| 1. |
- Lindqvist, A, et al.
(författare)
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Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels
- 2020
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 511
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Tidskriftsartikel (refereegranskat)abstract
- It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells. The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls. Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.
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| 2. |
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| 3. |
- Zhang, R., et al.
(författare)
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Systematic review of risk prediction models for diabetes after bariatric surgery
- 2016
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 103:11, s. 1420-1427
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Forskningsöversikt (refereegranskat)abstract
- Background: Diabetes remission is an important outcome after bariatric surgery. The purpose of this study was to identify risk prediction models of diabetes remission after bariatric surgery. Methods: A systematic literature review was performed in MEDLINE, MEDLINE-In-Process, Embase and the Cochrane Central Register of Controlled Trials databases in April 2015. All English-language full-text published derivation and validation studies for risk prediction models on diabetic outcomes after bariatric surgery were included. Data extraction included population, outcomes, variables, intervention, model discrimination and calibration. Results: Of 2330 studies retrieved, eight met the inclusion criteria. Of these, six presented development of risk prediction models and two reported validation of existing models. All included models were developed to predict diabetes remission. Internal validation using tenfold validation was reported for one model. Two models (ABCD score and DiaRem score) had external validation using independent patient cohorts with diabetes remission assessed at 12 and 14 months respectively. Of the 11 cohorts included in the eight studies, calibration was not reported in any cohort, and discrimination was reported in two. Conclusion: A variety of models are available for predicting risk of diabetes following bariatric surgery, but only two have undergone external validation.
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| 4. |
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| 5. |
- Carlsson, M, et al.
(författare)
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Common variants in the beta2-(Gln27Glu) and beta3-(Trp64Arg)--adrenoceptor genes are associated with elevated serum NEFA concentrations and type II diabetes
- 2001
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 44:5, s. 629-636
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Higher NEFA concentrations predict Type II (non-insulin-dependent) diabetes mellitus but it is not known whether higher NEFA concentrations are genetically determined or reflect coexisting obesity. To address this question we studied whether common variants in two genes encoding for key regulators of lipolysis, the beta2- and beta3- adrenoceptors (B2AR and B3AR) are associated with NEFA concentrations and Type II diabetes. METHODS: A total of 1054 Swedish subjects with varying degrees of glucose tolerance were genotyped for the Gln27Glu variant in the B2AR and for the Trp64Arg variant in the B3AR genes using PCR-RFLP. RESULTS: The B2AR Gln27 allele was more frequent in 219 Type II diabetic patients than in 237 non-diabetic subjects (59.8 % vs 52.3 %; OR = 1.72, p = 0.02) while there was no significant difference in the frequency of the B3AR Arg64 allele. Subjects homozygous for the protective alleles (Glu27 and Trp64) had, however, a lower prevalence of diabetes than subjects with other genotype combinations (OR = 0.58, p = 0.03). Among sibling pairs discordant for the B2AR Gln27Glu polymorphism, siblings with an excess of the Gln27 allele had higher fasting insulin (n = 217; p = 0.02) and NEFA concentrations (107 sex-matched pairs; p = 0.01) than siblings with an excess of the Glu27 allele. Among sibling pairs discordant for the B3AR Trp64Arg variant, siblings with the Arg64 allele had higher 2 h glucose (n = 48; p = 0.01) and NEFA concentrations (16 pairs matched for sex; p < 0.04) than siblings with the Trp64Trp64 genotype. CONCLUSIONS/INTERPRETATION: Common variants in the beta2- and beta3- adrenoceptor genes are associated with increased fasting insulin and NEFA concentrations and could increase susceptibility to Type II diabetes.
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| 6. |
- Hedenbro, Jan, et al.
(författare)
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Formation of the Scandinavian Obesity Surgery Registry, SOReg
- 2015
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 25:10, s. 1893-1900
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Tidskriftsartikel (refereegranskat)abstract
- Obesity surgery is expanding, the quality of care is ever more important, and learning curve assessment should be established. A large registry cohort can show long-term effects on obesity and its comorbidities, complications, and long-term side effects of surgery, as well as changes in health-related quality of life (QoL). Sweden is ideally suited to the task of data collection and audit, with universal use of personal identification numbers, nation-wide registries permitting cross-matching to analyze causes of death, in-hospital care, and health-related absenteeism. In 2004, the Scandinavian Obesity Surgery Registry (SOReg) was initiated and government financing secured. A project group created a national database covering all public as well as private hospitals. Data entry was to be made online, operative definitions of comorbidity were formed, and complication severity scored. Several forms of audit were devised. After pilot studies, the system has been running in its present form since 2007. Since 15 January 2013, SOReg covers all bariatric surgery centers in Sweden. The number of operations in the database exceeded 40,000 (March 2014), with a median follow-up of 2.94 years. Audit shows that > 98 % of data are correct. All results are publicized annually on the Internet. Using this systematic approach, it has been possible to cover > 99 % of all bariatric surgery, cross-matching our data with nation-wide registries for in-hospital care, cause of death, and permitting regular nation-wide audit. Several scientific studies have used, or are using, what seems to be the most comprehensive database in obesity surgery.
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| 7. |
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| 8. |
- Jönsson, E., et al.
(författare)
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Diabetes Resolution and Work Absenteeism After Gastric Bypass : a 6-Year Study
- 2017
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 27:9, s. 2246-2252
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity-related diseases cause costs to society. We studied the cost of work absenteeism before and after gastric bypass and the effects of postoperative diabetes resolution. Patients and Methods: Data were obtained from the Scandinavian Obesity Surgery Registry (SOReg) (national coverage >98%) and cross-matched with data from the Social insurance Agency (coverage 100%) for the period ±3 years from operation. In 2010, a total of 7454 bariatric surgeries were performed; the study group is 4971 unique individuals with an annual income of >10,750 Euros and complete data sets. A sex-, age-, and income-matched reference population was identified for comparison. Results: Patients with obesity had preoperatively a 3.5-fold higher absenteeism. During follow-up (FU), the ratio relative to the reference population remained constant. An increase of 12–14 net absenteeism days was observed in the first 3 months after surgery. Female sex (OR 1.5, CI 1.13–1.8), preoperative anti-depressant use (OR 1.5, CI 1.3–1.9), low income (OR 1.4, CI 1.2–1.8), and a history of sick leave (OR 1.004, CI 1.003–1.004) were associated with increased absenteeism during FU. Diabetes resolution did not decrease absenteeism from preoperative values. Conclusions: Patients with obesity have higher preoperative absenteeism than the reference population. Operation caused an increase the first 90 days after surgery of 12–13 days. There were no relative increases in absenteeism in the next 3 years; patients did not deviate from preoperative patterns but followed the trend of the reference population. Preoperative diabetes did not elevate that level during FU; diabetes resolution did not lower absenteeism.
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| 9. |
- Lindqvist, Andreas, et al.
(författare)
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The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Background A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood. In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder. A similar weight development in both groups of pigs validated our experimental model. Despite similar changes in fasting insulin, RYGB-pigs had lower fasting glucose levels. During an IVGTT RYGB-pigs had higher insulin and lower glucose levels. VLDL and IDL were lower in RYGB-than in sham-pigs. RYGB-pigs had increased levels of most amino acids, including branched-chain amino acids, but these were more efficiently suppressed by glucose. Levels of bile acids in the gallbladder were higher, whereas plasma and faecal bile acid levels were lower in RYGB-than in sham-pigs. In a lean model RYGB caused lower plasma lipid and bile acid levels, which were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period.
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| 10. |
- Nergård, Bent J, et al.
(författare)
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Mucosal glucagon-like peptide-1 and gastric inhibitory polypeptide cell numbers in the super-obese human foregut after gastric bypass.
- 2015
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289. ; 11:6, s. 1237-1246
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Tidskriftsartikel (refereegranskat)abstract
- Super-obesity, a body mass index>50 kg/m(2), is difficult to treat. Many studies have focused on the anatomic changes of the intestines; the physiologic background is not clearly identified. It is established that Roux-en-Y gastric bypass (RYGB) augments secretion of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and insulin, but other aspects of gut hormone cell function in the alimentary limb are unknown.
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