| 21. |
- Eriksson, Olof, et al.
(författare)
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Species differences in pancreatic binding of DO3A-VS-Cys40-Exendin4
- 2017
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 54:11, s. 1039-1045
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Radiolabeled Exendin-4 has been proposed as suitable imaging marker for pancreatic beta cell mass quantification mediated by Glucagon-like peptide-1 receptor (GLP-1R). However, noticeable species variations in basal pancreatic uptake as well as uptake reduction degree due to selective beta cell ablation were observed.METHODS: -Exendin4 Positron Emission Tomography (PET) in the same species. In vitro, ex vivo, and in vivo data formed the basis for calculating the theoretical in vivo contribution of each pancreatic compartment.RESULTS: -Exendin4.CONCLUSIONS: IPR as well as the exocrine GLP-1R density is the main determinants of the species variability in pancreatic uptake. Thus, the IPR in human is an important factor for assessing the potential of GLP-1R as an imaging biomarker for pancreatic beta cells.
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| 22. |
- Espes, Daniel, 1985-, et al.
(författare)
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Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI
- 2019
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Ingår i: Acta Diabetologica. - : Springer. - 0940-5429 .- 1432-5233. ; 56:10, s. 1113-1120
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Perfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique.METHODS: Pigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose.RESULTS: Pancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p < 0.01). The absolute quantification of pancreatic perfusion (ml/min/g) by [15O]H2O PET was within a 15% error of margin of the microsphere technique.CONCLUSION: Pancreatic perfusion by [15O]H2O PET was in agreement with the microsphere technique assessment. The IVIM MRI method has the potential to replace [15O]H2O PET if the pancreatic perfusion is sufficiently large, but not when absolute quantitation is required.
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| 23. |
- Fagher, Katarina, et al.
(författare)
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The combined impact of ankle–brachial index and transcutaneous oxygen pressure on mortality in patients with type 2 diabetes and foot ulcers
- 2021
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 58:10, s. 1359-1365
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Tidskriftsartikel (refereegranskat)abstract
- Aims: A diabetic foot ulcer (DFU) is associated with increased cardiovascular risk and mortality, independently of ulcer etiology (ischemic, neuro-ischemic or neuropathic). Ankle–brachial index (ABI) is the most commonly used test when diagnosing peripheral macrovascular disease and is a well-known marker for increased cardiovascular risk. Transcutaneous oxygen pressure (TcPO2) is considered to better evaluate microvascular function and has in previous studies shown correlations with both wound healing and survival. The aim of this study was to evaluate the combined impact of a low TcPO2 (<30 mmHg) and a pathological ABI (<0.9 or ≥1.4) on three-year mortality in patients with DFU. Methods: Type 2 diabetes patients aged <90 years, with at least one DFU who underwent vascular assessment with ABI and TcPO2 were screened for participation. The primary endpoint was mortality after three years, assessed from the National Death Registry in Sweden. Results: The study enrolled 235 participants with a median age of 76 years. Individuals with either an abnormally high or low ABI in combination with a low TcPO2 had the worst survival rates, with three-year mortality of 54%, compared to 42% in those with one abnormal variable (either ABI or TcPO2), and 21% in those with normal ABI and TcPO2. Conclusions: Combining ABI and TcPO2 when risk stratifying DFU patients seems to provide additional predictive information, not only concerning ulcer healing and limb salvage, but also on survival.
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| 24. |
- Fagher, K., et al.
(författare)
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Transcutaneous oxygen pressure as a predictor for short-term survival in patients with type 2 diabetes and foot ulcers : a comparison with ankle–brachial index and toe blood pressure
- 2018
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 55:8, s. 781-788
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Ankle–brachial index (ABI) is the most commonly used test when diagnosing peripheral vascular disease and is considered a marker for cardiovascular risk. Transcutaneous oxygen pressure (TcPO2), a test associated with microvascular function, has in several studies shown better correlation with diabetic foot ulcer (DFU) healing. Whether a low TcPO2 could be a marker for mortality in the high-risk population of DFU patients has not been evaluated before. The aim of this study was to evaluate the predictive value of TcPO2 in comparison with ABI and toe blood pressure (TBP) on 1-year mortality in type 2 diabetes patients with DFU. Methods: Type 2 diabetes patients aged ≤ 90 years, with one DFU who attended our multidisciplinary DFU-unit during year 2013–2015 and were screened with TcPO2, ABI and TBP were retrospectively evaluated. One-year mortality was assessed from the national death register in Sweden. Results: A total of 236 patients (30% women) with a median age of 76 (69–82) years were evaluated in this study. Within 1 year, 14.8% of the patients died. TcPO2 < 25 mmHg was associated with a higher 1-year mortality compared with TcPO2 ≥ 25 mmHg (27.7 vs. 11.6%, p = 0.003). TBP and ABI did not significantly influence 1-year mortality. In a Cox regression analysis adjusted for confounders, TcPO2 was independently predicting 1-year mortality with a hazard ratio for TcPO2 < 25 mmHg of 2.8 (95% CI 1.34–5.91, p = 0.006). Conclusions: This study indicates that a low TcPO2 is an independent prognostic marker for 1-year mortality among patients with type 2 diabetes and DFU.
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| 25. |
- Fugmann, Andreas, et al.
(författare)
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Blood flow is an important determinant of forearm glucose uptake following a mixed meal
- 2003
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 40:3, s. 113-117
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-mediated vasodilation has been suggested to be of importance for glucose uptake during normoglycemic hyperinsulinemia. If this also is valid after an ordinary mixed meal remains to be evaluated. Forearm blood flow (FBF) and forearm glucose uptake change (evaluated by venous occlusion plethysmography) and glucose arteriovenous differences were evaluated over 120 minutes in 10 healthy volunteers following an ordinary mixed meal (700-900 kcal, 34% of energy from fat). Fasting arterial glucose level was 4.9+/-0.9 mmol/l, and the maximum glucose level was reached 30 minutes after the start of ingestion (6.6+/-0.8 mmol/l, p<0.0001). Plasma insulin levels were increased four-fold. FBF increased rapidly within 20 minutes after the start of ingestion and reached its maximum after 50 minutes (94% higher than baseline level, p<0.01). After 2 hours FBF was still substantially elevated (75% above baseline level, p<0.01). Forearm glucose uptake increased fivefold already after 20 minutes ( p<0.01). During the 2 hours, the increase in FBF contributed to 41% of the forearm glucose uptake ( p<0.05). The present study showed that the increase in FBF seen after an ordinary mixed meal is important for the change in forearm glucose uptake. These results support the view that modulation of limb blood flow is a determinant of glucose uptake.
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| 26. |
- Fugmann, Andreas, et al.
(författare)
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The effect of euglucaemic hyperinsulinaemia on forearm blood flow and glucose uptake in the human forearm
- 1998
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 35:4, s. 203-206
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-mediated stimulation of blood flow to skeletal muscle has been proposed to be of major importance for insulin-mediated glucose uptake. The aim of this study was to investigate the relative importance of blood flow and glucose extraction as determinants of insulin-mediated glucose uptake in the human forearm. Forearm blood flow (FBF), glucose extraction and oxygen consumption were evaluated for 100 min during the euglycaemic hyperinsulinaemic clamp (92 mU/l) in nine healthy subjects. FBF was measured by venous occlusion plethysmography. Forearm glucose uptake increased sevenfold during the hyperinsulinaemia (P<0.001). Forearm glucose extraction showed a minor increase during the first 10 min of hyperinsulinaemia, but the most marked increase took place between 10 and 20 min (+170%). Thereafter, only a minor further increase was seen. During the first 10 min of hyperinsulinaemia FBF was unchanged. Thereafter, FBF increased steadily to a plateau reached after 60 min (+50%, P<0.001). A close relationship between whole body glucose uptake and FBF was seen at the end of the clamp (r = 0.75, P<0.02), but at this time the relationship between whole body glucose uptake and forearm glucose extraction was not significant. The modest increase in O2 consumption seen at the beginning of the clamp (+19%) was not related to FBF during the early phase of the clamp. In conclusion, the early course of insulin-mediated glucose uptake in the human forearm was mainly due to an increase in glucose extraction. However, with time the insulin-mediated increase in blood flow increased in importance and after 100 min of hyperinsulinaemia FBF was the major determinant of glucose uptake.
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| 27. |
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| 28. |
- Granlund, Louise, 1992-, et al.
(författare)
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Extra-islet cells expressing insulin or glucagon in the pancreas of young organ donors
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Ingår i: Acta Diabetologica. - 0940-5429 .- 1432-5233.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aims: The existence of insulin- or glucagon-expressing extra-islet endocrine cells scattered in the pancreas is well-known, but they have been sparsely characterized. The aim of this study was to examine their density, distribution, transcription-factor expression, and mitotic activity in young non-diabetic subjects.Methods: Multispectral imaging was used to examine PDX1, ARX, Ki67, insulin and glucagon in extra-islet endocrine cells in pancreatic tissue from organ donors aged 1-25 years.Results: Extra-islet insulin- or glucagon-positive cells were frequent in all donors (median 17.3 and 22.9 cells/mm2 respectively), with an insulin:glucagon cell ratio of 0.9. The density was similar regardless of age. PDX1 localized mainly to insulin-, and ARX mainly to glucagon-positive cells but, interestingly, many of the cells were negative for both transcription factors. Double-hormone-positive cells were rare but found in all age groups, as were insulin-positive cells expressing ARX and glucagon-positive cells expressing PDX1. Extra-islet endocrine cells with Ki67 expression were present but rare in all age groups (0-2%).Conclusions: Extra-islet endocrine cells are more frequent than islets. The preserved density during pancreas expansion from childhood- to adulthood indicates that new cells are formed, likely from replication, as cells with mitotic activity were discovered. The lack of transcription-factor expression in many cells could indicate that they are immature, newly formed or plastic. This, together with the mitotic activity, suggest that these cells play an important role in the expansion of beta-cell mass in situations of increasing demand, or in the turnover of the endocrine cell population.
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| 29. |
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| 30. |
- Haupt, Dan, et al.
(författare)
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Refill adherence to oral antihyperglycaemic drugs in Sweden
- 2009
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 46:3, s. 203-208
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Tidskriftsartikel (refereegranskat)abstract
- Only 49% of the patients with T2D in Sweden that medicate with oral antihyperglycaemic drugs (AHGD) had good blood glucose control (HbA1C < 6.0%). The reason can be low medication adherence. The aim of this study was, therefore, to determine the adherence to different oral AHGD. Included were all patients in Sweden, older than 40 years and having at least two expenditures of AHGD between 1 December 2005 and 30 November 2006. After exclusions of inpatients and patients with unspecified daily dosage 171,220 patients (57% men) remained. Medication possession ratio (MPR) was used for estimating adherence and patients were regarded adherent if MPR ≥80%. The overall refill adherence average 90%, with mean MPR (SD) = 107% (30). Eighty-five percent of the patients in their 40s were adherent compared to 91% of the patients in their 80s. About 90.1% of the women were adherent whereas 89.5% of the men were adherent. Patients with an indication for the medicine were more adherent than patients without this information. We conclude that the unsatisfactory blood glucose control showed among many Swedish T2D patients is not the result of non-adherence to prescribed medication.
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