Dietary Sugar Absorptive Phenotype for Prediction of Weight Loss Outcome

Overview

About this study

Using stem cell derived intestinal epithelial cultures (enteroids) derived from obese (BMI> 30) patients and non-obese and metabolically normal patients (either post-bariatric surgery (BS) or BS-naïve with BMI < 25), dietary glucose absorption was measured. We identified that enteroids from obese patients were characterized by glucose hyper-absorption (~ 5 fold) compared to non-obese patients. Significant upregulation of major intestinal sugar transporters, including SGLT1, GLU2 and GLUT5 was responsible for hyper-absorptive phenotype and their pharmacologic inhibition significantly decreased glucose absorption. Importantly, we observed that enteroids from post-BS non-obese patients exhibited low dietary glucose absorption, indicating that altered glucose absorption is a potential mechanism for the immediate and clinically significant improvement in glucose homeostasis after BS, represented clinically by resolution of Type 2 Diabetes (T2D) within weeks to months of surgery. However, BS confers these benefits in only in ~ 60% of patients, indicating a desperate need to identify the cohort of patients likely to benefit from such an invasive operation.
Thus, our results and other published data led us to the current hypothesis: an intestinal glucose hyper-absorptive phenotype in obese patients may be a predictor for successful outcome of BS. Additionally, sugar transporters responsible for hyper-absorptive phenotype represent potential targets for future drugs that could provide an alternative approach to BS.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Age ≥ 18 years.
Obese patients (BMI ≥ 30) scheduled for BS undergoing standard of care screening EGD, or lean BS-naïve individuals (BMI ≤ 25) subjected to EGD for routine clinical indications as part of standard care.

Exclusion Criteria:

Individuals < 18 years.
Adults unable to consent, including non-English speakers.
Pregnant women because endoscopy is a risk factor. All patients of childbearing age undergo history as well as urine pregnancy test as a standard of care prior to undergoing endoscopy as the procedure is performed under anesthesia.
Prisoners.
Subjects with preexisting conditions (e.g., bleeding at the time of the procedure, suspected perforation during the standard-of-care procedure) will be excluded from the study at the time of the endoscopy.
Have a contraindication to endoscopy.
A history of surgery on the stomach or small intestine.
Type 1 diabetes (clinical diagnosis and/or positive GAD antibodies).
Using weight loss medications.
Active malignancy within the last 5 years.

Eligibility last updated 2/11/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Jacksonville, Fla. Mayo Clinic principal investigator Dilhana Badurdeen, M.B.B.S., M.D.	Closed-enrolling by invitation What is this? (?) "Close" Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.	Contact information: Zhen Li M.D., Ph.D. Li.Zhen@mayo.edu

Mayo Clinic Location

Status

Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Dilhana Badurdeen, M.B.B.S., M.D.

Closed-enrolling by invitation

Contact information:

Zhen Li M.D., Ph.D.

Li.Zhen@mayo.edu

More information

Publications

Publications are currently not available

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