| 1. |
- Hüttner, Silvia, 1984, et al.
(författare)
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Combined genome and transcriptome sequencing to investigate the plant cell wall degrading enzyme system in the thermophilic fungus Malbranchea cinnamomea
- 2017
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834 .- 1754-6834. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genome and transcriptome sequencing has greatly facilitated the understanding of biomass-degrading mechanisms in a number of fungal species. The information obtained enables the investigation and discovery of genes encoding proteins involved in plant cell wall degradation, which are crucial for saccharification of lignocellulosic biomass in second-generation biorefinery applications. The thermophilic fungus Malbranchea cinnamomea is an efficient producer of many industrially relevant enzymes and a detailed analysis of its genomic content will considerably enhance our understanding of its lignocellulolytic system and promote the discovery of novel proteins. Results: The 25-million-base-pair genome of M. cinnamomea FCH 10.5 was sequenced with 225x coverage. A total of 9437 protein-coding genes were predicted and annotated, among which 301 carbohydrate-active enzyme (CAZyme) domains were found. The putative CAZymes of M. cinnamomea cover cellulases, hemicellulases, chitinases and pectinases, equipping the fungus with the ability to grow on a wide variety of biomass types. Upregulation of 438 and 150 genes during growth on wheat bran and xylan, respectively, in comparison to growth on glucose was revealed. Among the most highly upregulated CAZymes on xylan were glycoside hydrolase family GH10 and GH11 xylanases, as well as a putative glucuronoyl esterase and a putative lytic polysaccharide monooxygenase (LPMO). AA9-domain-containing proteins were also found to be upregulated on wheat bran, as well as a putative cutinase and a protein harbouring a CBM9 domain. Several genes encoding secreted proteins of unknown function were also more abundant on wheat bran and xylan than on glucose. Conclusions: The comprehensive combined genome and transcriptome analysis of M. cinnamomea provides a detailed insight into its response to growth on different types of biomass. In addition, the study facilitates the further exploration and exploitation of the repertoire of industrially relevant lignocellulolytic enzymes of this fungus.
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| 2. |
- Damm, S., et al.
(författare)
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Wall motion abnormalities in male elite orienteers are aggravated by exercise
- 1999
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Ingår i: Clinical Physiology. - : Wiley. - 0144-5979 .- 1365-2281. ; 19:2, s. 121-126
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Tidskriftsartikel (refereegranskat)abstract
- During the period 1979-92, 16 (15 men and one woman) sudden unexpected cardiac deaths occurred among young Swedish orienteers. This finding indicated a sharp increase in the death rate of orienteers, and necropsy demonstrated that myocarditis was a common histopathological finding. Therefore, an extensive non-invasive cardiac investigation was performed. A total of 59 male élite orienteers (mean age 23 years) and 36 cross-country skiers and middle-distance runners (mean age 22 years), serving as controls, were examined by both echocardiography at rest and radionuclide ventriculography at rest and during exercise. Wall motion abnormalities were found in eight orienteers using echocardiography. The purpose of this study was to examine whether the group of orienteers with wall motion abnormalities found using echocardiography had a smaller increase in ejection fraction from rest to exercise using radionuclide ventriculography than the rest of the orienteers and the controls, indicating an aggravation of the wall motion abnormalities during exercise. There were no significant differences in the ejection fraction at rest between the groups. In the orienteers with wall motion abnormalities (group 1), 62% (five out of eight) had less than a 0.05 unit increase in left ventricular ejection fraction compared with 27% (14 out of 51) of the remaining orienteers (group 2) and 19% (7 out of 36) of the controls (group 3). A comparison of athletes in group 1 with those in groups 2 and 3 combined revealed a statistically significant difference (P < 0.05). The divergent response in left ventricular ejection fraction during exercise suggests an aggravation of the wall motion abnormalities with exercise. Both the echocardiographic and the radionuclide ventriculographic findings indicate that the orienteers in group 1 had concealed left ventricular damage.
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| 3. |
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| 4. |
- Ahmadi, Shilan Seyed, et al.
(författare)
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Effect of liraglutide on anthropometric measurements, sagittal abdominal diameter and adiponectin levels in people with type 2 diabetes treated with multiple daily insulin injections: evaluations from a randomized trial (MDI-liraglutide study 5)
- 2019
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Ingår i: Obesity Science and Practice. - : Wiley. - 2055-2238. ; 5:2, s. 130-140
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Tidskriftsartikel (refereegranskat)abstract
- Aim Use of the glucagon-like peptide 1 receptor agonist liraglutide has been shown to reduce weight. Different types of anthropometric measurements can be used to measure adiposity. This study evaluated the effect of liraglutide on sagittal abdominal diameter, waist circumference, waist-to-hip ratio and adiponectin levels in people with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDI). Materials and methods In the multicentre, double-blind, placebo-controlled MDI-liraglutide trial, 124 individuals with T2D treated with MDI were randomized to either liraglutide or placebo. Basal values of weight, waist circumference, waist-to-hip ratio, sagittal abdominal diameter and adiponectin were compared with measurements at 12 and 24 weeks after randomization. Results Baseline-adjusted mean weight loss was 3.8 +/- 2.9 kg greater in liraglutide than placebo-treated individuals (p < 0.0001). Waist circumference was reduced by 2.9 +/- 4.3 cm and 0.2 +/- 3.6 cm in the liraglutide and placebo groups, respectively, after 24 weeks (baseline-adjusted mean difference: 2.6 +/- 4.0 cm, p = 0.0005). Corresponding reductions in sagittal abdominal diameter were 1.1 +/- 1.7 cm and 0.0 +/- 1.8 cm (baseline-adjusted mean difference: 1.1 +/- 1.7 cm, p = 0.0008). Hip circumference was reduced in patients randomized to liraglutide (baseline-adjusted mean difference between treatment groups: 2.8 +/- 3.8 cm, p = 0.0001), but there was no significant difference between the groups in either waist-to-hip ratio (baseline-adjusted mean difference: 0.0 +/- 0.04 cm, p = 0.51) or adiponectin levels (baseline-adjusted mean difference: 0.8 +/- 3.3 mg L-1, p = 0.17). Lower HbA1c and mean glucose levels measured by masked continuous glucose monitoring at baseline were associated with greater effects of liraglutide on reductions in waist circumference and sagittal abdominal diameter. Conclusions In patients with T2D, adding liraglutide to MDI may reduce abdominal and hip obesity to a similar extent, suggesting an effect on both visceral and subcutaneous fat. Liraglutide had greater effects on reducing abdominal obesity in patients with less pronounced long-term hyperglycaemia but did not affect adiponectin levels.
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| 5. |
- Ahrén, Bo, et al.
(författare)
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HARMONY 3: 104-Week Randomized, Double-Blind, Placebo- and Active-Controlled Trial Assessing the Efficacy and Safety of Albiglutide Compared With Placebo, Sitagliptin, and Glimepiride in Patients With Type 2 Diabetes Taking Metformin.
- 2014
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 37:8, s. 2141-2148
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Tidskriftsartikel (refereegranskat)abstract
- To compare the efficacy and safety of weekly albiglutide with daily sitagliptin, daily glimepiride, and placebo.RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes receiving metformin were randomized to albiglutide (30 mg), sitagliptin (100 mg), glimepiride (2 mg), or placebo. Blinded dose titration for albiglutide (to 50 mg) and glimepiride (to 4 mg) was based on predefined hyperglycemia criteria. The primary end point was change in HbA1c from baseline at week 104. Secondary end points included fasting plasma glucose (FPG), weight, and time to hyperglycemic rescue.RESULTS: Baseline characteristics were similar among the albiglutide (n = 302), glimepiride (n = 307), sitagliptin (n = 302), and placebo (n = 101) groups. Baseline HbA1c was 8.1% (65.0 mmol/mol); mean age was 54.5 years. The mean doses for albiglutide and glimepiride at week 104 were 40.5 and 3.1 mg, respectively. At week 104, albiglutide significantly reduced HbA1c compared with placebo (-0.9% [-9.8 mmol/mol]; P < 0.0001), sitagliptin (-0.4% [-4.4 mmol/mol]; P = 0.0001), and glimepiride (-0.3% [-3.3 mmol/mol]; P = 0.0033). Outcomes for FPG and HbA1c were similar. Weight change from baseline for each were as follows: albiglutide -1.21 kg (95% CI -1.68 to -0.74), placebo -1.00 kg (95% CI -1.81 to -0.20), sitagliptin -0.86 kg (95% CI -1.32 to -0.39), glimepiride 1.17 kg (95% CI 0.70-1.63). The difference between albiglutide and glimepiride was statistically significant (P < 0.0001). Hyperglycemic rescue rate at week 104 was 25.8% for albiglutide compared with 59.2% (P < 0.0001), 36.4% (P = 0.0118), and 32.7% (P = 0.1504) for placebo, sitagliptin, and glimepiride, respectively. Rates of serious adverse events in the albiglutide group were similar to comparison groups. Diarrhea (albiglutide 12.9%, other groups 8.6-10.9%) and nausea (albiglutide 10.3%, other groups 6.2-10.9%) were generally the most frequently reported gastrointestinal events.CONCLUSION: Added to metformin, albiglutide was well-tolerated; produced superior reductions in HbA1c and FPG at week 104 compared with placebo, sitagliptin, and glimepiride; and resulted in weight loss compared with glimepiride.
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| 6. |
- Dahlqvist, S., et al.
(författare)
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Variables associated with HbA1c and weight reductions when adding liraglutide to multiple daily insulin injections in persons with type 2 diabetes (MDI Liraglutide trial 3)
- 2018
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Ingår i: BMC Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate variables associated with hemoglobin A1c (HbA1c) and weight reduction when adding liraglutide to persons with type 2 diabetes treated with multiple daily insulin injections (MDI). Research design and methods This was a reanalysis of a previous trial where 124 patients were enrolled in a double-blind, placebo-controlled, multicenter randomized trial carried out over 24 weeks. Predictors for effect on change in HbA1c and weight were analyzed within the treatment group and with concurrent interaction analyses. Correlation analyses for change in HbA1c and weight from baseline to week 24 were made. Results The mean age at baseline was 63.7 years, 64.8% were men, the mean number of insulin injections was 4.4 per day, the mean daily insulin dose was 105 units and the mean HbA1c was 74.5 mmol/mol (9.0%). The mean HbA1c and weight reductions were 12.3 mmol/mol (1.13%; P<0.001) and 3.8 kg (P<0.001) greater in liraglutide than placebo-Treated persons. There was no significant predictor for greater effect on HbA1c that existed in all analyses (univariate, multivariate and interaction analyses against controls). For a greater weight reduction when adding liraglutide, a lower HbA1c level at baseline was a predictor (liraglutide group P=0.002, P=0.020 for liraglutide group vs placebo). During follow-up in the liraglutide group, no significant correlation was found between change in weight and change in HbA1c (r=0.09, P=0.46), whereas a correlation existed between weight and insulin dose reduction (r=0.44, P<0.001). Conclusion Weight reduction becomes greater when adding liraglutide in patients with type 2 diabetes treated with MDI who had a lower HbA1c level compared with those with a higher HbA1c level. There was no correlation between reductions in HbA1c and weight when liraglutide was added, that is, different patient groups responded with HbA1c and weight reductions. Trial registration number EudraCT nr: 2012-001941-42. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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| 7. |
- Davani, B, et al.
(författare)
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Aged transgenic mice with increased glucocorticoid sensitivity in pancreatic beta-cells develop diabetes
- 2004
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 5353 Suppl 1, s. S51-S59
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are diabetogenic hormones because they decrease glucose uptake, increase hepatic glucose production, and inhibit insulin release. To study the long-term effects of increased glucocorticoid sensitivity in β-cells, we studied transgenic mice overexpressing the rat glucocorticoid receptor targeted to the β-cells using the rat insulin I promoter. Here we report that these mice developed hyperglycemia both in the fed and the overnight-fasted states at 12–15 months of age. Progression from impaired glucose tolerance, previously observed in the same colony at the age of 3 months, to manifest diabetes was not associated with morphological changes or increased apoptosis in the β-cells. Instead, our current results suggest that the development of diabetes is due to augmented inhibition of insulin secretion through α2-adrenergic receptors (α2-ARs). Thus, we found a significantly higher density of α2-ARs in the islets of transgenic mice compared with controls, based on binding studies with the α2-AR agonist UK 14304. Furthermore, incubation of islets with benextramine, a selective antagonist of the α2-AR, restored insulin secretion in response to glucose in isolated islets from transgenic mice, whereas it had no effect on control islets. These results indicate that the chronic enhancement of glucocorticoid signaling in pancreatic β-cells results in hyperglycemia and impaired glucose tolerance. This effect may involve signaling pathways that participate in the regulation of insulin secretion via the α2-AR.
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| 8. |
- Gram, DX, et al.
(författare)
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Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats
- 2005
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 153:6, s. 963-969
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Tidskriftsartikel (refereegranskat)abstract
- Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity - and therefore might be involved in the pathophysiology - is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin. Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1 +/- 3.4 pmol/l in pre-obese Zucker rats vs 6.9 +/- 1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3 +/- 0.2 mmol/l vs 5.1 +/- 0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8 +/- 0.3 mmol/l vs 8.6 +/- 0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver. Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.
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| 9. |
- Home, Philip D., et al.
(författare)
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Three-year data from 5 HARMONY phase 3 clinical trials of albiglutide in type 2 diabetes mellitus : Long-term efficacy with or without rescue therapy
- 2017
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227. ; 131, s. 49-60
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Tidskriftsartikel (refereegranskat)abstract
- Aims Diabetes therapies that provide durable glycaemic control for people with type 2 diabetes mellitus (T2DM) are needed. We present efficacy results of albiglutide, a glucagon-like peptide-1 receptor agonist, in people with T2DM over a 3-year period. Methods Five of the 8 HARMONY phase 3 trials, comparing albiglutide with other therapies or placebo across a spectrum of clinical care, lasted for a preplanned 3 years. Participants with uncontrolled hyperglycaemia who met predetermined criteria could receive rescue medication. The ability to remain on study medication without needing additional rescue was an efficacy measure. Glycaemic measures and body weight were analysed in 2 populations: those who remained rescue-free and all participants. Results Participants (n = 3132) were randomised to albiglutide or comparator. A greater proportion of participants who received albiglutide remained rescue-free (55–71%) compared with placebo (35–51%; p < 0.001 to p = 0.002). The proportion of rescue-free participants with albiglutide did not differ from glimepiride or insulin glargine, was higher than with sitagliptin (p = 0.013), and lower than with pioglitazone (p = 0.045). At 3 years, albiglutide was associated with clinically significant reductions in hyperglycaemia (eg, rescue-free participants: HbA1c −0.52% [SE0.11] to −0.98% [0.12]; −5.7 mmol/mol [1.2] to −10.7 mmol/mol [1.3] and all participants: HbA1c −0.29% [0.11] to − 0.92% [0.13]; −3.2 mmol/mol [1.2] to −10.1 mmol/mol [1.4]). Albiglutide was also associated with modest reductions in body weight vs pioglitazone, glimepiride, and insulin glargine, which were associated with weight gain. Conclusion These 3-year efficacy data support long-term use of albiglutide in the management of people with T2DM. ClinicalTrials.gov NCT00849056, NCT00849017, NCT00838903, NCT00838916, NCT00839527.
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| 10. |
- Hägg, S, et al.
(författare)
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Leptin concentrations are increased in subjects treated with clozapine or conventional antipsychotics.
- 2001
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Ingår i: Journal of Clinical Psychiatry. - 0160-6689 .- 1555-2101. ; 62:11, s. 843-848
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Overweight is a considerable clinical problem in patients treated with antipsychotic agents. Recent results suggest that insulin resistance with increased insulin levels is also associated with treatment with the atypical antipsychotic agent clozapine. Leptin is important for the control of body weight and has been proposed to be a link between obesity and the insulin resistance syndrome. This study examined if clozapine-treated subjects and subjects treated with conventional antipsychotics had increased leptin levels compared with the general population and whether there was a gender difference in this respect.METHOD: Clozapine-treated patients (N = 41), patients treated with conventional antipsychotic drugs (N = 62), and healthy subjects from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) project (N = 189) were investigated with a cross-sectional study design. Weight, body mass index (BMI), and plasma leptin concentrations were measured, and all study subjects were investigated for the presence of diabetes mellitus. Drug treatment, health status, and smoking habits were registered.RESULTS: After adjustment for gender, BMI, smoking habits, age, and diabetes, hyperleptinemia was independently (p < .001) associated with clozapine treatment and with treatment with conventional antipsychotics (p < .005) within a multiple regression analysis. In separate multiple regression analyses, leptin levels were significantly associated with clozapine treatment in men (p = .002) and women (p =.023) and with conventional antipsychotic treatment in men (p = .027) but not in women.CONCLUSION: Treatment with clozapine as well as with conventional antipsychotics is associated with increased levels of circulating leptin. Hyperleptinemia can be an important link in the development of overweight and the insulin resistance syndrome in subjects receiving antipsychotic drugs, especially atypical agents like clozapine.
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| 11. |
- Jansson, Per-Anders, 1961, et al.
(författare)
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Probiotic treatment using a mix of three Lactobacillus strains for lumbar spine bone loss in postmenopausal women: a randomised, double-blind, placebo-controlled, multicentre trial
- 2019
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Ingår i: Lancet Rheumatology. - : Elsevier BV. - 2665-9913. ; 1:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Postmenopausal bone loss in the spine is associated with an increased risk of vertebral fractures. Certain probiotic treatment protects rodents from ovariectomy-induced bone loss. The aim of the present study was to determine if treatment with a combination of three bacterial strains protects against the rapid spine bone loss occurring in healthy early postmenopausal women. Methods This randomised, double-blind, placebo-controlled, multicentre trial was done at four study centres in Sweden. Early postmenopausal women were randomly assigned in a 1:1 ratio to receive probiotic treatment consisting of three Lactobacillus strains (Lactobacillus paracasei DSM 13434, Lactobacillus plantarum DSM 15312, and Lactobacillus plantarum DSM 15313; 1 x 10(10 )colony-forming units per capsule) or placebo once daily for 12 months. The primary outcome was the percentage change from baseline in lumbar spine bone mineral density (LS-BMD) at 12 months. The primary analysis was done in all participants with BMD measurements available both at baseline and at 12 months. Analyses of adverse events and safety included all participants who had taken at least one capsule of placebo or Lactobacillus. This trial is registered with ClinicalTrials.gov, NCT02722980, and is completed. Findings Between April 18 and Nov 11,2016,249 participants were randomly assigned to receive probiotic product or placebo, and 234 (94%) completed the analyses required for the primary outcome. Lactobacillus treatment reduced the LS-BMD loss compared with placebo (mean difference 0.71%, 95% CI 0.06 to 1.35). The LS-BMD loss was significant in the placebo group (-0.72%, -1.22 to -0.22), whereas no bone loss was observed in the Lactobacillus-treated group (-0.01%, -0.50 to 0.48). The adverse events were similar between the two groups. Interpretation Probiotic treatment using a mix of three Lactobacillus strains protects against lumbar spine bone loss in healthy postmenopausal women. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 12. |
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| 13. |
- Johansson, A, et al.
(författare)
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Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy
- 2002
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 146:3, s. 397-405
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown. An interesting model for the study of hormonal perturbations accompanying marked insulin resistance without concomitant diabetes is myotonic dystrophy (DM1). Design: The work was carried out in an out-patient setting. Methods: An oral glucose tolerance test was performed in 18 males with DM1 and 18 controls to examine the release of incretins and counter-regulatory hormones. Genetic analyses were also performed in patients. Results: We found that the increment in GLP-1 after oral glucose was significantly greater in patients, while there was no significant difference in GIP or glucagon responses between patients and controls, although long CTG repeat expansions were associated with a more pronounced GIP response. Interestingly, the GLP-1 response to oral glucose correlated with the insulin response in patients but not in controls whereas, in controls, the insulin response closely correlated with the GIP response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions. Conclusions: This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1. patients and that CTG triplet repeats are linked to GIP release. These abnormalities may contribute both to the severe insulin resistance and hyperinsulinemia in DM1 and to the preservation of adequate islet function, enabling glucose tolerance to be normal in spite of this marked insulin resistance in DM1.
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| 14. |
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| 15. |
- Johansson, A, et al.
(författare)
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Testosterone and diurnal rhythmicity of leptin, TNF-alpha and TNF-II receptor in insulin-resistant myotonic dystrophy patients
- 2002
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 26:10, s. 1386-1392
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the leptin and TNF systems in relation to testosterone in insulin resistant myotonic dystrophy (DM1) subjects. DESIGN AND SUBJECTS: Fasting morning samples and diurnal sampling during 24 h. Forty-two DM1 subjects (20 women and 22 men; age 41.5 (28.5-58.7)y, body mass index (BMI) 23.3 (18.6-29.2)kg/m(2); median and 10th and 90th percentile, respectively). Fifty healthy volunteers (23 women and 27 men; age 42 (27.0-56.9)y, BMI 24.0 (20.7-29.7) kg/m(2)). Nine men with DM1 and nine healthy men participated in diurnal sampling. MEASUREMENTS: Body composition was measured by bioelectric impedance analysis. Circulating levels of leptin, TNF-alpha, TNFR-II, insulin, testosterone and lipids were measured. The number of CTG triplet repeats was analysed. RESULTS: Basal as well as median 24 h levels of leptin and TNFR-II were significantly increased in DM1 patients, independent of body fat mass. This was associated with higher insulin and lower testosterone levels in DM1 patients. The genetic defect was related to leptin and TNFR-II levels in DM1 patients. CONCLUSION: Hyperleptinemia in DM1 is clearly linked to the concomitant hypogonadism. The genetic defect may directly or indirectly contribute to increased leptin levels. Increased exposure of cytokines may contribute to insulin resistance and other hormonal disturbances in DM1.
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| 16. |
- Kjellberg, L, et al.
(författare)
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Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection.
- 2000
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 82:7, s. 1332-8
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Tidskriftsartikel (refereegranskat)abstract
- Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case-control study in the Vasterbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2-3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis (P < 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2-3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2-3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7-4.0), the effect was dose-dependent (P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3-4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9-4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia.
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| 17. |
- Nystrom, T, et al.
(författare)
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Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease
- 2004
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Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 287:6, s. 1209-1215
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Tidskriftsartikel (refereegranskat)abstract
- GLP-1 stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying, and inhibits small bowel motility, all actions contributing to the anti-diabetogenic peptide effect. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease. Therefore, interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients. We investigated GLP-1's effect on endothelial function and insulin sensitivity (S-I) in two groups: 1) 12 type 2 diabetes patients with stable coronary artery disease and 2) 10 healthy subjects with normal endothelial function and S-I. Subjects underwent infusion of recombinant GLP-1 or saline in a random crossover study. Endothelial function was measured by postischemic FMD of brachial artery, using ultrasonography. S-I [in (10(-4) dl.kg(-1).min(-1))/(muU/ml)] was measured by hyperinsulinemic isoglycemic clamp technique. In type 2 diabetic subjects, GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(%) (3.1 +/- 0.6 vs. 6.6 +/- 1.0%, P < 0.05), with no significant effects on S-I (4.5 &PLUSMN; 0.8 vs. 5.2 &PLUSMN; 0.9, P = NS). In healthy subjects, GLP-1 infusion affected neither FMD(%) (11.9 &PLUSMN; 0.9 vs. 10.3 &PLUSMN; 1.0%, P = NS) nor S-I (14.8 &PLUSMN; 1.8 vs. 11.6 &PLUSMN; 2.0, P = NS). We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease. This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment.
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| 19. |
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