Biliopancreatic diversion with duodenal switch leads to better postprandial glucose level and beta cell function than sleeve gastrectomy in individuals with type 2 diabetes very early after surgery.

OBJECTIVE: The aim of this study was to compare the short-term effect of sleeve gastrectomy (SG) and biliopancreatic diversion with duodenal switch (DS) in order to determine if exclusion of the upper gastrointestinal tract confers greater metabolic improvement, independent of weight loss. METHODS: Standard meals were administered before and on day 3 and 4 after SG to assess insulin sensitivity, ß-cell function and gastrointestinal hormone responses in matched normoglycemic (NG) and type 2 diabetes (T2D) participants. A third group of matched T2D participants who underwent DS with the same meal test administered prior to and 3days after surgery was also recruited. RESULTS: Despite significant metabolic improvement, T2D participants failed to fully normalize insulin resistance and ß-cell dysfunction 3 and 4days after SG. Our results demonstrate the superiority of DS over SG in terms of short-term improvement in postprandial glucose excursion and ß-cell function 3days after the surgery, with similar improvement in hepatic insulin sensitivity. CONCLUSION: Our findings support the notion that caloric restriction represents an important mechanism to explain the very early anti-diabetic effects observed after bariatric surgery. However, exclusion of the upper gastrointestinal tract also provides further metabolic improvements, possibly mediated by gastrointestinal hormonal responses and altered postprandial glucose absorption.

Biliopancreatic diversion with duodenal switch improves insulin sensitivity and secretion through caloric restriction.

OBJECTIVE: To assess the rapid improvement of insulin sensitivity and ß-cell function following biliopancreatic diversion with duodenal switch (BPD-DS) and determine the role played by caloric restriction in these changes. METHODS: Standard meals were administrated before and on day 3, 4, and 5 after BPD-DS to measure total caloric intake, glucose excursion, insulin sensitivity, and secretion in matched type 2 diabetes and normoglycemic (NG) subjects. In a second set of study, other subjects with type 2 diabetes had the same meal tests prior to and after a 3-day caloric restriction identical to that observed after BPD-DS and then 3 days after actually undergoing BPD-DS. RESULTS: Improvement of HOMA-IR occurred at day 3 after BPD-DS in diabetes and after 3 days of caloric restriction. The disposition index (DI) improved rapidly in diabetes after BPD-DS and to a similar extent after caloric restriction. DI was higher and did not change after BPD-DS in NG. Changes in glucagon-like peptide-1, gastric inhibitory peptide, peptide tyrosine tyrosine, ghrelin, and pancreatic polypeptide levels were not associated with modulation of DI in the participants. CONCLUSIONS: Caloric restriction is the major mechanism underlying the early improvement of insulin sensitivity and ß-cell function after BPD-DS in type 2 diabetes.

PPARalpha L162V polymorphism alters the potential of n-3 fatty acids to increase lipoprotein lipase activity.

Omega-3 fatty acids (FAs) may accelerate plasma triglyceride (TG) clearance by altering lipoprotein lipase (LPL) activity. Yet, the ability of n-3 FAs to increase LPL activity is dependent on transcription factors such as peroxisome proliferator-activated receptor alpha (PPARalpha). The objective was to examine the effects of n-3 FAs on LPL activity considering the occurrence of PPARalpha L162V polymorphism. First, 14 pairs of men either L162 homozygotes or carriers of the V162 allele were supplemented with n-3 FAs. Second, transient transfections in HepG2 cells, for the L162- and V162-PPARalpha variants with the peroxisome proliferator-response element from the human LPL gene, were transactivated with n-3 FAs. In vivo results demonstrate that the LPL activity increased non-significantly by 14.4% in L162 homozygotes compared with 6.6% in carriers of the PPARalpha-V162 allele, after n-3 FA supplementation. Additionally, the L162 homozygotes tended towards an inverse correlation between LPL activities and plasma TG levels. Conversely, carriers of the V162 allele showed no such relationship. In vitro data demonstrates that transcription rates of LPL tended to be higher for the L162-PPARalpha than V162-PPARalpha after n-3 FAs activation. Overall, these results indicate that n-3 FA supplementation increases the transcription rate of LPL to a greater extent in L162-PPARalpha than V162-PPARalpha.

Effect of the PPAR-Alpha L162V polymorphism on the cardiovascular disease risk factor in response to n-3 polyunsaturated fatty acids.

BACKGROUND: Dietary n-3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor-alpha (PPARalpha) can also modulate CVD risk factors. Since fatty acids, including n-3 PUFAs, are natural ligands of PPARalpha, a gene-diet interaction effect could be observed. AIMS: To examine whether n-3 PUFA- induced changes in CVD risk factors are influenced by the PPARalpha L162V polymorphism. METHODS: Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks. RESULTS: Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p < 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01). CONCLUSIONS: The PPARalpha L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n-3 PUFAs.