Understanding the Causes of Post-Bariatric Hypoglycemia and Identifying New Approaches to Treatment of this Condition

New! (September 2024)

Congrats to postdoctoral fellow Rafael Ferraz-Bannitz and the entire team on the publication of our paper in Journal of Clinical Investigation this month!  In this paper we identify alterations in serotonin-dependent signaling as a potential contribution to post-bariatric hypoglycemia.   We thank the entire research team and our volunteers who give so generously of their time and blood samples to find new approaches to treat hypoglycemia!  We are excited to begin translating these findings!  The PDF is posted below.

New!

Pasiphy Study to Evaluate  Pasireotide as a New Treatment for Post-Bariatric Hypoglycemia

The purpose of this study is to evaluate the efficacy of the medication pasireotide for treatment of post-bariatric hypoglycemia (PBH). This study involves 16 total visits (over 13 months) to Joslin Diabetes Center. Over the course of those visits, the following will occur:

• Medical history, physical exams and vitals, ECG, laboratory testing, and imaging
• Meal tests with collection of blood samples measuring glucose levels and a variety of  hormones
  • You would have between 5-7 meal tests, and arrive to the tests fasting

At home between visits, you would be responsible for:

• Wearing a continuous glucose monitor, and taking finger-stick glucose readings at least weekly
• Performing self-injections of the treatment at home before each meal
• Keeping a daily, virtual eDiary logging meals, physical activity, and symptoms/episodes of hypoglycemia

Recruitment:

• Ages 18 and older
• Individuals who have had bariatric surgery (including gastric bypass, sleeve gastrectomy, or fundoplication) and have developed low blood sugars

Enrolled participants will receive continuous glucose monitors and blood glucose testing supplies. Compensation and travel costs will be provided.

Contact: Email: Hypoglycemiastudy@joslin.harvard.edu; Alessandra Amore at (617) 309-1940

CHS(#STUDY00000244)

Determining the Efficacy of Continuous Glucose Monitoring to Reduce Hypoglycemia and Improve Safety in Patients with Hypoglycemia after Gastric Surgery

*This study has been completed!  Results were presented at the 2023 American Diabetes Association and published in the medical journal Diabetes Obesity and Metabolism:

Continuous glucose monitoring in patients with post-bariatric hypoglycaemia reduces hypoglycaemia and glycaemic variability. Cummings C, Jiang A, Sheehan A, Ferraz-Bannitz R, Puleio A, Simonson DC, Dreyfuss JM, Patti ME.Diabetes Obes Metab. 2023 Aug;25(8):2191-2202. doi: 10.1111/dom.15096. Epub 2023 May 3.PMID: 37046360

The conclusions of this study: 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. 

Mechanisms of Post-Bariatric Hypoglycemia:

Enrollment has been completed, and analysis of data is in progress.

Mechanisms of Hypoglycemia in Patients without Diabetes: 

Analysis of data is in progress.

Hypoglycemia and the Gut Microbiome:  Analysis of the data from this study is in progress.

Understanding the Role of Bariatric Surgery as a Treatment for Type 2 Diabetes

The ARMMS-T2D Study

• The first report from this study was just published in JAMA (Journal of American Medical Association) in February 2024!  Additional data analysis is in progress, so stay posted!
• Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes. Courcoulas AP, Patti ME, Hu B, Arterburn DE, Simonson DC, Gourash WF, Jakicic JM, Vernon AH, Beck GJ, Schauer PR, Kashyap SR, Aminian A, Cummings DE, Kirwan JP.JAMA. 2024 Feb 27;331(8):654-664. doi: 10.1001/jama.2024.0318.PMID: 38411644

• Abstract of manuscript:

• 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.

Understanding How Metabolism and Diabetes Can Affect Men's Health and Reproduction

• The JEST Study:  Enrollment has been completed, and analysis of the data from this study is ongoing.

Please contact Dr Patti at mary.elizabeth.patti@joslin.harvard.edu if you are interested in learning more about any of these studies!