Diabetes Remission Rates Research Articles

Type 2 diabetes mellitus outcomes after laparoscopic gastric bypass in patients with BMI

Mild obesity (BMI 30-34.9kg/m2) is highly prevalent worldwide and is associated with type 2 diabetes mellitus. The efficacy of bariatric surgery remains unclear, including among Mexicans. The criteria for diabetes remission are inconsistent, as they are based on different thresholds for glycated hemoglobin, with remission rates ranging from 43 to 73%. Mildly obese patients with type 2 diabetes mellitus who underwent laparoscopic gastric bypass were prospectively analyzed. The primary objective was to determine the impact of surgery on their metabolic profiles. Demographic, clinical, and biochemical parameters were measured at baseline and at 3, 6, 9, 12, and 18months. Diabetes remission rate was defined as an HbA1c <5.7%. Complications within 30days and weight loss (% total weight loss) were also analyzed. Twenty-three Mexican patients underwent surgery. Of the 19 patients, evaluable at 18months, nine (47.4%) achieved complete diabetes remission, seven (36.8%) showed partial remission, and three (15.8%) showed improvement. Significant improvements in lipid profile, cardiovascular risk, blood pressure, and every metabolic parameter were observed, beginning at the first month and throughout the study. The final total percentage weight loss was 24.9%. Three patients (13%) experienced complications, but none required reoperation or died. Laparoscopic gastric bypass is a safe and effective method to improve the metabolic profile of mildly obese Mexican patients with type 2 diabetes mellitus, inducing high remission rates even when the strictest model is used.

Efficacy of Sleeve Gastrectomy with Duodenal-Jejunal Bypass for the Treatment of Obese Severe Diabetes Patients in Japan: a Retrospective Multicenter Study.

The incidence of obesity with type 2 diabetes (T2DM) is increasing in Japan. The main bariatric surgery procedures in Japan are laparoscopic sleeve gastrectomy (LSG) and LSG with duodenal-jejunal bypass (LSG/DJB) because of the high incidence of gastric cancer and difficulty exploring a remnant stomach after gastric bypass. However, few studies have compared the antidiabetic effect of LSG/DJB with LSG alone. The purpose of this study is to compare the antidiabetic effect of LSG/DJB with that of LSG alone in Japanese obese diabetic patients. This was a retrospective multicenter study including 298 cases: 177 and 121 LSG and LSG/DJB cases, respectively. We investigated the antidiabetic effect of these two procedures at 12months after surgery. Univariate and multivariate analyses were done to evaluate the predictive factors of T2DM remission. The diabetes remission rate at 12months after surgery was 80.8% for LSG and 86.0% for LSG/DJB. Insulin use and HbA1c ≤6.7% were significant predictive factors in multivariate analysis for all patients. In patients with ABCD score ≥6, the diabetes remission rate was 94.8% and there was no difference between procedures. Only duration of diabetes and insulin use were significant predictive factors both in univariate and multivariate analyses. However, in cases with ABCD score ≤5, the remission rate was 70.3% and procedure type was the most significant predictive factor for diabetes remission (odds ratio [OR] 5.140). Although both LSG and LSG/DJB have good antidiabetic effects in Japanese obese patients, LSG/DJB is more effective for patients with lower ABCD scores.

Effect of laparoscopic sleeve gatrectomy on type 2 diabetes mellitus in obese patients with body mass index less than 40 kg/m2

To evaluate the effect of laparoscopic sleeve gastrectomy(LSG) on type 2 diabetes mellitus (T2DM) in patient with a body mass index(BMI) less than 40 kg/m2. Twenty four obese patients with T2DM and BMI less than 40 kg/m2 received LSG between 1 January 2011 and 1 September 2013 at the Department of General Surgery in Chinese PLA General Hospital. The clinical data and 3-year follow-up outcomes regarding weight loss and remission of diabetes were retrospectively analyzed. There were 10 males and 14 females with a median age of 40.8(35 to 48) years. The preoperative body weight and BMI was(99.9±15.0) kg and (34.4±2.8) kg/m2, respectively. The median duration of type 2 diabetes was 4.3(2 to 15) years. The preoperative fasting blood glucose and glycosylated hemoglobin(HbAlc) was (11.4±1.3) mmol/L and (8.7±0.8)%, respectively. All these patients were preoperatively diagnosed as T2DM by the multidisciplinary experts of the surgical treatment team for obesity and diabetes in our center. All these patients were eligible for surgical treatment through the screening and evaluation by the multidisciplinary joint outpatient service. All the procedures were successfully completed without conversion to laparotomy. There were no severe postoperative complications. The mean fasting blood glucose was (6.4±1.8) mmol/L, (6.1±1.7) mmol/L, (6.0±1.5) mmol/L, (5.9±1.4) mmol/L and (6.0±1.4) mmol/L, respectively, at 6, 9, 12, 24 and 36 months after operation. The mean HbA1c in the same observation intervals was (6.6±1.1)%, (6.2±1.2)%, (6.1±1.2)%, (6.0±1.3)% and (6.1±1.3)%, respectively. The body weight was (89.4±11.4) kg, (86.3±10.6) kg, (83.1±10.2) kg,(80.6±9.8) kg and (81.3±10.1) kg, respectively. The corresponding BMI was (30.8±1.6) kg/m2, (29.8±1.5) kg/m2, (28.7±1.5) kg/m2, (27.8±1.8) kg/m2 and (28.1±1.8) kg/m2, respectively. The %EWL was (36.7±8.7)%, (47.6±12.5)%, (58.8±16.4)%, (67.2±20.3)% and (64.8±21.5)%, respectively. The overall remission rate of diabetes at 6, 9, 12, 24 and 36 months was 50.0%(12/24), 79.2%(19/24), 70.8%(17/24), 66.7%(16/24) and 62.5%(15/24), respectively. The complete remission rate was 33.3%(8/24), 50.0%(12/24), 54.2%(13/24), 45.8%(11/24) and 50.0%(12/24), respectively. For patients with a duration of T2DM shorter than 5 years, the overall remission rate at 9, 12 and 24 months after operation was 10/10, 9/10 and 9/10, respectively, significantly higher than that of patients with a duration of 11-15 years (2/6, 2/6 and 2/6, Fisher's exact tests, P=0.008, 0.036 and 0.036, respectively). The present study confirms the efficacy of LSG in the treatment of T2DM patients with a BMI less than 40 kg/m2.

Clinical investigation on minimal invasive surgery for Cushing syndrome caused by adrenocortical adenoma: experience of 121 cases in a single center

Objective To explore the efficacy and safety of minimal invasive adrenal sparing surgery for the treatment of Cushing syndrome caused by adrenocortical adenoma. Methods Patients who underwent minimal invasive adrenal surgery for adrenocortical adenoma in our institution from January 2010 to December 2015 were retrospectively analyzed. Preoperative, intraoperative, and postoperative variables were reviewed from the database. The mean patient age at diagnosis was 39 years and male∶female ratio was 10∶111. Of the 121 adenomas, 50 were located in the right adrenal and 71 in the left. The mean tumor size was 2.6 cm.84 cases had hypertension (69.4%), 36 cases had diabetes mellitus (29.8%), and 45 cases had obesity (37.2%). Postoperative follow-up was performed by evaluating adrenal gland function and imaging. Results Mininal invasive partial adrenalectomy was performed in 121 cases and the success rate of operation was 99.2%(120/121). Sixty-two cases received operation through retroperitoneal approach, and 59 cases were through transperitoneal approach. The median operative time was 50 min with a median blood loss of 50 ml. The mean postoperative hospital stay were (5.0±3.2) days.The vascular injury occurred in 2 cases (1 case in each surgical approach), while the abdominal organ injury occurred in 2 cases with 1 case of spleen injury and 1 case of liver injury (both in transperitoneal approach). Postoperative complications were observed in 6 cases: 1 case of deep venous thrombosis, 1 case of wound hematoma, 4 cases of wound infection. Cortisol substitution was given in 2 to 12 months (mean 6.2 months) postoperatively. One year after operation, the remission rate of hypertension, diabetes and obesity was 58.3%(49/84), 30.6%(11/36) and 60.0%(30/45), respectively. Conclusions Minimal invasive adrenal surgery using retroperitoneal and transperitoneal laparoscopic technique can be performed with low morbidity and achieve an excellent outcome.The perioperative hormone therapy may also play an important role. Key words: Cushing syndrome; Partial adrenalectomy; Transperitoneal laparoscopic surgery; Retroperitoneal laparoscopic surgery

Type 2 diabetes remission rates 1-year post-Roux-en-Y gastric bypass and validation of the DiaRem score: the Ontario Bariatric Network experience.

Roux-en-Y gastric bypass (RYGB) is associated with the remission of type 2 diabetes mellitus (DM). There are a number of scoring systems available that help predict type 2 diabetes remission rates after bariatric surgery; however, relatively few have been validated externally. The DiaRem score, comprised of four preoperative variables (age, haemoglobin A1c [HbA1c], sulfonylurea and insulin-sensitizing agent use and insulin use), allows for the identification of patients who are most likely to have DM remission following RYGB. Our primary objective was to determine the variables predictive of DM remission 1 year post-RYGB, determine how well the DiaRem score predicts DM remission 1 year post-RYGB and identify the optimal cut-off DiaRem score. The study is based on results of RYGB performed across multiple centres in Ontario, Canada, overseen by the Centre for Surgical Invention and Innovation in Hamilton, with direction from the Ontario Bariatric Network. Regression analysis was used to determine the predictive value of demographic and clinical variables and that of the DiaRem score. The optimal DiaRem cut-off score was determined using sensitivity and specificity analysis. Of 3874 patients in the Ontario Bariatric Registry between January 2010 and February 2015, 915 had complete 1-year follow-up data. Among these, 15 were not classified as having DM at baseline and were excluded. Of the remaining 900 patients with type 2 diabetes and who underwent RYGB surgery, 333 (37.0%) had DM remission at 1-year follow-up. Three of four DiaRem variables (age, HbA1c, insulin use), in addition to use of any hypoglycaemic agent, were associated with DM remission. DiaRem score had moderate predictive value. A DiaRem score cut-off of <5 had a sensitivity of 71.8% and specificity of 71.3%. This study provides guidance to clinicians in using the DiaRem score to inform the selection and prioritization of patients to ensure timely access to bariatric surgery for those who are likely to benefit the most.

Decreased Cardiovascular Risk after Roux-en-Y Gastric Bypass Surgery in Chinese Diabetic Patients with Obesity.

Background The influence of bariatric surgery on cardiovascular risks in Chinese diabetic patients remains unclear. Here, we aimed to explore the impact of Roux-en-Y gastric bypass surgery (RYGB) on cardiovascular risks in Chinese diabetic patients with obesity. Methods Twenty Chinese patients with T2DM and obesity undergoing RYGB surgery were included in this study. Cardiovascular risk factors were measured before and 18 months after surgery. A 10-year cardiovascular risk was calculated by the UKPDS risk engine. Linear regression analysis was performed on CHD risk, stroke risk, and baseline metabolic parameters. Results The complete remission rate of diabetes was 90% after RYGB surgery, with significant improvements in blood pressure, BMI, glucose, and lipid metabolism (P < 0.05). The 10-year cardiovascular risk of coronary heart disease reduced from 13.05% to 3.81% (P = 0.001) and the 10-year risk of stroke reduced from 19.66% to 14.22% (P = 0.002). In subgroup analysis, Chinese diabetic patients who were women, <45 years old, with BMI < 35 kg/m2, and DM duration > 5 years, using noninsulin therapy presented more obvious improvements in the 10-year cardiovascular risk after RYGB surgery. WHR, age, LDL-C, and HbA1c were the most important factors influencing CHD or stroke risk after RYGB surgery (P < 0.01). Conclusion RYGB surgery is an effective treatment to reduce cardiovascular risk in Chinese diabetic patients with obesity.

Oligofructose as an adjunct in treatment of diabetes in NOD mice.

In type 1 diabetes, restoration of normoglycemia can be achieved if the autoimmune attack on beta cells ceases and insulin requirement is met by the residual beta cells. We hypothesize that an adjunctive therapy that reduces insulin demand by increasing insulin sensitivity will improve the efficacy of an immunotherapy in reversing diabetes. We tested the gut microbiota-modulating prebiotic, oligofructose (OFS), as the adjunctive therapy. We treated non-obese diabetic mice with an immunotherapy, monoclonal anti-CD3 antibody (aCD3), with or without concurrent dietary supplement of OFS. After 8 weeks of OFS supplement, the group that received both aCD3 and OFS (aCD3 + OFS) had a higher diabetes remission rate than the group that received aCD3 alone. The aCD3 + OFS group had higher insulin sensitivity accompanied by reduced lymphocytic infiltrate into the pancreatic islets, higher beta-cell proliferation rate, higher pancreatic insulin content, and secreted more insulin in response to glucose. The addition of OFS also caused a change in gut microbiota, with a higher level of Bifidobacterium and lower Clostridium leptum. Hence, our results suggest that OFS can potentially be an effective therapeutic adjunct in the treatment of type 1 diabetes by improving insulin sensitivity and beta-cell function, leading to improved glycemic control.

Reconciliation of Type 2 Diabetes Remission Rates in Studies of Roux-en-Y Gastric Bypass.

Bariatric surgery may induce remission of type 2 diabetes in obese patients. However, estimates of remission rates reported in the literature range from 25 to 81%, contributing to the uncertainty patients and physicians both face as they assess treatment options. This analysis attempts to reconcile the seemingly disparate rates of diabetes remission reported in studies of Roux-en-Y gastric bypass (RYGB) surgery. It examines variation in the methodologies used to derive the estimates and proposes outcomes that should be reported by all studies. A literature review yielded 10 large (n > 100), recent (index surgery since 2000) studies of diabetes remission after RYGB. These studies differed in definitions of remission (partial vs. complete), lengths of follow-up (1 year vs. ≥3 years), reported outcomes (cumulative vs. prevalent remission), and risks of attrition bias. Reported rates of partial remission were 10-30 percentage points higher than rates of complete remission. Study duration explained 69% of the variability in cumulative remission rates, plateauing at 3 years. Adjustment for attrition increased the explained variability to 87%. Attrition-adjusted, 3-year cumulative, complete remission rates ranged from 63 to 65%; however, this does not account for relapse. Attrition-adjusted, 3-year prevalent complete remission rates that accounted for relapse were 23%. Variations in reported rates of diabetes remission after RYGB are primarily related to definitions and study duration. Future studies should report both cumulative and prevalent remission to aid decision making and more easily compare studies.

Is Early Bariatric Surgery the Answer for Diabetes in Obesity?

The article by Aung et al1 in this issue of JAMA Surgery continues the excellent clinical research from the group in Taiwan.Multiple randomized studies havedemonstrated the efficacy of bariatric surgery in treatingtype2diabetes (T2D), and the term metabolic surgery is being increasingly used, although it is not alwayswell defined. In their introduction, Aung and colleagues define this surgery as “the application of bariatric surgical procedures to patients with a body mass index (BMI) (calculated as weight in kilograms divided by height inmeters squared) of less than 35who also have severe comorbidities.”1 We feel defining it as the manipulation of the gastrointestinal tractwith the goal of treatingT2D isnot only more appropriate but also more representative of what the authors have evaluated in their study. In this article, the authors compare the outcomes of bariatric surgery in those with early-onset T2D (age <40 years) and late-onset T2D (age ≥40 years) and conclude that early intervention leads to better ratesofcompletediabetes remission (hemoglobinA1c<6.0% [toconvert toproportionof totalhemoglobin,multiplyby0.01] without antidiabetic medication).1 Previous studies have shown that the duration of diabetes,useof insulin,degreeofpostoperativeweight loss, andtype of surgeryperformed can influence the remission rates of diabetes following bariatric surgery.2 The studybyAung and colleagues shows that age at diabetes onset canbeused as an additionalpredictorof success,whichsuggestseitheradifference in the pathophysiology of early-onset diabetes or preserved pancreatic reserve in young patients, as inferred by higher C-peptide levels. These data are in keepingwith a 2016 study by Inge et al3 showing a 95%diabetes remission rate at 3 years in their adolescent cohort (aged 13-19 years). Taken together, there appears to be an amassing body of data in support of early consideration of bariatric surgery for obese individualswithT2D. This not only has thepotential to reduce their long-termneed for multiple medications but also has the potential to significantly mitigate their risks of health complications compounded over their lifetime. Thestudy’s5-yearoutcomesareamajor strengthof this article. Although the follow-up ratewas around 50%, these data pointsarerareandvaluabletothefield.Theauthorsaretobecongratulatedforcollectingthesedata,whichreveal thatT2Drecurrence,anAchillesheelofbariatricsurgery,occurseveninthemost idealofpatients—onewithearlyonsetandshortdurationofT2D. Thus, identifyingmarkersof long-termT2Dremissionis,andwill continue to be, an area of heavy interest in the field.

A5185 - Type 2 diabetes remission rate after bariatric surgery in Hospital DIPRECA, CHILE

A5185 - Type 2 diabetes remission rate after bariatric surgery in Hospital DIPRECA, CHILE

One Year Follow-up Results after Sleeve Gastrectomy in Type 2 Diabetes Mellitus Patients with Morbid Obesity

Abstract Background and aims: Bariatric surgery has been shown to be superior to nonsurgical approaches in terms of weight loss and remission of type 2 diabetes (T2DM) and metabolic syndrome. This prospective, single-center, follow-up study assessed percentage of excessive weight loss (%EWL), glycosylated hemoglobin (HbA1c) levels, prescribed antidiabetes drugs and diabetes remission rates in obese T2DM patients who underwent laparoscopic sleeve gastrectomy. Materials and methods: 81 patients were selected and data recorded preoperatively, 3, 6 and 12 months postoperatively. Results: We recorded - 69.3% EWL at 12 months (p&lt;0.0001 compared to baseline) and a fall of HbA1c from 8.1±2.6% to 6.7±2.8% at 12 months postoperatively (p&lt;0.0001). The percentage of patients with HbA1c&lt;6.5% showed an increase to 40.7% (p=0.0004) and the one year T2DM remission rate was 20.9% (p=0.0012). Conclusions: Laparoscopic sleeve gastrectomy can significantly reduce the BMI, with near 70% EWL and near 21% T2DM remission rate in 1 year.

Costs and outcomes of increasing access to bariatric surgery for obesity: cohort study and cost-effectiveness analysis using electronic health records

BackgroundBariatric surgery is known to be an effective treatment for extreme obesity but access to these procedures is currently limited.ObjectiveThis study aimed to evaluate the costs and outcomes of increasing access to bariatric surgery for severe and morbid obesity.Design and methodsPrimary care electronic health records from the UK Clinical Practice Research Datalink were analysed for 3045 participants who received bariatric surgery and 247,537 general population controls. The cost-effectiveness of bariatric surgery was evaluated in severe and morbid obesity through a probabilistic Markov model populated with empirical data from electronic health records.ResultsIn participants who did not undergo bariatric surgery, the probability of participants with morbid obesity attaining normal body weight was 1 in 1290 annually for men and 1 in 677 for women. Costs of health-care utilisation increased with body mass index category but obesity-related physical and psychological comorbidities were the main drivers of health-care costs. In a cohort of 3045 adult obese patients with first bariatric surgery procedures between 2002 and 2014, bariatric surgery procedure rates were greatest among those aged 35–54 years, with a peak of 37 procedures per 100,000 population per year in women and 10 per 100,000 per year in men. During 7 years of follow-up, the incidence of diabetes diagnosis was 28.2 [95% confidence interval (CI) 24.4 to 32.7] per 1000 person-years in controls and 5.7 (95% CI 4.2 to 7.8) per 1000 person-years in bariatric surgery patients (adjusted hazard ratio was 0.20, 95% CI 0.13 to 0.30;p &lt; 0.0001). In 826 obese participants with type 2 diabetes mellitus who received bariatric surgery, the relative rate of diabetes remission, compared with controls, was 5.97 (95% CI 4.86 to 7.33;p &lt; 0.001). There was a slight reduction in depression in the first 3 years following bariatric surgery that was not maintained. Incremental lifetime costs associated with bariatric surgery were £15,258 (95% CI £15,184 to £15,330), including costs associated with bariatric surgical procedures of £9164 per participant. Incremental quality-adjusted life-years (QALYs) were 2.142 (95% CI 2.031 to 2.256) per participant. The estimated cost per QALY gained was £7129 (95% CI £6775 to £7506). Estimates were similar across gender, age and deprivation subgroups.LimitationsIntervention effects were derived from a randomised trial with generally short follow-up and non-randomised studies of longer duration.ConclusionsBariatric surgery is associated with increased immediate and long-term health-care costs but these are exceeded by expected health benefits to obese individuals with reduced onset of new diabetes, remission of existing diabetes and lower mortality. Diverse obese individuals have clear capacity to benefit from bariatric surgery at acceptable cost.Future workFuture research should evaluate longer-term outcomes of currently used procedures, and ways of delivering these more efficiently and safely.FundingThe National Institute for Health Research (NIHR) Health Services and Delivery Research programme. Martin C Gulliford and A Toby Prevost were supported by the NIHR Biomedical Research Centre at Guy’s and St Thomas’ Hospitals. Peter Littlejohns was supported by the South London Collaboration for Leadership in Applied Health Research and Care. The funders did not engage in the design, conduct or reporting of the research.

Total gastrectomy improves glucose metabolism on gastric cancer patients: a nationwide population-based study

BackgroundTotal gastrectomy (TG) is potentially curative for upper gastric cancer (GC) and includes both stomach removal and enteral bypass reconstruction. Therefore, similar to bariatric surgery, TG may contribute to a change in glucose metabolism. ObjectivesThe aim of this population-based study was to determine if there are any changes in glucose metabolism after TG in patients with GC. SettingNationwide population database. MethodsWe conducted a nationwide cohort study using data from Taiwan’s National Health Insurance Research Database collected between 2000 and 2011. Two cohorts were sampled for further analysis of changes in glucose metabolism after TG, including a diabetes group and non-diabetes group. ResultsA total of 8593 patients with TG were identified. Of the 579 patients with diabetes with GC, 178 (30.7%) achieved diabetes remission after TG. On Cox multivariate analysis, patients aged 50 to 64 years (odds ratio [OR], .48; 95% confidence interval [CI], .31–.75; P<.01) and those who used insulin (OR, .31; 95% CI, .19–.51; P<.01) had lower rates of diabetes remission, whereas liver cirrhosis patients had higher rates of diabetes remission (OR, 1.77; 95% CI, 1.16–2.69; P<.01). On the other hand, patients without diabetes but who had GC (n = 1565) had lower rates of newly diagnosed diabetes after TG compared with the general population as assessed by control-to-case analysis (OR, .56; 95% CI, .47–.66; P< .01). ConclusionOur data showed that TG contributes to improved glucose metabolism in patients with GC.

A120 - Early Feeding Post Bariatric Surgery Reduces Length of Stay

patients in the WL group had significantly higher rates (%) of hypertension remission for all procedures: RYGB (46, 46, 51, p1⁄40.035), SG (35, 41, 46, p1⁄40.046) and AGB (17, 18, 24, p1⁄40.029). Conclusions: Preoperative weight loss was associated with a lower adjusted rate of any complication with RYGB but otherwise did not affect rates of any or serious complication with any of the other bariatric procedures. Nor did it affect adjusted rates of diabetes remission with any procedure. However, preoperative weight loss was associated with a significant increase in excess weight loss and remission of hypertension across all procedures. Preoperative weight loss over 5% serves as a useful marker for an enhanced weight loss response to RYGB, SG and AGB.

Bariatric–metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial

Randomised controlled trials have shown that bariatric surgery is more effective than conventional treatment for the short-term control of type-2 diabetes. However, published studies are characterised by a relatively short follow-up. We aimed to assess 5 year outcomes from our randomised trial designed to compare surgery with conventional medical treatment for the treatment of type 2 diabetes in obese patients. We did our open-label, randomised controlled trial at one diabetes centre in Italy. Patients aged 30-60 years with a body-mass index of 35 kg/m(2) or more and a history of type 2 diabetes lasting at least 5 years were randomly assigned (1:1:1), via a computer-generated randomisation procedure, to receive either medical treatment or surgery by Roux-en-Y gastric bypass or biliopancreatic diversion. Participants were aware of treatment allocation before the operation and study investigators were aware from the point of randomisation. The primary endpoint was the rate of diabetes remission at 2 years, defined as a glycated haemaglobin A1c (HbA1c) concentration of 6·5% or less (≤47·5 mmol/mol) and a fasting glucose concentration of 5·6 mmol/L or less without active pharmacological treatment for 1 year. Here we analyse glycaemic and metabolic control, cardiovascular risk, medication use, quality of life, and long-term complications 5 years after randomisation. Analysis was by intention to treat for the primary endpoint and by per protocol for the 5 year follow-up. This study is registered with ClinicalTrials.gov, number NCT00888836. Between April 27, 2009, and Oct 31, 2009, we randomly assigned 60 patients to receive either medical treatment (n=20) or surgery by gastric bypass (n=20) or biliopancreatic diversion (n=20); 53 (88%) patients completed 5 years' follow-up. Overall, 19 (50%) of the 38 surgical patients (seven [37%] of 19 in the gastric bypass group and 12 [63%] of 19 in the bilipancreatic diversion group) maintained diabetes remission at 5 years, compared with none of the 15 medically treated patients (p=0·0007). We recorded relapse of hyperglycaemia in eight (53%) of the 15 patients who achieved 2 year remission in the gastric bypass group and seven (37%) of the 19 patients who achieved 2 year remission in the biliopancreatic diversion group. Eight (42%) patients who underwent gastric bypass and 13 (68%) patients who underwent biliopancreatic diversion had an HbA1c concentration of 6·5% or less (≤47·5 mmol/mol) with or without medication, compared with four (27%) medically treated patients (p=0·0457). Surgical patients lost more weight than medically treated patients, but weight changes did not predict diabetes remission or relapse after surgery. Both surgical procedures were associated with significantly lower plasma lipids, cardiovascular risk, and medication use. Five major complications of diabetes (including one fatal myocardial infarction) arose in four (27%) patients in the medical group compared with only one complication in the gastric bypass group and no complications in the biliopancreatic diversion group. No late complications or deaths occurred in the surgery groups. Nutritional side-effects were noted mainly after biliopancreatic diversion. Surgery is more effective than medical treatment for the long-term control of obese patients with type 2 diabetes and should be considered in the treatment algorithm of this disease. However, continued monitoring of glycaemic control is warranted because of potential relapse of hyperglycaemia. Catholic University of Rome.

CXC chemokine ligand 10 DNA vaccination plus Complete Freund's Adjuvant reverses hyperglycemia in non-obese diabetic mice.

Complete Freund's Adjuvant (CFA) is known to arrest autoimmune diabetes development in non-obese diabetic (NOD) mice. However, CFA alone cannot induce effective remission in diabetic NOD mice. Previously, we reported that anti-CXC chemokine ligand 10 (CXCL10) antibody can promote beta-cell proliferation in NOD mice. In the present study, we aimed to examine whether anti-CXCL10 plus CFA treatment can effectively reverse autoimmune diabetes development. Systemic supply of anti-CXCL10 antibody by CXCL10 DNA vaccination in combination with CFA injection was performed in new-onset diabetic NOD mice. Remission rate of diabetes, histological characteristics of residual insulitis lesions, residual beta-cell mass, and regulatory T cell population in local pancreas were examined. A high frequency of diabetes reversal was observed after combination treatment with anti-CXCL10 plus CFA. In mice showing diabetes reversal, residual beta-cell mass was significantly increased, and some beta-cells were in a proliferative state. Although systemic cytokine profiles were unaffected, the frequency of "hybrid regulatory T cells", i.e. regulatory T cells expressing CXCR3, was significantly increased in local pancreatic lesions. This was possibly associated with the regulation of anti-islet autoimmunity. Anti-CXCL10 plus appropriate immune adjuvant therapy arrested, and reversed, type 1 diabetes development.

Gastric Band Surgery Leads to Improved Insulin Secretion in Overweight People with Type 2 Diabetes.

We aimed to determine the effects of laparoscopic adjustable gastric band (LAGB) on beta-cell function in overweight people with type 2 diabetes and to assess the relationship between baseline beta-cell function and glycemic outcomes. We studied 44 overweight but not obese people with type 2 diabetes who participated in a randomized trial whose primary outcome was the rate of diabetes remission after 2 years of multidisciplinary diabetes care (MDC group) or multidisciplinary care combined with LAGB. Dynamic beta-cell function was assessed by intravenous glucose challenge, and basal beta-cell function (HOMA-B) and insulin sensitivity (HOMA-S) were determined using the homeostatic model. Twelve LAGB participants and two MDC participants were in diabetes remission at 2 years. HOMA-S and the C-peptide response to intravenous glucose increased significantly in LAGB but not in MDC participants. The insulin response to glucose did not change in LAGB participants, whereas their fasting C-peptide/insulin ratio increased. Baseline measures of beta-cell function correlated with diabetes remission but not with reduction in HbA1c following LAGB. In overweight people with diabetes, LAGB improves endogenous beta-cell function after 2 years. Baseline beta-cell function correlated with diabetes remission, but not with HbA1c change following LAGB.

Predictors of remission of diabetes mellitus in severely obese individuals undergoing bariatric surgery: do BMI or procedure choice matter? A meta-analysis.

To compare diabetes remission after bariatric surgery in subjects with body mass index (BMI) of 35 kg/m2 or more or BMI of less than 35 kg/m to determine which predictors are best. BMI is currently the only selection criterion for bariatric surgery in diabetic subjects. Many studies have challenged BMI for predicting diabetes remission. Data sources were PubMed, Cochrane Library, and EMBASE databases from January 1980 to June 2013. The selected studies were randomized controlled trials, controlled clinical trials, or cohort studies with 10 or more patients per arm. Of 1437 screened articles, 94 studies were included with 94,579 patients undergoing surgical procedures (4944 with type 2 diabetes mellitus). Weight, BMI, glycated hemoglobin A1c, fasting glucose, and insulin were abstracted by 2 independent reviewers. The effect size was the percent diabetes remission. Meta-analysis was performed for BMI less than 35 kg/m2 (group 1) and BMI 35 kg/m2 or more (group 2). Diabetes remission was 72% [95% confidence interval (CI), 65-80] in group 1 and 71% (95% CI, 65-77) in group 2. Diabetes resolution was 89% (95% CI, 83-94) after biliopancreatic diversion, 77% (95% CI, 72-82) after Roux-en-Y bypass, 62% (95% CI, 46-79) after gastric banding, and 60% (95% CI, 51-70) after sleeve gastrectomy. The only significant predictor of glycated hemoglobin A1c reduction was waist circumference, lower baseline waist associating with higher reduction. Bariatric surgery determines similar diabetes remission rates in patients with BMI of 35 kg/m2 or more or BMI of less than 35 kg/m2. Baseline BMI is unrelated to diabetes remission. The association of baseline waist circumference with glycated hemoglobin A1c reduction is likely due to selection bias. Bariatric or metabolic effects of the surgical procedures appear independent, and different indices are needed to predict them.

Detailed characterization of incretin cell distribution along the human small intestine

BackgroundIncretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are physiologic stimulants of insulin release that have been implicated in diabetes remission after bariatric surgery. The detailed distribution of incretin cells along the human small gut, so far unknown, is of utmost importance for the understanding of the metabolic changes observed after bariatric surgery because diabetes remission rate varies according to the type of anatomic rearrangement. ObjectiveTo characterize the distribution of incretin producing cells along the human jejunum-ileum. SettingAcademic public institution. MethodsSmall intestines (n = 30) from autopsies were sampled every 20 cm along their entire length and tissue microarrays were constructed. The percentage of immunohistochemistry-stained cell areas for GLP-1, GIP, and chromogranin A at each segment length was quantified using a computer-aided analysis tool. ResultsThe percentage of stained area for GLP-1 immunoreactive cells was found to be significantly higher from 200 cm from Treitz ligament onward compared with the first 80 cm of the small intestine, whereas GIP immunoreactive cells were predominant expressed in the first 80 cm. In contrast, chromogranin A expression was constant along the entire jejunum-ileum. ConclusionThe uneven distribution of GLP-1–expressing cells, with a higher density from 200 cm of the jejunum-ileum, could contribute to explain the improvement of glycemic profile of diabetic patients observed after anatomic rearrangement of the intestinal tract, in particular when subjected to gastric bypass with longer biliopancreatic limbs.

Insulin cessation and diabetes remission after bariatric surgery in adults with insulin-treated type 2 diabetes.

The impact of bariatric surgeries on insulin-treated type 2 diabetes (I-T2D) in the general population is largely undocumented. We assessed changes in insulin treatment after bariatric surgery in a large cohort of I-T2D patients, comparing Roux-en-Y gastric bypass surgery (RYGB) with laparoscopic adjustable gastric banding (LAGB), controlling for differences in weight loss between procedures. Of 113,638 adult surgical patients in the Bariatric Outcomes Longitudinal Database (BOLD), 10% had I-T2D. Analysis was restricted to 5,225 patients with I-T2D and at least 1 year of postoperative follow-up. Regression models were used to identify factors that predict cessation of insulin therapy. To control for differences in weight loss patterns between RYGB and LAGB, a case-matched analysis was also performed. Of I-T2D patients who underwent RYGB (n = 3,318), 62% were off insulin at 12 months compared with 34% (n = 1,907) after LAGB (P < 0.001). Regression analysis indicated that RYGB strongly predicted insulin cessation at both 1 and 12 months postoperatively. In the case-matched analysis at 3 months, the proportion of insulin cessation was significantly higher in the RYGB group than in the LAGB group (P = 0.03), and the diabetes remission rate was higher at all time points after this surgery. RYGB was a weight-independent predictor of insulin therapy cessation early after surgery, whereas insulin cessation after LAGB was linked to weight loss. I-T2D patients have a greater probability of stopping insulin after RYGB than after LAGB (62% vs. 34%, respectively, at 1 year), with weight-independent effects in the early months after surgery. These findings support RYGB as the procedure of choice for reversing I-T2D.