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1.
Sci Rep ; 14(1): 8211, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589596

RESUMO

Although bariatric surgery is an effective treatment for type 2 diabetes by inducing weight loss and augmenting gut hormone secretion, the immediate effect on beta-cell function itself remains to be elucidated in type 2 diabetes. Therefore, a prospective, randomized trial was performed in 30 patients with insulin-treated type 2 diabetes and a body mass index ≥ 35 kg/m2. Patients were randomly assigned (1:1:1) to Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in combination with protein-sparing modified fast (PSMF), or to PSMF alone. Eu- and hyperglycemic clamps were performed before and 3 weeks after surgery and/or PSMF initiation. The primary outcome was the evolution of insulin sensitivity and beta-cell function after surgery, calculated using the composite measures of glucose disposal rate, insulin secretion rate, and disposition index (DI). Results revealed that markers of insulin sensitivity increased similarly in all arms (p = 0.43). A higher marker for maximal beta-cell function was observed when comparing SG to PSMF (p = 0.007). The DI showed a clear positive evolution after RYGB and SG, but not after PSMF alone. Altogether, these findings indicate that bariatric surgery results in an immediate beta-cell function recovery in insulin-treated type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Resistência à Insulina , Obesidade Mórbida , Humanos , Derivação Gástrica/métodos , Insulina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Estudos Prospectivos , Glicemia , Resultado do Tratamento , Dieta , Gastrectomia/métodos , Obesidade Mórbida/cirurgia
2.
Diabetologia ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517484

RESUMO

AIMS/HYPOTHESIS: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual's clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis. METHODS: Data were collected from the large INNODIA cohort of individuals (aged 1.0-45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10-17 years; and ≥18 years. RESULTS: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0-382.0) pmol/l (AUC 749.3 [466.2-1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001). CONCLUSIONS/INTERPRETATION: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline.

4.
Neurogastroenterol Motil ; 36(4): e14758, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342973

RESUMO

BACKGROUND AND PURPOSE: The pathophysiology of obesity has been the product of extensive research, revealing multiple interconnected mechanisms contributing to body weight regulation. The regulation of energy balance involves an intricate network, including the gut-neuroendocrine interplay. As a consequence, research on the gut-brain-microbiota axis in obesity has grown extensively. The physiology of the gastrointestinal tract, far from being underexplored, has significant implications for the development of specific complications in people living with obesity across the fields of gastroenterology, nutrition, and pharmacology. Clinical research indicates higher fasting bile acids serum levels, and blunted postprandial increases in bilious secretions in people living with obesity. Findings are less straightforward for the impact of obesity on gastric emptying with various studies reporting accelerated, normal, or delayed gastric emptying rates. Conversely, the effect of obesity on gastrointestinal pH, gastrointestinal transit, and gastric and pancreatic enzyme secretion is largely unknown. In this review, we explore the current evidence on the gastrointestinal physiology of obesity.


Assuntos
Trânsito Gastrointestinal , Obesidade , Humanos , Obesidade/complicações , Trânsito Gastrointestinal/fisiologia , Peso Corporal , Jejum , Estômago , Motilidade Gastrointestinal/fisiologia , Esvaziamento Gástrico , Trato Gastrointestinal
5.
iScience ; 26(12): 108517, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38125020

RESUMO

Stem cells are a keystone of intestinal homeostasis, but their function could be shifted during energy imbalance or by crosstalk with microbial metabolites in the stem cell niche. This study reports the effect of obesity and microbiota-derived short-chain fatty acids (SCFAs) on intestinal stem cell (ISC) fate in human crypt-derived intestinal organoids (enteroids). ISC fate decision was impaired in obesity, resulting in smaller enteroids with less outward protruding crypts. Our key finding is that SCFAs switch ISC commitment to the absorptive enterocytes, resulting in reduced intestinal permeability in obese enteroids. Mechanistically, SCFAs act as HDAC inhibitors in stem cells to enhance Notch signaling, resulting in transcriptional activation of the Notch target gene HES1 to promote enterocyte differentiation. In summary, targeted reprogramming of ISC fate, using HDAC inhibitors, may represent a potential, robust therapeutic strategy to improve gut integrity in obesity.

6.
Lancet Reg Health Eur ; 33: 100720, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37953999
7.
EClinicalMedicine ; 62: 102061, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37554127

RESUMO

Background: Obesity is recognized by the World Health Organization as a chronic disease. As such, it should be referred to using the language of chronic diseases, with correct and established terminology and definitions. This study was designed to map the current language used to discuss obesity and to compare this with the standard language used for chronic disease. Methods: We performed a modified Delphi study to identify the language of chronic disease that is being used in the context of obesity, and to identify discrepancies and potential use of inadequate language with respect to the standard language used for chronic diseases. Participants (n = 24) were identified from relevant stakeholder groups and desk research, and included patients, healthcare professionals, policymakers, researchers, industry, and payers (social insurers) of 18 nationalities/regions in Europe, North/South America, and South Africa. Participants were enrolled between 20.10.2020 and 30.10.2020. The study comprised two rounds of qualitative surveys. In Round 1, participants responded to six open-ended questions. Round 2 comprised 38 statements based on key terms/themes identified in Round 1 and covered the definition, causes, progression, treatment, management, and complications of obesity. Consensus was defined as ≥70% participant agreement on a statement. Findings: All participants completed Round 1 and 23 participants completed Round 2. In Round 2, consensus was reached for 28 of the 38 statements. Participants reached a consensus regarding the use of statements that acknowledge the heterogeneous nature of obesity, but not on the use of statements that: defined obesity based on body mass index; regarded psychological, physical, or physiological factors among the main causes of obesity; or implied that weight loss should be the aim of obesity treatment. Interpretation: This study uses expert consensus to provide insight into the language used to describe obesity as a chronic disease, and forms the basis for a unified language of obesity. Funding: Innovative Medicines Initiative, Novo Nordisk A/S.

8.
J Exp Med ; 220(9)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37347461

RESUMO

Healthy adipose tissue (AT) contains ST2+ Tregs, ILC2s, and alternatively activated macrophages that are lost in mice or humans on high caloric diet. Understanding how this form of type 2 immunity is regulated could improve treatment of obesity. The STE20 kinase Thousand And One amino acid Kinase-3 (TAOK3) has been linked to obesity in mice and humans, but its precise function is unknown. We found that ST2+ Tregs are upregulated in visceral epididymal white AT (eWAT) of Taok3-/- mice, dependent on IL-33 and the kinase activity of TAOK3. Upon high fat diet feeding, metabolic dysfunction was attenuated in Taok3-/- mice. ST2+ Tregs disappeared from eWAT in obese wild-type mice, but this was not the case in Taok3-/- mice. Mechanistically, AT Taok3-/- Tregs were intrinsically more responsive to IL-33, through higher expression of ST2, and expressed more PPARγ and type 2 cytokines. Thus, TAOK3 inhibits adipose tissue Tregs and regulates immunometabolism under excessive caloric intake.


Assuntos
Imunidade Inata , Interleucina-33 , Animais , Humanos , Camundongos , Dieta Hiperlipídica/efeitos adversos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Linfócitos/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
9.
Nutr Health ; : 2601060231166821, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37006189

RESUMO

Background and objectives: To investigate the effect of carbohydrate intake before laparoscopic Roux-en-Y gastric bypass (LRYGB) on body weight, body composition and glycaemic status after surgery. Methods: In a tertiary centre cohort study, dietary habits, body composition and glycaemic status were evaluated before and 3, 6 and 12 months after LRYGB. Detailed dietary food records were processed by specialized dietitians on the basis of a standard protocol. The study population was subdivided according to relative carbohydrate intake before surgery. Results: Before surgery, 30 patients had a moderate relative carbohydrate intake (26%-45%, M-CHO), a mean body mass index (BMI) of 40.4 ± 3.9 kg/m² and a mean glycated haemoglobin A1c (A1C) of 6.5 ± 1.2% compared to 20 patients with a high relative carbohydrate intake (> 45%, H-CHO), mean BMI of 40.9 ± 3.7 kg/m² (non-significant, NS) and a mean A1C of 6.2% (NS). One year after surgery, body weight, body composition and glycaemic status were similar in the M-CHO (n = 25) and H-CHO groups (n = 16), despite less caloric intake in the H-CHO group (1317 ± 285 g vs. 1646 ± 345 g in M-CHO, p < 0.01). Their relative carbohydrate intake converged to 46% in both groups, but the H-CHO group reduced the absolute total carbohydrate consumption more than the M-CHO group (190 ± 50 g in M-CHO vs. 153 ± 39 g in H-CHO, p < 0.05), and this was especially pronounced for the mono- and disaccharides (86 ± 30 g in M-CHO vs. 65 ± 27 g in H-CHO, p < 0.05). Conclusion: A high relative carbohydrate intake before LRYGB, did not influence the change in body composition or diabetes status after surgery, despite a significantly lower total energy intake and less mono- and disaccharide consumption after surgery.

10.
Adv Nutr ; 14(2): 270-282, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36796437

RESUMO

The evidence from clinical trials concerning the efficacy of dietary polyphenols on cardiometabolic health is divergent. Therefore, this review aimed to determine the pooled effect of dietary polyphenols on cardiometabolic risk markers and compare the difference in efficacy between whole polyphenol-rich foods and purified food polyphenol extracts. We conducted a random-effect model meta-analysis of randomized controlled trials (RCTs) on the effect of polyphenols on blood pressure, lipid profile, flow-mediated dilation (FMD), fasting blood glucose (FBG), waist circumference, and markers of inflammation. Effect size was expressed as weighted mean difference and 95% CI. RCTs published in English between 2000 and 2021 involving adult participants with cardiometabolic risks were searched in electronic databases. Forty-six RCTs involving 2494 participants with a mean age of 53.3 ±10 y were included in this review. Whole polyphenol-rich food but not purified food polyphenol extracts significantly reduced systolic blood pressure (SBP, -3.69 mmHg; 95% CI: -4.24, -3.15 mmHg; P = 0.00001) and diastolic blood pressure (DBP, -1.44 mmHg; 95% CI: -2.56, -0.31 mmHg; P = 0.0002). Concerning waist circumference, purified food polyphenol extracts led to a larger effect (-3.04 cm; 95% CI: -7.06, -0.98 cm; P = 0.14). Significant effects on total cholesterol (-9.03 mg/dL; 95% CI: -16.46, -1.06 mg/dL; P = 0.02) and TGs (-13.43 mg/dL; 95% CI: -23.63, -3.23; P = 0.01) were observed when purified food polyphenol extracts were considered separately. None of the intervention materials significantly affected LDL-cholesterol, HDL-cholesterol, FBG, IL-6, and CRP. When both whole food and extracts were pooled together, there was a significant reduction in SBP, DBP, FMD, TGs, and total cholesterol. These findings suggest that polyphenols both as whole food and purified extracts can be efficacious in reducing cardiometabolic risks. However, these results must be interpreted with caution because of high heterogeneity and risk of bias among RCTs. This study was registered on PROSPERO as CRD42021241807.


Assuntos
Doenças Cardiovasculares , Polifenóis , Adulto , Humanos , Pessoa de Meia-Idade , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , LDL-Colesterol , HDL-Colesterol , Pressão Sanguínea , Doenças Cardiovasculares/prevenção & controle
11.
Am J Clin Nutr ; 117(2): 436-443, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36811566

RESUMO

BACKGROUND: The metabolic health of urban Ugandans, mostly females, is increasingly becoming sub-optimal. OBJECTIVES: We assessed the effect of a complex lifestyle intervention, based on a small change approach, on metabolic health among females of reproductive age in urban Uganda. METHODS: A cluster randomized controlled two-arm trial with a 1:1 allocation involving church communities in Kampala (Uganda) was undertaken. The intervention arm received infographics and face-to-face group sessions, whereas the comparison arm received infographics only. Eligible participants were aged 18 to 45 years with a waist circumference of ≥80 cm and without cardiometabolic diseases. The study included a 3-month intervention and a 3-month postintervention follow-up. The primary outcome was a reduction in waist circumference. Secondary outcomes included optimization of cardiometabolic health, physical activity, and fruit and vegetable intake. Intention to treat analyses were performed using linear mixed models. This trial was registered at clinicaltrials.gov as NCT04635332. RESULTS: The study was conducted between 21 November 2020 and 8 May 2021. Six church communities were randomly selected, 3 (n = 66) per study arm. At 3 months and postintervention follow-up, 118 and 100 participants were analyzed, respectively. At 3 months, waist circumference tended to be lower in the intervention arm (-1.48 cm (95% CI: -3.05, 0.10) P = 0.06). The intervention showed an effect on fasting blood glucose concentrations (-6.95 mg/dL (95% CI: -13.37, -0.53) P = 0.034). Participants in the intervention arm consumed more fruits (62.6 g (95% CI: 1.9, 123.3) P = 0.046) and vegetables (66.2 g (95% CI: 25.5, 106.8) P = 0.002), whereas physical activity increased with no notable differences across the study arms. At 6 months, we found an intervention effect on waist circumference (-1.87 cm (95% CI: -3.32, -0.44) P = 0.011), fasting blood glucose concentration (-6.48 mg/dL (95% CI: -12.76, -0.21) P = 0.043), fruit consumption (29.7 g (95% CI: 5.8, 53.7) P = 0.015), and physical activity (2675.1 MET-mins/wk (95% CI: 1045.7, 4304.4) P = 0.001). CONCLUSIONS: The intervention improved and sustained physical activity and fruit and vegetable intake, but these changes were accompanied by minimal cardiometabolic health improvements. If maintained over time, the attained lifestyle improvements may result in substantial cardiometabolic health improvements.


Assuntos
Doenças Cardiovasculares , Dieta , Humanos , Feminino , Masculino , Glicemia , Uganda , Estilo de Vida , Doenças Cardiovasculares/prevenção & controle
12.
Eur J Pharm Biopharm ; 183: 92-101, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603693

RESUMO

BACKGROUND: Knowledge regarding the gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass is urgently needed to understand, prevent and treat the nutritional and pharmacological complications of bariatric surgery. AIM: To investigate the effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal motility (e.g., transit and pressure), pH, and intestinal bile acid concentration. MATERIAL AND METHODS: An exploratory cross-sectional study was performed in six participants living with obesity, six participants who underwent sleeve gastrectomy, and six participants who underwent Roux-en-Y gastric bypass. During the first visit, a wireless motility capsule (SmartPill©) was ingested after an overnight fast to measure gastrointestinal transit, pH, and pressure. During the second visit, a gastric emptying scintigraphy test of a nutritional drink labeled with 99mTc-colloid by a dual-head SPECT gamma camera was performed to measure gastric emptying half-time (GET1/2). During the third visit, two customized multiple lumen aspiration catheters were positioned to collect fasting and postprandial intestinal fluids to measure bile acid concentration. RESULTS: Immediate pouch emptying (P = 0.0007) and a trend for faster GET1/2 (P = 0.09) were observed in both bariatric groups. There was a tendency for a shorter orocecal transit in participants with sleeve gastrectomy and Roux-en-Y gastric bypass (P = 0.08). The orocecal segment was characterized by a higher 25th percentile pH (P = 0.004) and a trend for a higher median pH in both bariatric groups (P = 0.07). Fasting total bile acid concentration was 7.5-fold higher in the common limb after Roux-en-Y gastric bypass (P < 0.0001) and 3.5-fold higher in the jejunum after sleeve gastrectomy (P = 0.009) compared to obesity. Postprandial bile acid concentration was 3-fold higher in the jejunum after sleeve gastrectomy (P = 0.0004) and 6.5-fold higher in the common limb after Roux-en-Y gastric bypass (P < 0.0001) compared to obesity. CONCLUSION: The anatomical alterations of sleeve gastrectomy and Roux-en-Y gastric bypass have an important impact on gastrointestinal physiology. This data confirms changes in transit and pH and provides the first evidence for altered intraluminal bile acid concentration.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Humanos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Estudos Transversais , Obesidade/cirurgia , Obesidade/complicações , Gastrectomia/métodos , Ácidos e Sais Biliares
14.
Obes Surg ; 33(1): 284-292, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36460941

RESUMO

PURPOSE: Patients with prior bariatric surgery (BS) are at risk to develop alcohol use disorder (AUD) and alcohol-related liver disease (ALD). Severe alcoholic hepatitis (sAH) is one of the most severe manifestations of ALD with a 28-day mortality of 20-50%. The impact of prior BS on patients presenting with sAH was assessed. METHODS: From 01/2008 to 04/2021, consecutive patients admitted to a tertiary referral center with biopsy-proven sAH were included in a database. RESULTS: One hundred fifty-eight sAH patients of which 28 patients had a history of BS (BS group) were identified. Of this BS group, 24 patients underwent a Roux-en-Y gastric bypass (RYGB), 3 a biliopancreatic diversion, 1 an adjustable gastric band, and no patients a sleeve gastrectomy. The proportion of patients with BS increased threefold over time during the study period. Patients in the BS group were significantly younger at diagnosis of sAH (44.3 years vs 52.4 years), were more frequently female, and had a higher body mass index and a higher grade of steatosis on liver biopsy. The correlation between BS and a younger age at diagnosis remained significant in a multivariate regression analysis. There were no differences in disease severity between both groups. Furthermore, there were no differences in corticosteroid response, 28-day, 90-day, or 1-year survival. CONCLUSION: Prior BS is independently associated with a younger age of presentation with sAH, but is not independently associated with a different disease severity or outcome. These findings support the need for early detection of AUD in patients who underwent BS, in particular RYGB.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Hepatite Alcoólica , Obesidade Mórbida , Humanos , Feminino , Obesidade Mórbida/cirurgia , Hepatite Alcoólica/cirurgia , Hepatite Alcoólica/complicações , Estudos Retrospectivos , Cirurgia Bariátrica/efeitos adversos , Derivação Gástrica/efeitos adversos , Gastrectomia/efeitos adversos , Resultado do Tratamento
15.
Nutr Res Rev ; 36(2): 512-525, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36426645

RESUMO

The clinical effectiveness of bariatric surgery has encouraged the use of bariatric procedures for the treatment of morbid obesity and its comorbidities, with sleeve gastrectomy and Roux-en-Y gastric bypass being the most common procedures. Notwithstanding its success, bariatric procedures are recognised to predispose the development of nutritional deficiencies. A framework is proposed that provides clarity regarding the immediate role of diet, the gastrointestinal tract and the medical state of the patient in the development of nutritional deficiencies after bariatric surgery, while highlighting different enabling resources that may contribute. Untreated, these nutritional deficiencies can progress in the short term into haematological, muscular and neurological complications and in the long term into skeletal complications. In this review, we explore the development of nutritional deficiencies after bariatric surgery through a newly developed conceptual framework. An in-depth understanding will enable the optimisation of the post-operative follow-up, including detecting clinical signs of complications, screening for laboratory abnormalities and treating nutritional deficiencies.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Desnutrição , Obesidade Mórbida , Humanos , Cirurgia Bariátrica/efeitos adversos , Desnutrição/etiologia , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Comorbidade
16.
Case Rep Endocrinol ; 2023: 9769119, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38161769

RESUMO

Introduction: Cystic fibrosis transmembrane regulator (CFTR) modulator therapies improve respiratory function and glycaemic control in patients with cystic fibrosis (CF). The direct effect of CFTR modulator therapies on pancreatic function in patients without preexisting diabetes remains unclear. Case Presentation. An 18-year-old female with CF caused by F508del/F508del mutation, who had no diabetes, developed postprandial hypoglycaemias 6 months after initiation of elexacaftor, tezacaftor, and ivacaftor combination therapy (ETI). Symptoms were persisted after brief discontinuation of ETI, but her symptoms and time-in-hypoglycaemia had improved remarkably by avoiding high glycaemic index-foods. Discussion. This case of hypoglycaemia associated with CFTR modulator therapy in a patient without preexisting diabetes suggests that CFTR modulator therapy has the potential to directly affect glucose homeostasis. There might be an improvement in insulin secretion as well as a reduction in systemic insulin resistance. Conclusion: Treatment of CF patients without diabetes with CFTR modulator therapies can cause recurrent hypoglycaemic episodes which resolve with dietary measures.

17.
BMC Med Inform Decis Mak ; 22(1): 296, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397108

RESUMO

BACKGROUND: The development of technological applications in clinical research, such as electronic informed consent (eIC), is on the rise. The involvement of end users throughout the design process of eIC is of utmost importance to improve the current informed consent process. METHODS: Using a provocative design, we conducted interviews with 30 clinical research participants. Provotypes were used as a starting base to discuss various aspects relevant to eIC. By providing a medium to encourage divergent thinking, participants' views and concerns were solicited. Thematic analysis was undertaken using NVivo. RESULTS: The majority of participants placed trust in the principal investigator or the hospital to perform the role of eIC hosting party. Differing opinions were reported on the amount of information required related to stakeholders' access to an eIC system, and thus, to participants' personal data, to enable trust in an eIC system. Nevertheless, this study indicates a general willingness of participants to share personal data with physicians and pharmaceutical companies on an international level, and to receive requests for new research studies via an eIC system. Participants suggested to tailor an eIC system based upon their preferences, for example, regarding whom they want to share their personal data with. Moreover, they expressed a desire to choose how they can contact the research team, and to indicate which study-related information they would like to receive electronically. In addition, positive opinions were voiced on the integration of a test to assess participants' understanding before providing their eIC. CONCLUSIONS: Following a research through design approach, insights have been generated which inform the design of eIC. Provotypes were designed to help participants think beyond what is familiar to them. Study findings revealed that not all situations were perceived as provocative, because of participants' motivation to advance scientific research and the trust they place in the research team. Nevertheless, the use of provocative design resulted in additional insights, generated by clinical research participants, which could be considered in the further design of eIC.


Assuntos
Atitude , Consentimento Livre e Esclarecido , Humanos , Confiança , Eletrônica , Tecnologia
18.
Eur J Drug Metab Pharmacokinet ; 47(6): 827-839, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36057030

RESUMO

BACKGROUND AND OBJECTIVES: Rebaudioside A, a steviol glycoside, is deglycosylated by intestinal microflora prior to the absorption of steviol and conjugation to steviol glucuronide. While glucose-lowering properties are observed for rebaudioside A in mice, they have been attributed to the metabolites steviol and steviol glucuronide. We aimed to characterize the pharmacokinetic and pharmacodynamic properties of rebaudioside A and its metabolites in patients with early-onset type 2 diabetes mellitus (T2DM). METHODS: This randomized, placebo-controlled, open-label, two-way crossover trial was performed in subjects with T2DM on metformin or no therapy at the University Hospitals Leuven, Belgium. Following oral rebaudioside A (3 g), plasma concentrations of rebaudioside A, steviol and steviol glucuronide were determined. The effect on glucose homeostasis was examined by an oral glucose tolerance test (OGTT) performed 19 h following rebaudioside A administration, i.e. the presumed time of maximal steviol and steviol glucuronide concentrations. The primary pharmacodynamic endpoint was the difference in area under the blood glucose concentration-time curve during the first 2 h of the OGTT (AUCGlucose(0-2h)) for rebaudioside A vs. placebo. RESULTS: In total, 30 subjects [63.5 (57.8-69.0) years of age, 86.7% male] completed the trial. Rebaudioside A was detected as early as 1 h after administration in nearly all subjects. As expected, steviol and steviol glucuronide reached their maximal concentrations at 19.5 h following rebaudioside A administration. Rebaudioside A did not lower the AUCGlucose(0-2h) compared to placebo (- 0.7 (95% CI - 22.3; 20.9) h·mg/dL, P = 0.95). Insulin and C-peptide concentrations were also comparable between both conditions (P > 0.05). CONCLUSION: Rebaudioside A is readily absorbed after oral administration and metabolized to steviol and steviol glucuronide. However, no effect on glucose nor insulin or C-peptide excursion was observed during the OGTT at the time of maximal metabolite concentrations. Thus, no antidiabetic properties of rebaudioside A could be observed in patients with T2DM after single oral use. CLINICAL TRIAL REGISTRATION: Registered on ClinicalTrials.gov (NCT03510624).


Assuntos
Diabetes Mellitus Tipo 2 , Masculino , Animais , Camundongos , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo C , Estudos Cross-Over , Glucuronídeos , Homeostase , Glucose , Glicemia
19.
Front Nutr ; 9: 976744, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034927

RESUMO

Introduction: Suboptimal diet and physical inactivity downgrade the putative benefits of Antiretroviral Therapy (ART) among People Living with HIV (PLWH). However, there is paucity of literature on dietary intake and cardiometabolic profiles of PLWH in Uganda. Methods: A cross-sectional study among PLWH in Uganda was conducted. Dietary intake was assessed using a 24h recall method of 2 non-consecutive days. The short International Physical Activity Questionnaire assessed participants' physical activity. Fasted blood samples were analyzed for Fasting Blood Glucose (FBG), total cholesterol, LDL-c, HDL-c and triglycerides. Blood pressure and anthropometric measurements were performed following step 2 of the WHO STEPS. Results: 253 patients completed in this study. A high prevalence of low HDL-c (31.9%), abdominal obesity (44.5%), high BMI (51.6%), raised FBG (45.3%), high SBP (31.5%), elevated triglycerides (26.4%) and metabolic syndrome (28%) was found. More women were identified with metabolic syndrome (31.5%) than men (19.2%). Low prevalence of high LDL-c (4.7%) and total cholesterol (9.8%) was found. Diets had a high carbohydrate (65.8 ± 10.4) E% and fiber intake (30.1 ± 12.7) g with minimal PUFA (6.1 ± 2.3) E%, fruits and vegetables (1.4 servings). High proportions were found of unmet intake for vitamin A (38.2%), B1(48.8%), B2 (29.6%), B12 (29%), folate (61.4%), Ca (76%), Zn (53.1%) and Mg (41.7%). Mean MET min was 6,700 ± 5,509 and over 68% of the participants had >3,000 MET min. Conclusion: Our findings reveal a high prevalence of metabolic disturbances among PLWH in Uganda and further highlight that their diets are suboptimal with low fruits and vegetable intake.

20.
Obes Surg ; 32(8): 2625-2631, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35705782

RESUMO

INTRODUCTION: Aside from an impact on health, obesity is also associated with higher social and economic costs such as impaired productivity, increased work absenteeism, and higher rates of unemployment. The aim of this study was to assess the effect of bariatric surgery on employment status in a large nationwide database, using data from all patients that underwent bariatric surgery in Belgium. METHODS: This is a retrospective analysis of all Belgian patients that underwent bariatric surgery between 2014 and 2015. The work status of these patients was examined yearly: 4 years before and 3 years after surgery. Increased employment after surgery was defined (1) as a reduction in days of unemployment and incapacity and (2) as the resumption of work among the unemployed. RESULTS: In total, 16,276 patients were included. The number of working people rose from 49.7% before to 61.2% 3 years after bariatric surgery, i.e., an increase of 11.5% between pre- and post-surgery. The largest improvement in reduction in unemployment was found in individuals who were absent from work for more than 9 months, namely, a reduction from 13.4 to 7.2%. In the population of unemployed patients, 20.9% became employed after bariatric surgery. CONCLUSION: We found an increase in employment rate and a decrease in work incapacity and unemployment after bariatric surgery. Higher rates of employment after bariatric surgery may also contribute to an increased cost-effectiveness of bariatric surgery. It would be interesting to research possible targeting strategies to increase the employment rate even more after bariatric surgery.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Bélgica/epidemiologia , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Retorno ao Trabalho , Desemprego
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