Long-term nutritional impact of sleeve gastrectomy

Author’s Accepted Manuscript Long-term nutritional impact of sleeve gastrectomy M. Caron, F.S. Hould, O. Lescelleur, S. Marceau, S. Lebel, F. Julien, S. Simard, L. Biertho www.elsevier.com/locate/buildenv PII: DOI: Reference: S1550-7289(17)30345-3 http://dx.doi.org/10.1016/j.soard.2017.07.019 SOARD3076 To appear in: Surgery for Obesity and Related Diseases Cite this article as: M. Caron, F.S. Hould, O. Lescelleur, S. Marceau, S. Lebel, F. Julien, S. Simard and L. Biertho, Long-term nutritional impact of sleeve g a s t r e c t o my, Surgery for Obesity and Related Diseases, http://dx.doi.org/10.1016/j.soard.2017.07.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Long-term nutritional impact of sleeve gastrectomy. M Caron, MD1; FS Hould, MD2; O Lescelleur, MD1; S Marceau, MD1; S Lebel, MD1; F Julien, MD1; S Simard, MSc3; L Biertho, MD1 Quebec Heart and Lung Institute - Laval University, Quebec, QC, Canada 1. Department of Internal Medicine, Laval University 2. Department of Surgery, IUCPQ - Laval University 3. Department of Biostatistics, IUCPQ – Laval University All authors have contributed to the study, including planning, execution, analysis of the data, and redaction. Correspondence: Laurent Biertho, MD. Institut Universitaire de Cardiologie et de Pneumologie de Québec 2725, Chemin Ste-Foy Quebec, QC, Canada, G1V 4G5 Tel: 418.656.4810 Fax: 418.656.4825 Email: laurentbiertho@gmail.com Keywords: Bariatric Surgery, Sleeve Gastrectomy, Nutrition Running title: Nutritional Impact of SG Long-term nutritional impact of sleeve gastrectomy. -1- Running title: Nutritional Impact of SG ABSTRACT BACKGROUND: Sleeve gastrectomy (SG) has become a predominant bariatric procedure throughout the world. The long-term nutritional impact of this procedure is however unknown. OBJECTIVES: To describe the nutritional deficiencies before and after SG, and analyse the influence of baseline weight on nutritional status. SETTING: University-affiliated tertiary care center. METHODS: All patients who underwent a SG as a stand-alone procedure between 2008 and 2012 were included in this study. Patients were given multivitamin supplementation. Data were obtained from our prospectively maintained electronic database and are reported as means ± standard deviation and percentages. Bivariate analyses were conducted to evaluate the influence of selected variables on outcomes. RESULTS: The mean age of the 537 patients was 48.0±11.3 years, with an initial BMI of 48.1±8.7kg/m2. Excess weight loss and total weight loss were 56.2% and 28.0% at 1 year and 43.0% and 21.1% at five years, respectively (p<0.0001). Percentage of follow-up was 74% at 5 years (n=79). The mean follow-up time was 34.3±17.2 months. Hypoalbuminemia was present in 1.1% pre-op and 4.2% at five years (p=0.0043), low ferritin levels in 8.6% and 37.8% (p<0.0001), low vitamin B12 in 30.3% and 16.4% (p<0.0001), low vitamin D 63.2% and 24.3% (p<0.0001), and hyperparathyroidism in 23.4% and 20.8% (p<0.0001). There was no significant difference in the prevalence of anemia over time (p=0.4301). The prevalence of vitamin A insufficiency peaked from 7.9% pre-op to 28.7% at 3 months (p<0.0001), and returned to baseline thereafter. Baseline weight was negatively correlated with vitamin B12 and vitamin D. -2- CONCLUSION: Nutritional deficiencies are common in patients with morbid obesity, before and after surgery. Pre-operative supplementation and long-term nutritional follow-up are required to prevent nutritional deficiencies. Keywords: Bariatric surgery, Sleeve Gastrectomy, Nutrition Background The prevalence of obesity has been increasing steadily over the last two decades. However, the prevalence of severe obesity has increased in an exponential manner, with a 225% increase in Canada between 1990 and 2003(1). Even though recent studies suggest that the obesity epidemic has stabilized, obesity and obesity-related diseases represent a major healthcare and economical burden in developed countries(2). Indeed, non-surgical management of morbid obesity is usually ineffective on the long term and surgery remains the only effective solution for these patients(3). A number of surgical procedures have thus been described over the last 40 years. Sleeve gastrectomy (SG) was endorsed in 2011 by the American Society for Metabolic and Bariatric Surgery as a stand-alone treatment for morbid obesity(4). However, SG was described in 1991 in association with biliopancreatic diversion by Hess and Marceau(5,6). This component of the surgery was designed originally as the restrictive and acid suppressing part of a biliopancreatic diversion with duodenal switch (BPD-DS). Indeed, our Centre started using sleeve gastrectomy with duodenal switch (SGDS) in the early 90’s, to decrease the risk of dumping syndrome and marginal ulcers associated with standard BPD. To date, more than four thousand SG-DS have been performed in our institution, but we started using routinely laparoscopic SG as a stand-alone surgery in 2008. -3- All our bariatric patients undergo a standardized follow-up, including blood work and nutritional evaluation. We perceive that, even if the amount of weight loss and the risk for nutritional deficiencies are somewhat lower after SG than other procedures, these patients often require vitamin and mineral supplementation on a long-term basis. Considering these observations, the aims of this study were to (i) report weight loss parameters in a series of SG patients over a five year follow-up, (ii) describe nutritional deficiencies before and after surgery, and (iii) analyze the relationship between baseline weight and pre-operative and post-operative selected nutritional deficiencies. Methods All patients who underwent a primary SG between January 2008 and December 2012 were included in this trial. Procedures were performed at a University-affiliated tertiary care center by a team of five surgeons. Data were extracted from our prospectively maintained electronic database and reviewed retrospectively. Follow-up ended when patients died or underwent another bariatric surgery after SG. For each time point, the follow-up rate was calculated from the number of patients for whom a weight was obtained, divided by the number of operated patients still included in the study at that time. Patients’ selection Patient selection followed the standard NIH recommendations for bariatric surgery(7). All patients were assessed by a bariatric surgeon, dietician, nurse specialized in bariatric surgery, and social worker. All patients underwent an electrocardiogram, chest X-ray, complete bloodwork, sleep apnea testing, and consultation in pneumology. Patients were screened for nutritional deficiencies before surgery and supplementation was started at that time according to standard supplementation protocols. A consultation with a psychiatrist was requested when -4- a patient had a history of psychiatric disease. Standard pre-op education specific to SG was given to all patients. Surgical Technique All patients followed our routine pre-op preparation including a low-residue diet for 2 days before surgery, prophylactic antibiotics (cefazolin two to three grams at the time of surgery) and venous thromboembolism prophylaxis (low-dose standard or low-molecular weight subcutaneous heparin). A 15-mm Hg pneumo-peritoneum is first created. The greater curvature of the stomach is mobilized using ultrasonic shears (Ace Ultrasonic, Ethicon EndoSurgery, Cincinnati, OH, USA). A 48 Fr Bougie (used between 2008 and 2010) or a 34Fr Bougie (used after 2010) is used for the calibration of the SG. The stomach is then transected along the Bougie using an articulating linear stapler-cutter (Echelon-Flex long 60, Ethicon EndoSurgery, Cincinnati, OH, USA), starting 4-5cm from the pylorus. Standardized post-operative orders were used including ulcer prevention, venous thromboembolism prophylaxis (comprising post-op compression stockings and a low dose of either standard or low-molecular weight heparin for three weeks post-op), and feeding protocols. Nutritional management Patients were discharged when tolerating a soft diet, with a multivitamin complex (Centrum Forte®) once daily. Each Centrum Forte® caplet contains, among other elements, vitamin A 1000 IU, vitamin B12 20 µg, folic acid 0.4 mg, thiamin 2.25 mg, vitamin D 600 IU, calcium 200 mg, and iron 10 mg. In addition, patients with pre-op nutritional deficiencies were treated for a minimum of 6 months after surgery. In the particular case of vitamin D deficiency, patients received vitamin D3 10000 IU once daily for one month, followed by 1000 IU daily before and after surgery, until blood levels normalized. -5- Follow-up Patients were followed at the clinic at 3, 6, 9, 12, 18 and 24 months post-operatively (postop), and then yearly thereafter. Similar blood analyses were performed before surgery and at these times, including a complete blood count, electrolytes, urea and creatinine, albumin, calcium, phosphate, PTH, vitamin D, serum iron, total iron binding capacity (TIBC), ferritin, vitamin B12, and folic acid. Supplementations were adjusted over time according to these analyses using standardized supplementation protocols. Patients were weighed at each visit. The body mass index (BMI) was calculated with the formula: Mass (in kg)/[Height (in meters)]2. The ideal weight was calculated as patient’s height (in meters)2 X 23, for an ideal BMI of 23 kg/m2. Excess body weight (EBW) was calculated as: Current Weight – Ideal Weight. Initial excess weight (IEW) was calculated as: Initial Weight – Ideal weight. Total body weight loss (TBWL) was calculated as: (Initial Weight – Current Weight)/Initial Weight X 100. The percentage of excess weight loss (EWL) was calculated as: (Initial Weight – Current Weight)/(Initial Weight – KID) X 100. Statistical analyses Nominal variables were expressed using percentages. Continuous variables from subject’s characteristics were expressed using the mean±SD or median with interquartile range (IQR) according to the distribution. To analyze changes among different scheduled endpoints, a mixed model with two experimental factors was used. The factors were defined as one linked to the variability among patients, a random factor and the other associated to the comparison among the different periods, fixed factors. The latter was analyzed as a repeated-measure factor with the use of a heterogeneous autoregressive covariance structure. We used residual maximum likelihood as the method of estimation and the Kenward–Roger method to estimate -6- denominator degrees of freedom for time effect. Different distributions functions were investigated (normal, lognormal, exponential and gamma) to best fit the continuous response variables according to the Akaike information criteria. The binomial distribution was used for binomial response variables. The model assumption was verified with the quantile-quantile plot representation after a Cholesky factorization on residuals from the appropriate theoretical distribution response variable. The same approach was used to validate the normality distribution of the variability among patients (random effect). The Pearson correlation coefficient (R) was reported to measure the relationship between variables. The results were considered significant with p-values  0.05. All statistical analyses were performed with SAS v9.4 (SAS Institute, Cary, NC, USA). Results Clinical characteristics and weight loss A total of 537 patients underwent a SG. Their baseline characteristics are described in Table 1. There were two peri-operative deaths in the first 90 post-operative days (0.4%). The first one occurred 33 days after surgery from portal thrombosis, and the second 67 days after surgery from pulmonary embolism. There were fourteen long-term deaths (2.6%) from cancer (n=5 at 105, 453, 779, 1175 and 1776 days), kidney failure (n=2 at 823 and 1293 days), cardiovascular disease (n=2 at 775 and 1190 days), cirrhosis (n=1 at 888 days), trauma (n=1 at 1273 days) and of unknown cause (n=3 at 257, 1058 and 1434 days). The mean follow-up was 34.3±17.2 months, with a follow-up rate of 74% at 5 years. Figure 1 and Table 2 summarize data regarding weight loss over time. Weight loss was maximal at 18 months -7- after surgery, with a TBWL of 28.2% and an EWL of 57.0%. It was followed with weight regain, up to 5 years when EWL reached 43.0%. Vitamin and mineral supplementation We used each patient’s last follow-up visit to evaluate the use of vitamins or minerals supplements. At a mean 34±17 months, 89.6% of patients were taking a daily or twice daily multivitamin complex, 24.4% iron, 38.5% calcium, 58.2% vitamin D, and 7.5% vitamin A. Nutritional deficiencies Figure 2 and Tables 3 and 4 show the evolution of lab values and prevalence of nutritional deficiencies after surgery. There was an increase in the prevalence of albumin deficiency after SG (1.1% pre-op vs 6.6% one year post-op, p=0.0043). Baseline weight was negatively correlated with albumin levels pre-operatively (R= –0.18, p<0.0001) and over time, i.e. patients with higher pre-operative weight had lower albumin levels before and after surgery. Anemia was present in 13.5% of women and 30.2% of men before surgery and its prevalence decreased to 11.6% and 17.3% one year post-op, respectively. These rates remained stable at five years of follow-up. New-onset anemia ranged from 34.6% at 3 months to 80.6% at four years. However, severe anemia (hemoglobin level under 100 g/L) was infrequent (0.4 to 2.6% over 5 years). Baseline weight was positively correlated with pre-op (R=0.11, p=0.0150) and post-op hemoglobin. The prevalence of vitamin B12 possible (below 221 pmol/L) and definite (below 148 pmol/L) deficiency decreased over time (30.3% and 5.0% pre-op versus 16.4% [p<0.0001] and 1.4% at five years, respectively). Baseline weight was negatively correlated with pre-op (R= –0.12, p=0.0064) and post-op vitamin B12 levels. True folic acid deficiency remained virtually absent throughout the study. The prevalence of low ferritin levels (below 30.0 µg/L) increased sustainably (8.6% vs 37.8%, p<0.0001) at five years. Furthermore, severe -8- deficiency (below 9.0 µg/L) became more prevalent (0.2% at baseline vs 10.8%) at five years. Initial weight was positively correlated with ferritin levels pre-operatively (R=0.16, p=0.0003) and over time. High TIBC, which is a marker of iron deficiency, was noted in 3.6% of patients at baseline and in 15.1% (p=0.0004) after four years. Low vitamin D levels (below 70.0 nmol/L), which were highly prevalent before surgery, decreased sustainably (63.2% pre-op and 24.3% at five years, p<0.0001). We found a negative correlation between baseline weight and pre-op (R= –0.24, p<0.0001) and post-op vitamin D levels over time. Hyperparathyroidism was noted in 23.4% of patients at baseline, 12.5% at 18 months and 20.8% at five years (p<0.0001). There was a positive relationship between baseline weight and PTH levels before (R=0.18, p<0.0001) and after SG. The prevalence of vitamin A insufficiency (below 1.4 µmol/L) temporarily increased from 7.9% pre-op to 28.7% at three months and then decreased to pre-operative values at 2 years (p<0.0001). Yet, vitamin A deficiency (below 0.7 µmol/L) was almost inexistent throughout the study. Discussion To our knowledge, this is the largest study assessing nutritional deficiencies following SG. Despite an excess in calories and refined carbohydrate intakes, poor dietary choices may lead to unmet micronutrient needs in people with morbid obesity(8,9). Several studies have investigated nutritional deficiencies in SG patients before and after surgery(10,11,12,13,14,15). Results from previous work support routine use of nutrition monitoring and supplementations to prevent such deficiencies(16,17). Current guidelines from the American Society for Metabolic & Bariatric Surgery(18) recommend post-op routine preventative micronutrient supplementation via multivitamin caplets and specific supplements. However, the optimal -9- duration of supplementation is not specified, although experts have suggested time schedules for nutritional follow-up(19). Evolution of weight loss At two years, the expected EWL is approximately 60% for SG. This is consistent with the results from our study and from others, even though few studies were designed with such a long follow-up duration(10,12,13,20). Weight regain is common after 2 years and this is what we experienced between 2 and 5 years. In addition, we initially used a 48 Fr Bougie to calibrate the SG, which could have potentially led to increased risk of weight regain. Also, patients who had a second-stage surgery during the study period (n=90), typically between 18 and 24 months post-op, were excluded from the study thereafter. This might have led to a selection bias of patients (i.e. patients who were good candidates for a second-stage duodenal switch were excluded from the population). Protein malnutrition Sufficient protein amounts are mandatory to avoid post-op complications such as poor wound healing and infections. In addition, protein depletion is associated with loss of lean tissue mass including skeletal muscle(21), which may promote the development of insulin resistance. In our case, we did not record energy and macronutrients consumption, but hypoalbuminemia served as an indicator of protein depletion. Prevalence of hypoalbuminemia peaked at one year post-op, and then decreased slightly. This observation correlates with reduced stomach size and ensuing food intolerance, diminished overall food intake, and accelerated gastric emptying, all of which improve with time. Results are heterogeneous, but most reports have shown low prevalence or absence of hypoalbuminemia after SG(10,13,22). On the other hand, in two studies, prealbumin concentrations below 200 mg/L were observed in 14 to 52% of - 10 - patients one year after surgery(11,22), despite routine protein supplementation in the former study. Thus, prealbumin might be more sensitive than albumin in detecting protein depletion. Anemia and related disorders Anemia was noticeably prevalent at baseline, mostly in men. However, changes in hemoglobin were minor over time. This is consistent with previous results(11,12,23). Other studies have observed decreased hemoglobin levels after SG(10,13,20). In contrast, ferritin levels decreased sustainably throughout follow-up. Unlike ours, most studies did not show a significant change in the prevalence of low ferritin levels after SG, but their follow-up was shorter(11,12,13,20). In another long term follow-up SG study, low ferritin levels were observed in 36.2% of patients at five years compared to 3.3% at baseline(14). The prevalence of vitamin B12 deficiency is estimated to approximately five percent among patients with obesity, depending on defined lower limit of normal(8), which is consistent with our pre-operative data. To date, changes in vitamin B12 levels after SG have shown mixed results. Some SG studies have described a worsening of vitamin B12 after one year of follow-up(12,20,24). The underlying mechanism is that resection of the gastric fundus during SG leads to a decreased production of intrinsic factor and, as a result, impaired absorption of vitamin B12. Moreover, reduced stomach size puts patients at risk for insufficient food intake. Other references, as in our study, report unchanged or improved vitamin B12 levels after surgery(10,13). Supplementation with a multivitamin containing vitamin B12 seems sufficient in maintaining normal levels for most patients. Additionally, in case of discontinuation of medication and return to bad nutritional habits, it would take at least three to four years for vitamin B12 stores to deplete. Therefore, our follow-up was not long enough to assess this occurrence. Unsurprisingly, folate levels were almost always normal in our population. Folate deficiency - 11 - is a rarely encountered disorder in Western countries due to regulations concerning fortification of grain products. In comparison, a recent Chinese study found high prevalence (32.2%) of folate deficiency in patients presenting for bariatric surgery(25). Phosphocalcium metabolism Vitamin D deficiency is a common finding in people with obesity and its prevalence is higher than in normal subjects. Multiple etiologies for this phenomenon have been hypothesized. Insufficient sun exposure, low intake of food rich in vitamin D, and poor food fortification may contribute to low serum levels of vitamin D. In addition, vitamin D deposition in adipose tissue is thought to enhance the problem in patients with obesity(9). One study found vitamin D insufficiency in up to 90% of patients awaiting bariatric surgery and therefore suggested routine vitamin D repletion for this population, regardless of ethnicity. The mean BMI was only slightly higher than in our study (52.6 vs 48.0)(26). Unsurprisingly, we found a high prevalence of low vitamin D levels (63%) and vitamin D insufficiency (37%). Even though improved, rates remained high after surgery, and tended to head back towards baseline after a few years. This could be explained by a combination of weight gain, recurrence of bad nutritional habits, and discontinuation of supplements after some time. In the same way, high prevalence of hyperparathyroidism was observed prior to surgery. In fact, total body fat and BMI are inversely associated with vitamin D levels and positively associated with PTH. Additionally, PTH excess has been shown to promote weight gain(27,28). PTH increases intracellular calcium, which enhances lipogenesis in the adipocytes. Thus, vitamin D deficiency and hyperparathyroidism are clearly a consequence of, but might also contribute to obesity. - 12 - As expected, hypocalcemia was rare throughout the study. Serum calcium tends to be preserved in the normal range even in presence of hyperparathyroidism, which confirms the need for PTH dosage pre-operatively(29). Rates of low phosphate levels followed the same pattern as those of low vitamin D levels, but a normal value could not rule out a vitamin D insufficiency. Vitamin A Vitamin A is a fat soluble vitamin. Low vitamin A levels are reported in up to 12.5% of patients undergoing bariatric surgery(9). Rates of new onset or worsening hypovitaminosis A after SG alone are not clearly defined. In our study, there was a temporarily increased prevalence of vitamin A insufficiency immediately after surgery. This might be explained by reduced total food intake in the first months post-op. Routine dosage of vitamin A is currently recommended within the first post-operative year(18), but our results show that it might be beneficial to do so earlier, i.e. in the first months after SG. Study limits We used a prospective design with retrospective analysis. Thus, we could not isolate the influence of each specific variable, such as weight loss, use of supplements, dietary intake, and clinical characteristics of patients, among others. For that reason, nutritional deficiencies observed in our study cannot be solely attributed to SG. Although the current standard is to use a BMI of 25 kg/m2 to calculate ideal weights, our center has been using a 23 kg/m2 BMI in all its databases and its other publications. Thus, we retained this parameter for practical and historical purposes. A number of patients were lost to follow-up after three years. Yet, the absolute number of patients remained substantial. Nonetheless, this might have led to an underestimation of - 13 - nutritional deficiencies among SG patients, supposing that the least engaged participants had poorer medical adherence to supplements. Unfortunately, due to the design of our database, we could not retrieve patients’ supplements intake at each time point, but only at the last visit. Therefore, we could not determine the effect of this parameter on the occurrence of nutritional deficiencies. In addition, we relied on patients’ word to assess their use of supplements, so compliance might have been overestimated. As outlined previously, our micronutrient routine supplementation protocol differed from current guidelines(18), which generally suggest higher micronutrient doses post-op, especially for calcium, vitamin D, vitamin B12, and thiamin. However, since 2016, our multivitamin complex dose was increased to two caplets daily for all patients. Also, we did not monitor thiamine levels. This lab test is seldom requested in our setting because the sample has to be sent abroad, which results in high cost and significant delay in analysis. Conclusions Nutritional deficiencies are common in patients with morbid obesity, before and after SG. Pre and post-operative supplementation with a multivitamin complex and other appropriate micronutrients according to nutritional status, as well as a long-term nutritional follow-up, are required to prevent and correct nutritional deficiencies. Further studies are needed to define optimal supplement types and doses for these patients. Acknowledgements We wish to acknowledge the help of Mrs Paule Marceau, research assistant, for the collection, verification of the data. - 14 - Disclosures The authors have no disclosures. References 1. Katzmarzyk PT, Mason C. Prevalence of class I, II and III obesity in Canada. CMAJ 2006;174:156-157. 2. Schneider H, Dietrich ES, Venetz WP. 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Obes Surg 2008;18(7):870–876. 9. Xanthakos S. Nutritional deficiencies in obesity and after bariatric surgery. Pediatr Clin North Am 2009;56(5):1–16. - 15 - 10. Zarshenas N, Nacher M, Loi KW, & Jorgensen JO. Investigating Nutritional Deficiencies in a Group of Patients 3 Years Post Laparoscopic Sleeve Gastrectomy. Obes Surg 2016; http://dx.doi.org/10.1007/s11695-016-2211-3. 11. Verger EO, Aron-Wisnewsky J, Dao MC, et al. Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up. Obes Surg 2016;26(4):785–796. 12. van Rutte PWJ, Aarts EO, Smulders JF, Nienhuijs SW. Nutrient Deficiencies Before and After Sleeve Gastrectomy. Obes Surg 2014;24:1639-1646. 13. Toh SY, Zarshenas N, Jorgensen J. Prevalence of nutrient deficiencies in bariatric patients. Nutrition 2009;25(11-12):1150-1156. 14. Gillon S, Jeanes YM, Andersen JR, Vage V. Micronutrient Status in Morbidly Obese Patients Prior to Laparoscopic Sleeve Gastrectomy and Micronutrient Changes 5 years Post-surgery. Obes Surg 2016:1-7. 15. Saif T, Strain GW, Dakin G, Gagner M, Costa R, Pomp A. Evaluation of nutrient status after laparoscopic sleeve gastrectomy 1, 3, and 5 years after surgery. Surg Obes Relat Dis 2012;8(5):542-547. 16. Ernst B, Thurnheer M, Schmid SM, Schultes B. Evidence for the necessity to systematically assess micronutrient status prior to bariatric surgery. Obes Surg 2009;19(1):66-73. 17. Kwon Y, Kim HJ, Lo Menzo E, Park S, Szomstein S, Rosenthal RJ. Anemia, iron and vitamin B12 deficiencies after sleeve gastrectomy compared to Roux-en-Y gastric bypass: A meta-analysis. Surg Obes Relat Dis 2014;10(4):589-599. 18. Parrot J, Frank L, Rabena R, et al. American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update: Micronutrients. 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Damms-Machado A, Friedrich A, Kramer KM, et al. Pre- and post-operative nutritional deficiencies in obese patients undergoing laparoscopic sleeve gastrectomy. Obes Surg 2012;22(6):881-889. 25. Wang C, Guan B, Yang W, Yang J, Cao G, Lee S. Prevalence of electrolyte and nutritional deficiencies in Chinese bariatric surgery candidates. Surg Obes Relat Dis 2016;12(3):629-634. 26. Grace C, Vincent R. High prevalence of vitamin D insufficiency in a United Kingdom urban morbidly obese population: Implications for testing and treatment. Surg Obes Relat Dis 2014;10(2):355-360. 27. Snijder MB, van Dam RM, Visser M, et al. Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women. J Clin Endocrinol Metab 2005;90(7):4119-4123. - 17 - 28. McCarty MF, Thomas CA. PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium, vitamin D, and alcohol on body weight. Med Hypotheses 2003;61(5-6):535-542. 29. Hamoui N, Anthone G, Crookes PF. Calcium Metabolism in the Morbidly Obese. Obes Surg 2004;14(1):9-12. Legends of figures Figure 1. Evolution of weight over time. EWL = excess weight loss; EBW = excess body weight; SE = standard error; N = number of patients with available data. Figure 2. Evolution of nutritional parameters over time. This figure shows evolution of anemia (A), iron studies (B), phosphocalcium parameters (C), and other nutritional parameters (D). Hb = hemoglobin; TSat = transferrin saturation; PTH = parathyroid hormone. Table 1. Anthropometry and clinical characteristics of patients preoperatively. Total number of patients N = 537 Female sex, N (%) Mean age at operation, years±SD Mean Weight, kg±SD Mean BMI, kg/m2±SD Mean IEW, kg±SD %IEW±SD Indication for sleeve gastrectomy alone instead of other bariatric procedures, N (%) Patient’s desire Compliance issue Surgical risk or comorbidities Two-stage approach initially planned Per-operative decision 341 (63.5) 48.0±11.3 132.9±28.0 48.1±8.7 69.2±25.2 109.0±37.7 - 18 - 211 (39.3) 169 (31.5) 98 (18.2) 21 (3.9) 38 (7.1) CKD, N (%) Stage 4 (GFR 15-29) 2 (0.4) Stage 5 (GFR <15) 3 (0.6) Type II diabetes, N (%) 302 (56.2) OSA, N (%) 337 (62.8) HTN, N (%) 337 (62.8) CAD, N (%) 79 (14.7) Dyslipidemia, N (%) 258 (48.0) Cirrhosis, N (%) 18 (3.4) Arthrosis, N (%) 111 (20.7) GERD, N (%) 161 (30.0) Depression, N (%) 110 (20.5) Other, N (%) 267 (49.7) N: number of patients; SD: standard deviation; IEW: initial excess weight; BMI: body mass index; CKD: chronic kidney disease; GFR: glomerular filtration rate (mL/min/1.73m2); OSA: obstructive sleep apnea; HTN: hypertension; CAD: coronary artery disease; GERD: gastroesophageal reflux disease. Other comorbidities include heart failure, asthma, gout, venous stasis, polycystic ovary syndrome, migraines, thyroid disorders, and fibromyalgia. Table 2. Evolution of weight loss over 5 years of follow-up. P value Baseline 3 mo 6 mo 1 year 18 mo 2 years 3 years 4 years 5 years n/N (%) 537/537 (100) 439/536 (98.7) 443/535 (97.4) 132.9±2 8.0 110.8±2 3.5 101.1±2 3.2 235/53 2 (44.2) 94.3±2 2.6 317/53 2 (59.6) 95.5±2 2.4 278/42 6 (65.3) 95.8±2 4.5 142/23 3 (60.9) 97.1±2 2.9 79/107 (73.8) Weig ht (kg) EBW (kg) BMI 425/53 4 (79.6) 95.2±2 1.2 104.4±2 9.6 <0.00 01 69.2±25 .2 48.1±8. 7 0 47.4±20 .7 40.3±7. 4 31.7±10 .6 15.5±4. 5 37.8±21 .2 36.8±7. 6 47.7±15 .3 23.5±6. 3 32.0±1 9.6 34.7±7. 1 56.2±1 8.3 28.0±8. 2 30.7±2 0.3 34.1±7. 2 57.0±2 0.1 28.2±9. 5 32.0±2 0.7 34.7±7. 6 55.2±2 1.6 27.6±1 0.4 32.8±2 2.6 35.0±8. 1 52.9±2 3.0 26.1±1 1.3 34.7±2 1.2 35.8±7. 9 50.0±2 2.7 24.7±1 0.8 42.7±27 .2 38.3±9. 8 43.0±22 .9 21.1±11 .5 <0.00 01 <0.00 01 <0.00 01 <0.00 01 EWL (%) TBW 0 L (%) Values are indicated as mean±SD. Many patients who underwent surgery later in the recruitment phase had not reached a five-year cumulative follow-up period at time of analysis. n = number of patients for whom a weight was obtained; N = number of patients available for follow-up; Mo = months; EBW = excess body weight; BMI = body mass index; EWL = excess weight loss; TBWL = total body weight loss. - 19 - Table 3. Laboratory values over 5 years of follow-up. Nor mal rang e Albu min Hb MCV Iron Ferriti n TSat TIBC Vitam in B12 Folic Acid Vitam in D PTH Calciu 35.050.0 g/L Fem ale : 125165 g/L Male : 135185 g/L 80.096.0 FL 10.030.0 µmo l/L 30.0200. 0 µg/L 0.200.50 45.075.0 mol/ L 145. 01000 .0 pmol /L 9.555.0 nmol /L 70.0125. 0 nmol /L 9.065.0 ng/L 2.15- Baselin e 3 mo 6 mo 1 year 18 mo 2 years 3 years 4 years 5 years P value 42.1±2. 8 (526) 40.9±3. 6 (482) 40.7±3. 6 (459) 40.8±3. 7 (423) 40.8±3. 8 (265) 41.4±3. 6 (314) 40.7±3. 7 (269) 40.9±3. 7 (158) 40.5±3. 6 (71) <0.0 001 134.0±1 2.5 (526) 135.5±1 2.3 (490) 135.7±1 2.3 (465) 135.6±1 2.2 (434) 135.0±1 2.9 (269) 135.5±1 2.2 (326) 135.2±1 3.1 (280) 132.8±1 4.7 (156) 135.5±1 4.5 (76) 0.00 06 88.8±4. 9 (525) 88.6±4. 5 (488) 89.8±4. 6 (466) 90.5±4. 3 (431) 90.0±6. 3 (267) 90.2±4. 3 (324) 90.2±4. 5 (280) 89.1±5. 7 (155) 89.7±5. 0 (75) <0.0 001 13.2±4. 5 (521) 13.0±4. 6 (477) 15.0±5. 0 (456) 16.8±5. 9 (425) 17.4±5. 9 (257) 17.8±5. 6 (311) 17.3±6. 4 (267) 16.5±6. 7 (150) 17.3±5. 6 (73) <0.0 001 137.6±1 34.7 (486) 123.5±1 21.9 (468) 111.0±1 02.9 (456) 109.0±1 08.9 (425) 100.0±9 8.9 (254) 96.3±98 .5 (314) 89.3±94 .3 (265) 79.3±14 6.4 (153) 99.1±18 5.4 (74) <0.0 001 0.240±0 .094 (331) 57.5±8. 7 (333) 0.240±0 .097 (216) 54.9±10 .7 (187) 0.280±0 .110 (246) 56.2±9. 7 (211) 0.300±0 .115 (258) 56.7±10 .1 (225) 0.310±0 .113 (198) 57.8±10 .0 (165) 0.310±0 .117 (255) 58.0±9. 5 (217) 0.300±0 .122 (242) 59.0±9. 2 (205) 0.270±0 .121 (145) 62.0±11 .0 (119) 0.290±0 .126 (71) 62.7±11 .5 (58) <0.0 001 293.9±1 22.1 (522) 322.4±1 30.9 (460) 308.0±1 36.3 (453) 325.5±1 51.7 (419) 352.1±1 56.0 (256) 360.5±1 64.4 (313) 367.1±1 67.4 (270) 361.4±1 63.9 (154) 336.9±1 19.8 (73) <0.0 001 29.5±8. 4 (521) 32.7±11 .3 (452) 38.1±10 .8 (443) 39.1±10 .7 (412) 39.8±11 .2 (255) 39.6±10 .3 (305) 38.2±11 .5 (229) 38.0±11 .4 (117) 38.3±11 .6 (54) <0.0 001 62.3±27 .8 (516) 82.6±32 .2 (435) 88.8±29 .6 (440) 94.2±39 .4 (403) 90.7±49 .3 (254) 96.4±35 .4 (309) 90.3±26 .8 (267) 87.9±27 .5 (151) 84.7±23 .9 (74) <0.0 001 52.0±33 .1 (521) 50.9±22 .7 (440) 47.6±25 .0 (436) 47.6±33 .9 (408) 45.8±24 .6 (248) 47.4±19 .3 (305) 52.3±21 .9 (144) 55.0±31 .0 (72) <0.0 001 2.34±0. 2.34±0. 2.34±0. 2.33±0. 2.32±0. 2.33±0. 59.2±11 8.6 (258) 2.33±0. 2.31±0. 2.32±0. 0.00 - 20 - <0.0 001 m 2.55 09 10 11 10 11 11 10 10 10 (72) 77 mmo (518) (474) (454) (422) (262) (313) (270) (156) l/L Phosp 0.87- 1.00±0. 1.08±0. 1.14±0. 1.17±0. 1.14±0. 1.12±0. 1.11±0. 1.12±0. 1.09±0. <0.0 hate 1.50 18 19 20 20 17 17 22 18 18 (72) 001 mmo (523) (472) (452) (412) (259) (309) (268) (151) l/L Vitam 1.40- 2.14±0. 1.71±0. 1.83±0. 1.96±0. 2.01±0. 2.11±0. 2.08±0. 2.06±0. 2.10±0. <0.0 in A 3.40 60 55 60 61 56 55 58 55 64 (72) 001 µmo (518) (436) (436) (400) (250) (303) (259) (141) l/L All values are indicated as mean±SD (number of data) unless otherwise specified. The number of data varies depending on which variables were tested at each visit. Mo = months; Hb = hemoglobin; MCV = mean corpuscular volume; TSat = transferrin saturation; TIBC = total iron binding capacity; PTH = parathyroid hormone. Table 4. Prevalence of nutritional deficiencies preoperatively and over 5 years of follow-up. Hypoalbuminemi a Definition of deficiency Baselin e <35.0 g/L 6 (1.1) De novo Anemia Women : Hb <120 g/L 45 (13.5) Men : Hb <135 g/L 58 (30.2) Overall Severe, Hb <100 g/L De novo Iron 103 (19.6) 2 (0.4) <10.0 µmol/L 104 (20.0) Severe, <4.0 µmol/L <30.0 µg/L 2 (0.4) Severe, <9.0 µg/L 1 (0.2) TSat <0.20 117 (35.3) TIBC >75.0 mol/L 12 (3.6) Ferritin 42 (8.6) 1 year 18 mo 2 years 3 years 4 years 5 years 28 (6.6) 24 (85.7 ) 33 (11.6 ) 26 (17.3 ) 59 (13.6 ) 0 12 (4.5) 11 (91.7 ) 25 (13.7 ) 17 (19.8 ) 42 (15.6 ) 3 (1.1) 25 (59.5 ) 21 (8.2) 10 (3.2) 9 (90.0 ) 24 (11.1 ) 20 (18.2 ) 44 (13.5 ) 3 (0.9) 20 (45.5 ) 19 (6.1) 11 (4.1) 10 (90.9 ) 24 (12.6 ) 18 (20.0 ) 42 (15.0 ) 1 (0.4) 20 (47.6 ) 22 (8.2) 3 (4.2) 2 (66.7 ) 5 (10.0 ) 4 (15.4 ) 9 (11.8 ) 2 (2.6) 6 (66.7 ) 6 (8.2) 0 0 69 (22.0 ) 6 (1.9) 65 (24.5 ) 6 (2.3) 77 (35.6 ) 7 52 (21.1 ) 7 43 (16.7 ) 9 30 (15.2 ) 10 50 (19.6 ) 11 44 (18.2 ) 8 41 (28.3 ) 18 1 (1.4) 28 (37.8 ) 8 (10.8 ) 14 (19.7 ) 8 ---- 81 (19.1 ) 7 (1.6) 2 (0.8) 45 (17.7 ) 5 (2.0) 6 (3.8) 4 (66.7 ) 18 (15.5 ) 13 (32.5 ) 31 (19.9 ) 3 (1.9) 25 (80.6 ) 20 (13.3 ) 4 (2.7) 55 (35.9 ) 11 (7.2) 0.0043 51 (29.3 ) 81 (16.5 ) 2 (0.4) 28 (34.6 ) 115 (24.1 ) 2 (0.4) 68 (14.5 ) 4 (0.9) 26 (5.7) 23 (88.5 ) 31 (10.1 ) 35 (22.0 ) 66 (14.2 ) 2 (0.4) 28 (42.4 ) 66 (14.5 ) 2 (0.4) 71 (15.6 ) 5 (1.1) 3 mo 6 mo 19 (3.9) 16 (84.2 ) 30 (9.5) - 21 - 29 (49.2 ) 38 (8.9) 0 P value ---- 0.4301 0.0150 0.4301 ------- <0.000 1 <0.000 1 ---- <0.000 1 0.0004 Vitamin B12 Folic Acid Vitamin D HyperPTH Calcium Phosphate (3.7) (3.3) (4.0) (6.1) (5.1) (3.9) 100 (21.7 ) 16 (3.5) 124 (27.4 ) 17 (3.8) 108 (25.8 ) 20 (4.8) 44 (17.2 ) 6 (2.3) 42 (13.4 ) 9 (2.9) 42 (15.6 ) 9 (3.3) 23 (23.0 ) 5 (1.1) 153 (35.2 ) 43 (9.9) 41 (33.1 ) 6 (1.4) 105 (23.9 ) 26 (5.9) 44 (40.7 ) 2 (0.5) 77 (19.1 ) 22 (5.5) 18 (40.9 ) 0 15 (35.7 ) 0 64 (25.2 ) 17 (6.7) 11 (26.2 ) 1 (0.3) 56 (18.1 ) 6 (1.9) 0 1 (0.2) 0 0 0 25 (4.8) 13 (3.0) 91 (20.7 ) 13 (2.7) 0 12 (2.8) 56 (12.8 ) 14 (3.1) 0 14 (3.4) 55 (13.5 ) 11 (2.6) 0 6 (2.4) 31 (12.5 ) 13 (5.0) 0 Possible, <221.0 pmol/L Definite, <148.0 pmol/L De novo, <221.0 pmol/L <9.5 nmol/L 158 (30.3) <70.0 nmol/L 326 (63.2) Insufficienc y, <50.0 nmol/L Deficiency, <12.5 nmol/L Severe, PTH >100.0 ng/L PTH >65.0 ng/L 192 (37.2) <2.15 mmol/L Severe, <2.00 mmol/L <0.87 mmol/L 10 (1.9) 26 (5.0) 0 122 (23.4) 1 (0.2) 114 (21.8) (15.1 ) 23 (14.9 ) 2 (1.3) (13.8 ) 12 (16.4 ) 1 (1.4) 7 (58.3 ) 0 ---- 52 (19.5 ) 13 (4.9) 10 (43.5 ) 2 (1.7) 32 (21.2 ) 9 (6.0) 18 (24.3 ) 3 (4.1) <0.000 1 0 0 0 0 ---- 5 (1.6) 41 (13.4 ) 7 (2.2) 1 (0.3) 8 (3.1) 54 (20.9 ) 7 (2.6) 0 3 (2.1) 32 (22.2 ) 6 (3.8) 0 4 (5.6) 15 (20.8 ) 2 (2.8) 0 ---- <0.000 1 ---- ---- <0.000 1 <0.000 1 0.5811 ---- 66 22 16 12 15 20 11 6 <0.000 (14.0 (4.9) (3.9) (4.6) (4.9) (7.5) (7.3) (8.3) 1 ) Vitamin A Excess, >3.4 18 (3.5) 7 11 8 6 6 6 3 3 ---µmol/L (1.6) (2.5) (2.0) (2.4) (2.0) (2.3) (2.1) (4.2) Insufficienc 41 (7.9) 125 97 61 24 22 20 18 8 <0.000 y, <1.40 (28.7 (22.2 (15.3 (9.6) (7.3) (7.7) (12.8 (11.1 1 µmol/L ) ) ) ) ) Deficiency, 0 2 3 3 0 0 0 0 0 ---<0.7 µmol/L (0.5) (0.7) (0.8) All values are indicated as number of affected patients (%). The number of data for each variable and time point is the same as the matching cell in Table 3. Mo = months; Hb = hemoglobin; de novo = was not present at baseline; TSat = transferrin saturation; TIBC = total iron binding capacity; HyperPTH = hyperparathyroidism; PTH = parathyroid hormone. - 22 - - 23 -