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- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 4. |
- Walford, G. A., et al.
(författare)
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Genome-wide association study of the modified stumvoll insulin sensitivity index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:10, s. 3200-3211
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci. © 2016 by the American Diabetes Association.
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| 6. |
- Boesgaard, T. W., et al.
(författare)
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Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients--EUGENE2 study
- 2009
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Ingår i: PLoS One. - 1932-6203. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKROUND: A meta-analysis combining results from three genome-wide association studies and followed by large-scale replication identified six novel type 2 diabetes loci. Subsequent studies of the effect of these variants on estimates of the beta-cell function and insulin sensitivity have been inconclusive. We examined these variants located in or near the JAZF1 (rs864745), THADA (rs7578597), TSPAN8 (rs7961581), ADAMTS9 (rs4607103), NOTCH2 (rs10923931) and the CDC123/CAMK1D (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity. METHODOLOGY/RESULTS: Oral and intravenous glucose stimulated insulin release (n = 849) and insulin sensitivity (n = 596) estimated from a hyperinsulinemic euglycemic clamp were measured in non-diabetic offspring of type 2 diabetic patients from five European populations. Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp. However, following intravenous and oral administration of glucose serum insulin release was increased in individuals with the C-allele (p = 0.003 and p = 0.01, respectively). A meta-analyse combining clamp and IVGTT data from a total of 905 non-diabetic individuals showed that the C-risk allele associated with decreased insulin sensitivity (p = 0.003) and increased insulin release (p = 0.002). The major T-allele of the intronic JAZF1 rs864745 conferring increased diabetes risk was associated with increased 2(nd) phase serum insulin release during an IVGTT (p = 0.03), and an increased fasting serum insulin level (p = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits. CONCLUSION: The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues.
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| 8. |
- Gero, D., et al.
(författare)
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Defining Global Benchmarks in Bariatric Surgery A Retrospective Multicenter Analysis of Minimally Invasive Roux-en-Y Gastric Bypass and Sleeve Gastrectomy
- 2019
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Ingår i: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 270:5, s. 859-867
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To define "best possible'' outcomes for bariatric surgery (BS)(Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]). Background: Reference values for optimal surgical outcomes in welldefined low-risk bariatric patients have not been established so far. Consequently, outcome comparison across centers and over time is impeded by heterogeneity in case-mix. Methods: Out of 39,424 elective BS performed in 19 high-volume academic centers from 3 continents between June 2012 and May 2017, we identified 4120 RYGB and 1457 SG low-risk cases defined by absence of previous abdominal surgery, concomitant procedures, diabetes mellitus, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, anticoagulation, BMI>50 kg/m(2) and age>65 years. We chose clinically relevant endpoints covering the intra- and postoperative course. Complications were graded by severity using the comprehensive complication index. Benchmark values were defined as the 75th percentile of the participating centers' median values for respective quality indicators. Results: Patients were mainly females (78%), aged 38+/-11 years, with a baseline BMI 40.8 +/- 5.8 kg/m(2). Over 90 days, 7.2% of RYGB and 6.2% of SG patients presented at least 1 complication and no patients died (mortality in nonbenchmark cases: 0.06%). The most frequent reasons for readmission after 90-days following both procedures were symptomatic cholelithiasis and abdominal pain of unknown origin. Benchmark values for both RYGB and SG at 90-days postoperatively were 5.5% Clavien-Dindo grade >= IIIa complication rate, 5.5% readmission rate, and comprehensive complication index <= 33.73 in the subgroup of patients presenting at least 1 grade >= II complication. Conclusion: Benchmark cutoffs targeting perioperative outcomes in BS offer a new tool in surgical quality-metrics and may be implemented in qualityimprovement cycle. ClinicalTrials.gov Identifier NCT03440138
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- Staiger, H., et al.
(författare)
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A candidate type 2 diabetes polymorphism near the HHEX locus affects acute glucose-stimulated insulin release in European populations: results from the EUGENE2 study
- 2008
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Ingår i: Diabetes. - 1939-327X. ; 57:2, s. 514-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In recent genome-wide association studies, two single nucleotide polymorphisms (SNPs) near the HHEX locus were shown to be more frequent in type 2 diabetic patients than in control subjects. Based on HHEX's function during embryonic development of the ventral pancreas in mice, we investigated whether these SNPs affect beta-cell function in humans. RESEARCH DESIGN AND METHODS: A total of 854 nondiabetic subjects, collected from five European clinical centers, were genotyped for the HHEX SNPs rs1111875 and rs7923837 and thoroughly characterized by an oral glucose tolerance test (OGTT). To assess glucose-stimulated insulin release, a subgroup of 758 subjects underwent an intravenous glucose tolerance test (IVGTT). RESULTS: SNPs rs1111875 and rs7923837 were not associated with anthropometric data (age, weight, height, BMI, body fat, and waist and hip circumference). After adjustment for center, family relationship, sex, age, and BMI, both SNPs were also not associated with glucose and insulin concentrations in the fasting state and during the OGTT or with measures of insulin sensitivity. Furthermore, HHEX SNP rs1111875 was not associated with insulin release during the IVGTT. By contrast, the minor A-allele of HHEX SNP rs7923837 was significantly associated with higher IVGTT-derived first-phase insulin release before and after appropriate adjustment (P = 0.013 and P = 0.014, respectively). CONCLUSIONS: A common genetic variation in the 3'-flanking region of the HHEX locus, i.e., SNP rs7923837, is associated with altered glucose-stimulated insulin release. This SNP's major allele represents a risk allele for beta-cell dysfunction and, thus, might confer increased susceptibility of beta-cells toward adverse environmental factors.
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