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21.
  • Pourhamidi, Kaveh, et al. (författare)
  • Heat shock protein 27 is associated with better nerve function and fewer signs of neuropathy
  • 2011
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 54:12, s. 3143-3149
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis High levels of serum heat shock protein 27 (sHSP27) have been associated with distal symmetric polyneuropathy in patients with type 1 diabetes. Our objective was to investigate the association between sHSP27, neuropathic signs and nerve function in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes.Methods Participants were recruited consecutively from the population-based Vasterbotten Intervention Program (NGT, n=39, IGT, n=29, and type 2 diabetes, n=51) and were matched for age and sex. sHSP27 levels were measured and nerve conduction studies were performed (peroneal and sural nerves). z Scores for each nerve conduction measure were calculated and compiled into a composite z score for the leg. Neuropathy disability score (NDS) was used to assess neuropathic signs.Results Patients with diabetes had significantly lower sHSP27 levels (geometric mean sHSP27 206 pg/ml, 95% CI 142, 299) than those with IGT (geometric mean sHSP27 455 pg/ml, 95% CI 319, 650, p<0.05) and controls (geometric mean sHSP27 361 pg/ml, 95% CI 282, 461, p<0.05). Participants with few signs of neuropathy (first tertile, NDS <= 2) had significantly higher sHSP27 levels (geometric mean sHSP27 401 pg/ml, 95% CI 310, 520) than participants with many signs (third tertile, NDS >= 7) (geometric mean sHSP27 192 pg/ml, 95% CI 128, 288, p=0.007). The highest sHSP27 tertile was associated with better nerve function, adjusted for age, sex, statin medication and HbA(1c) (OR 2.51, 95% CI 1.25, 5.05, p<0.05).Conclusions/interpretation High sHSP27 levels were associated with better nerve function and fewer neuropathic signs in NGT, IGT and type 2 diabetes.
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22.
  • Pourhamidi, Kaveh, 1985- (författare)
  • Peripheral nerve function : metabolic features, clinical assessment, and heat shock protein 27
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Peripheral neuropathy is a common complication among patients with diabetes mellitus, but whether peripheral neuropathy is present in individuals with impaired glucose tolerance (IGT) is debatable. In order to identify and diagnose peripheral neuropathy correctly, it is important to evaluate diagnostic tools that can be implemented in routine health care to assess both large and small nerve fibre function. There is currently limited knowledge about neuroprotective factors that could be useful for measuring peripheral nerve function in individuals at risk of developing neuropathy such as those with diabetes mellitus. Thus, studies are needed to investigate potential neuroprotective factors in relation to peripheral nerve function in humans.Objectives: The overall goal of this thesis was to study the metabolic features and clinical assessment of peripheral nerve function and the potential relationship between the neuroprotective factor heat shock protein 27 (HSP27) and peripheral nerve function.Methods: Thirty-nine participants with normal glucose tolerance (NGT) and 29 participants with IGT were recruited from the population-based Västerbotten Intervention Programme in 2003–2004. Patients with type 2 diabetes mellitus (T2DM, n = 51) were recruited from primary health care centres. NGT and IGT individuals underwent two separate oral glucose tolerance tests to verify their glucose status. The peripheral nerve function in the lower limb was assessed by nerve conduction studies, neuropathy disability scoring, quantitative sensory tests, and skin biopsies with subsequent quantification of intraepidermal nerve fibre density (IENFD). The concentrations of HSP27 in serum were determined in the NGT, IGT, and T2DM individuals. Patients with type 1 diabetes mellitus (T1DM) were recruited from the Diabetes Clinic, Skåne University Hospital in Malmö, Sweden (n = 27) in 1992 and were followed-up in 2005. Baseline and follow-up concentrations of HSP27 were determined in T1DM patients as well as in healthy non-diabetic controls (n = 397). The T1DM patients underwent nerve conduction studies and thermal and vibration perception threshold tests at baseline and at follow-up. Delta changes in HSP27 concentrations and small and large nerve fibre function were calculated.Results: There was no difference between IGT and NGT in sural nerve conduction, intraepidermal nerve fibre density, or thermal thresholds. The biothesiometer had a sensitivity of 82% and a specificity of 72% in identifying peripheral neuropathy with a cut-off value of ≥24.5 V at the medial malleolus. Adding the quantification of IENFD to the combination of the tuning fork and biothesiometer increased the diagnostic sensitivity from 81% to 95%, the negative predictive value from 87% to 94%, and the positive likelihood ratio from 1.8 to 1.9 when identifying small nerve fibre dysfunction. T2DM patients had lower HSP27 concentrations (mean HSP27 = 412 pg/mL, 95% CI 284–598 pg/mL) than NGT (mean HSP27 = 722 pg/mL, 95% CI 564–922 pg/mL) and IGT (mean HSP27 = 1010 pg/mL, 95% CI 638–1300 pg/mL) individuals (p <0.05 for both comparisons). T1DM patients had lower HSP27 concentrations at baseline (mean HSP27 = 547 pg/mL, 95% CI 421–711 pg/mL) and at follow-up (mean HSP27 = 538 pg/mL, 95% CI 417–693 pg/mL) compared to healthy controls (mean HSP27 = 785 pg/mL, 95% CI 732–842 pg/mL), p <0.05 for both comparisons). High concentrations of HSP27 were associated with better large nerve fibre function (Odds ratio = 2.51, 95% CI 1.25–5.05, p <0.05). Deteriorating large nerve fibre function correlated with decreasing HSP27 concentrations over time in T1DM patients (r = 0.50, p = 0.01).Conclusions: Measures of large and small nerve fibre function in IGT individuals do not differ significantly from NGT individuals. The existence of peripheral neuropathy as a consequence of IGT is not likely, and extensive control of neuropathy in IGT individuals is not advocated by this thesis. The biothesiometer is a useful clinical tool to identify peripheral neuropathy in routine health care. Quantification of IENFD using skin biopsies in combination with methods measuring vibrotactile sense, such as the biothesiometer and the tuning fork, increase the diagnostic usefulness of identifying small nerve fibre dysfunction. High HSP27 concentrations are associated with better peripheral large nerve fibre function. Patients with diabetes mellitus have lower HSP27 concentrations than healthy non-diabetic controls, and deterioration of large nerve fibre function correlates with a decrease in HSP27 concentrations over time in T1DM. This could be indicative of insufficient neuroprotection in patients with diabetes mellitus.
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23.
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24.
  • Robledo-Sierra, J., et al. (författare)
  • A mechanistic linkage between oral lichen planus and autoimmune thyroid disease
  • 2018
  • Ingår i: Oral Diseases. - : John Wiley & Sons. - 1354-523X .- 1601-0825. ; 24:6, s. 1001-1011
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions. Subjects and MethodsVenous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT4-). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects. ResultsNo association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT4- group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa. ConclusionsA significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP.
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25.
  • Rosengren, Björn, et al. (författare)
  • Inferior physical performance test results of 10,998 men in the MrOS Study is associated with high fracture risk.
  • 2012
  • Ingår i: Age and ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 41:3, s. 339-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: most fractures are preceded by falls. Objective: the aim of this study was to determine whether tests of physical performance are associated with fractures. Subjects: a total of 10,998 men aged 65 years or above were recruited. Methods: questionnaires evaluated falls sustained 12 months before administration of the grip strength test, the timed stand test, the six-metre walk test and the twenty-centimetre narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.05 is a statistically significant difference. Results: fallers with a fracture performed worse than non-fallers on all tests (all P < 0.001). Fallers with a fracture performed worse than fallers with no fractures both on the right-hand-grip strength test and on the six-metre walk test (P < 0.001). A score below –2 standard deviations in the right-hand-grip strength test was associated with an odds ratio of 3.9 (95% CI: 2.1–7.4) for having had a fall with a fracture compared with having had no fall and with an odds ratio of 2.6 (95% CI: 1.3–5.2) for having had a fall with a fracture compared with having had a fall with no fracture. Conclusion: the right-hand-grip strength test and the six-metre walk test performed by old men help discriminate fallers with a fracture from both fallers with no fracture and non-fallers.
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26.
  • Sarwar, Nadeem, et al. (författare)
  • Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
  • 2012
  • Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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27.
  • Spångeus, Anna, Bitr Professor, 1975-, et al. (författare)
  • Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection
  • 2024
  • Ingår i: Osteoporosis International. - : SPRINGER LONDON LTD. - 0937-941X .- 1433-2965. ; 35:1, s. 173-180
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary: We assessed the prevalence of hypocalcemia after denosumab injections in a real-world cohort routinely monitored for calcium during up to 7.5 years of treatment. Among 1096 injections in 242 patients, 6.3% resulted in hypocalcemia, and was independent of the injection number. Severe hypocalcemia was rare (1%).Purpose: To assess the prevalence of and risk factors for hypocalcemia after administration of denosumab in a patient cohort routinely monitored for ionized calcium after each dose.Methods: In this retrospective observational study, we analyzed denosumab-induced hypocalcemia in a real-world cohort who were routinely followed up with ionized calcium pre- and post-injection (within 31 days after injection) during the period 2011 to 2020.Results: In total, we included data from 1096 denosumab injections in 242 individuals (1–15 injections per patient). The mean age for the first injection was 74 ± 10 years, and 88% were female. Post-injection hypocalcemia occurred after 6.3% of all injections (4.6% mild, 0.6% moderate, and 1.1% severe) and was independent of the number of injections (rate of hypocalcemia varied from 3–8%). Risk factors for hypocalcemia were male sex, severe renal failure, pre-injection hypocalcemia, hypomagnesemia, hypophosphatemia, and vitamin D insufficiency. Furthermore, older age was not associated with an increased hypocalcemia risk.Conclusions: Denosumab-induced hypocalcemia is a prevalent adverse event, which occurs independently of the number of injections. However, severe hypocalcemia is a rare occurrence, and severe renal failure and nutritional status appear to be important predictive factors. Magnesium and phosphate might add value in the pre-injection risk assessment; however, this observation needs to be confirmed in larger cohorts.
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28.
  • Steineck, I., et al. (författare)
  • Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study
  • 2015
  • Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 350
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes. Design Observational study. 18 168 people with type 1 diabetes, 2441 using insulin pump therapy and 15 727 using multiple daily insulin injections. Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases. Follow-up was for a mean of 6.8 years until December 2012, with 114 135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in > 80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association. Among people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections.
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29.
  • Sundbom, Magnus, et al. (författare)
  • Substantial Decrease in Comorbidity 5 Years After Gastric Bypass: A Population-based Study From the Scandinavian Obesity Surgery Registry.
  • 2017
  • Ingår i: Annals of Surgery. - Philadelphia PA, USA : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 265:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate effect on comorbid disease and weight loss 5 years after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity in a large nationwide cohort. Background: The number patients having surgical procedures to treat obesity and obesity-related disease are increasing. Yet, population-based, long-term outcome studies are few. Methods: Data on 26,119 individuals [75.8% women, 41.0 years, and body mass index (BMI) 42.8 kg/m2] undergoing primary RYGB between May 1, 2007 and June 30, 2012, were collected from 2 Swedish quality registries: Scandinavian Obesity Surgery Registry and the Prescribed Drug Registry. Weight, remission of type 2 diabetes mellitus, hypertension, dyslipidemia, depression, and sleep apnea, and changes in corresponding laboratory data were studied. Five-year follow-up was 100% (9774 eligible individuals) for comorbid diseases. Results: BMI decreased from 42.8 ± 5.5 to 31.2 ± 5.5 kg/m2 at 5 years, corresponding to 27.7% reduction in total body weight. Prevalence of type 2 diabetes mellitus (15.5%–5.9%), hypertension (29.7%–19.5%), dyslipidemia (14.0%–6.8%), and sleep apnea (9.6%–2.6%) was reduced. Greater weight loss was a positive prognostic factor, whereas increasing age or BMI at baseline was a negative prognostic factor for remission. The use of antidepressants increased (24.1%–27.5%). Laboratory status was improved, for example, fasting glucose and glycated hemoglobin decreased from 6.1 to 5.4 mmol/mol and 41.8% to 37.7%, respectively. Conclusions: In this nationwide study, gastric bypass resulted in large improvements in obesity-related comorbid disease and sustained weight loss over a 5-year period. The increased use of antidepressants warrants further investigation. Studies with long-term results after bariatric surgery are surprisingly rare, 1–5 especially in the light of the large number of procedures performed worldwide. In most studies there is a 1 to 2-year follow-up, 6 and at such an early point in time, it is impossible to evaluate the true effect of gastric bypass, because patients have just reached their nadir in weight. Moreover, for this group of patients, the longstanding remission of obesity-related comorbidities, for example, diabetes mellitus, hypertension, dyslipidemia, and sleep apnea, are of utmost importance. The Scandinavian Obesity Surgery Registry (SOReg) was launched in 2007 as a quality registry for the expanding number of bariatric surgeries in Sweden. 7 In 2015, SOReg contained more than 50,000 bariatric procedures (>98% national coverage), with all 43 operating centers reporting to the registry. There has been an expansion of bariatric surgery, with 3300 bariatric procedures performed in 2008, 4800 in 2009, 7800 in 2010, and 8600 in 2011. There has been a slight decrease in procedures, and currently approximately 7000 performed annually, and approximately 95% of the reported procedures have been primary laparoscopic gastric bypass. 8 Perioperative complication rates (eg, 1.2% leaks) and mortality are low (0.04%), the latter validated with the Swedish Population Register. Regular audits are performed by randomly comparing data in SOReg with patient charts at the surgical centers, demonstrating a high validity with less than 2% incorrect values. 7 Furthermore, by cross-linkage with the national Prescribed Drug Registry (PDR), a 100% follow-up of the occurrence of comorbid disease (defined as medical treatment) can be achieved. The present study reports outcome in weight and obesity-related comorbid disease in a nationwide cohort of 26,119 individuals over 5 years after primary Roux-en-Y gastric bypass (RYGB) in Sweden, using the prospective SOReg database with cross-linkage with the PDR.
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30.
  • Taddei, C, et al. (författare)
  • Repositioning of the global epicentre of non-optimal cholesterol
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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