| 1. |
- Biörserud, Christina, et al.
(författare)
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SESQ, a patient-reported outcome instrument addressing excess skin; report on the updated version and the validation process
- 2023
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 57:1-6, s. 360-364
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Tidskriftsartikel (refereegranskat)abstract
- Excess skin after weight loss is perceived as a major problem for the majority of the bariatric patients, between 68 and 90% desire additional reconstructive surgery. However, only about 20% of the patients actually have the possibility to undergo these procedures. Reliable and valid patient-reported outcome instruments, PROM, are required in order to consider the patients' perspective of excess skin when discussing reconstructive surgery. The aim of this study was to present the updated version of Sahlgrenska Excess Skin Questionnaire, SESQ and to report on the validation process. The material for the process to evaluate internal consistency and known group validity was based on four different studies conducted at the Department of Plastic Surgery at Sahlgrenska University Hospital, Sweden. Internal consistency was high in all four groups examined; the normal population, the obese patients, the post-bariatric patients and the post-abdominoplasty patients. Values for Cronbach's alpha were >0.86 in all groups, and the highest value was seen in the obese patients (0.92). Furthermore, regarding known group validity, there were strong significant differences between the answers from the normal population in comparison with most of the other studies. In conclusion, patients thought that the questions in SESQ were easy to understand, that they covered all appropriate aspects of excess skin and the patients did not think that SESQ overlooked any questions or aspects concerning excess skin. SESQ is a valid questionnaire addressing excess skin in post-bariatric patients. The updated version of the SESQ is both accurate and user-friendly.
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| 2. |
- Börgeson, Emma, et al.
(författare)
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Challenges in PhD education due to COVID-19-disrupted supervision or business as usual: a cross-sectional survey of Swedish biomedical sciences graduate students
- 2021
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Ingår i: Bmc Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background It remains unclear to what extent the SARS-CoV-2/COVID-19 pandemic disrupted the normal progression of biomedical and medical science graduate programs and if there was a lasting impact on the quality and quantity of supervision of PhD-students. To date, multiple editorials and commentaries indicate the severity of the disruption without providing sufficient evidence with quantifiable data. Methods An online survey was submitted to the administrative offices of biomedical and medical PhD-programs at eight major universities in Sweden to gauge the impact of the pandemic on the students. It consisted of multiple-choice and open-ended questions where students could provide examples of positive and/or negative supervision strategies. Open answered questions were coded as either examples of positive or negative support. Results PhD students were divided into two groups: those with improved or unchanged supervision during the pandemic (group 1, n = 185), versus those whose supervision worsened (group 2, n = 69). Group 1 received more help from supervisors and more frequent supervision via both online and alternative platforms (email/messages and telephone). There was no significant difference in educational-stage, gender or caretaking responsibilities between the groups. Conclusions It is important for the scientific community to learn how to provide the best possible supervision for PhD students during the pandemic. Our data suggests that more frequent supervision, and using a diverse array of meeting platforms is helpful. In addition, it is important for the students to feel that they have their supervisor's emotional support. Several students also expressed that they would benefit from an extension of their PhD programs due to delays caused by the pandemic.
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| 3. |
- Elander, Anna, 1955, et al.
(författare)
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Excess skin after weight loss following bariatric surgery: focus on the abdomen.
- 2021
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Ingår i: Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. - : Elsevier BV. - 1878-7533. ; 17:5, s. 986-993
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Tidskriftsartikel (refereegranskat)abstract
- The majority of postbariatric patients experience major problems from excess skin, with most desiring abdominoplasty.To present visual assessments and objective measurements of excess abdominal skin; analyze relationships between patient-reported outcomes, objective measurements of excess skin, and visual assessments; and discuss criteria for reconstructive abdominal surgery in public healthcare.An academic hospital in Sweden.This is a secondary analysis of a prospective, longitudinal study that included 200 obese patients undergoing bariatric surgery, with 147 of these patients participating in follow-up 18-months postsurgery. Patients rated their symptoms related to excess skin and quality of life (QoL) according to the Sahlgrenska Excess Skin Questionnaire and EuroQol-5 D before and after bariatric surgery. Abdominal ptosis was measured at different anatomic locations.Waist circumference and ptosis were significantly reduced at all anatomic locations after weight loss, and abdominal ptosis was significantly larger laterally than at the midline (P < .001). The majority of patients had a ptosis ≥3 cm following bariatric surgery and had significantly more symptoms related to excess skin relative to those reported preoperation (P < .05). Additionally, the number of patients experiencing discomfort from excess skin increased along with increased ptosis size, but the correlation between ptosis size and QoL was low. Reconstructive abdominal surgery was requested by 70% of patients, all having significantly larger ptosis and significantly more symptoms than those not desiring surgery.Criteria for abdominal reconstruction should be based on both patient-reported symptoms and objective measures to ensure more patient-centered care than is possible only using objective measurements.
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| 4. |
- Fagevik Olsén, Monika, 1964, et al.
(författare)
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Physical activity with hindrances: a qualitative study of post bariatric patients' experiences of physical activity in relation to excess skin
- 2022
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 56:6, s. 320-325
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Tidskriftsartikel (refereegranskat)abstract
- A common side effect after massive weight loss is excess skin. Knowledge about the experience of excess skin in relation to physical activity is limited. The aim of this study was therefore to investigate how post bariatric surgery patients experience physical activity in relation to excess skin. Fifteen semi-structured interviews were performed with individuals who experienced excess skin after massive weight loss after bariatric surgery. The interviews were transcribed, and data were analyzed by qualitative content analysis. An overall theme emerged, that the body was still a hindrance for physical activity but now because of excess skin. There were major changes in the participants' ability to be active after the weight loss, but there were still obstacles and some of them remained from the time when they were obese. The analysis resulted in three main categories containing the participants' knowledge about, changes in and wishes for physical activity after weight loss, factors that affected the ability and the role of mental processes. The result contributes to increased knowledge about post bariatric patients' experiences of excess skin in relation to physical activity. After weight loss, the body was still a hindrance for physical activity but now because of excess skin. As physical activity is important for general health, excess skin inhibiting physical activity ought to be an indicator for reconstructive surgery.
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| 5. |
- Fagevik Olsén, Monika, 1964, et al.
(författare)
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Translation and validation of a Swedish version of the BODY-Q: a patient-reported outcome instrument for weight loss and body contouring surgery
- 2022
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 56:6, s. 348-352
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Tidskriftsartikel (refereegranskat)abstract
- BODY-Q is self-administered questionnaire that evaluates appearance, function and symptoms related to bariatric- and body contouring surgery. The purpose of this article was to describe the translation process of a Swedish version of BODY-Q and to evaluate its criterion validity to the Swedish questionnaire Sahlgrenska Excess Skin Questionnaire, SESQ. Materials and methods BODY-Q was translated according to International Society for Pharmacoeconomics and Outcome Research's guidelines. The test of validity was made between parts which were comparable to SESQ. Both questionnaires were responded by 30 subjects who were suffering from excess skin after massive weight loss following bariatric surgery or dieting. Results The correlation between the two questionnaires varied. The parts of BODY-Q evaluating excess skin on the whole body and parts of the body had higher correlations (r(s) 0.328-0.766) than the parts evaluating side effects of excess skin and body-image (r(s) 0.103-0.574). Conclusion The Swedish version of BODY-Q has a good criterion validity and can be recommended in the healthcare for patients with excess skin after massive weight loss and for evaluation of the outcomes from reconstructive surgical procedures.
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| 6. |
- Labori, Knut Jørgen, et al.
(författare)
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Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1) : a multicentre, randomised, phase 2 trial
- 2024
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Ingår i: The Lancet Gastroenterology & Hepatology. - : The Lancet Group. - 2468-1253. ; 9:3, s. 205-217
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma.MethodsNORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing.FindingsBetween Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49–71) in the neoadjuvant FOLFIRINOX group versus 73% (62–84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2–34·9) versus 38·5 months (27·6–not reached; hazard ratio [HR] 1·52 [95% CI 1·00–2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46–67) in the neoadjuvant FOLFIRINOX group versus 70% (55–83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2–34·9) versus 34·4 months (19·4–not reached; HR 1·46 [95% CI 0·99–2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event.InterpretationThis phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven.
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| 7. |
- Labori, Knut Jørgen, et al.
(författare)
-
Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1) : a multicentre, randomised, phase 2 trial
- 2024
-
Ingår i: The Lancet Gastroenterology & Hepatology. - : Elsevier. - 2468-1253. ; 9:3, s. 205-217
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma.Methods: NORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing.Findings: Between Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49–71) in the neoadjuvant FOLFIRINOX group versus 73% (62–84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2–34·9) versus 38·5 months (27·6–not reached; hazard ratio [HR] 1·52 [95% CI 1·00–2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46–67) in the neoadjuvant FOLFIRINOX group versus 70% (55–83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2–34·9) versus 34·4 months (19·4–not reached; HR 1·46 [95% CI 0·99–2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event.Interpretation: This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven.
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| 8. |
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| 9. |
- Ockell, Jonas, et al.
(författare)
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Physical measurements and patients' perception of excess skin on arms and thighs before and after bariatric surgery
- 2022
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Ingår i: European Journal of Plastic Surgery. - : Springer Science and Business Media LLC. - 0930-343X .- 1435-0130. ; 45:4, s. 631-640
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Tidskriftsartikel (refereegranskat)abstract
- Background Bariatric surgery is an effective weight loss method for patients with obesity. One side effect of bariatric surgery is uncomfortable excess skin. Much remains to be learned about physical measurements and patients' subjective perceptions of it. Here, we investigated the pre- to post-bariatric changes in patients' perception and physical measurements of the skin on the arms and thighs, in order to find possible subgroups especially affected by post-operative excess skin and to identify predicting factors. Methods One hundred forty-seven patients eligible for bariatric surgery completed the Sahlgrenska Excess Skin Questionnaire (SESQ) and underwent measurements of their skin before and 18 months after the procedure. Results Although most physical measurements decreased post-operatively, many patients reported increased discomfort. We identified one subgroup particularly prone to report excess skin on the arms post-operatively: women with high discomfort from excess skin on the arms and high body mass index (BMI), pre-operatively. Ptosis of the excess skin seems to be a feasible measurement for predicting post-operative discomfort. For every centimetre of ptosis pre-operatively, patients had 1.37- and 1.31-fold higher odds of achieving a score for post-operative discomfort from excess skin on the upper arms and thighs, respectively, of >= 6 (on a 0-10 scale). Conclusions We identified a subgroup especially affected by discomforting excess skin on arms and thighs after weight loss. Furthermore, we suggest a pre-operative pro-operative ptosis measuring to predict post-operative discomfort level. The result of this study further increases the knowledge of excess skin and should be useful in further improving patient education.
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| 10. |
- Sotak, Matus, et al.
(författare)
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Healthy Subcutaneous and Omental Adipose Tissue Is Associated with High Expression of Extracellular Matrix Components
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture, including its microenvironment and extracellular matrix (ECM). Although obesity has been reported to induce adipose tissue fibrosis, the composition of the ECM under healthy physiological conditions has remained underexplored and debated. Here, we used a combination of three established techniques (picrosirius red staining, a colorimetric hydroxyproline assay, and sensitive gene expression measurements) to evaluate the status of the ECM in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) subjects. We investigated ECM deposition in the two major human adipose tissues, namely the omental and subcutaneous depots. Biopsies were obtained from the same anatomic region of respective individuals. We found robust ECM deposition in MHL subjects, which correlated with high expression of collagens and enzymes involved in ECM remodeling. In contrast, MUO individuals showed lower expression of ECM components but elevated levels of ECM cross-linking and adhesion proteins, e.g., lysyl oxidase and thrombospondin. Our data suggests that subcutaneous fat is more prone to express proteins involved in ECM remodeling than omental adipose tissues. We conclude that a more dynamic ability to deposit and remodel ECM may be a key signature of healthy adipose tissue, and that subcutaneous fat may adapt more readily to changing metabolic conditions than omental fat.
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| 11. |
- Sotak, Matus, et al.
(författare)
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Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue inflammation drives obesity-related cardiometabolic diseases. Enhancing endogenous resolution mechanisms through administration of lipoxin A4, a specialized pro-resolving lipid mediator, was shown to reduce adipose inflammation and subsequently protects againstobesity-inducedsystemic disease inmice. Here, we demonstrate that lipoxins reduce inflammation in 3D-cultured human adipocytes and adipose tissue explants from obese patients. Approximately 50% of patients responded particularlywell to lipoxins by reducing inflammatory cytokines and promoting an anti-inflammatory M2 macrophage phenotype. Responding patients were characterized by elevated systemic levels of C-reactive protein, which causes inflammation in cultured human adipocytes. Responders appeared more prone to producing anti-inflammatory oxylipins and displayed elevated prostaglandin D2 levels, which has been interlinked with transcription of lipoxin-generatingenzymes. Using explant cultures, this study provides the first proof-of-concept evidence supporting the therapeutic potential of lipoxins in reducing human adipose tissue inflammation. Our data further indicate that lipoxin treatment may require a tailored personalized-medicine approach.
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| 12. |
- Wallenius, Ville, 1970, et al.
(författare)
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Glycemic Control and Metabolic Adaptation in Response to High-Fat versus High-Carbohydrate Diets-Data from a Randomized Cross-Over Study in Healthy Subjects.
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and α-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.
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