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CONTEXT: Proneurotensin (pNT) is associated with obesity and T2D, but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied. OBJECTIVE: Assess effects of RYGB versus very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMT), and long-term effects of RYGB on fasting pNT.Study participants: Cohort 1: Nine normoglycemic (NG) and ten T2D patients underwent MMT before and after VLED, immediately post-RYGB and six weeks post-RYGB. Cohort 2: Ten controls with normal weight and ten patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), were subjected to MMTs and GIP infusions pre-surgery and three months post-surgery. GLP-1 infusions were performed in normal weight participants. Cohort 3: Fasting pNT was assessed pre-RYGB (n=161), two months post-RYGB (n=92) and 1-year post-RYGB (n=118) in NG and T2D patients. pNT levels were measured using ELISA. RESULTS: Reduced fasting and postprandial pNT were evident after VLED and immediately following RYGB. Reintroduction of solid food post-RYGB increased fasting and postprandial pNT. Prior to RYGB, all patients lacked a meal response in pNT, but this was evident post-RYGB/VSG. GIP- or GLP-1 infusion had no effect on pNT levels. Fasting pNT were higher 1-year post-RYGB regardless of glycemic status. CONCLUSION: RYGB causes a transient reduction in pNT as a consequence of caloric restriction. The RYGB/VSG-induced rise in postprandial pNT is independent of GIP and GLP-1 and higher fasting pNT are maintained one year post-surgically.
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Bariatric surgery is an efficient method to induce weight loss and also, frequently, remission of type 2 diabetes (T2D). Unpaired studies have shown bariatric surgery and dietary interventions to differentially affect multiple hormonal and metabolic parameters, suggesting that bariatric surgery causes T2D remission at least partially via unique mechanisms. In the current study, plasma metabolite profiling was conducted in patients with (n = 10) and without T2D (n = 9) subjected to Roux-en-Y gastric bypass surgery (RYGB). Mixed-meal tests were conducted at baseline, after the presurgical very-low-calorie diet (VLCD) intervention, immediately after RYGB, and after a 6-week recovery period. Thereby, we could compare fasted and postprandial metabolic consequences of RYGB and VLCD in the same patients. VLCD yielded a pronounced increase in fasting acylcarnitine levels, whereas RYGB, both immediately and after a recovery period, resulted in a smaller but opposite effect. Furthermore, we observed profound changes in lipid metabolism following VLCD but not in response to RYGB. Most changes previously associated with RYGB were found to be consequences of the presurgical dietary intervention. Overall, our results question previous findings of unique metabolic effects of RYGB and suggest that the effect of RYGB on the metabolite profile is mainly attributed to caloric restriction.
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Restricción Calórica/métodos , Diabetes Mellitus Tipo 2/cirugía , Ayuno/sangre , Derivación Gástrica/métodos , Obesidad Mórbida/cirugía , Adulto , Glucemia/metabolismo , Carnitina/análogos & derivados , Carnitina/sangre , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/metabolismo , Periodo PosprandialRESUMEN
OBJECTIVE: To study the immediate effects of Roux-en-Y gastric bypass (RYGB) on glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared with the effects of calorie restriction (CR). SETTING: University-affiliated bariatric surgery clinic. BACKGROUND: RYGB induces remission of type 2 diabetes (T2D) long before significant weight loss occurs. The time course and underlying mechanisms of this remission remain enigmatic. A prevailing theory is that secretory patterns of incretin hormones are altered due to rearrangement of the gastrointestinal tract. To what extent reduced calorie intake contributes to the remission of T2D is unknown. METHODS: Nine normoglycemic patients and 10 T2D patients were subjected to mixed-meal tests (MMT) 4 weeks before surgery before initiation of a very low calorie diet regimen (MMT-4 w), 1 day before surgery on a very low calorie diet regimen (MMT-1 d), on the morning of the first day after surgery (MMT+1 d; first postsurgical meal), and 6 weeks after surgery (MMT+6 w). Insulin, glucose, active glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. RESULTS: CR lowered insulin in T2D patients, whereas glucose, GIP, and GLP-1 were unaffected. RYGB immediately increased plasma insulin and GIP. The GLP-1 response was delayed compared with the GIP response. T2D patients exhibited lower insulin responses after RYGB compared with normoglycemic patients. GIP responses were similar in both groups at all occasions, whereas T2D patients displayed markedly elevated GLP-1 responses 6 weeks after RYGB. Glucose was unaffected by CR and RYGB in both groups. Insulin sensitivity was unaffected by CR but improved with RYGB. CONCLUSION: RYGB exerts powerful and immediate effects on insulin and incretin responses to food, independently of changes caused by CR.
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Restricción Calórica , Diabetes Mellitus Tipo 2/terapia , Derivación Gástrica , Incretinas/metabolismo , Insulina/metabolismo , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Polipéptido Inhibidor Gástrico/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Homeostasis/fisiología , Humanos , Hipoglucemiantes/uso terapéutico , Insulinas/uso terapéutico , Comidas , Obesidad/cirugíaRESUMEN
BACKGROUND: Changing social conditions and life-styles in Sweden may have affected the spread of varicella-zoster virus (VZV), herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). OBJECTIVES: To study possible changes over 30 years in prevalence of antibodies against VZV, HSV, CMV, and EBV in Swedish children, using modern serological methods. STUDY DESIGN: Serum samples from 819 Swedish children who were 9-12 years old in 1967-1968, in 1977-1978 (two cohorts), and in 1997, respectively, were examined. IgG antibodies against VZV, HSV, and CMV were measured by well validated enzyme-linked immunosorbent assays and against EBV by indirect immunoflourescense. RESULTS: The seropositivity for VZV for 9-12 years old children was 50% in 1967-1968, 74-82% in 1977-1978, and 98% in 1997. The corresponding figures were 31%, 53%, 50%, and 58% for CMV, 35%, 35%, 32%, and 38% for HSV, and 64% in 1967-1968 and in 1977-1978 (both cohorts), and 62% in 1997 for EBV. CONCLUSIONS: The seroprevalence for VZV increased significantly from 1967-1968 to 1997, and there was also a significant but smaller increase in the CMV seroprevalence, while seroprevalence to HSV and EBV remained relatively stable.