| 41. |
- Brorsson, C., et al.
(författare)
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Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data
- 2009
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 11:S1, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- To develop novel methods for identifying new genes that contribute to the risk of developing type 1 diabetes within the Major Histocompatibility Complex (MHC) region on chromosome 6, independently of the known linkage disequilibrium (LD) between human leucocyte antigen (HLA)-DRB1, -DQA1, -DQB1 genes. We have developed a novel method that combines single nucleotide polymorphism (SNP) genotyping data with protein-protein interaction (ppi) networks to identify disease-associated network modules enriched for proteins encoded from the MHC region. Approximately 2500 SNPs located in the 4 Mb MHC region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein modules were statistically evaluated using permutation. A total of 151 genes could be mapped to nodes within the protein interaction network and their interaction partners were identified. Five protein interaction modules reached statistical significance using this approach. The identified proteins are well known in the pathogenesis of T1D, but the modules also contain additional candidates that have been implicated in beta-cell development and diabetic complications. The extensive LD within the MHC region makes it important to develop new methods for analysing genotyping data for identification of additional risk genes for T1D. Combining genetic data with knowledge about functional pathways provides new insight into mechanisms underlying T1D.
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| 42. |
- Bunck, M. C., et al.
(författare)
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Exenatide treatment did not affect bone mineral density despite body weight reduction in patients with type 2 diabetes
- 2011
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Ingår i: Diabetes, obesity & metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 13:4, s. 374-377
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that incretin-based therapies may be beneficial for the bone; however, clinical data are largely lacking. We assessed whether the differential effects of these therapies on body weight differed with respect to their effect on bone mineral density (BMD) and markers of calcium homeostasis in patients with type 2 diabetes (T2D). Sixty-nine metformin-treated patients with T2D were randomized to exenatide twice daily (n = 36) or insulin glargine once daily (n = 33). Total body BMD, measured by dual-energy X-ray absorptiometry, and serum markers of calcium homeostasis were assessed before and after 44-week treatment. Exenatide or insulin glargine treatment decreased body weight by 6%. Endpoint BMD was similar in both groups after 44-week therapy (LSmean +/- s.e.m. between-group difference -0.002 +/- 0.007 g/cm(2) ; p = 0.782). Fasting serum alkaline phosphatase, calcium and phosphate remained unaffected. Forty-four-week treatment with exenatide or insulin glargine had no adverse effects on bone density in patients with T2D, despite differential effects on body weight.
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| 43. |
- Bøg-Hansen, Erik, et al.
(författare)
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Impaired glucose metabolism and obesity in Swedish patients with borderline isolated systolic hypertension: Skaraborg Hypertension and Diabetes Project
- 2001
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 3:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To assess the prevalence of borderline isolated systolic hypertension (borderline ISH), and to examine its association with other cardiovascular risk factors. METHODS: A cross-sectional community-based study was carried out in 1993-1994 in Skara, Sweden, including 1109 randomly chosen subjects > or = 40 years old. Normotension (NT) was defined as systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg, borderline ISH as SBP 140-159 and DBP < 90 mmHg and hypertension (HT) as SBP > or = 160 or DBP > or = 90 mmHg or ongoing treatment. RESULTS: The prevalence of borderline ISH (n = 203) by age was 4% in ages 40-49 years, 15% in ages 50-59 years, 28% in ages 60-69 years and 25% in ages 70-79 years. With borderline ISH as reference, normotensive subjects less often had fasting blood glucose > 5.5 mmol/l (odds ratio (OR): 0.4, 95% CI: 0.26-0.75), BMI > 27 kg/m2 (OR: 0.6, 95% confidence intervals (CI): 0.42-0.85) and known diabetes (OR: 0.4, 95% CI: 0.16-0.95). Hypertensive subjects more often had high density lipoprotein (HDL) cholesterol < 1.0 mmol/l (OR: 2.0, 95% CI: 1.35-2.99), a history of previous cardiovascular disease (CVD) (OR: 1.7, 95% CI: 1.01-2.72), known diabetes (OR: 2.4, 95% CI: 1.29-4.58) and microalbuminuria (men) (OR: 1.9, 95% CI: 1.15-3.11). CONCLUSION: Borderline ISH is a common condition. It is associated with a more unfavourable risk factor profile than that of normotensive subjects concerning primarily glucose metabolism and obesity. The prevalence of known diabetes increased with the degree of hypertension.
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| 44. |
- Bøg-Hansen, Erik, et al.
(författare)
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Metabolic disorders associated with uncontrolled hypertension.
- 2003
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 5:6, s. 379-387
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the prevalence and characteristics of uncontrolled hypertension (HT). Methods: A cross-sectional community-based study (1992-93) was carried out in Skara, Sweden, including 894 patients who consecutively underwent an annual follow-up at the hypertension outpatient clinic in primary care. Controlled HT was defined as diastolic blood pressure (DBP) <=90 mmHg and systolic blood pressure (SBP) <=160 mmHg and was used as reference. Uncontrolled DBP was defined as DBP >90 mmHg regardless of SBP level, and isolated uncontrolled SBP was defined as SBP >160 mmHg and DBP <=90 mmHg. Proportions were age-standardized using the Skara population as reference. Results: The prevalence of uncontrolled HT was 43% (isolated uncontrolled SBP 18% and uncontrolled DBP 25%). Both men and women with isolated uncontrolled SBP were older (73 years, CI: 70-75; and 73 years; CI: 72-75) than patients with controlled HT (64 years, CI: 63-66; and 65 years, CI: 64-66). Men and women with known cardiovascular disease (CVD) less often had isolated uncontrolled SBP (OR: 0.4, CI: 0.2-0.9; and OR: 0.5, CI: 0.3-0.9), whereas men and women with known diabetes more often had uncontrolled DBP (OR: 2.3, CI: 1.3-4.1; and OR: 3.3, CI: 1.9-5.7). Men with known CVD less often had uncontrolled DBP (OR: 0.5, CI: 0.3-1.0, p = 0.04), and men with fasting blood glucose >5.5 mmol/l more often had isolated uncontrolled SBP (OR: 1.9, CI: 1.0-3.5, p = 0.04). In women, the following high risk factor levels were associated with uncontrolled DBP: fasting blood glucose >5.5 mmol/l (OR: 1.4, CI: 1.1-1.8), fasting triglycerides >=1.7 mmol/l (OR: 1.4, CI: 1.1-1.8), body mass index (BMI) >30 kg/m2 (OR: 1.5, CI: 1.1-1.9), waist/hip ratio (WHR) >0.85 cm/cm (OR: 1.7, CI: 1.3-2.2), insulin resistance (homeostasis model assessment (HOMA) >third quartile) (OR: 1.4, CI: 1.1-1.9) and microalbuminuria (OR: 3.2, CI: 1.7-6.2). Conclusion: Uncontrolled DBP is in both sexes related to type 2 diabetes, whereas isolated uncontrolled SBP is related to older age. In women, uncontrolled DBP, furthermore, is related to several other CVD risk factors of the metabolic syndrome. Patients with uncontrolled DBP should be carefully evaluated for metabolic disorders.
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| 45. |
- Cariou, Bertrand, et al.
(författare)
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Effect of tirzepatide on body fat distribution pattern in people with type 2 diabetes
- 2024
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Ingår i: Diabetes, obesity and metabolism. - : WILEY. - 1462-8902 .- 1463-1326.
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo describe the overall fat distribution patterns independent of body mass index (BMI) in participants with type 2 diabetes (T2D) in the SURPASS-3 MRI substudy by comparison with sex- and BMI-matched virtual control groups (VCGs) derived from the UK Biobank imaging study at baseline and Week 52. MethodsFor each study participant at baseline and Week 52 (N = 296), a VCG of >= 150 participants with the same sex and similar BMI was identified from the UK Biobank imaging study (N = 40 172). Average visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT) and liver fat (LF) levels and the observed standard deviations (SDs; standardized normal z-scores: z-VAT, z-aSAT and z-LF) were calculated based on the matched VCGs. Differences in z-scores between baseline and Week 52 were calculated to describe potential shifts in fat distribution pattern independent of weight change. ResultsBaseline fat distribution patterns were similar across pooled tirzepatide (5, 10 and 15 mg) and insulin degludec (IDeg) arms. Compared with matched VCGs, SURPASS-3 participants had higher baseline VAT (mean [SD] z-VAT +0.42 [1.23]; p < 0.001) and LF (z-LF +1.24 [0.92]; p < 0.001) but similar aSAT (z-aSAT -0.13 [1.11]; p = 0.083). Tirzepatide-treated participants had significant decreases in z-VAT (-0.18 [0.58]; p < 0.001) and z-LF (-0.54 [0.84]; p < 0.001) but increased z-aSAT (+0.11 [0.50]; p = 0.012). Participants treated with IDeg had a significant change in z-LF only (-0.46 [0.90]; p = 0.001), while no significant changes were observed for z-VAT (+0.13 [0.52]; p = 0.096) and z-aSAT (+0.09 [0.61]; p = 0.303). ConclusionIn this exploratory analysis, treatment with tirzepatide in people with T2D resulted in a significant reduction of z-VAT and z-LF, while z-aSAT was increased from an initially negative value, suggesting a possible treatment-related shift towards a more balanced fat distribution pattern with prominent VAT and LF loss.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Da Silva, Julien, et al.
(författare)
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Real-world performance of the MiniMed™ 670G system in Europe
- 2021
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Ingår i: Diabetes, obesity and metabolism. - : Wiley-Blackwell Publishing Inc.. - 1462-8902 .- 1463-1326. ; 23:8, s. 1942-1949
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The MiniMed™ 670G system has been available in Europe since October 2018. Herein, the system's real-world performance in individuals with diabetes is evaluated.MATERIALS AND METHODS: Data uploaded October 2018 to July 2020 by individuals living in Europe were aggregated and retrospectively analyzed. The mean Glucose Management Indicator (GMI), percentage of time spent within (TIR), below (TBR) and above (TAR) glycemic ranges, system use and insulin consumed in users with ≥10 days of SG data after initial Auto Mode start were determined. Another analysis based on suboptimally- (GMI >8.0%) and well-controlled (GMI <7.0%) glycemia pre-Auto Mode initiation was also performed.RESULTS: Users (N=14,899) spent a mean of 81.4% of the time in Auto Mode and achieved a mean GMI of 7.0±0.4%, TIR of 72.0±9.7%, TBR <3.9 mmol/L of 2.4±2.1% and TAR >10 mmol/L of 25.7±10%, after initiating Auto Mode. When compared to pre-Auto Mode initiation, GMI reduced by 0.3±0.4% and TIR increased by 9.6±9.9% (p<0.0001 for both). Significantly improved glycemic control was observed irrespectively of pre-Auto Mode GMI level <7.0% or >8.0%. While total daily dose of insulin increased for both groups, a greater increase was observed in the latter: an increase due primarily to increased basal insulin delivery. In contrast, basal insulin decreased slightly in well-controlled users.CONCLUSIONS: Most MiniMed™ 670G system users in Europe achieved TIR >70% and GMI <7% while minimizing hypoglycemia, in a real-world environment. These international consensus-met outcomes were enabled by automated insulin delivery meeting real-time insulin requirements adapted to each individual user.
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