| 191. |
- TEDDY study group, The, et al.
(författare)
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The environmental determinants of diabetes in the young (TEDDY) study: Study design
- 2007
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 8:5, s. 286-298
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective of this multicenter, multinational, epidemiological study is the identification of infectious agents, dietary factors, or other environmental exposures that are associated with increased risk of autoimmunity and type 1 diabetes mellitus (T1DM). Factors affecting specific phenotypic manifestations such as early age of onset or rate of progression or with protection from the development of T1DM will also be identified. The Environmental Determinants of Diabetes in the Young (TEDDY) is an observational cohort study in which newborns who are younger than 4 months and have high-risk human leukocyte antigen alleles in the general population or are first-degree relatives (FDRs) of patients affected with T1DM will be enrolled. Six clinical centers in the USA and Europe will screen 361 588 newborns, of which it is anticipated that 17 804 will be eligible for enrollment with just over 7800 followed. Recruitment will occur over 5 yr, with children being followed to the age of 15 yr. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay, or reverse T1DM.
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| 192. |
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| 193. |
- Tripathy, Devjit, et al.
(författare)
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Contribution of insulin-stimulated glucose uptake and basal hepatic insulin sensitivity to surrogate measures of insulin sensitivity.
- 2004
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 27:9, s. 2204-2210
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—The goal of this study was to evaluate the performance of surrogate measures of insulin sensitivity and insulin secretion. RESEARCH DESIGN AND METHODS—The homeostasis model assessment (HOMA) of insulin resistance (IR) and the insulin sensitivity index (Si) from oral glucose tolerance test (OGTT) were compared with the M value from a hyperinsulinemic-euglycemic clamp in 467 subjects with various degrees of glucose tolerance. Endogenous glucose production (EGP) and hepatic insulin sensitivity were determined in a subset (n = 143). Insulin secretion was estimated as the HOMA ß-cell index and as the insulinogenic index from the first 30 min of the OGTT (I/G30) and compared with the first-phase insulin response (FPIR) to an intravenous glucose tolerance test (n = 218). RESULTS—The M value correlated with the HOMA-IR (r = –0.591, P < 0.0001) and the Si (r = 0.533, P < 0.0001) indexes in the total study group. HOMA-IR correlated with basal EGP in the total study group (r = 0.378, P < 0.0005) and in subjects with diabetes (r = 0.330, P = 0.01). However, neither HOMA-IR nor Si correlated significantly with the M value in subjects with impaired fasting glucose (IFG) (r = –0.108, P = 0.5; r = 0.01, P = 0.9) or IFG/impaired glucose tolerance (IGT) (r = –0.167, P = 0.4; r = 0.09, P = 0.6). The HOMA-IR correlated with hepatic insulin sensitivity in the whole study group (r = –0.395, P < 0.005) as well as in the IFG/IGT subgroup (r = –0.634, P = 0.002) and in the diabetic subgroup (r = –0.348, P = 0.008). In subjects with IFG/IGT, hepatic insulin sensitivity was the most important determinant of HOMA-IR, explaining 40% of its variation. The HOMA ß-cell index showed a weak correlation with FPIR in the whole study group (r = 0.294, P = 0.001) but not in the subgroups. In contrast, the I/G30 correlated with FPIR in the whole study group (r = 0.472, P < 0.0005) and in the IFG/IGT subgroup (r = 0.493, P < 0.005). CONCLUSIONS—HOMA-IR is dependent upon both peripheral and hepatic insulin sensitivity, the contribution of which differs between subjects with normal and elevated fasting glucose concentrations. These discrepancies develop as a consequence of a nonparallel deterioration of the variables included in the equations with worsening of glucose tolerance.
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| 194. |
- Tuomi, Tiinamaija, et al.
(författare)
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Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes
- 2016
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 23:6, s. 1067-1077
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release.
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| 195. |
- Valstar, A., et al.
(författare)
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Heat-set bovine serum albumin-sodium dodecyl sulfate gels studied by fluorescence probe methods, NMR, and light scattering
- 2001
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 17:11, s. 3208-3215
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Tidskriftsartikel (refereegranskat)abstract
- In this work, concentrated protein-surfactant solutions and their corresponding heat-set gels; were studied by fluorescence probe methods, NMR, and light scattering. Bovine serum albumin (BSA) was used as the protein, and sodium dodecyl sulfate (SDS) as the surfactant. Heating concentrated BSA solutions gives turbid gels. Heat-setBSA-SDS gels are transparent. From fluorescence measurements it was concluded that SDS forms micelle-like clusters on BSA, both in solution and in the corresponding heat-set gel. Aggregation numbers were found to be similar in solution and gel. Also, I-1/I-3 values in solution and gel were similar. H-2 NMR relaxation measurements of specifically deuterated SDS at the ct-carbon position next to the headgroup were performed, and the longitudinal relaxation rates R-1 were found to be the same in solution and gel. High values for the transverse relaxation rate R-2 (indicating slow motions of SDS bound to large aggregates) were obtained, and the largest R-2 value was found for the gel. Dynamic light scattering on BSA-SDS gels was used to obtain the correlation length xi, which defines a mean distance between two points of entanglements. The decrease of xi with increasing [SDS]/[BSA] molar ratio was explained by the size of the BSA-SDS complex and the possibility that micelle-like structures might form cross-links between different BSA molecules. With static light scattering the extent of inhomogeneities in BSA and BSA-SDS gels was found to decrease with increasing SDS concentration. Also, the gel region in the ternary phase diagram BSA-SDS-3.1 mM NaN3 at room temperature and constant pressure (1 atm) was determined.
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| 196. |
- van Zuydam, NR, et al.
(författare)
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A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes
- 2018
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 67:7, s. 1414-1427
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Tidskriftsartikel (refereegranskat)abstract
- Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10−8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
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| 197. |
- Velasquez, Ilais Moreno, et al.
(författare)
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Duffy antigen receptor genetic variant and the association with Interleukin 8 levels
- 2015
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 72:2, s. 178-184
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to identify loci associated with circulating levels of Interleukin 8 (IL8). We investigated the associations of 121,445 single nucleotide polymorphisms (SNPs) from the Illumina 200K CardioMetabochip with IL8 levels in 1077 controls from the Stockholm Heart Epidemiology Program (SHEEP) study, using linear regression under an additive model of inheritance. Five SNPs (rs12075A/G, rs13179413C/T, rs6907989T/A, rs9352745A/C, rs1779553T/C) reached the predefined threshold of genome-wide significance (p < 1.0 x 10(-5)) and were tested for in silico replication in three independent populations, derived from the PIVUS, MDC-CC and SCARF studies. IL8 was measured in serum (SHEEP, PIVUS) and plasma (MDC-CC, SCARF). The strongest association was found with the SNP rs12075 A/G, Asp42Gly (p = 1.6 x 10(-6)), mapping to the Duffy antigen receptor for chemokines (DARC) gene on chromosome 1. The minor allele G was associated with 15.6% and 10.4% reduction in serum IL8 per copy of the allele in SHEEP and PIVUS studies respectively. No association was observed between rs12075 and plasma IL8. Conclusion: rs12075 was associated with serum levels but not with plasma levels of IL8. It is likely that serum IL8 represents the combination of levels of circulating plasma IL8 and additional chemokine liberated from the erythrocyte DARC reservoir due to clotting. These findings highlight the importance of understanding ILS as a biomarker in cardiometabolic diseases.
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| 198. |
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| 199. |
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