Gut feelings about diabetes

Studies of patients going into diabetes remission after gastric bypass surgery have demonstrated the important role of the gut in glucose control. The improvement of type 2 diabetes after gastric bypass surgery occurs via weight dependent and weight independent mechanisms. The rapid improvement of glucose levels within days after the surgery, in relation to change of meal pattern, rapid nutrient transit, enhanced incretin release and improved incretin effect on insulin secretion, suggest mechanisms independent of weight loss. Alternatively, insulin sensitivity improves over time as a function of weight loss. The role of bile acids and microbiome in the metabolic improvement after bariatric surgery remains to be determined. While most patients after bariatric surgery experienced sustained weight loss and improved metabolism, small scale studies have shown weight regain and diabetes relapse, the mechanisms of which remain unknown.     

Metabolic surgery for type 2 diabetes mellitus

Background: Metabolic surgery for morbid obesity induces significant weight loss and resolution of many obesity-related comorbidities, the most notable of which is remission of type 2 diabetes mellitus (DM). Such changes seem to precede significant weight loss in this population shortly after undergoing diversionary procedures.Objective: This article explores the evidence for salutary metabolic benefits of bariatric surgery, with special emphasis on glycemic control and remission of type 2 DM.Methods: We conducted a query of the PubMed database for articles published in English within the past 15 years using the search terms bariatric surgery, obesity, type 2 diabetes, gastric bypass, gastric banding, incretins, enteroinsular axis, GLP-1 (glucagon-like peptide-1), and GIP (glucose-dependent insulinotropic polypeptide). We targeted review articles as well as those discussing the effects of bariatric surgery on the enteroinsular axis and the respective effects on glyce-mic control.Results: Most of the clinical reports indicated a high remission rate (≥85%) for type 2 DM, and relatively higher rates in patients who underwent diversionary procedures. Studies with small cohorts and laboratory data suggested a role for gastrointestinal hormones in the regulation of glucose homeostasis after bariatric surgery.Conclusions: Gastrointestinal surgery for severe obesity, through restrictive and/or neurohormonal effects, is an effective treatment for type 2 DM. Surgically induced weight loss was found to be sustainable, durable, and associated with remission of type 2 DM, a reduction in mortality, and improvement in quality of life.     

Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care

Background

Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities.

Methods and Findings

This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88–5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55–0.83); hypertension, 0.35 (95% CI 0.27–0.45); angina, 0.59 (95% CI 0.40–0.87);MI, 0.28 (95% CI 0.10–0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40–0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84–12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65–11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66–1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes.

Conclusions

Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.     

Durable remission of diabetes after bariatric surgery: What is the underlying pathway?

Background: In the past, type 2 diabetes mellitus (DM) was regarded as a progressive, incurable disease for which palliative therapy could not, over the long term, prevent the associated amputations, blindness, renal failure, and early mortality. This is no longer true. Full and durable remission of type 2 DM, with major decreases in morbidity and mortality, is now achieved regularly with several types of surgery that reduce contact between food and the foregut.Objectives: The aims of this article are to review the impact of bariatric surgery on obesity, remission of DM, and obesity-related morbidity and mortality, and the possible mechanisms for this advance.Methods: This article is based on our 2 meta-analyses of the literature published through April 30, 2006, as well as the most significant reports in the bariatric surgical literature that have been published in English since April 30, 2006. The studies included in our second meta-analysis provided the details of the methodology for the present literature review, including the levels of evidence.Results: Results of our 2 meta-analyses were published previously. Briefly, the analyses revealed that the clinical and laboratory manifestations of type 2 DM resolved or improved in most of the patients who underwent bariatric surgery; the responses were greatest in the patients who lost the most excess body weight; and the improvements were maintained for ≥2 years. The studies reported that intestinal operations such as gastric bypass reduced contact between food and the foregut, produced full and durable remission of DM, reduced mortality, and reversed other comorbidities associated with severe obesity (eg, asthma, gastroesophageal reflux, hypertension, stress incontinence). Insulin levels decreased markedly after surgery, as did glycosylated hemoglobin (A1C) and fasting blood glucose levels. Although these effects were initially attributed to weight loss, the rapid reversal of DM within a matter of days after surgery suggest that bariatric surgery changes the signaling mechanism of the gut with pancreatic islet cells, muscles, fat, the liver, and other organs.Conclusions: Bariatric surgery has opened new vistas, producing durable full remission of type 2 DM—a breakthrough previously considered impossible—with normalization of A1C levels over time and discontinuation of all antidiabetes medication for many patients. These advances create new opportunities for exploring the mechanisms of type 2 DM and its control through pharmaceutical approaches. DM is no longer an irreversible, incurable, or hopeless disease.     

Superior Appetite Hormone Profile After Equivalent Weight Loss by Gastric Bypass Compared to Gastric Banding

The goal of this study was to understand the mechanisms of greater weight loss by gastric bypass (GBP) compared to gastric banding (GB) surgery. Obese weight‐ and age‐matched subjects were studied before (T0), after a 12 kg weight loss (T1) by GBP (n = 11) or GB (n = 9), and at 1 year after surgery (T2). peptide YY_3–36 (PYY_3–36), ghrelin, glucagon‐like peptide‐1 (GLP‐1), leptin, and amylin were measured after an oral glucose challenge. At T1, glucose‐stimulated GLP‐1 and PYY levels increased significantly after GBP but not GB. Ghrelin levels did not change significantly after either surgery. In spite of equivalent weight loss, leptin and amylin decreased after GBP, but not after GB. At T2, weight loss was greater after GBP than GB (P = 0.003). GLP‐1, PYY, and amylin levels did not significantly change from T1 to T2; leptin levels continued to decrease after GBP, but not after GB at T2. Surprisingly, ghrelin area under the curve (AUC) increased 1 year after GBP (P = 0.03). These data show that, at equivalent weight loss, favorable GLP‐1 and PYY changes occur after GBP, but not GB, and could explain the difference in weight loss at 1 year. Mechanisms other than weight loss may explain changes of leptin and amylin after GBP.     

Bariatric surgery for patients with type 2 diabetes mellitus requiring insulin: Clinical outcome and cost-effectiveness analyses

BackgroundAlthough bariatric surgery is well established as an effective treatment for patients with obesity and type 2 diabetes mellitus (T2DM), there exists reluctance to increase its availability for patients with severe T2DM. The aims of this study were to examine the impact of bariatric surgery on T2DM resolution in patients with obesity and T2DM requiring insulin (T2DM-Ins) using data from a national database and to develop a health economic model to evaluate the cost-effectiveness of surgery in this cohort when compared to best medical treatment (BMT).Methods and findingsClinical data from the National Bariatric Surgical Registry (NBSR), a comprehensive database of bariatric surgery in the United Kingdom, were extracted to analyse outcomes of patients with obesity and T2DM-Ins who underwent primary bariatric surgery between 2009 and 2017. Outcomes for this group were combined with data sourced from a comprehensive literature review in order to develop a state-transition microsimulation model to evaluate cost-effectiveness of bariatric surgery versus BMT for patients over a 5-year time horizon. The main outcome measure for the clinical study was insulin cessation at 1-year post-surgery: relative risks (RR) summarising predictive factors were determined, unadjusted, and after adjusting for variables including age, initial body mass index (BMI), duration of T2DM, and weight loss. Main outcome measures for the economic evaluation were total costs, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) at willingness-to-pay threshold of GBP£20,000.A total of 2,484 patients were eligible for inclusion, of which 1,847 had 1-year follow-up data (mean age of 51 years, mean initial BMI 47.2 kg/m², and 64% female). 67% of patients no longer required insulin at 1-year postoperatively: these rates persisted for 4 years. Roux-en-Y gastric bypass (RYGB) was associated with a higher rate of insulin cessation (71.7%) than sleeve gastrectomy (SG; 64.5%; RR 0.92, confidence interval (CI) 0.86–0.99) and adjustable gastric band (AGB; 33.6%; RR 0.45, CI 0.34–0.60; p < 0.001). When adjusted for percentage total weight loss and demographic variables, insulin cessation following surgery was comparable for RYGB and SG (RR 0.97, CI 0.90–1.04), with AGB having the lowest cessation rates (RR 0.55, CI 0.40–0.74; p < 0.001). Over 5 years, bariatric surgery was cost saving compared to BMT (total cost GBP£22,057 versus GBP£26,286 respectively, incremental difference GBP£4,229). This was due to lower treatment costs as well as reduced diabetes-related complications costs and increased health benefits. Limitations of this study include loss to follow-up of patients within the NBSR dataset and that the time horizon for the economic analysis is limited to 5 years. In addition, the study reflects current medical and surgical treatment regimens for this cohort of patients, which may change.ConclusionsIn this study, we observed that in patients with obesity and T2DM-Ins, bariatric surgery was associated with high rates of postoperative cessation of insulin therapy, which is, in turn, a major driver of overall reductions in direct healthcare cost. Our findings suggest that a strategy utilising bariatric surgery for patients with obesity and T2DM-Ins is cost saving to the national healthcare provider (National Health Service (NHS)) over a 5-year time horizon.

Emma Rose McGlone and colleagues report the clinical and cost- effectiveness of bariatric surgery for patients with Type 2 diabetes.     

Metabolic surgery: Quo Vadis?

The impact of bariatric surgery beyond its effect on weight loss has entailed a change in the way of regarding it. The term metabolic surgery has become more popular to designate those interventions that aim at resolving diseases that have been traditionally considered as of exclusive medical management, such as type 2 diabetes mellitus (T2D). Recommendations for metabolic surgery have been largely addressed and discussed in worldwide meetings, but no definitive consensus has been reached yet. Rates of diabetes remission after metabolic surgery have been one of the most debated hot topics, with heterogeneity being a current concern. This review aims to identify and clarify controversies regarding metabolic surgery, by focusing on a critical analysis of T2D remission rates achieved with different bariatric procedures, and using different criteria for its definition. Indications for metabolic surgery for patients with T2D who are not morbidly obese are also discussed.     

Obstructive Sleep Apnea in Extremely Overweight Adolescents undergoing Bariatric Surgery

Objectives: To determine the prevalence of obstructive sleep apnea (OSA) in extremely overweight adolescents and to examine the effect of significant weight loss on OSA severity. Research Methods and Procedures: We reviewed the anthropometric and polysomnographic data on all extremely overweight adolescents who underwent laparoscopic Roux en Y gastric bypass surgery at Cincinnati Children's Hospital Medical Center from July 2001 to September 2004. Repeat polysomnograms were performed after significant weight loss. Comparisons were made between pre‐ and postoperative polysomnographic data. Results: Nineteen of 34 patients (55%) who underwent bariatric surgery were diagnosed with OSA. Subsequent to surgery, 10 of these patients returned for follow‐up polysomnographic testing. After significant weight loss (mean, 58 kg), OSA severity markedly decreased in all patients (median apnea‐hypopnea index at baseline vs. after weight loss, 9.1 vs. 0.65). Discussion: Our study indicated that OSA was highly prevalent in extremely overweight adolescents meeting eligibility criteria for bariatric surgery. The significant weight loss after gastric bypass was associated with a marked reduction in OSA severity.     

Lower Fetuin-A,Retinol Binding Protein 4 and Several Metabolites after Gastric Bypass Compared to Sleeve Gastrectomy in Patients with Type 2 Diabetes

Background

Bypass of foregut secreted factors promoting insulin resistance is hypothesized to be one of the mechanisms by which resolution of type 2 diabetes (T2D) follows roux-en-y gastric bypass (GBP) surgery.

Aim

To identify insulin resistance-associated proteins and metabolites which decrease more after GBP than after sleeve gastrectomy (SG) prior to diabetes remission.

Methods

Fasting plasma from 15 subjects with T2D undergoing GBP or SG was analyzed by proteomic and metabolomic methods 3 days before and 3 days after surgery. Subjects were matched for age, BMI, metformin therapy and glycemic control. Insulin resistance was calculated using homeostasis model assessment (HOMA-IR). For proteomics, samples were depleted of abundant plasma proteins, digested with trypsin and labeled with iTRAQ isobaric tags prior to liquid chromatography-tandem mass spectrometry analysis. Metabolomic analysis was performed using gas chromatography-mass spectrometry. The effect of the respective bariatric surgery on identified proteins and metabolites was evaluated using two-way analysis of variance and appropriate post-hoc tests.

Results

HOMA-IR improved, albeit not significantly, in both groups after surgery. Proteomic analysis yielded seven proteins which decreased significantly after GBP only, including Fetuin-A and Retinol binding protein 4, both previously linked to insulin resistance. Significant decrease in Fetuin-A and Retinol binding protein 4 after GBP was confirmed using ELISA and immunoassay. Metabolomic analysis identified significant decrease of citrate, proline, histidine and decanoic acid specifically after GBP.

Conclusion

Greater early decrease was seen for Fetuin-A, Retinol binding protein 4, and several metabolites after GBP compared to SG, preceding significant weight loss. This may contribute to enhanced T2D remission observed following foregut bypass procedures.     

Impact of bariatric surgery on type 2 diabetes

The management and prevention of diabetes through lifestyle modifications and weight loss should be the mainstay of therapy in appropriate candidates. Although the results from the Diabetes Prevention Trial and the Finnish Prevention Study support this approach, over 95% of patients not participating in a prevention research study are unable to achieve and maintain any significant weight loss over time. Bariatric surgery for weight loss is an emerging option for more sustainable weight loss in the severely obese subject, especially when obesity is complicated by diabetes or other co-morbidities. The two most common types of procedures currently used in the United States are adjustable gastric bands and Roux-en-Y gastric bypass. These procedures can be performed laparoscopically, further reducing the perioperative morbidity and mortality associated with the surgery. While the gastric bypass procedure usually results is greater sustained weight loss (40–50%) than adjustable gastric banding (20–30%), it also carries greater morbidity and nutritional/metabolic issues, such as deficiencies in iron, B12, calcium, and vitamin D. Following bariatric surgery most subjects experience improvements in diabetes control, hypertension, dyslipidemia, and other obesity-related conditions. In patients with impaired glucose tolerance most studies report 99–100% prevention of progression to diabetes, while in subjects with diabetes prior to surgery, resolution of the disease is reported in 64–93% of the cases. While improvements in insulin resistance and beta-cell function are related to surgically induced weight loss, the rapid post-operative improvement in glycemia is possibly due to a combination of decreased nutrient intake and changes in gut hormones as a result of the bypassed intestine. Post-prandial hyperinsulinemic hypoglycemia associated with nesidioblastosis has been described in a series of patients following gastric bypass surgery, and may be related to the described changes in GLP-1 and other gut hormones.     

The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones

Bariatric surgery for obesity has proved to be an extremely effective method of promoting long-term weight reduction with additional beneficial metabolic effects, such as improved glucose tolerance and remission of type 2 diabetes. A range of bariatric procedures are in common use, including gastric banding, sleeve gastrectomy and the Roux-en-Y gastric bypass. Although the mechanisms underlying the efficacy of bariatric surgery are unclear, gastrointestinal and pancreatic peptides are thought to play an important role. The aim of this review is to summarise the effects of different bariatric surgery procedures upon gastrointestinal and pancreatic peptides, including ghrelin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic hormone (GIP), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), oxyntomodulin, insulin, glucagon and somatostatin.     

减重手术改善肥胖症认知功能障碍及其机制

越来越多的证据表明，肥胖会对大脑功能和结构产生负面影响。肥胖个体在食物线索、味觉和嗅觉、静息状态活动和功能连接方面显示出异常的神经反应，同时在决策、抑制控制、学习、记忆和注意力等认知任务中表现出异常。减重手术作为一种专门的治疗方案，可以改变消化系统解剖和生理机制，从而限制食物摄入或改变营养吸收来实现短期和长期的减重效果，改善并发症，降低死亡率，并提高生活质量。最近的研究表明，减重手术对改善肥胖症相关的认知功能障碍具有积极的影响。本文概述了肥胖与认知功能之间的关联，并重点阐述了近年来减重手术改善肥胖相关认知损伤的研究进展。涉及的内容包括奖励处理、食物摄入控制、大脑区域对认知功能的调控、大脑结构异常的恢复、激素调节改变以及对肠道微生物组成的改变，这些变化可能会影响脑功能和认知过程，这些研究成果有望为改善肥胖症患者的认知功能提供新的治疗策略和临床指导。     

Bariatric Surgery Improves the Cavernosal Neuronal,Vasorelaxation, and Contraction Mechanisms for Erectile Dysfunction As Result of Amelioration of Glucose Homeostasis in a Diabetic Rat Model

Background

Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM). However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum.

Material and Method

Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10) or a bariatric surgery group (gastric bypass surgery, n = 15). Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT). The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson''s trichrome staining. Endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Rho kinase, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in the corpus cavernosum were assayed by using western blot and ELISA.

Results

The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002). The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014), and this was lower than the preoperative value (p = 0.037). The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021), and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025). Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively). Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032).

Conclusion

In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to structural and biochemical changes in the corpus cavernosum, and thus, results in improvement of erectile dysfunction associated with T2DM.     

Melanocortin-4 Receptor Mutations and Polymorphisms Do Not Affect Weight Loss after Bariatric Surgery

Bariatric surgery is the most effective long term weight-loss therapy for severe and morbidly obese patients. Melanocortin-4 Receptor (MC4R) mutations, the most frequent known cause of monogenic obesity, affect the regulation of energy homeostasis. The impact of such mutations on weight loss after bariatric surgery is still debated.The objective is to determine the impact of MC4R status on weight loss in obese subjects over one year after bariatric surgery.A total of 648 patients, who were referred to bariatric surgery in a single clinical nutrition department, were genotyped for their MC4R status. The following four groups were categorized: functional MC4R mutations, MC4R single nucleotide polymorphisms (SNPs): Val103Ile (V103L) and Ile251Leu (I251L), MC4R variant rs17782313 (downstream of MC4R) and MC4R SNP A-178C on the promoter. Each patient was matched with two randomly paired controls without mutation. Matching factors were age, sex, baseline weight and type of surgery procedure (Roux-en-Y gastric bypass and adjustable gastric banding). We compared weight loss between cases and controls at 3, 6 and 12 months after surgery.Among 648 patients, we identified 9 carriers of functional MC4R mutations, 10 carriers of MC4R V103L and I251L SNPs, 7 carriers of the rs17792313 variant and 22 carriers of the A-178C SNP. Weight loss at 3, 6 and 12 months did not differ between cases and controls, whatever the MC4R mutations.This is the first case-control study to show that MC4R mutations and polymorphisms do not affect weight loss and body composition over one year after bariatric surgery.     

Increased Postprandial Energy Expenditure May Explain Superior Long Term Weight Loss after Roux-en-Y Gastric Bypass Compared to Vertical Banded Gastroplasty

Background and Aims

Gastric bypass results in greater weight loss than Vertical banded gastroplasty (VBG), but the underlying mechanisms remain unclear. In addition to effects on energy intake the two bariatric techniques may differentially influence energy expenditure (EE). Gastric bypass in rats increases postprandial EE enough to result in elevated EE over 24 hours. This study aimed to investigate alterations in postprandial EE after gastric bypass and VBG in humans.

Methods

Fourteen women from a randomized clinical trial between gastric bypass (n = 7) and VBG (n = 7) were included. Nine years postoperatively and at weight stability patients were assessed for body composition and calorie intake. EE was measured using indirect calorimetry in a respiratory chamber over 24 hours and focused on the periods surrounding meals and sleep. Blood samples were analysed for postprandial gut hormone responses.

Results

Groups did not differ regarding body composition or food intake either preoperatively or at study visit. Gastric bypass patients had higher EE postprandially (p = 0.018) and over 24 hours (p = 0.048) compared to VBG patients. Postprandial peptide YY (PYY) and glucagon like peptide 1 (GLP-1) levels were higher after gastric bypass (both p<0.001).

Conclusions

Gastric bypass patients have greater meal induced EE and total 24 hours EE compared to VBG patients when assessed 9 years postoperatively. Postprandial satiety gut hormone responses were exaggerated after gastric bypass compared to VBG. Long-term weight loss maintenance may require significant changes in several physiological mechanisms which will be important to understand if non-surgical approaches are to mimic the effects of bariatric surgery.     

Impact of Weight loss Trajectory Following Randomization to Bariatric Surgery on Long-Term Diabetes Glycemic and Cardiometabolic Parameters

Objective: It is unclear whether acute weight loss or the chronic trajectory of weight loss after bariatric surgery is associated with long-term type 2 diabetes mellitus (T2DM) glycemic improvement. This ancillary study of the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial aimed to answer this question.Methods: In STAMPEDE, 150 patients with T2DM were randomized to bariatric surgery, and 96 had 5-year follow-up. Data post–Roux-en-Y gastric bypass (RYGB, n = 49) and sleeve gastrectomy (SG, n = 47) were analyzed. We defined percent weight loss in the first year as negative percent decrease from baseline weight to lowest weight in the first year. Percent weight regain was positive percent change from lowest weight in the first year to fifth year. Weight change was then correlated with cardiometabolic (CM) and glycemic outcomes at 5 years using Spearman rank correlations and multivariate analysis.Results: In both RYGB and SG, less weight loss in the first year positively correlated with higher 5-year glycated hemoglobin (HbA1c) (RYGB, β = +0.13; P<.001 and SG, β = 0.14; P<.001). In SG, greater weight regain from nadir positively correlated with higher HbA1c (β = 0.06; P = .02), but not in RYGB. Reduced first-year weight loss was also correlated with increased 5-year triglycerides (β = 1.81; P = .01), but not systolic blood pressure. Weight regain did not correlate with CM outcomes.Conclusion: Acute weight loss may be more important for T2DM glycemic control following both RYGB and SG as compared with weight regain. Clinicians should aim to assist patients with achieving maximal weight loss in the first year post-op to maximize long-term health of patients.Abbreviations: BMI = body mass index; HbA1c = glycated hemoglobin; RYGB = Roux-en-Y gastric bypass; SBP = systolic blood pressure; SG = sleeve gastrectomy; STAMPEDE = Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently; T2DM = type 2 diabetes mellitus; TG = triglyceride     

Increased PTH and 1.25(OH)(2)D levels associated with increased markers of bone turnover following bariatric surgery

The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH)(2)D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH)(2)D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)(2)D levels and increased bone turnover markers.     

The influence of bariatric surgery on calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity

INTRODUCTION: Obese patients may have abnormal calcium homeostasis because of unbalanced diet and decreased sun exposure. Bariatric surgery itself may lead to disturbances in calcium homeostasis (and in consequence changes in bone mass) or increase preexisting metabolic derangements. The aim of the study was: 1. To assess calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity. 2. To determine the impact of bariatric surgery on parameters mentioned above. 3. To establish recommendations for supplementation with calcium and vitamin D in morbidly obese patients after bariatric surgery. MATERIAL AND METHODS: Serum calcium, parathormone (PTH), vitamin D (25(OH)D), biochemical markers of bone turnover (beta-CrossLaps as a marker of bone resorption and osteocalcin as a marker of bone formation) and urine calcium as well as fat mass, lean mass and bone mineral content (by DXA) were measured before bariatric surgery of the stomach (VBG or GBP) in 57 morbidly obese patients (48 women, 9 men; mean age 35.9 y). The same procedures were repeated six months after operation in 28 of them (24 women, 4 men). Daily calcium intake was also determined based on food questionnaire. RESULTS: Biochemical findings in the group of patients before bariatric surgery were as follows: serum calcium, beta-CrossLaps and urine calcium were within normal range, PTH concentration was increased to 81.0 pg/ml and 25(OH)D as well as osteocalcin concentration decreased (4.9 ng/ml and 13.6 ng/ml, respectively). Six months after bariatric surgery there was no change in serum and urine calcium, PTH concentration decreased to normal level (46.8 pg/ml), 25(OH)D concentration increased to 6.5 ng/ml (not significant) and still remained below normal range. Markers of bone turnover--both resorption and formation--increased (beta-CrossLaps over normal range to 0.594 ng/ml, osteocalcin to normal range 26.8 ng/ml). Daily calcium intake was below RDA before and after bariatric procedure. CONCLUSIONS: 1. Patients with morbid obesity have secondary hyperparathyroidism and deficiency of vitamin D. 2. Abrupt weight loss after bariatric surgery is accompanied by the regression of secondary hyperparathyroidism, decrease of the deficiency of vitamin D and increase in bone turnover. 3. Supplementation with vitamin D and calcium is recommended for patients with morbid obesity after bariatric surgery.