Bileopancreatic diversion with duodenal switch lowers both early and late phases of glucose, insulin and proinsulin responses after meal.
ABSTRACT Hyperproinsulinemia is associated with obesity and type 2 diabetes. We explored the after-meal dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in patients treated with bileopancreatic diversion with duodenal switch (BPD-DS) surgery compared with normal-weight controls [body mass index (BMI)+/-SD, 23.2 +/- 2.4 kg/m(2)].
Ten previously morbidly obese (BMI+/-SD, 53.5 +/- 3.8 kg/m(2)) patients free from diabetes who had undergone BPD-DS (BMI+/-SD, 29.0 +/- 5.2 kg/m(2)) 2 years earlier were recruited. A standardised meal (2400 kJ) was ingested, and glucose, proinsulin, insulin, free fatty acids and triglycerides (TGs) were determined during 180 min. Follow-up characteristics yearly on glucose, lipids, creatinine and uric acid over 3 years after BPD-DS are presented.
Fasting glucose and insulin were lower, 0.4 mmol/L and 4.6 pmol/L, respectively, in the BPD-DS group despite higher BMI. Fasting proinsulin was similar in both groups. Postprandial area under the curve (AUC) for glucose, proinsulin and insulin did not differ between the two groups (p = 0.106-734). Postprandial changes in glucose, proinsulin and insulin were essentially similar but absolute concentrations of proinsulin and insulin were lower in the later phases in the BPD-DS group (p = 0.052-0.001). Postprandial AUC for TGs was lower in the BPD-DS group (p = 0.005). Postprandial changes in TGs were lowered in the intermediate phase (p = 0.07-0.08) and in the late phase (0.002). Follow-up data showed markedly lowered creatinine and uric acid after BPD-DS.
BPD-DS surgery induces a large weight loss and lowers, close to normal, postprandial responses of glucose, proinsulin and insulin but with marked lowering of TGs.
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ABSTRACT: PURPOSE: To evaluate the foregut and hindgut hypotheses for metabolic surgery in obese rats with diabetes. METHODS: Otsuka Long-Evans Tokushima fatty rats were divided into a sham operation group, a partial duodeno-jejunal bypass (P-DJB) group, and a complete DJB (C-DJB) group. P-DJB is a model to test foregut hypothesis, whereas C-DJB is a model to test both hypotheses. We performed oral glucose tolerance tests (OGTT) on all groups at baseline, and then 4 and 8 weeks postoperatively. The rats were killed thereafter and the plasma levels of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured. A separate sub-group of C-DJB rats underwent OGTT after treatment with the GLP-1 antagonist, the PYY antagonist, or saline. RESULTS: Marked improvement of the blood glucose control during the OGTT was noted 8 weeks after C-DJB, but not 8 weeks after P-DJB or the sham operation. The serum GLP-1 and PYY levels were higher in the C-DJB group than in the other two groups. Pretreatment with the GLP-1 antagonist increased the blood glucose levels 30 min after the OGTT in the C-DJB rats. CONCLUSIONS: Improvement in glucose metabolism after DJB was associated with the inflow of bile and pancreatic juice into the ileum, supporting validity of the hindgut hypothesis. GLP-1 appears to play a role in this improvement.Surgery Today 06/2013; 44(2). · 1.21 Impact Factor
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ABSTRACT: Hyperinsulinemic hypoglycemia is common after Roux-en-Y gastric bypass (RYGB) and may result in weight regain. The purpose of our investigation was to compare the effect of RYGB, vertical sleeve gastrectomy (VSG), and duodenal switch (DS) on insulin and glucose response to carbohydrate challenge. Patients meeting National Institutes of Health criteria for bariatric surgery selected their bariatric procedure after evaluation and education in this prospective nonrandomized study. Preoperatively and at 6, 9, and 12 months' follow-up, patients underwent blood draw to determine levels of fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), C-peptide, and 2-h oral glucose challenge test. Homoeostatic Model Assessment (HOMA)-IR, fasting to 1-h and 1- to 2-h ratios of glucose and insulin, were calculated. Statistical analysis was performed using ANOVA and Student's paired t test. All procedures were performed via a laparoscopic technique at a single institution. Data from a total of 38 patients (13 RYGB, 12 VSG, 13 DS) were available for analysis. At baseline, all groups were similar; the only statistically significant difference was that DS patients had a higher preoperative weight and body mass index (BMI). All operations caused weight loss (BMI 47.7 ± 10-30.7 ± 6.4 kg/m(2) in RYGB; 45.7 ± 8.5-31.1 ± 5.5 kg/m(2) in VSG; 55.9 ± 11.4-27.5 ± 5.6 kg/m(2) in DS), reduction of fasting glucose, and improved insulin sensitivity. RYGB patients had a rapid rise in glucose with an accompanying rise in 1-h insulin to a level that exceeded preoperative levels. This was followed by a rapid decrease in glucose level. In comparison, DS patients had a lower increase in glucose and 1-h insulin, and the lowest HbA1c. These differences were statistically significant at various data points. For VSG, the results were intermediary. Compared to gastric bypass, DS results in greater weight loss and improves insulin sensitivity and glucose homeostasis without causing a hyperinsulinemic response. Because the response to challenge after VSG is intermediary, pyloric preservation alone cannot account for this difference.Surgical Endoscopy 09/2013; 28(1). · 3.31 Impact Factor
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ABSTRACT: Alterations in fat metabolism, in particular elevated plasma concentrations of free fatty acids (FFA) and triglycerides (TG), have been implicated in the pathogenesis of type 2 diabetes, obesity and cardiovascular disease. Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a member of the large family of membrane-bound O-acyltransferases, catalyzes the final step in triacylglycerol formation. In the intestine, DGAT1 is the predominate enzyme in the re-esterficiation of dietary TG. Following a single dose of a selective pharmacological inhibitor of DGAT1, PF-04620110, a dose-dependent inhibition of TG and vitamin A absorption postprandially was demonstrated in rodents and human subjects. In C57/BL6J mice, acute DGAT1 inhibition alters the temporal and spatial pattern of dietary lipid absorption. To understand the impact of DGAT1 inhibition on enterocyte lipid metabolism, lipomic profiling was performed in rat intestine and plasma as well as human plasma. DGAT1 inhibition causes an enrichment of polyunsaturated fatty acids within the TG class of lipids. This pharmacological intervention gives us insight as to the role of DGAT1 in human dietary lipid absorption. Future longer term studies in humans will allow us to understand the potential therapeutic benefit of modulating DGAT1 activity on metabolic diseases.AJP Gastrointestinal and Liver Physiology 04/2013; · 3.65 Impact Factor