Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β

Hepprich, Matthias; Wiedemann, Sophia J.; Schelker, Benjamin L.; Trinh, Beckey; Starkle, A; Geigges, Marco; Löliger, Jordan; Böni-Schnetzler, Marianne; Rudofsky, Gottfried; Donath, Marc Y.

doi:10.1016/j.cmet.2020.02.013

Cited by 34 publications

(30 citation statements)

References 40 publications

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“…Third, we approached the patients in our clinic and the Hypo-BEAR trial participants (15) to collect in unstructured discussions with individual patients any potential patient-relevant outcome measures which we then presented to two of the most severely affected patients in our clinic with postprandial hypoglycemia (s. supplements, preliminary questionnaire) who agreed to support us for this project with their patient feedback. We expected that quality of life and hypoglycemia would be the most relevant outcome domains.…”

Section: Methodsmentioning

confidence: 99%

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Patient Involvement to Inform the Design of a Clinical Trial in Postbariatric Hypoglycemia

Hepprich¹,

Donath

Hemkens

2020

Preprint

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Background: Bariatric surgery may lead to symptomatic postprandial hypoglycemia as a major side effect without established therapy so far. We aimed to develop an evidence-based study design of a clinical trial that tests treatment options and can provide useful patient-relevant evidence.Methods: We searched systematically for guidance of core outcome sets to determine the most relevant types of outcomes and duration of such a trial. Our search comprised literature databases, a database of core outcome sets and self-help organizations. We then developed a simple online questionnaire based on interviews with German-speaking patients with postprandial hypoglycemia after bariatric surgery. We recruited participants by reaching out to all German speaking endocrinologists in Switzerland and large Swiss bariatric centers. We asked for preferences regarding outcome types and acceptable duration of being included in a corresponding clinical trial.Results: The systematic search did not identify evidence-based guidance for informing our study design. Experience of clinical and research routine as well as patient interviews helped in identifying potential outcomes and the design of an online questionnaire. Therein, a total of 29 persons started the questionnaire and 22 answered questions related to the primary outcome. Of these, 17 (77.3%) deemed quality of life more relevant as primary outcome than the rate of hypoglycemic episodes. A trial length of four weeks or longer was regarded as acceptable for 19 of 21 respondents to this question (91.4 %) and of six months or longer for 12 respondents (56 %). Conclusions: In situations with no other guidance, a simple questionnaire may help to inform trial design decisions. This study identifies a patient preference for “quality of life” as a primary outcome and supports the evidence-based conception of a patient-centered clinical trial in postbariatric hypoglycemia.

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Section: Methodsmentioning

confidence: 99%

“…A recent exploratory trial with 12 patients after gastric bypass indicated that both the SGLT2-inhibitor empagli ozin and the IL-1 receptor antagonist anakinra may reduce postprandial insulin release and prevents hypoglycemia (15). These ndings call for further evaluation in a larger randomized clinical trial.…”

Section: Introductionmentioning

confidence: 99%

Patient Involvement to Inform the Design of a Clinical Trial in Postbariatric Hypoglycemia

Hepprich¹,

Donath

Hemkens

2020

Preprint

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“…33,34 Treatment of individuals with PBH with an Il-1B antagonist increased nadir glucose during meal testing. 35 Whether aberrant inflammatory responses contribute more broadly to PBH will require additional study.…”

Section: Etiologymentioning

confidence: 99%

<p>Hypoglycemia After Upper Gastrointestinal Surgery: Clinical Approach to Assessment, Diagnosis, and Treatment</p>

Sheehan¹,

Patti²

2020

DMSO

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“…Elevated IL-1β leads to an exaggerated postprandial insulin release. [ 44 ] A previous study reported that β-cell mass also increased in patients with PRH. [ 45 ] However, another study was designed to reduce β-cell mass by partial pancreatectomy, but it had no effects on improving hypoglycemia in patients with PRH, which indicated that β-cell mass was not the dominant contributor to hypoglycemia.…”

Section: Currently Possible Mechanisms Underlying Prhmentioning

confidence: 99%

Potential contribution of the gut microbiota to hypoglycemia after gastric bypass surgery

Zhou

Deng

Xiao

2020

Chinese Medical Journal

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Obesity has become a global health problem. Lifestyle modification and medical treatment only appear to yield short-term weight loss. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it sustains weight reduction and results in the remission of obesity-associated comorbidities for obese individuals. However, patients who undergo this surgery may develop hypoglycemia. To date, the diagnosis is challenging and the prevalence of post-RYGB hypoglycemia (PRH) is unclear. RYGB alters the anatomy of the upper gastrointestinal tract and has a combined effect of caloric intake restriction and nutrient malabsorption. Nevertheless, the physiologic changes after RYGB are complex. Although hyperinsulinemia, incretin effects, dysfunction of β-cells and α-cells, and some other factors have been widely investigated and are reported to be possible mediators of PRH, the pathogenesis is still not completely understood. In light of the important role of the gut microbiome in metabolism, we hypothesized that the gut microbiome might also be a critical link between RYGB and hypoglycemia. In this review, we mainly highlight the current possible factors predisposing individuals to PRH, particularly related to the gut microbiota, which may yield significant insights into the intestinal regulation of glucose metabolic homeostasis and provide novel clues to improve the treatment of type 2 diabetes mellitus.

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Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β

Cited by 34 publications

References 40 publications

Patient Involvement to Inform the Design of a Clinical Trial in Postbariatric Hypoglycemia

Patient Involvement to Inform the Design of a Clinical Trial in Postbariatric Hypoglycemia

<p>Hypoglycemia After Upper Gastrointestinal Surgery: Clinical Approach to Assessment, Diagnosis, and Treatment</p>

Potential contribution of the gut microbiota to hypoglycemia after gastric bypass surgery

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