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| 2. |
- Christensen, Diana Hedevang, et al.
(författare)
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Type 2 diabetes classification : a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort
- 2022
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A Swedish data-driven cluster study identified four distinct type 2 diabetes (T2D) clusters, based on age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c) level, and homeostatic model assessment 2 (HOMA2) estimates of insulin resistance and beta-cell function. A Danish study proposed three T2D phenotypes (insulinopenic, hyperinsulinemic, and classical) based on HOMA2 measures only. We examined these two new T2D classifications using the Danish Centre for Strategic Research in Type 2 Diabetes cohort. Research design and methods In 3529 individuals, we first performed a k-means cluster analysis with a forced k-value of four to replicate the Swedish clusters: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild age-related (MARD), and mild obesity-related (MOD) diabetes. Next, we did an analysis open to alternative k-values (ie, data determined the optimal number of clusters). Finally, we compared the data-driven clusters with the three Danish phenotypes. Results Compared with the Swedish findings, the replicated Danish SIDD cluster included patients with lower mean HbA1c (86 mmol/mol vs 101 mmol/mol), and the Danish MOD cluster patients were less obese (mean BMI 32 kg/m 2 vs 36 kg/m 2). Our data-driven alternative k-value analysis suggested the optimal number of T2D clusters in our data to be three, rather than four. When comparing the four replicated Swedish clusters with the three proposed Danish phenotypes, 81%, 79%, and 69% of the SIDD, MOD, and MARD patients, respectively, fitted the classical T2D phenotype, whereas 70% of SIRD patients fitted the hyperinsulinemic phenotype. Among the three alternative data-driven clusters, 60% of patients in the most insulin-resistant cluster constituted 76% of patients with a hyperinsulinemic phenotype. Conclusion Different HOMA2-based approaches did not classify patients with T2D in a consistent manner. The T2D classes characterized by high insulin resistance/hyperinsulinemia appeared most distinct.
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| 4. |
- Clementson, Martin, et al.
(författare)
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Acute scaphoid fractures : Guidelines for diagnosis and treatment
- 2020
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Ingår i: EFORT Open Reviews. - : Bioscientifica. - 2396-7544 .- 2058-5241. ; 5:2, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- In cases of suspected scaphoid fracture where the initial radiographs are negative, a supplementary MRI, or alternatively CT, should be carried out within three to five days. Fracture classification, assessment of dislocation as well as evaluation of fracture healing is best done on CT with reconstructions in the coronal and sagittal planes, following the longitudinal axis of the scaphoid. After adequate conservative management, union is achieved at six weeks for approximately 90% of nondisplaced or minimally displaced (≤ 0.5 mm) scaphoid waist fractures. Scaphoid waist fractures with moderate displacement (0.5-1.5 mm) can be treated conservatively, but require prolonged cast immobilization for approximately eight to ten weeks. Internal fixation is recommended for all scaphoid waist fractures with dislocation ≥ 1.5 mm. Distal scaphoid fractures can be treated conservatively. The majority heal uneventfully after four to six weeks of immobilization, depending on fracture type. In general, proximal scaphoid fractures should be treated with internal fixation.
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| 5. |
- Dahlin, Lars B., et al.
(författare)
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Three-dimensional architecture of human diabetic peripheral nerves revealed by X-ray phase contrast holographic nanotomography
- 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
- A deeper knowledge of the architecture of the peripheral nerve with three-dimensional (3D) imaging of the nerve tissue at the sub-cellular scale may contribute to unravel the pathophysiology of neuropathy. Here we demonstrate the feasibility of X-ray phase contrast holographic nanotomography to enable 3D imaging of nerves at high resolution, while covering a relatively large tissue volume. We show various subcomponents of human peripheral nerves in biopsies from patients with type 1 and 2 diabetes and in a healthy subject. Together with well-organized, parallel myelinated nerve fibres we show regenerative clusters with twisted nerve fibres, a sprouted axon from a node of Ranvier and other specific details. A novel 3D construction (with movie created) of a node of Ranvier with end segment of a degenerated axon and sprout of a regenerated one is captured. Many of these architectural elements are not described in the literature. Thus, X-ray phase contrast holographic nanotomography enables identifying specific morphological structures in 3D in peripheral nerve biopsies from a healthy subject and from patients with type 1 and 2 diabetes.
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| 6. |
- Ekman, Linnéa, et al.
(författare)
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Evaluation of small nerve fiber dysfunction in type 2 diabetes
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:1, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. Materials and methods: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). Results: Absent IENF was seen in subjects with T2DM (n = 10; 21%) and IGT (n = 1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r = −.268, P =.013) and Total Neuropathy Score (r = −.219, P =.042). Positive correlations were found between IENFD and sural nerve amplitude (r =.371, P =.001) as well as conduction velocity of both the sural (r =.241, P =.029) and peroneal nerve (r =.258, P =.018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC = 0.887). Conclusions: Signs of neuropathy are becoming more prevalent with decreasing IENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.
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| 7. |
- Hansen, Aleksander L., et al.
(författare)
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Birthweight is associated with clinical characteristics in people with recently diagnosed type 2 diabetes
- 2023
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Ingår i: Diabetologia. - 0012-186X. ; 66:9, s. 1680-1692
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes but it is unknown whether low birthweight is associated with distinct clinical characteristics at disease onset. We examined whether a lower or higher birthweight in type 2 diabetes is associated with clinically relevant characteristics at disease onset. Methods: Midwife records were traced for 6866 individuals with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Using a cross-sectional design, we assessed age at diagnosis, anthropomorphic measures, comorbidities, medications, metabolic variables and family history of type 2 diabetes in individuals with the lowest 25% of birthweight (<3000 g) and highest 25% of birthweight (>3700 g), compared with a birthweight of 3000–3700 g as reference, using log-binomial and Poisson regression. Continuous relationships across the entire birthweight spectrum were assessed with linear and restricted cubic spline regression. Weighted polygenic scores (PS) for type 2 diabetes and birthweight were calculated to assess the impact of genetic predispositions. Results: Each 1000 g decrease in birthweight was associated with a 3.3 year (95% CI 2.9, 3.8) younger age of diabetes onset, 1.5 kg/m2 (95% CI 1.2, 1.7) lower BMI and 3.9 cm (95% CI 3.3, 4.5) smaller waist circumference. Compared with the reference birthweight, a birthweight of <3000 g was associated with more overall comorbidity (prevalence ratio [PR] for Charlson Comorbidity Index Score ≥3 was 1.36 [95% CI 1.07, 1.73]), having a systolic BP ≥155 mmHg (PR 1.26 [95% CI 0.99, 1.59]), lower prevalence of diabetes-associated neurological disease, less likelihood of family history of type 2 diabetes, use of three or more glucose-lowering drugs (PR 1.33 [95% CI 1.06, 1.65]) and use of three or more antihypertensive drugs (PR 1.09 [95% CI 0.99, 1.20]). Clinically defined low birthweight (<2500 g) yielded stronger associations. Most associations between birthweight and clinical characteristics appeared linear, and a higher birthweight was associated with characteristics mirroring lower birthweight in opposite directions. Results were robust to adjustments for PS representing weighted genetic predisposition for type 2 diabetes and birthweight. Conclusion/interpretation: Despite younger age at diagnosis, and fewer individuals with obesity and family history of type 2 diabetes, a birthweight <3000 g was associated with more comorbidities, including a higher systolic BP, as well as with greater use of glucose-lowering and antihypertensive medications, in individuals with recently diagnosed type 2 diabetes.
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| 8. |
- Ising, Erik, et al.
(författare)
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Quantification of heat shock proteins in the posterior interosseous nerve among subjects with type 1 and type 2 diabetes compared to healthy controls
- 2023
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Ingår i: Frontiers in Neuroscience. - : FRONTIERS MEDIA SA. - 1662-4548 .- 1662-453X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 (T1D) and type 2 diabetes (T2D). No cure for DPN is available, but several potential targets have been proposed for treatment. Heat shock proteins (HSPs) are known to respond to both hyper- and hypoglycemia. DPN can be diagnosed using electrophysiology and studied using peripheral nerve biopsies.Aim: This study aimed to analyze the presence and patterns of HSPs in peripheral nerve biopsies from subjects with T1D, T2D, and healthy controls.Methods: Posterior interosseous nerves (PIN) from a total of 56 subjects with T1D (n = 9), with T2D (n = 24), and without diabetes (i.e., healthy controls, n = 23) were harvested under local anesthesia and prepared for quantitative mass spectrometry analysis. Protein intensities were associated with electrophysiology data of the ulnar nerve and morphometry of the same PIN, and differences in protein intensities between groups were analyzed.Results: In total, 32 different HSPs were identified and quantified in the nerve specimens. No statistically significant differences were observed regarding protein intensities between groups. Furthermore, protein intensities did not correlate with amplitude or conduction velocity in the ulnar nerve or with the myelinated nerve fiber density of PIN.Conclusion: Quantitative proteomics can be used to study HSPs in nerve biopsies, but no clear differences in protein quantities were observed between groups in this cohort.
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| 9. |
- Ising, Erik, et al.
(författare)
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Quantitative proteomic analysis of human peripheral nerves from subjects with type 2 diabetes
- 2021
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Ingår i: Diabetic Medicine: A journal of the British Diabetic Association. - : Wiley. - 1464-5491. ; 38:11
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes (T2D). The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior interosseous nerve (PIN) have proposed PIN a useful indicator of DPN.METHODS: A quantitative mass spectrometry-based proteomics analysis was made of peripheral nerves from age- and gender-matched living human male tissue donors; nine T2D subjects, with decreased sural nerve action potentials indicating DPN, and six controls without T2D, with normal electrophysiology results.RESULTS: A total of 2617 proteins were identified. Linear regression was used to discover which proteins were differentially expressed between T2D and controls. Only soft signals were found. Therefore, clustering of the 500 most variable proteins were made in order to find clusters of similar proteins in T2D subjects and healthy controls.CONCLUSIONS: This feasibility study shows, for the first time, that the use of quantitative mass spectrometry enables quantification of proteins from nerve biopsies from subjects with and without T2D, which may aid in finding biomarkers of importance to DPN development.
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| 10. |
- Jorgsholm, Peter, et al.
(författare)
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Epidemiology of scaphoid fractures and non-unions: A systematic review
- 2020
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Ingår i: Handchirurgie Mikrochirurgie Plastische Chirurgie. - : Georg Thieme Verlag KG. - 0722-1819 .- 1439-3980. ; 52:5, s. 374-381
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Tidskriftsartikel (refereegranskat)abstract
- Background The scaphoid is the most commonly fractured carpal bone in adults as well as in children. Previous studies have reported a wide range of fracture incidences. Scaphoid fractures and non-unions in children have been sparsely investigated. Aim To perform a systematic review of the current literature on epidemiology of scaphoid fractures and non-unions in adults and children. Methods An electronic literature search was conducted investigating all studies in the literature published between January 1989 and June 23 2020. The systematic review following the PRISMA guidelines and searching in PubMed, Embase, Web of Science and Cochrane library databases was done in June 2020. Results 42 studies met our inclusion criteria, 6 studies were prospective, 32 were retrospective and 4 were register studies. The majority of studies relied on conventional radiographs for diagnosis. Scaphoid fractures in adults are predominately found in males with a peak incidence in the age group from 20 to 29 years. Incidence rates in males are reported from 107 to 151/100 000. Females have an earlier peak, in the age group 10 to 19 years, with an incidence from 14 to 46/100 000. Most fractures occur in the middle third of the scaphoid representing 60 69 % of cases. Scaphoid fractures in children are predominately found in boys age 12 and above, while it seldomly occur for children younger than 9 years. In adults the risk for developing a scaphoid non-union is between 2 % and 5 %, the majority affecting males and predominately located at the middle third of the scaphoid. Non-unions among children are rare and mainly due to missed or delayed diagnosis of a fracture in the middle third of the scaphoid. Conclusion This review revealed a substantial heterogeneity among studies concerning study population, diagnosis criterial and outcome measures. Currently, evidence on epidemiology for scaphoid fractures and non-unions are low. © 2020 American Institute of Physics Inc.. All rights reserved.
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