Frédéric S. Hould

MALABSORPTIVE OBESITY SURGERY

Biliopancreatic diversion is the only valuable surgical approach for changing intestinal absorption. It is efficient in producing appropriate permanent weight loss and has a considerable psychological advantage because it does not impose abnormal food restriction. It not only decreases caloric absorption, but it also directly improves insulin and lipid metabolism. The ideal technique for the construction of BPD is not yet established, but our current preference is for the duodenal switch type. BPD must be seen as a means to change an intolerable and untreatable disease to a tolerable and treatable one, with substantial improvement in quality of life.

Does bone change after biliopancreatic diversion

This prospective study evaluated bone changes after biliopancreatic diversion (BPD) consisting of a distal gastrectomy, a 250 cm alimentary channel, and a 50 cm common channel. Thirty-three consecutive patients had clinical, biochemical, and bone mineral density analysis before surgery and 4 and 10 years after surgery. Iliac crest bone biopsies and special tests including parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-OH2-D), bone-specific alkaline phosphatase (BAP), and osteocalcin were obtained at surgery and 4 years postoperatively. Over the years, with close metabolic surveillance, additional calcium and vitamin D were given as indicated. After BPD, serum levels of calcium and vitamin D were decreased and serum levels of PTH, BAP, and osteocalcin were increased. Bone turnover and mineralization were both increased. Mean osteoid volume (P < 0.0007) and bone formation rate in relation to bone volume (P < 0.02) were increased. Static measures of bone were altered as follows: cortical thickness decreased (P < 0.01) and trabecular bone volume increased (P < 0.01). Ten years after surgery, overall bone mineral density was unchanged at the hip and was decreased by 4% at the lumbar spine. Overall fracture risk, based on the Z score, was unchanged. Preoperative factors predicting bone loss included menopause, smoking, and preexisting osteopenia. An elevated level of 1,25-OH2-D was also found to be a predictor of future bone loss (r = 0.40; P < 0.002). After surgery, a greater increase in bone markers and bone turnover was associated with an increased risk of bone loss. Although elevated osteocalcin levels were associated with overall bone loss (r = 0.52; P < 0.002), lower albumin levels were associated only with bone loss at hip level (r = 0.44; P < 0.02), whereas lower calcium levels were associated only with the loss at the lumbar spine (r = 0.39; P < 0.02). Ten years after surgery, bone loss at the hip continued to depend on albumin levels (r = 0.37; P < 0.03). We concluded that bone was relatively tolerant to the metabolic changes due to BPD. Provided that there is close surveillance for metabolic disturbances, the use of appropriate supplements, and the avoidance of malnutrition, the beneficial effects of surgery far outweigh the risk of postoperative bone disease.

Asthma and sleep apnea in patients with morbid obesity: outcome after bariatric surgery.

Background: Asthma and sleep apnea syndrome (SAS) are frequently reported in obese patients. The authors determined the prevalence of asthma and SAS in morbidly obese patients and the effect of biliopancreatic diversion with duodenal switch (BPD-DS) on these conditions. Methods: 398 patients were evaluated for bariatric surgery in a university-affiliated tertiary care center. All patients completed a written questionnaire on asthma and SAS before BPD-DS. In addition, 139 patients also completed a questionnaire on their general health status, including asthma and SAS, 2 years after the procedure. Results: For the cohort of 398 patients, the prevalence of self-reported asthma was 30.4% and that of SAS, 32.2%. No significant association was found between asthma and SAS diagnosis (P =0.10). Significant relationships were observed between the diagnosis of asthma and age, hip circumference, waist/hip ratio, weight and BMI of the patients as well as between a diagnosis of SAS and gender, waist circumference, hip circumference, waist/hip ratio, weight and BMI. 2 years after surgery (mean BMI was reduced from 51.4 to 30.5 kg/m2), asthma was reported improved in 79.3% of patients and SAS was improved in all but one with this condition; among 29 SAS patients using CPAP before surgery, only 4 were still using this treatment after 2 years. Conclusion: The prevalence of asthma and SAS is high in the morbidly obese population and is associated with markers of obesity. We found no association between the diagnosis of asthma and SAS diagnosis in this population. BPD-DS improved self-reported severity of asthma and SAS symptoms.

Effects of the biliopancreatic diversion on energy balance in the rat.

Objective:This study was carried out to determine the effects of the biliopancreatic diversion (BPD), a bariatric surgery applied to the treatment of morbidly obese humans, on energy balance in rats.Methods:BPD was performed on a group of male Wistar rats. Body weight and food intake were measured daily throughout the study. Feces were also collected to assess energy losses and the determination of digestible energy. Energy expenditure and body composition were also determined for the 50-day length of the protocol. On the day of killing, the brain, the entire intestinal tract and white and brown adipose tissues were collected and weighed. Expression of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the ARC nucleus were assessed by in situ hybridization.Results:Marked changes in the regulation of energy balance were observed in the BPD-operated rats. A decrease in digestible energy and food intake coupled with an increase in the fecal energy density and protein fecal energy led to an important weight loss in the BPD-operated rats. This weight loss was observed in the loss of fat mass (specifically the white epididymal, inguinal, retroperitoneal and brown adipose tissues). The rats modified their food intake pattern to be able to potentially eat more during the entire day. An increase in the surfaces of all intestinal structures (muscular and mucosal layers) was observed in the BPD-operated rats. The NPY and AgRP expression in the brain were both shown to be greater in the BPD-operated rats than in the control animals. At the beginning of the study, the surgery led to an energy expenditure decrease, which, however, did not persist throughout the study despite the fact that BPD-operated rats exhibited persistent lower fat free masses.Conclusion:BPD led to a noticeable reduction in weight and fat gains in rats, which was in large part owing to a decrease in digestible energy intake led to by the gastrectomy, the intestinal malabsorption inherent to the surgery and to potentially a thermogenesis stimulation that occurred in the second end of the study. The reduction in energy gain occurs despite adaptations to thwart the intestinal malabsorption and the hunger signals from the central nervous system.

Should metabolic surgery be offered in morbidly obese patients with type I diabetes

BACKGROUND Bariatric surgery has recently been endorsed as an effective treatment of type 2 diabetes (T2D) in severely obese patients. Little is known about its metabolic effects in type 1 diabetes (T1D). The objectives were to assess bariatric surgery outcomes in T1D obese patients who underwent either a biliopancreatic diversion (BPD) or a sleeve gastrectomy (SG) and who were matched with T2D obese patients requiring insulin therapy. The study setting was at a university-affiliated tertiary care center. METHODS Through retrospective analysis of prospectively collected data, ten patients with T1D (7 BPD, 3 SG) were matched with 20 patients with T2D (14 BPD, 6 SG) according to age, gender, type of surgery, initial Body Mass Index and insulin requirements (1:2 matching). Weight loss, diabetes control, and remission of co-morbidities were compared. RESULTS Mean follow-up was 55.1 months. Mean Excess BMI Loss% tended to be greater in T1D patients compared to T2D (77.1% versus 68.3%, P = .14). The remission and improvement rates of T2D were 55% and 45% versus 0% and 90% for T1D. The remission rate of T2D was significantly greater after BPD (71.43%) compared to SG (16.67%, P = .04). Insulin requirements were significantly reduced in both groups after surgery (T1D: .44 ±.24 versus 1.09 ±.7 units/kg/d, P = 0.03, T2D: .03 ±.12 versus .89 ±.77 units/kg/d, P = .0001). Remission rates of hypertension and dyslipidemia were similar for T1D and T2D (66.7% versus 62.5%, P = .63 and 88.9% versus 75%, P = .23). CONCLUSIONS Even if metabolic surgery has limited effect on glycemic control in T1D, it improves insulin sensitivity and other co-morbidities. It should be considered as a therapeutic option in selected obese patients with metabolic syndrome and high cardio-vascular risk.

Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis

BackgroundMetabolic alterations relevant to postprandial dyslipidemia were previously identified in the intestine of obese insulin-resistant subjects. The aim of the study was to identify the genes deregulated by systemic insulin resistance in the intestine of severely obese subjects.MethodsTranscripts from duodenal samples of insulin-sensitive (HOMA-IR < 3, n = 9) and insulin-resistant (HOMA-IR > 7, n = 9) obese subjects were assayed by microarray (Illumina HumanHT-12).ResultsA total of 195 annotated genes were identified as differentially expressed between these two groups (Fold change > 1.2). Of these genes, 36 were found to be directly involved in known intestinal functions, including digestion, extracellular matrix, endocrine system, immunity and cholesterol metabolism. Interestingly, all differentially expressed genes (n = 8) implicated in inflammation and oxidative stress were found to be upregulated in the intestine of insulin-resistant compared to insulin-sensitive subjects. Metabolic pathway analysis revealed that several signaling pathways involved in immunity and inflammation were significantly enriched in differently expressed genes and were predicted to be activated in the intestine of insulin-resistant subjects. Using stringent criteria (Fold change > 1.5; FDR < 0.05), three genes were found to be significantly and differently expressed in the intestine of insulin-resistant compared to insulin-sensitive subjects: the transcripts of the insulinotropic glucose-dependant peptide (GIP) and of the β-microseminoprotein (MSMB) were significantly reduced, but that of the humanin like-1 (MTRNR2L1) was significantly increased.ConclusionThese results underline that systemic insulin resistance is associated with remodeling of key intestinal functions. Moreover, these data indicate that small intestine metabolic dysfunction is accompanied with a local amplification of low-grade inflammatory process implicating several pathways. Genes identified in this study are potentially triggered throughout the development of intestinal metabolic abnormalities, which could contribute to dyslipidemia, a component of metabolic syndrome and diabetes.

Metabolic and cardiovascular improvements after biliopancreatic diversion in a severely obese patient

BackgroundSevere obesity is associated with important morbidity and increased mortality. The successes of lifestyle modifications and drug therapy have been partial and mostly unsustained in reducing obesity and its comorbidities. Bariatric surgery, particularly biliopancreatic diversion with duodenal switch reduces efficiently excess body weight and improves metabolic and cardiovascular functions.Case presentationA 56-year-old man with severe clinical obesity underwent a biliopancreatic diversion with a duodenal switch after unsuccessful treatment with weight loss pharmacotherapy. He had diabetes, hypertension and sleep apnea syndrome and was on three medications for hypertension and two hypoglycemic agents in addition to > 200 insulin units daily. Eleven months after the surgery, he had lost 40% of his body weight. The lipid profile showed great improvement and the hypertension and diabetes were more easily controlled with no more insulin needed. The pseudonormalized pattern of left ventricular diastolic function improved and ventricular walls showed decreased thickness.ConclusionBiliopancreatic diversion may bring metabolic and cardiovascular benefits in severely obese patients from a cardiovascular perspective.

Long alimentary limb duodenal switch (LADS): a short-term prospective randomized trial

BACKGROUND Biliopancreatic diversion with duodenal switch (BPD-DS) is one of the most effective bariatric surgeries, in terms of weight loss and remission of co-morbidities. It is however associated with a significant risk of protein and nutritional deficiency, as well as gastrointestinal side effects. OBJECTIVES To assess the effect of increasing the strict alimentary limb on weight loss, nutritional deficiency and quality of life, compared with standard BPD-DS. SETTINGS University-affiliated tertiary care center. METHODS Prospective randomized double blind (patient-evaluator) trial in which patients were assigned in a 1:1 ratio to undergo a modified BPD-DS with a long alimentary limb (1 m from Treitz ligament, n = 10) or a standard biliopancreatic diversion (strict alimentary limb of 1.5 m, n = 10). Common channel was kept at 100 cm in both groups. Follow-up at 12 months was completed in all patients. RESULTS Initial weight (126 ± 10 versus 125 ± 17, P = .92), age (40 ± 7 versus 37 ± 8, P = .35), and sex ratio (1 female/9 males) were similar in both groups. Excess weight loss and total weight loss were significantly higher in the standard BPD-DS group (93.4 ± 12% versus 73.3 ± 7%, P = .0007 and 46 ± 5.6% versus 37 ± 3.4%, P = .0004). The study group had significantly higher vitamin D, manganese, and copper levels at 12 months. Both groups had similar drop in glycated hemoglobin, cholesterol levels, and resolution of co-morbidities at 12 months. Long alimentary limb was associated with significantly less bowel movements a day (1.6 ± .97 versus 2.55 ± 1.01, P = .01), less gastrointestinal side effects (bloating and gas, P<.05) and required less pancreatic enzymes supplements (0 versus 40%, P = .04) and calcium supplement. Quality of life was significantly improved in both groups in all domains (all P<.05). CONCLUSION At 12 months, weight loss was lesser in the long alimentary limb group. There was however no difference in the remission of co-morbidities and higher levels of vitamin D, manganese, and copper. Gastrointestinal adverse effects and the need for pancreatic enzymes were less with similarly excellent quality of life at 12 months. Longer follow-up is necessary to evaluate long-term weight loss and nutritional deficiencies.

Plasma Lactoferrin Levels Positively Correlate with Insulin Resistance despite an Inverse Association with Total Adiposity in Lean and Severely Obese Patients

Context Lactoferrin (Lf) is an important protein found on mucosal surfaces, within neutrophils and various cells, and in biological fluids. It displays multiple functions, including iron-binding as well as antimicrobial, immunomodulatory and anti-inflammatory activities. Although Lf ingestion has been suggested to cause adiposity reduction in murine models and humans, its relationship with insulin resistance (IR) has not been studied thoroughly. Objective To establish the association between circulating Lf levels, glucose status and blood lipid/lipoprotein profile. Methods Two independent cohorts were examined: lean to moderately obese women admitted for gynecological surgery (n = 53) and severely obese subjects undergoing biliopancreatic diversion (n = 62). Results Although body mass index (BMI) and total body fat mass were negatively associated with Lf, IR (assessed by the HOMA-IR index) was positively and independently associated with plasma Lf concentrations of the first cohort of lean to moderately obese women. These observations were validated in the second cohort in view of the positive correlation between plasma Lf concentrations and the HOMA-IR index, but without a significant association with the body mass index (BMI) of severely obese subjects. In subsamples of severely obese subjects matched for sex, age and BMI, but with either relatively low (1.89 ± 0.73) or high (13.77 ± 8.81) IR states (according to HOMA-IR), higher plasma Lf levels were noted in insulin-resistant vs insulin-sensitive subjects (P<0.05). Finally, Lf levels were significantly higher in lean to moderately obese women than in severely obese subjects (P<0.05). Conclusion Our findings revealed that plasma Lf levels are strongly associated with IR independently of total adiposity, which suggests an intriguing Lf regulation mechanism in conditions of obesity and IR.