| 21. |
- Andersson, Sofia A, et al.
(author)
-
Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.
- 2012
-
In: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 364:1-2, s. 36-45
-
Journal article (peer-reviewed)abstract
- Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis.
|
|
| 22. |
- Bengtsson Boström, Kristina, et al.
(author)
-
Polymorphisms in α- And β-adrenergic receptor genes, hypertension, and obstructive sleep apnea : The skaraborg sleep study
- 2010
-
In: International Journal of Hypertension. - : Hindawi Limited. - 2090-0384 .- 2090-0392. ; 2010
-
Journal article (peer-reviewed)abstract
- The sympathetic nervous system and the adrenergic receptors play an important role in regulation of blood pressure. This study explored the associations between functional polymorphisms of the α 2B -, β 1 -, and β 2 -adrenergic receptor genes and obstructive sleep apnea (OSA) in hypertensive patients and hypertension in patients with OSA in a populationbased sample of 157 hypertensive patients and 181 healthy control subjects. Only the Arg389Gly polymorphism of the β 1 -adrenergic receptor gene was associated with increased risk for mild OSA in hypertensive patients (Arg/Arg versus Gly/Arg/Gly/Gly, 2.1, 95% CI, 1.02-4.7). Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes. When adjusted also for BMI this difference became borderline significant. This difference was not observed in women. The risk of hypertension in mild OSA was associated with increasing number of Arg-alleles (Arg/Arg OR 5.4, 95 CI 1.4-21.2).
|
|
| 23. |
- Bennet, Louise, et al.
(author)
-
Ethnic differences in the contribution of insulin action and secretion to type 2 diabetes in immigrants from the Middle East compared to native Swedes
- 2014
-
In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 105:1, s. 79-87
-
Journal article (peer-reviewed)abstract
- Aims: We investigated insulin action (insulin sensitivity index, ISI) and insulin secretion (oral disposition indices, DIo) and studied metabolic, demographic and lifestyle-related risk factors for type 2 diabetes and insulin action, in the largest non-European immigrant group to Sweden, immigrants from Iraq and native Swedes.Methods: Population-based, cross-sectional study conducted 2010-2012 including residents 30-75 years of age born in Iraq or Sweden, in whom oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors were characterized.Results: In Iraqis compared to Swedes, ISI was more impaired (76.9 vs. 102.3, p < .001) whereas corrected insulin response CIR was higher (226.6 vs. 188.6, p = .016). However, insulin secretion was inadequate given the substantial insulin resistance, as indicated by lower DIo indices in Iraqis than in Swedes (DIo 12,712.9 vs. 14,659.2, p < .001). The crude ethnic difference in ISI was not offset by traditional risk factors like waist circumference, body mass index or family history of diabetes. In Iraqis, ISI conveyed somewhat higher odds of type 2 diabetes than in Swedes (odds ratio OR 0.98, 95% CI 0.97-0.99) vs. OR 0.95, 0.92-0.99), as indicated by an interaction between country of birth and ISI (P-interaction = .044).Conclusion: This study reports ethnic differences in the contribution of insulin action to type 2 diabetes. Our data suggests that the impaired insulin action observed in immigrants from the Middle East to Sweden is not fully explained by established risk factors.(C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
|
|
| 24. |
- Bennet, Louise, et al.
(author)
-
Ethnicity is an independent risk indicator when estimating diabetes risk with FINDRISC scores: A cross sectional study comparing immigrants from the Middle East and native Swedes
- 2014
-
In: Primary Care Diabetes. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 8:3, s. 231-238
-
Journal article (peer-reviewed)abstract
- Aims: This study sought to compare type 2 diabetes (T2D) risk indicators in Iraqi immigrants with those in ethnic Swedes living in southern Sweden. Methods: Population-based, cross-sectional cohort study of men and women, aged 30-75 years, born in Iraq or Sweden conducted in 2010-2012 in Malmö, Sweden. A 75 g oral glucose tolerance test was performed and sociodemographic and lifestyle data were collected. T2D risk was assessed by the Finnish Diabetes Risk Score (FINDRISC). Results: In Iraqi versus Swedish participants, T2D was twice as prevalent (11.6 vs. 5.8%, p < 0.001). A large proportion of the excess T2D risk was attributable to larger waist circumference and first-degree family history of diabetes. However, Iraqi ethnicity was a risk factor for T2D independently of other FINDRISC factors (odds ratio (OR) 2.5, 95% CI 1.6-3.9). The FINDRISC algorithm predicted that more Iraqis than Swedes (16.2 vs. 12.3%, p < 0.001) will develop T2D within the next decade. The total annual costs for excess T2D risk in Iraqis are estimated to exceed 2.3 million euros in 2005, not accounting for worse quality of life. Conclusions: Our study suggests that Middle Eastern ethnicity should be considered an independent risk indicator for diabetes. Accordingly, the implementation of culturally tailored prevention programs may be warranted. © 2014 Primary Care Diabetes Europe.
|
|
| 25. |
- Bennet, Louise, et al.
(author)
-
High prevalence of type 2 diabetes in Iraqi and Swedish residents in a deprived Swedish neighbourhood - a population based study
- 2011
-
In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 11
-
Journal article (peer-reviewed)abstract
- Background: Immigrants from the Middle-East are at high risk of developing type 2 diabetes (T2D). The aim of the present survey was to measure, in a single deprived neighbourhood, the prevalence rates of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D in residents originating from Iraq and to compare them to those in residents born in Sweden. An additional aim was to identify metabolic, lifestyle and socioeconomic risk factors associated with IFG/IGT and T2D in these residents. Methods: The study was conducted February 1'st to March 31'st 2010. Men and women aged 45 to 65 years of Swedish or Iraqi origin, living in the neighbourhood of Rosengard, Malmo, Sweden, were randomly selected from the census register. Each participant signed a written informed consent form, underwent a physical examination and an oral glucose tolerance test (OGTT), provided blood samples and filled in a questionnaire. A total of 175 subjects participated (Swedish origin n = 79, Iraqi origin n = 96), reflecting an overall response rate of almost 60%. Results: In total, 21.9% and 19.0% of the Iraqi and Swedish participants, respectively, suffered from T2D, while 24.0% of the Iraqi participants and 25.3% of the Swedish participants had IFG/IGT. There were no significant differences in prevalence rates relating to country of origin. Obesity (BMI >= 30 kg/m(2)) and sedentary leisure time physical activity were highly prevalent in both groups, while a family history of diabetes was more prevalent in participants from Iraq (49.2%) than in those from Sweden (22.8%) (p = 0.001). Being obese or having a sedentary leisure time were, independently associated with T2D (OR 5.43 (95% CI 2.10-14.02) and 2.89 (95% CI 1.03-8.10) respectively), while economic difficulties were independently associated with IFG/IGT (OR 2.55 (95% CI 1.06-6.15)) after adjustment for the confounding effects of other common risk factors for T2D. Conclusions: This study reveals a high prevalence of T2D, independently of country of origin (Iraq or Sweden), in a socially vulnerable area and additionally presents a risk factor profile that is markedly different from that of Sweden in general.
|
|
| 26. |
- Berndt, Sonja I., et al.
(author)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
|
|
| 27. |
- Boström, Kristina Bengtsson, et al.
(author)
-
Polymorphisms in alpha - and betaadrenergic receptor genes, hypertension and obstructive sleep apnea. The Skaraborg Sleep Study. J Hypertension
- 2010
-
In: International Journal of Hypertension. - 2090-0392. ; 2010:Art ID 458410
-
Journal article (peer-reviewed)abstract
- The sympathetic nervous system and the adrenergic receptors play an important role in regulation of blood pressure. This study explored the associations between functional polymorphisms of the α(2B)-, β(1)-, and β(2)-adrenergic receptor genes and obstructive sleep apnea (OSA) in hypertensive patients and hypertension in patients with OSA in a populationbased sample of 157 hypertensive patients and 181 healthy control subjects. Only the Arg389Gly polymorphism of the β(1)-adrenergic receptor gene was associated with increased risk for mild OSA in hypertensive patients (Arg/Arg versus Gly/Arg/Gly/Gly, 2.1, 95% CI, 1.02-4.7). Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes. When adjusted also for BMI this difference became borderline significant. This difference was not observed in women. The risk of hypertension in mild OSA was associated with increasing number of Arg-alleles (Arg/Arg OR 5.4, 95% CI 1.4-21.2).
|
|
| 28. |
- Brand, Judith S., et al.
(author)
-
Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk
- 2013
-
In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:4, s. 1012-1019
-
Journal article (peer-reviewed)abstract
- OBJECTIVE-Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.RESEARCH DESIGN AND METHODS-Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied.RESULTS-Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and >= 55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [ 1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05).CONCLUSIONS-Early menopause is associated with a greater risk of type 2 diabetes. Diabetes Care 36:1012-1019, 2013
|
|
| 29. |
- Brøns, Charlotte, et al.
(author)
-
Deoxyribonucleic Acid Methylation and Gene Expression of PPARGC1A in Human Muscle Is Influenced by High-Fat Overfeeding in a Birth-Weight-Dependent Manner.
- 2010
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 3048-3056
-
Journal article (peer-reviewed)abstract
- Context: Low birth weight (LBW) and unhealthy diets are risk factors of metabolic disease including type 2 diabetes (T2D). Genetic, nongenetic, and epigenetic data propose a role of the key metabolic regulator peroxisome proliferator-activated receptor gamma, coactivator 1alpha (PPARGC1A) in the development of T2D. Objective: Our objective was to investigate gene expression and DNA methylation of PPARGC1A and coregulated oxidative phosphorylation (OXPHOS) genes in LBW and normal birth weight (NBW) subjects during control and high-fat diets. Design, Subjects, and Main Outcome Measures: Twenty young healthy men with LBW and 26 matched NBW controls were studied after 5 d high-fat overfeeding (+50% calories) and after a control diet in a randomized manner. Hyperinsulinemic-euglycemic clamps were performed and skeletal muscle biopsies excised. DNA methylation and gene expression were measured using bisulfite sequencing and quantitative real-time PCR, respectively. Results: When challenged with high-fat overfeeding, LBW subjects developed peripheral insulin resistance and reduced PPARGC1A and OXPHOS (P < 0.05) gene expression. PPARGC1A methylation was significantly higher in LBW subjects (P = 0.0002) during the control diet. However, PPARGC1A methylation increased in only NBW subjects after overfeeding in a reversible manner. DNA methylation of PPARGC1A did not correlate with mRNA expression. Conclusions: LBW subjects developed peripheral insulin resistance and decreased gene expression of PPARGC1A and OXPHOS genes when challenged with fat overfeeding. The extent to which our finding of a constitutively increased DNA methylation in the PPARGC1A promoter in LBW subjects may contribute needs to be determined. We provide the first experimental support in humans that DNA methylation induced by overfeeding is reversible.
|
|
| 30. |
- Carlsson, Björn, 1958, et al.
(author)
-
Differences in associations between HSD11B1 gene expression and metabolic parameters in subjects with and without impaired glucose homeostasis
- 2010
-
In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 88:3, s. 252-258
-
Journal article (peer-reviewed)abstract
- Aims: Animal studies indicate a role for 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) in the development of obesity. The association to glucose homeostasis is less clear. We investigated the relationship between HSD11B1 mRNA levels in adipose tissue and in skeletal muscle and anthropometric and metabolic measurements in humans with and without impaired glucose homeostasis. Methods: Twelve obese subjects with impaired glucose homeostasis (MetS+) and 12 obese controls (MetS-) received a Very Low Calorie Diet for 16 weeks and adipose tissue biopsies, blood samples and measurements were obtained. In a second cohort, skeletal muscle biopsies, blood samples and measurements were obtained from 18 subjects with type 2 diabetes (T2DM) and 17 subjects with normal glucose tolerance (NGT). Gene expression was measured by DNA microarray in both studies. Results: HSD11B1 mRNA levels were reduced during diet, and anthropometric measurements and metabolic parameters were associated with HSD11B1 mRNA levels in the MetS-group. However, in the MetS+ group these associations were lost or in opposite direction. This difference was also observed in skeletal muscle between T2DM and NGT. Conclusions: HSD11B1 mRNA levels are associated with metabolic parameters and anthropometric measurements in subjects with normal glucose homeostasis but not in subjects with impaired glucose homeostasis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
|
|
