| 61. |
- Bennet, Louise, et al.
(författare)
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High prevalence of type 2 diabetes in Iraqi and Swedish residents in a deprived Swedish neighbourhood - a population based study
- 2011
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 11
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Tidskriftsartikel (refereegranskat)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.
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| 62. |
- BERGGREN, JOHAN, et al.
(författare)
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Roux-en-Y gastric bypass versus calorie restriction: support for surgery as the direct contributor to aloncltered responses of insulin and incretins to a mixed meal
- 2017
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289. ; 13:2, s. 234-242
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Tidskriftsartikel (refereegranskat)abstract
- AbstractObjectiveTo study the immediate effects of Roux-en-Y gastric bypass (RYGB) on glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared with the effects of calorie restriction (CR).SettingUniversity-affiliated bariatric surgery clinic.BackgroundRYGB induces remission of type 2 diabetes (T2 D) long before significant weight loss occurs. The time course and underlying mechanisms of this remission remain enigmatic. A prevailing theory is that secretory patterns of incretin hormones are altered due to rearrangement of the gastrointestinal tract. To what extent reduced calorie intake contributes to the remission of T2 D is unknown.MethodsNine normoglycemic patients and 10 T2 D patients were subjected to mixed-meal tests (MMT) 4 weeks before surgery before initiation of a very low calorie diet regimen (MMT-4 w), 1 day before surgery on a very low calorie diet regimen (MMT-1 d), on the morning of the first day after surgery (MMT+1 d; first postsurgical meal), and 6 weeks after surgery (MMT+6 w). Insulin, glucose, active glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured.ResultsCR lowered insulin in T2 D patients, whereas glucose, GIP, and GLP-1 were unaffected. RYGB immediately increased plasma insulin and GIP. The GLP-1 response was delayed compared with the GIP response. T2 D patients exhibited lower insulin responses after RYGB compared with normoglycemic patients. GIP responses were similar in both groups at all occasions, whereas T2 D patients displayed markedly elevated GLP-1 responses 6 weeks after RYGB. Glucose was unaffected by CR and RYGB in both groups. Insulin sensitivity was unaffected by CR but improved with RYGB.ConclusionRYGB exerts powerful and immediate effects on insulin and incretin responses to food, independently of changes caused by CR.
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| 63. |
- Berglund, Lisa, et al.
(författare)
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Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254
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Tidskriftsartikel (refereegranskat)abstract
- Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
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| 64. |
- Bergman, Michael, et al.
(författare)
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Lessons learned from the 1-hour post-load glucose level during OGTT : Current screening recommendations for dysglycaemia should be revised
- 2018
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Ingår i: Diabetes/Metabolism Research and Reviews. - : Wiley. - 1520-7552. ; 34:5
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Tidskriftsartikel (refereegranskat)abstract
- This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1-hour post-load glucose level during the 75-g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1-hour post-load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced β-cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA1c or 2-hour post-load glucose values. An elevated 1-hour post-load glucose level was a better predictor of type 2 diabetes than isolated 2-hour post-load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1-hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2-hour level was <140 mg/dl (7.8 mmol/L). The risk of myocardial infarction or fatal ischemic heart disease was also greater among subjects with elevated 1-hour glucose levels as were risks of retinopathy and peripheral vascular complications in a Swedish cohort. The authors believe that the considerable evidence base supports redefining current screening and diagnostic recommendations with the 1-hour post-load level. Measurement of the 1-hour PG level would increase the likelihood of identifying a larger, high-risk group with the additional practical advantage of potentially replacing the conventional 2-hour oral glucose tolerance test making it more acceptable in a clinical setting.
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| 65. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)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.
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| 66. |
- Bompada, Pradeep, et al.
(författare)
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Epigenome-Wide Histone Acetylation Changes in Peripheral Blood Mononuclear Cells in Patients with Type 2 Diabetes and Atherosclerotic Disease
- 2021
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- There is emerging evidence of an association between epigenetic modifications, glycemic control and atherosclerosis risk. In this study, we mapped genome-wide epigenetic changes in patients with type 2 diabetes (T2D) and advanced atherosclerotic disease. We performed chromatin immunoprecipitation sequencing (ChIP-seq) using a histone 3 lysine 9 acetylation (H3K9ac) mark in peripheral blood mononuclear cells from patients with atherosclerosis with T2D (n = 8) or without T2D (ND, n = 10). We mapped epigenome changes and identified 23,394 and 13,133 peaks in ND and T2D individuals, respectively. Out of all the peaks, 753 domains near the transcription start site (TSS) were unique to T2D. We found that T2D in atherosclerosis leads to an H3K9ac increase in 118, and loss in 63 genomic regions. Furthermore, we discovered an association between the genomic locations of significant H3K9ac changes with genetic variants identified in previous T2D GWAS. The transcription factor 7-like 2 (TCF7L2) rs7903146, together with several human leukocyte antigen (HLA) variants, were among the domains with the most dramatic changes of H3K9ac enrichments. Pathway analysis revealed multiple activated pathways involved in immunity, including type 1 diabetes. Our results present novel evidence on the interaction between genetics and epigenetics, as well as epigenetic changes related to immunity in patients with T2D and advanced atherosclerotic disease.
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| 67. |
- Boström, Kristina Bengtsson, et al.
(författare)
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Polymorphisms in alpha - and betaadrenergic receptor genes, hypertension and obstructive sleep apnea. The Skaraborg Sleep Study. J Hypertension
- 2010
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Ingår i: International Journal of Hypertension. - 2090-0392. ; 2010:Art ID 458410
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Tidskriftsartikel (refereegranskat)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).
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| 68. |
- Brand, Judith S., et al.
(författare)
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Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:4, s. 1012-1019
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Tidskriftsartikel (refereegranskat)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
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| 69. |
- Brorsson, Caroline, et al.
(författare)
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A non-synonymous variant in SLC30A8 is not associated with type 1 diabetes in the Danish population
- 2008
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 94:3, s. 386-388
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association scans in type 2 diabetes (T2D) have identified a risk variant, rs13266634 (Arg325Trp), in SLC30A8 on chromosome 8. SLC30A8 encodes a beta-cell specific zinc-ion transporter and rs13266634 has been shown to affect insulin secretion. Recently, autoantibodies for Slc30A8 with high predictive value were demonstrated in individuals with type 1 diabetes (T1 D), making this gene an interesting T1 D candidate gene. We genotyped rs13266634 in 3008 cases and controls and 246 families from Denmark. Association to T1 D could not be demonstrated.
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| 70. |
- Brøns, Charlotte, et al.
(författare)
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Deoxyribonucleic Acid Methylation and Gene Expression of PPARGC1A in Human Muscle Is Influenced by High-Fat Overfeeding in a Birth-Weight-Dependent Manner.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 3048-3056
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Tidskriftsartikel (refereegranskat)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.
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