| 31. |
- 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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| 32. |
- Hellstrom-Lindahl, E., et al.
(författare)
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Toward molecular imaging of the free fatty acid receptor 1
- 2017
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 54:7, s. 663-668
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Tidskriftsartikel (refereegranskat)abstract
- Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling. In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([H-3]AZ1, [H-3]AZ2 and [H-3]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma. [H-3]AZ1 showed improved specificity to FFAR1, with decreased off-target binding compared to [H-3]AZ2 and [H-3]TAK-875, while retaining high affinity in the nanomolar range. FFAR1 density in human islets was approximately 50% higher than in exocrine tissue. AZ1 is a suitable lead compound for PET labeling for molecular imaging of FFAR1 in humans, due to high affinity and reduced off-target binding.
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| 33. |
- Hellström-Lindahl, Ewa, et al.
(författare)
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GPR44 is a pancreatic protein restricted to the human beta cell
- 2016
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 53:3, s. 413-421
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To address questions regarding onset and progression of types 1 and 2 diabetes (T1D/T2D), surrogate imaging biomarkers for beta cell function and mass are needed. Here, we assess the potential of GPR44 as a surrogate marker for beta cells, in a direct comparison with clinically used biomarker VMAT2.METHODS: GPR44 surface availability was assessed by flow cytometry of human beta cells. RNA transcription levels in different pancreas compartments were evaluated. The density of GPR44 receptor in endocrine and exocrine tissues was assessed by the radiolabeled GPR44 ligand [(3)H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [(3)H]DTBZ.RESULTS: GPR44 was available on the cell surface, and pancreatic RNA levels were restricted to the islets of Langerhans. [(3)H]AZD 3825 had nanomolar affinity for GPR44 in human islets and EndoC-βH1 beta cells, and the specific binding to human beta cells was close to 50 times higher than in exocrine preparations. The endocrine-to-exocrine binding ratio was approximately 10 times higher for [(3)H]AZD 3825 than for [(3)H]DTBZ.CONCLUSION: GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas.
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| 34. |
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| 35. |
- Hopfgarten, Johan, et al.
(författare)
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Gene expression analysis of human islets in a subject at onset of type 1 diabetes
- 2014
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 51:2, s. 199-204
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Tidskriftsartikel (refereegranskat)abstract
- Swollen islet cells have been repeatedly described at onset of type 1 diabetes, but the underlying mechanism of this observation, termed hydropic degeneration, awaits characterization. In this study, laser capture microdissection was applied to extract the islets from an organ donor that died at onset of type 1 diabetes and from an organ donor without pancreatic disease. Morphologic analysis revealed extensive hydropic degeneration in 73 % of the islets from the donor with type 1 diabetes. Expression levels of genes involved in apoptosis, ER stress, beta cell function, and inflammation were analyzed in isolated and laser-captured islets by qPCR. The chemokine MCP-1 was expressed in islets from the donor with type 1 diabetes while undetectable in the control donor. No other signs of inflammation were detected. There were no signs of apoptosis on the gene expression level, which was also confirmed by negative immunostaining for cleaved caspase-8. There was an increased expression of the transcription factor ATF4, involved in transcription of ER stress genes, in the diabetic islets, but no further signs of ER stress were identified. In summary, on the transcription level, islets at onset of type 1 diabetes in which many beta cells display hydropic degeneration show no obvious signs of apoptosis, ER stress, or inflammation, supporting the notion that these cells are responding normally to high glucose and eventually succumbing to beta cell exhaustion. Also, this study validates the feasibility of performing qPCR analysis of RNA extracted from islets from subjects with recent onset of T1D and healthy controls by laser capture microdissection.
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| 36. |
- Håglin, Lena, et al.
(författare)
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Prediction of all-cause mortality in a patient population with hypertension and type 2 DM by using traditional risk factors and serum-phosphate, -calcium and -magnesium.
- 2007
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Ingår i: Acta Biabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 44:3
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to investigate whether the prediction of all-cause mortality from traditional risk factors is improved by adding electrolytes (serum-phosphate (S-P), serum-calcium (S-Ca) and serum-magnesium (S-Mg)) in a Cox regression. The study uses an 18-year follow-up of patients (n=2504) referred by physicians in primary health care and hospitals to the Vindeln Patient Education (VPE) Center, mainly with a diagnosis of hypertension (HT), type 2 diabetes mellitus (DM) and/or obesity.Cox regression, with the latest registered value and baseline values for risk factors, was used to study all-cause mortality in men and women. 221 out of 1096 men and 157 out of 1408 women died during the 18-year follow-up (20% and 11% respectively). The Cox regression analysis reveals that high blood glucose (B-Glu) and low S-Mg were significantly associated with increased all-cause mortality in the whole patient population as well as in men and women separately. Among women, type 2 DM and systolic blood pressure (SBP) and among men, high S-Ca, S-P, S-urate and body mass index (BMI) were the main predictors of all-cause mortality. There is significantly improved prediction of all-cause mortality with electrolytes added to the traditional risk factors. High B-Glu and low S-Mg in both men and women, and high S-Ca and S-P in men, are significantly associated with all-cause mortality. The metabolic disturbance in this high-risk group of patients can be more fully understood if ionic imbalance is included in the prediction of mortatlity.
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| 37. |
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| 38. |
- Ignell, Claes, et al.
(författare)
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The impact of ethnicity on glucose homeostasis after gestational diabetes mellitus.
- 2013
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429. ; 50:6, s. 927-934
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to examine measures of insulin resistance and beta cell function in relation to ethnicity and the development of diabetes after gestational diabetes mellitus (GDM). Glucose homeostasis was assessed during a 75 g oral glucose tolerance test 1-2 years after delivery in 456 women with previous GDM (362 European, 94 non-European; including 41 Arab and 43 Asian women) and 133 control women. Insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). The insulinogenic index (I/G30) and the disposition index [(I/G30)/HOMA-IR] were used to quantify insulin secretion. Women developing diabetes after GDM were characterized by increased HOMA-IR [p = 0.010, adjusted for body mass index (BMI)], whereas the disposition index was decreased in all women with previous GDM irrespective of glucose tolerance, most pronounced in the presence of diabetes (BMI-adjusted p = 1 × 10(-5)). Non-European origin was associated with increased HOMA-IR (p = 0.001 vs. European), strengthened by adjustment for BMI in Asian women (p = 0.046 vs. p = 0.016), but eradicated among Arab women (p = 0.004 vs. p = 0.65). Non-European women exhibited an increased frequency of diabetes after GDM (17 % vs. European 4 %, p = 2 × 10(-5)). In addition to BMI, non-European and Asian origin was associated with the development of diabetes after GDM in a multivariate logistic regression analysis, whereas Arab origin was not. Our results highlight the importance of preventive measures to ensure a healthy lifestyle in women with GDM, particularly in high-risk ethnic groups.
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| 39. |
- Inkeri, J., et al.
(författare)
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Carotid intima-media thickness and arterial stiffness in relation to cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes
- 2021
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 58:7, s. 929-937
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Tidskriftsartikel (refereegranskat)abstract
- Aims To determine if arterial functional and structural changes are associated with underlying cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes. Methods We enrolled 186 individuals (47.8% men; median age 40.0, IQR 33.0-45.0 years) with type 1 diabetes (median diabetes duration of 21.6, IQR 18.2-30.3 years), and 30 age- and sex-matched healthy controls, as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. All individuals underwent a biochemical work-up, brain magnetic resonance imaging (MRI), ultrasound of the common carotid arteries and arterial tonometry. Arterial structural and functional parameters were assessed by carotid intima-media thickness (CIMT), pulse wave velocity and augmentation index. Results Cerebral microbleeds (CMBs) were present in 23.7% and white matter hyperintensities (WMHs) in 16.7% of individuals with type 1 diabetes. Those with type 1 diabetes and CMBs had higher median (IQR) CIMT 583 (525 - 663) mu m than those without 556 (502 - 607) mu m, p = 0.016). Higher CIMT was associated with the presence of CMBs (p = 0.046) independent of age, eGFR, ApoB, systolic blood pressure, albuminuria, history of retinal photocoagulation and HbA(1c). Arterial stiffness and CIMT were increased in individuals with type 1 diabetes and WMHs compared to those without; however, these results were not independent of cardiovascular risk factors. Conclusions Structural, but not functional, arterial changes are associated with underlying CMBs in asymptomatic individuals with type 1 diabetes.
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| 40. |
- Inkeri, J., et al.
(författare)
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Glycemic control is not related to cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes
- 2022
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 59, s. 481-490
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Tidskriftsartikel (refereegranskat)abstract
- Aims To determine if medium- and long-term blood glucose control as well as glycemic variability, which are known to be strong predictors of vascular complications, are associated with underlying cerebral small vessel disease (cSVD) in neurologically asymptomatic individuals with type 1 diabetes. Methods A total of 189 individuals (47.1% men; median age 40.0, IQR 33.0-45.2 years) with type 1 diabetes (median diabetes duration of 21.7, IQR 18.3-30.7 years) were enrolled in a cross-sectional retrospective study, as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Glycated hemoglobin (HbA(1c)) values were collected over the course of ten years before the visit including a clinical examination, biochemical sampling, and brain magnetic resonance imaging. Markers of glycemic control, measured during the visit, included HbA(1c), fructosamine, and glycated albumin. Results Signs of cSVD were present in 66 (34.9%) individuals. Medium- and long-term glucose control and glycemic variability did not differ in individuals with signs of cSVD compared to those without. Further, no difference in any of the blood glucose variables and cSVD stratified for cerebral microbleeds (CMBs) or white matter hyperintensities were detected. Neither were numbers of CMBs associated with the studied glucose variables. Additionally, after dividing the studied variables into quartiles, no association with cSVD was observed. Conclusions We observed no association between glycemic control and cSVD in neurologically asymptomatic individuals with type 1 diabetes. This finding was unexpected considering the large number of signs of cerebrovascular pathology in these people after two decades of chronic hyperglycemia and warrants further studies searching for underlying factors of cSVD.
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