Association between geospatial disparities in food security with weight loss and nutritional outcomes of metabolic surgery.

BACKGROUND: Food insecurity has been linked to higher rates of obesity. It has also been shown to diminish the effectiveness of weight loss strategies, including intensive lifestyle interventions. One essential component of food insecurity is having a geospatial disadvantage in access to healthy, affordable food, such as living within a food desert. This study aims to determine if food insecurity also impacts weight loss and nutritional outcomes in patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). METHODS: Clinical outcomes of patients who underwent RYGB or SG at Cleveland Clinic or affiliate regional hospitals in the United States from 2010 to 2018 were collected. Modified Retail Food Environmental Index (mRFEI) data was collected from the Center for Disease Control and merged with patient census tract data, allowing the patient cohort to be divided into those living in areas identified as food secure (mRFEI > 10%), food swamps (mRFEI = 1-10%), or food deserts (mRFEI = 0). Postoperative weight change was evaluated with quadratic growth mixture models and stratified by surgery type. RESULTS: A total of 5097 patients were included in this study cohort, including 3424 patients who underwent RYGB and 1673 who underwent SG. The median duration of follow-up was 2.3 years (IQR 0.89-3.6 years). Food security status was not associated with postoperative weight change (RYGB p = 0.73, SG p = 0.60), weight loss nadir (RYGB p = 0.60, SG p = 0.79), or weight regain (RYGB p = 0.93, SG p = 0.85). Deficiencies in nutritional markers at 1-2 years after surgery were also not significantly different between food security groups. CONCLUSION: Despite the established relationship between food insecurity and obesity, food insecurity does not negatively impact weight loss or nutritional outcomes following RYGB or SG, demonstrating metabolic surgery as a powerful and equitable tool for treating obesity. LEVEL OF EVIDENCE: IV.

EndoBridge 2023: highlights and pearls.

EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11th Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challenging clinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders. As usual, the meeting was held in English with simultaneous translation into Russian, Arabic, and Turkish. The abstracts of clinical cases presented by the delegates during oral and poster sessions have been published in JCEM Case Reports. Herein, we provide a paper on highlights and pearls of the meeting sessions covering a wide range of subjects, from thyroid nodule stratification to secondary osteoporosis and from glycemic challenges in post-bariatric surgery to male hypogonadism. This report emphasizes the latest developments in the field, along with clinical approaches to common endocrine issues. The 12th annual meeting of EndoBridge will be held on October 17-20, 2024 in Antalya, Turkey.

Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes.

Importance: Randomized clinical trials of bariatric surgery have been limited in size, type of surgical procedure, and follow-up duration. Objective: To determine long-term glycemic control and safety of bariatric surgery compared with medical/lifestyle management of type 2 diabetes. Design, Setting, and Participants: ARMMS-T2D (Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes) is a pooled analysis from 4 US single-center randomized trials conducted between May 2007 and August 2013, with observational follow-up through July 2022. Intervention: Participants were originally randomized to undergo either medical/lifestyle management or 1 of the following 3 bariatric surgical procedures: Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding. Main Outcome and Measures: The primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 7 years for all participants. Data are reported for up to 12 years. Results: A total of 262 of 305 eligible participants (86%) enrolled in long-term follow-up for this pooled analysis. The mean (SD) age of participants was 49.9 (8.3) years, mean (SD) body mass index was 36.4 (3.5), 68.3% were women, 31% were Black, and 67.2% were White. During follow-up, 25% of participants randomized to undergo medical/lifestyle management underwent bariatric surgery. The median follow-up was 11 years. At 7 years, HbA1c decreased by 0.2% (95% CI, -0.5% to 0.2%), from a baseline of 8.2%, in the medical/lifestyle group and by 1.6% (95% CI, -1.8% to -1.3%), from a baseline of 8.7%, in the bariatric surgery group. The between-group difference was -1.4% (95% CI, -1.8% to -1.0%; P < .001) at 7 years and -1.1% (95% CI, -1.7% to -0.5%; P = .002) at 12 years. Fewer antidiabetes medications were used in the bariatric surgery group. Diabetes remission was greater after bariatric surgery (6.2% in the medical/lifestyle group vs 18.2% in the bariatric surgery group; P = .02) at 7 years and at 12 years (0.0% in the medical/lifestyle group vs 12.7% in the bariatric surgery group; P < .001). There were 4 deaths (2.2%), 2 in each group, and no differences in major cardiovascular adverse events. Anemia, fractures, and gastrointestinal adverse events were more common after bariatric surgery. Conclusion and Relevance: After 7 to 12 years of follow-up, individuals originally randomized to undergo bariatric surgery compared with medical/lifestyle intervention had superior glycemic control with less diabetes medication use and higher rates of diabetes remission. Trial Registration: ClinicalTrials.gov Identifier: NCT02328599.

Cognition in patients with post-bariatric hypoglycemia.

OBJECTIVE: Bariatric surgery, a highly effective treatment for obesity and associated comorbidities, may improve cognition and brain volume in parallel with cardiometabolic function. However, some post-bariatric individuals develop post-bariatric hypoglycemia (PBH), which can be frequent and severe. The impact of recurrent hypoglycemia on cognition in PBH is unknown. The objective of this study was to determine whether individuals with PBH display reduced cognitive function compared with postsurgical counterparts without hypoglycemia. METHODS: Fourteen adults with a history of Roux-en-Y gastric bypass with hypoglycemia (PBH+, n = 7) or without PBH (PBH-, n = 7) completed assessments of memory, executive function, attention, and psychomotor speed. RESULTS: PBH+ individuals displayed significantly decreased performance in category fluency (p < 0.01), category switching (p < 0.01), and category switching accuracy (p < 0.01), compared with PBH- individuals. Performance in the first (p = 0.03) and third intervals (p = 0.045) of verbal fluency was significantly lower in PBH+ individuals versus PBH- individuals. All other assessments did not differ. CONCLUSIONS: PBH+ individuals may be at greater risk for cognitive impairment compared with PBH- individuals, as suggested by impaired semantic processing and cognitive flexibility, as well as greater difficulty initiating and sustaining word retrieval.

Continuous glucose monitoring in patients with post-bariatric hypoglycaemia reduces hypoglycaemia and glycaemic variability.

AIM: To determine whether continuous glucose monitoring (CGM) can reduce hypoglycaemia in patients with post-bariatric hypoglycaemia (PBH). MATERIALS AND METHODS: In an open-label, nonrandomized, pre-post design with sequential assignment, CGM data were collected in 22 individuals with PBH in two sequential phases: (i) masked (no access to sensor glucose or alarms); and (ii) unmasked (access to sensor glucose and alarms for low or rapidly declining sensor glucose). Twelve participants wore the Dexcom G4 device for a total of 28 days, while 10 wore the Dexcom G6 device for a total of 20 days. RESULTS: Participants with PBH spent a lower percentage of time in hypoglycaemia over 24 hours with unmasked versus masked CGM (<3.3 mM/L, or <60 mg/dL: median [median absolute deviation {MAD}] 0.7 [0.8]% vs. 1.4 [1.7]%, P = 0.03; <3.9 mM/L, or <70 mg/dL: median [MAD] 2.9 [2.5]% vs. 4.7 [4.8]%; P = 0.04), with similar trends overnight. Sensor glucose data from the unmasked phase showed a greater percentage of time spent between 3.9 and 10 mM/L (70-180 mg/dL) (median [MAD] 94.8 [3.9]% vs. 90.8 [5.2]%; P = 0.004) and lower glycaemic variability over 24 hours (median [MAD] mean amplitude of glycaemic excursion 4.1 [0.98] vs. 4.4 [0.99] mM/L; P = 0.04). During the day, participants also spent a greater percentage of time in normoglycaemia with unmasked CGM (median [MAD] 94.2 [4.8]% vs. 90.9 [6.2]%; P = 0.005), largely due to a reduction in hyperglycaemia (>10 mM/L, or 180 mg/dL: median [MAD] 1.9 [2.2]% vs. 3.9 [3.6]%; P = 0.02). CONCLUSIONS: Real-time CGM data and alarms are associated with reductions in low sensor glucose, elevated sensor glucose, and glycaemic variability. This suggests CGM allows patients to detect hyperglycaemic peaks and imminent hypoglycaemia, allowing dietary modification and self-treatment to reduce hypoglycaemia. The use of CGM devices may improve safety in PBH, particularly for patients with hypoglycaemia unawareness.

Glucose metabolism after bariatric surgery: implications for T2DM remission and hypoglycaemia.

Although promising therapeutics are in the pipeline, bariatric surgery (also known as metabolic surgery) remains our most effective strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Of the many available options, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are currently the most widely used procedures. RYGB and VSG have very different anatomical restructuring but both surgeries are effective, to varying degrees, at inducing weight loss and T2DM remission. Both weight loss-dependent and weight loss-independent alterations in multiple tissues (such as the intestine, liver, pancreas, adipose tissue and skeletal muscle) yield net improvements in insulin resistance, insulin secretion and insulin-independent glucose metabolism. In a subset of patients, post-bariatric hypoglycaemia can develop months to years after surgery, potentially reflecting the extreme effects of potent glucose reduction after surgery. This Review addresses the effects of bariatric surgery on glucose regulation and the potential mechanisms responsible for both the resolution of T2DM and the induction of hypoglycaemia.

Medical Nutrition Therapy and Other Approaches to Management of Post-bariatric Hypoglycemia: A Team-Based Approach.

PURPOSE OF REVIEW: This manuscript provides a review of post-bariatric hypoglycemia (PBH) with a special focus on the role of the registered dietitian-nutritionist (RDN) and medical nutrition therapy (MNT) recommendations as foundational for management. RECENT FINDINGS: As the number of bariatric surgeries rises yearly, with 256,000 performed in 2019, PBH is an increasingly encountered late complication. Following Roux-en-Y (RYGB) or vertical sleeve gastrectomy (VSG), about 1/3 of patients report symptoms suggestive of at least mild postprandial hypoglycemia, with severe and/or medically confirmed hypoglycemia in 1-10%. Anatomical alterations, changes in GLP1 and other intestinally derived hormones, excessive insulin response, reduced insulin clearance, impaired counterregulatory hormone response to hypoglycemia, and other factors contribute to PBH. MNT is the cornerstone of multidisciplinary treatment, with utilization of personal continuous glucose monitoring to improve safety when possible. While many individuals require pharmacotherapy, there are no currently approved medications for PBH. Increasing awareness and identification of individuals at risk for or with PBH is critical given the potential impact on safety, nutrition, and quality of life. A team-based approach involving the individual, the RDN, and other clinicians is essential in providing ongoing assessment and individualization of MNT in the long-term management of PBH.

Growth Hormone and Counterregulation in the Pathogenesis of Diabetes.

PURPOSE OF REVIEW: Canonical growth hormone (GH)-dependent signaling is essential for growth and counterregulatory responses to hypoglycemia, but also may contribute to glucose homeostasis (even in the absence of hypoglycemia) via its impact on metabolism of carbohydrates, lipids and proteins, body composition, and cardiovascular risk profile. The aim of this review is to summarize recent data implicating GH action in metabolic control, including both IGF-1-dependent and -independent pathways, and its potential role as target for T2D therapy. RECENT FINDINGS: Experimental blockade of the GHR can modulate glucose metabolism. Moreover, the soluble form of the GH receptor (GHR, or GHBP) was recently identified as a mediator of improvement in glycemic control in patients with T2D randomized to bariatric surgery vs. medical therapy. Reductions in GHR were accompanied by increases in plasma GH, but unchanged levels of both total and free IGF-1. Likewise, hepatic GHR expression is reduced following both RYGB and VSG in rodents. Emerging data indicate that GH signaling is important for regulation of long-term glucose metabolism in T2D. Future studies will be required to dissect tissue-specific GH signaling and sensitivity and their contributions to systemic glucose metabolism.

Diabetes Remission in the Alliance of Randomized Trials of Medicine Versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D).

OBJECTIVE: The overall aim of the Alliance of Randomized Trials of Medicine versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) consortium is to assess the durability and longer-term effectiveness of metabolic surgery compared with medical/lifestyle management in patients with type 2 diabetes (NCT02328599). RESEARCH DESIGN AND METHODS: A total of 316 patients with type 2 diabetes previously randomly assigned to surgery (N = 195) or medical/lifestyle therapy (N = 121) in the STAMPEDE, TRIABETES, SLIMM-T2D, and CROSSROADS trials were enrolled into this prospective observational cohort. The primary outcome was the rate of diabetes remission (hemoglobin A1c [HbA1c] ≤6.5% for 3 months without usual glucose-lowering therapy) at 3 years. Secondary outcomes included glycemic control, body weight, biomarkers, and comorbidity reduction. RESULTS: Three-year data were available for 256 patients with mean 50 ± 8.3 years of age, BMI 36.5 ± 3.6 kg/m2, and duration of diabetes 8.8 ± 5.7 years. Diabetes remission was achieved in more participants following surgery than medical/lifestyle intervention (60 of 160 [37.5%] vs. 2 of 76 [2.6%], respectively; P < 0.001). Reductions in HbA1c (Δ = -1.9 ± 2.0 vs. -0.1 ± 2.0%; P < 0.001), fasting plasma glucose (Δ = -52 [-105, -5] vs. -12 [-48, 26] mg/dL; P < 0.001), and BMI (Δ = -8.0 ± 3.6 vs. -1.8 ± 2.9 kg/m2; P < 0.001) were also greater after surgery. The percentages of patients using medications to control diabetes, hypertension, and dyslipidemia were all lower after surgery (P < 0.001). CONCLUSIONS: Three-year follow-up of the largest cohort of randomized patients followed to date demonstrates that metabolic/bariatric surgery is more effective and durable than medical/lifestyle intervention in remission of type 2 diabetes, including among individuals with class I obesity, for whom surgery is not widely used.

Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D): Study rationale, design, and methods.

AIMS: Long-term data from randomized clinical trials comparing metabolic (bariatric) surgery versus a medical/lifestyle intervention for treatment of patients with obesity/overweight and type 2 diabetes (T2D) are lacking. The Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) is a consortium of four randomized trials designed to compare long-term efficacy and safety of surgery versus medical/lifestyle therapy on diabetes control and clinical outcomes. MATERIALS AND METHODS: Patients with T2D and body mass index (BMI) of 27-45 kg/m2 who were previously randomized to metabolic surgery (Roux-en-Y gastric bypass, adjustable gastric band, or sleeve gastrectomy) versus medical/lifestyle intervention in the STAMPEDE, SLIMM-T2D, TRIABETES, or CROSSROADS trials have been enrolled in ARMMS-T2D for observational follow-up. The primary outcome is change in glycated haemoglobin after a minimum 7 years of follow-up, with additional analyses to determine rates of diabetes remission and relapse, as well as cardiovascular and renal endpoints. RESULTS: In total, 302 patients (192 surgical, 110 medical/lifestyle) previously randomized in the four parent studies were eligible for participation in the ARMMS-T2D observational study. Participant demographics were 71% white, 27% African-American and 68% female. At baseline: age, 50 ± 8 years; BMI, 36.5 ± 3.5 kg/m2 ; duration of diabetes, 8.8 ± 5.6 years; glycated haemoglobin, 8.6% ± 1.6%; and fasting glucose, 168 ± 64 mg/dl. More than 35% of patients had a BMI <35 kg/m2 . CONCLUSIONS: ARMMS-T2D will provide the largest body of long-term, level 1 evidence to inform clinical decision-making regarding the comparative durability, efficacy and safety of metabolic surgery relative to a medical/lifestyle intervention among patients with T2D, including those with milder class I obesity or mere overweight.

Pramlintide for post-bariatric hypoglycaemia.

AIMS: The aim of this study was to examine the hypothesis that pramlintide would reduce hypoglycaemia by slowing gastric emptying and reducing postprandial glucagon secretion, thus limiting postprandial glycaemic excursions and insulin secretion, and thus to determine the efficacy of pramlintide on frequency and severity of hypoglycaemia in post-bariatric hypoglycaemia (PBH). MATERIALS AND METHODS: Participants with PBH following gastric bypass were recruited from outpatient clinics at the Joslin Diabetes Center, Boston, Massachusetts for an open-label study of pramlintide efficacy over 8 weeks. Twenty-three participants were assessed for eligibility, 20 participants had at least one pramlintide dose, and 14 completed the study. A mixed-meal tolerance test (MMTT) was performed at baseline and after 8 weeks of subcutaneous pramlintide with a sequential dose increase to a maximum of 120 micrograms (mean 69 ± 32 mcg) three times daily. The primary endpoint was change in glucose excursions during the MMTT. Secondary measures included MMTT insulin response, satiety and dumping score, percentage time with sensor glucose (SG) <3.9 mM, and number of days with minimum SG <3 mM, during masked continuous glucose monitoring. RESULTS: There were no differences in MMTT glucose, glucagon or insulin between baseline and post treatment. We observed no significant change in satiety or dumping scores. The overall frequency of low SG values did not change, although there was substantial inter-individual variability. CONCLUSIONS: In PBH, pramlintide does not modulate glycaemic or insulin responses, satiety, or dumping scores during an MMTT and does not impact glycaemic excursions or decrease low SG levels in the outpatient setting.

Hypoglycemia and Dysautonomia After Bariatric Surgery: a Systematic Review and Perspective.

INTRODUCTION: With the increasing performance of bariatric surgery, rare complications are becoming prevalent. We review the diagnosis and treatment of dysautonomia after bariatric surgery and the limited treatment options available. We summarize the suggested mechanisms and explain why a complete understanding of the etiology has yet to be determined. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed. RESULTS: Of 448 studies identified in the literature search, 4 studies were reviewed, describing 87 patients diagnosed with dysautonomia. We present a patient who developed severe dysautonomia following conversion of sleeve gastrectomy to gastric bypass. CONCLUSION: Treatment needs to focus on optimizing nutrition, avoiding hypoglycemia, and optimizing volume status.

Postbariatric hypoglycemia: symptom patterns and associated risk factors in the Longitudinal Assessment of Bariatric Surgery study.

BACKGROUND: Postbariatric hypoglycemia (PBH) can be a devastating complication for which current therapies are often incompletely effective. More information is needed regarding frequency, incidence, and risk factors for PBH. OBJECTIVES: To examine hypoglycemia symptoms following Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) and baseline and in-study risk factors. SETTING: Multicenter, at 10 US hospitals in 6 geographically diverse clinical centers. METHODS: A prospective, longitudinal cohort study of adults undergoing RYGB or LAGB as part of clinical care between 2006 and 2009 were recruited and followed until January 31, 2015, with baseline and annual postoperative research assessments. We analyzed baseline prevalence and post-operative incidence and frequency of self-reported hypoglycemia symptoms as well as potential preoperative risk factors. RESULTS: In all groups, postoperative prevalence of hypoglycemia symptoms was 38.5%. Symptom prevalence increased postoperatively from 2.8%-36.4% after RYGB in patients without preoperative diabetes (T2D), with similar patterns in prediabetes (4.9%-29.1%). Individuals with T2D had higher baseline hypoglycemia symptoms (28.9%), increasing after RYGB (57.9%). Hypoglycemia symptoms were lower after LAGB, with 39.1% reported hypoglycemia symptoms at only 1 postoperative visit with few (4.0%) having persistent symptoms at 6 or more annual visits. Timing of symptoms was not restricted to the postprandial state. Symptoms of severe hypoglycemia were reported in 2.6-3.6% after RYGB. The dominant risk factor for postoperative symptoms was preoperative symptoms; additionally, baseline selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor use was also associated with increased risk in multivariable analysis. Weight loss and regain were not related to hypoglycemia symptom reporting. CONCLUSION: Hypoglycemia symptoms increase over time after RYGB, particularly in patients without diabetes. In a small percentage, symptoms can be persistent or severe and require hospitalization. Preoperative hypoglycemia symptoms and SSRI/SNRI use in RYGB patients without diabetes is associated with increased risk of symptoms.

Glycemic Patterns Are Distinct in Post-Bariatric Hypoglycemia After Gastric Bypass (PBH-RYGB).

CONTEXT: Severe hypoglycemia with neuroglycopenia, termed post-bariatric hypoglycemia (PBH). typically occurs postprandially, but it is also reported after activity or mid-nocturnally. OBJECTIVE: To quantify glycemia, glycemic variability, and magnitude/duration of low sensor glucose (SG) values in patients with PBH after Roux-en-Y gastric bypass (PBH-RYGB). METHODS: This retrospective analysis of data from an academic medical center included individuals with PBH-RYGB (n = 40), reactive hypoglycemia without gastrointestinal surgery (Non-Surg Hypo, n = 20), prediabetes (Pre-DM, n = 14), newly diagnosed T2D (n = 5), and healthy controls (HC, n = 38). Masked continuous glucose monitoring (Dexcom G4) was used to assess patterns over 24 hours, daytime (6 am-midnight) and nighttime (midnight-6 am). Prespecified measures included mean and median SG, variability, and percent time at thresholds of sensor glucose. RESULTS: Mean and median SG were similar for PBH-RYGB and HC (mean: 99.8 ±â€…18.6 vs 96.9 ±â€…10.2 mg/dL; median: 93.0 ±â€…14.8 vs 94.5 ±â€…7.4 mg/dL). PBH-RYGB had a higher coefficient of variation (27.3 ±â€…6.8 vs 17.9 ±â€…2.4%, P < 0.0001) and range (154.5 ±â€…50.4 vs 112.0 ±â€…26.7 mg/dL, P < 0.0001). Nadir was lowest in PBH-RYGB (42.5 ±â€…3.7 vs HC 49.0 ±â€…11.9 mg/dL, P = 0.0046), with >2-fold greater time with SG < 70 mg/dL vs HC (7.7 ±â€…8.4 vs 3.2 ±â€…4.1%, P = 0.0013); these differences were greater at night (12.6 ±â€…16.9 vs 1.0 ±â€…1.5%, P < 0.0001). Non-Surg Hypo also had 4-fold greater time with SG < 70 at night vs HC (SG < 70: 4.0 ±â€…5.9% vs 1.0 ±â€…1.5%), but glycemic variability was not increased. CONCLUSION: Patients with PBH-RYGB experience higher glycemic variability and frequency of SG < 70 compared to HC, especially at night. These data suggest that additional pathophysiologic mechanisms beyond prandial changes contribute to PBH.