4,020 (0.80%) dying (vs 7,824,181 individuals without diabetes [41,810 hospitalizations (0.53%), 8,753 (0.11%) needing ICU care, and 10,160 (0.13%) deaths). Although those with type 1 diabetes had moderately raised odds of being hospitalized (multiple-adjusted OR 1.38 [95% CI 1.24-1.53]), there was no independent effect on ICU care or death (OR of 1.21 [95% CI 0.94-1.52] and 1.13 [95% CI 0.88-1.48], respectively). Age and socioeconomic factors were the dominating features for predicting hospitalization and death in both types of diabetes.Type 2 diabetes was associated with increased odds for all outcomes, whereas patients with type 1 diabetes had moderately increased odds of hospitalization but not ICU care and death.
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| 15. |
- Edqvist, Jon, 1988, et al.
(författare)
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Trajectories in HbA1c and other risk factors among adults with type 1 diabetes by age at onset
- 2021
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- In type 1 diabetes, potential loss of life-years is greatest in those who are youngest at the time of onset. Using data from a nationwide cohort of patients with type 1 diabetes, we aimed to study risk factor trajectories by age at diagnosis. We stratified 30005 patients with type 1 diabetes aged 18–75 years into categories based on age at onset: 0–10, 11–15, 16–20, 21–25, and 26–30 years. HbA1c, albuminuria, estimated glomerular filtration rate (eGFR), body mass index (BMI), low-denisty lipoprotein (LDL)-cholesterol, systolic blood pressure (SBP), and diastolic blood pressure trends were analyzed using mixed models. Variable importance for baseline HbA1c was analyzed using conditional random forest and gradient boosting machine approaches. Individuals aged ≥16 years at onset displayed a relatively low mean HbA1c level (~55–57mmol/mol) that gradually increased. In contrast, individuals diagnosed at ≤15 years old entered adulthood with a mean HbA1c of approximately 70mmol/mol. For all groups, HbA1c levels stabilized at a mean of approximately 65mmol/mol by about 40 years old. In patients who were young at the time of onset, albuminuria appeared at an earlier age, suggesting a more rapid decrease in eGFR, while there were no distinct differences in BMI, SBP, and LDL-cholesterol trajectories between groups. Low education, higher age, and poor risk factor control were associated with higher HbA1c levels. Young age at the diabetes onset plays a substantial role in subsequent glycemic control and the presence of albuminuria, where patients with early onset may accrue a substantial glycemic load during this period. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.
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| 16. |
- Friman, Ola, et al.
(författare)
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Performance of Subcutaneous Continuous Glucose Monitoring in Adult Critically Ill Patients Receiving Vasopressor Therapy
- 2024
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Ingår i: DIABETES TECHNOLOGY & THERAPEUTICS. - 1520-9156 .- 1557-8593.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Subcutaneous continuous glucose monitoring (CGM) may facilitate glucose control in the ICU. We aimed to assess the accuracy of CGM (Dexcom G6) against arterial blood glucose (ABG) in adult critically ill patients receiving intravenous insulin infusion and vasopressor therapy. We also aimed to assess feasibility and tolerability of CGM in this setting. Methods: We included ICU patients receiving mechanical ventilation, insulin, and vasopressor therapy. Numerical accuracy was assessed by the mean absolute relative difference (MARD), overall, across arterial glucose strata, over different noradrenaline equivalent infusion rates, and over time since CGM start. MARD <14% was considered acceptable. Clinical accuracy was assessed using Clarke Error Grid (CEG) analysis. Feasibility outcome included number and duration of interrupted sensor readings due to signal loss. Tolerability outcome included skin reactions related to sensor insertion or sensor adhesives. Results: We obtained 2946 paired samples from 40 patients (18 with type 2 diabetes) receiving a median (IQR) maximum noradrenaline equivalent infusion rate of 0.18 (0.08-0.33) g/kg/min during CGM. Overall, MARD was 12.7% (95% CI 10.7-15.3), and 99.8% of CGM readings were within CEG zones A and B. MARD values >= 14% were observed when ABG was outside target range (6-10 mmol/L [108-180 mg/dL]) and with noradrenaline equivalent infusion rates above 0.10 mu g/kg/min. Accuracy improved with time after CGM start, reaching MARD values <14% after 36 h. We observed four episodes of interrupted sensor readings due to signal loss, ranging from 5 to 20 min. We observed no skin reaction related to sensor insertion or sensor adhesives. Conclusions: In our ICU cohort of patients receiving vasopressor infusion, subcutaneous CGM demonstrated acceptable overall numerical and clinical accuracy. However, suboptimal accuracy may occur outside glucose ranges of 6-10 mmol/L (108-180 mg/dL), during higher dose vasopressor infusion, and during the first 36 h after CGM start.
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| 17. |
- Gabriel, R., et al.
(författare)
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Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. Methods: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 mu Siemens) and estimated glomerular filtration rate (eGFR). Results: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). Conclusions: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.
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| 18. |
- Gkaniatsa, Eleftheria, et al.
(författare)
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Mortality in Patients With Primary Aldosteronism: A Swedish Nationwide Study.
- 2023
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Ingår i: Hypertension (Dallas, Tex. : 1979). - 1524-4563. ; 80:12, s. 2601-2610
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Tidskriftsartikel (refereegranskat)abstract
- Primary aldosteronism (PA) is associated with increased mortality. The extent to which this phenomenon is affected by sex, age, comorbidities at diagnosis, and different treatment modalities is largely unknown. The objective was to determine all-cause and cause-specific mortality in a population-based cohort of patients with PA and the impact of age at diagnosis, sex, comorbidities, and treatment modalities.We used national registers to identify patients diagnosed with PA between 1997 and 2019 (n=2419) and controls (n=24187) from the general population, matched for sex, age, and county of residence. We obtained mortality data from the Cause-of-Death Register. We used Cox regression models, adjusted for socioeconomic factors and diabetes, to estimate adjusted hazard ratios (HRs [95% CI]).Overall, 346 (14.3%) patients with PA and 2736 (11.3%) controls died during a median follow-up time of 8.1 years. PA was associated with increased risk from all-cause mortality (HR, 1.23 [95% CI, 1.10-1.38]), death from cardiovascular disease (HR, 1.57 [95% CI, 1.30-1.89]), and stroke (HR, 1.85 [95% CI, 1.16-2.93]). Patients with cardiovascular disease at diagnosis (HR, 1.53 [1.26-1.85]), age >56 years (HR, 1.28 [95% CI, 1.13-1.45]), patients treated with a low dose of a mineralocorticoid receptor antagonist (HR, 1.30 [95% CI, 1.02-1.66]), and untreated patients (HR, 2.51 [95% CI, 1.72-3.67]) had excess mortality.Mortality, mainly due to cardiovascular disease, is increased in patients with PA compared with controls from the general population, particularly in patients aged >56 years, patients with preexisting cardiovascular comorbidities, and patients receiving low dose of a mineralocorticoid receptor antagonist.
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| 19. |
- Glynn, Linn, et al.
(författare)
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Trends in Survival After First Myocardial Infarction in People With Diabetes
- 2024
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Ingår i: JOURNAL OF THE AMERICAN HEART ASSOCIATION. - 2047-9980. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes.Methods and Results Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all-cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo-observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62 +/- 12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75 +/- 10.8 years; women, 38.1%), and individuals without diabetes (73 +/- 13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change -0.48% [95% CI, -0.52% to -0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, -0.33% [95% CI, -0.43% to -0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, -0.18% [95% CI, -0.53% to 0.17%]). Similar trends were observed with regard to 1-year death, cardiovascular death, and major adverse cardiovascular events.Conclusions During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.
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| 20. |
- Gonzalez Perez, A., et al.
(författare)
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Cardiovascular and renal outcomes among patients with type 2 diabetes using SGLT2 inhibitors added to metformin: a population-based cohort study from the UK
- 2023
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Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Large numbers of patients with type 2 diabetes receive treatment with a sodium-glucose co-transporter-2 inhibitor (SGLT2i). We investigated whether the cardiorenal preventative effects found in clinical trials are also seen in clinical practice where patient characteristics and adherence to treatment differ. RESEARCH DESIGN AND METHODS: Using UK primary care electronic health records, we followed two cohorts of patients with type 2 diabetes prescribed metformin: SGLT2is (N=12 978) and a matched comparator of patients not using an SGLT2i at the start of follow-up (N=44 286). Independent follow-ups were performed to identify the study outcomes: cardiovascular (CV) composite (comprising non-fatal myocardial infarction (MI)/ischemic stroke (IS) requiring hospitalization and CV death), severe renal disease, and all-cause mortality. Cox regression was used to estimate adjusted HRs. RESULTS: Mean follow-up was 2.3 years (SGLT2i cohort) and 2.1 years (comparison cohort). Mean age was 59.6 years (SD ±10.2, SGLT2i cohort) and 60.4 years (SD ±10.0, comparison cohort). SGLT2i new users were associated with a reduced risk of the CV composite (HR 0.75, 95% CI: 0.61 to 0.93), severe renal disease (HR 0.55, 95% CI: 0.46 to 0.67), and all-cause mortality (HR 0.56, 95% CI: 0.49 to 0.63), with risk reductions similar irrespective of baseline chronic kidney disease. Reduced risks were seen for IS (HR 0.51, 95% CI: 0.36 to 0.74) but not MI (HR 0.98, 95% CI: 0.74 to 1.28). Results were consistent in sensitivity analyses. CONCLUSIONS: In this population-based study, SGLT2is were associated with significant CV, renal and survival benefits among individuals with type 2 diabetes on metformin; the CV benefit was driven by a reduced risk of ischemic stroke.
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| 21. |
- González-Pérez, Antonio, et al.
(författare)
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Impact of chronic kidney disease definition on assessment of its incidence and risk factors in patients with newly diagnosed type 1 and type 2 diabetes in the UK: A cohort study using primary care data from the United Kingdom.
- 2020
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Ingår i: Primary care diabetes. - : Elsevier BV. - 1878-0210 .- 1751-9918. ; 14, s. 381-387
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Tidskriftsartikel (refereegranskat)abstract
- To estimate the incidence and risk factors of chronic kidney disease (CKD) in patients with newly-diagnosed diabetes using different CKD definitions.Using UK primary care data, patients with diabetes (type 1, 4691; type 2, 109,365) and no CKD were followed to identify newly-diagnosed CKD, classified by a broad and narrow CKD definition (to capture diabetes-induced CKD, termed diabetic kidney disease, DKD). Adjusted incidence rates of CKD/DKD were calculated, and risk factors identified using Cox regression.There were 404 CKD cases and 147 DKD cases among patients with type 1 diabetes (T1D), and 29,104 CKD cases, 9284 DKD cases among patients with type 2 diabetes (T2D). Adjusted incidence rates of CKD per 100 years were 5.4 (T1D) and 5.5 (T2D); for DKD they were 1.9 and 1.5, respectively. Risk factors for CKD/DKD were older age, high social deprivation, obesity, cardiovascular disease, hypertension and smoking. Poor glycaemic control in the year after diabetes diagnosis was a strong predictor of CKD/DKD occurrence beyond this first year, and a risk factor for CKD/DKD in T2D.CKD and DKD remain common in diabetics in the decade after diagnosis. Early prevention of T2D and aggressive treatment of risk factors is urgent.
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| 22. |
- González-Pérez, A., et al.
(författare)
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Incidence and risk factors for mortality and end-stage renal disease in people with type 2 diabetes and diabetic kidney disease: A population-based cohort study in the UK
- 2021
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction We aimed to determine the incidence of, and risk factors for all-cause/cardiovascular disease (CVD) mortality, and end-stage renal disease (ESRD) among people with type 2 diabetes with/without diabetic kidney disease (DKD) in the UK general population. Research design and methods We undertook a population-based cohort study using primary care UK electronic health records. We followed 8413 people with type 2 diabetes and DKD and a matched comparison cohort of people with type 2 diabetes without DKD. Risk factors for all-cause/CVD mortality (using both cohorts) and ESRD (DKD cohort only) were evaluated by estimating HRs with 95% CIs using Cox regression. Results In the DKD cohort (mean age 66.7 years, 62.4% male), incidence rates per 1000 person-years were 50.3 (all-cause mortality), 8.0 (CVD mortality) and 6.9 (ESRD). HRs (95% CIs; DKD vs comparison cohort) were 1.49 (1.35 to 1.64) for all-cause mortality and 1.60 (1.24 to 2.05) for CVD mortality. In general, higher all-cause mortality risks were seen with older age, underweight (body mass index <20 kg/m 2), reduced renal function, and cardiovascular/liver disease, and lower risks were seen with being female or overweight. In the DKD cohort, higher risks of ESRD were seen with reduced renal function at baseline, high material deprivation, cancer and non-insulin glucose-lowering drugs, and a lower risk was seen with overweight (≥25 kg/m 2). Conclusions Annually, one death will occur among every 20 people with type 2 diabetes and DKD. The identified risk factors in this study will help identify people with type 2 diabetes at most risk of death and progression of kidney disease, and help to direct effective management strategies. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 23. |
- Hallström, Sara, et al.
(författare)
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Characteristics of Continuous Glucose Monitoring Metrics in Persons with Type 1 and Type 2 Diabetes Treated with Multiple Daily Insulin Injections
- 2021
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 23:6, s. 425-433
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although guidelines advocate similar continuous glucose monitoring (CGM) targets for insulin-treated persons with type 1 diabetes (T1D) and type 2 diabetes (T2D), it is unclear how these persons differ with respect to hypoglycemia, glucose variability, and other CGM metrics in clinical practice. Methods: We used data from 2 multicenter randomized-controlled trials (GOLD and MDI-Liraglutide) where 161 persons with T1D and 124 persons with T2D treated with multiple daily injections were included and monitored with masked CGM. Results: Persons from both cohorts had similar mean glucose levels, 10.9 mmol/L (196 mg/dL) in persons with T1D and 10.8 mmol/L (194 mg/dL) in persons with T2D. Time in hypoglycemia (<3.9 mmol/L [70 mg/dL]) was 5.1% and 1.0% for persons with T1D and T2D, respectively (P < 0.001). Corresponding estimates for the standard deviations of mean glucose levels were 4.4 mmol/L (79 mg/dL) versus 3.0 (54 mg/dL) (P < 0.001), for coefficient of variation 41% versus 28% (P < 0.001), and for time in range 38.2% versus 45.3%, respectively (P = 0.004). Mean C-peptide levels were 0.05 nmol/L and 0.67 nmol/L (P < 0.001) for persons with T1D and T2D, respectively. Conclusions: Persons with T1D compared with persons with T2D treated with multiple daily insulin injections spend considerably more time in hypoglycemia, have higher glucose variability, and less "time in range." This needs to be taken into account in daily clinical care and in recommended targets for CGM metrics.
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| 24. |
- Hallström, Sara, et al.
(författare)
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Risk factors and incidence over time for lower extremity amputations in people with type 1 diabetes: an observational cohort study of 46,088 patients from the Swedish National Diabetes Registry
- 2021
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 2751-2761
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The aim of this work was to study the incidence over time of lower extremity amputations and determine variables associated with increased risk of amputations in people with type 1 diabetes. Methods Individuals with type 1 diabetes registered in the Swedish National Diabetes Registry with no previous amputation from 1 January 1998 and followed to 2 October 2019 were included. Time-updated Cox regression and gradient of risk per SD were used to evaluate the impact of risk factors on the incidence of amputation. Age- and sex-adjusted incidences were estimated over time. Results Of 46,088 people with type 1 diabetes with no previous amputation (mean age 32.5 years [SD 14.5], 25,354 [55%] male sex), 1519 (3.3%) underwent amputation. Median follow-up was 12.4 years. The standardised incidence for any amputation in 1998-2001 was 2.84 (95% CI 2.32, 3.36) per 1000 person-years and decreased to 1.64 (95% CI 1.38, 1.90) per 1000 person-years in 2017-2019. The incidence for minor and major amputations showed a similar pattern. Hyperglycaemia and renal dysfunction were the strongest risk factors for amputation, followed by older age, male sex, cardiovascular comorbidities, smoking and hypertension. Glycaemic control and age- and sex-adjusted renal function improved during the corresponding time period as amputations decreased. Conclusions/interpretation The incidence of amputation and of the most prominent risk factors for amputation, including renal dysfunction and hyperglycaemia, has improved considerably during recent years for people with type 1 diabetes. This finding has important implications for quality of life, health economics and prognosis regarding CVD, indicating a trend shift in the treatment of type 1 diabetes.
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| 25. |
- Hallström, Sara, et al.
(författare)
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Risk factors, mortality trends and cardiovasuclar diseases in people with Type 1 diabetes and controls: A Swedish observational cohort study
- 2022
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Ingår i: Lancet Regional Health-Europe. - : Elsevier BV. - 2666-7762. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background Historically, the incidence of cardiovascular disease and mortality in persons with Type I diabetes (TID) has been increased compared to the general population. Contemporary studies on time trends of mortality and cardiovascular disease are sparse. Methods In this observational study, TID persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141). Incidence rates from 2002 to 2019 were estimated with respect to mortality and cardiovascular disease in persons with TID overall and when stratified for prevalent cardiovascular and renal disease relative to controls. Findings Mean age in persons with TID was 32.4 years and 44.9% (20,446/45,575) were women. Age- and sex-adjusted mortality rates declined over time in both groups but remained significantly higher in those with TID compared to controls during 2017-2019, 7.62 (95% CI 7.16; 8.08) vs. 2.23 (95% CI 2.13; 2.33) deaths per 1,000 person years. Myocardial infarction, heart failure and stroke decreased over time in both groups, with persistent excess risks in the range of 3.4 -5.0 times from 2017 to 2019 in those with TID. TID persons >= 45 years without previous renal or cardiovascular complications had standardized mortality rates similar or even lower than controls 5.55 (4.51; 6.60) vs.7.08 (6.75; 7.40) respectively in the last time period. Interpretation Excess mortality persisted over time in persons with TID, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on individualized treatment is needed to dose the gap in mortality for individuals with TID.
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