Clinical trial NCT01763346: Beta Cell Restoration Through Fat Mitigation
Official title: Beta Cell Restoration Through Fat Mitigation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetes
Type 2 Diabetes
Obesity
Keywords: type 2 diabetes
prediabetes
obesity
gastric banding
metformin
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2013-01-08
Enrollment: 88
Sex: ALL
Minimum age (years): 22
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Weight loss achieved through gastric banding will be superior to treatment with metformin in preserving or restoring pancreatic beta cell function in people with prediabetes or mild type 2 diabetes.

Detailed description: BetaFat is a 2-arm, unblinded study to compare gastric banding to treatment with metformin over a 24-month period in moderately obese adults with pre- or mild type 2 diabetes. The primary outcome will be change in β-cell compensation for insulin resistance, which the investigators will compare between groups. Secondary analyses will include other potential markers of β-cell health and potential mediators of treatment-specific effects. The main focus will be on mediators related to obesity. Clinically, the project will serve as a test of concept for use of gastric banding relatively early in the spectrum of obesity and β-cell disease. Biologically, the results will provide crucial information on potential mediators of β-cell failure and its arrest or reversal in the context of obesity. Those mediators will guide the development of more effective treatment and monitoring for the β-cell disease that causes type 2 diabetes.

Eligibility criteria: Inclusion Criteria:

1. Prior completion of at least two months in a diet, exercise and lifestyle intervention program within the past two years
2. Fasting plasma glucose \>90 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus HbA1C ≤7.0%. There is no lower limit for the A1C and no upper limit for the OGTT 2-hour glucose based on prior studies that allow us to identify people with falling β-cell function
3. Age 22-65 years
4. Body mass index (BMI) 30-40 kg/m2
5. For participants with diabetes, known duration \<1 year
6. No history of use of antidiabetic medications except during pregnancy

Exclusion Criteria:

1. Contraindications to LapBand(see Appendix 1)
2. Contraindication to MRI (claustrophobia; permanent metal objects such as pacemakers, prostheses, aneurysm clips)
3. Underlying disease(s) likely to (a) limit life span to less than study duration and/or (b) increase risk of intervention outside of the study and/or (c) limit ability to participate in outcomes assessment and/or (d) limit participation
4. An underlying disease known to have important effects on glucose metabolism
5. Active infections
6. Renal disease (serum creatinine ≥1.4 mg/dl for men; ≥1.3 mg/dl for women) or serum potassium abnormality (\<3.4 or \>5.5 mmol/l)
7. Anemia (hemoglobin \<11g/dl in women, \<12 g/dl in men) or known coagulopathy
8. Cardiovascular disease, including uncontrolled hypertension and symptomatic congestive heart failure. Participants must be able to safely tolerate administration of fluid/volume challenges during clamp studies.
9. Serum AST \>3 times upper limit of normal in local clinical lab
10. Excessive alcohol intake
11. Suboptimally treated thyroid disease
12. Conditions or behaviors likely to affect the conduct of the study

    1. unable or unwilling to give informed consent
    2. unable to adequately communicate with clinic staff
    3. another household member is a participant or staff member
    4. current or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes
    5. likely to move away from participating clinic in next 2 years
    6. current (or anticipated) pregnancy and lactation.
    7. major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of the study
    8. weight loss \>5% in past three months for any reason except postpartum weight loss.
13. additional conditions may serve as criteria for exclusion at the discretion of the local site

Primary outcomes:
measure: Steady State Beta Cell Compensation
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
measure: Glycemia
timeFrame: 24 months
measure: Glycemia
timeFrame: 24 months
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
Study officials:
affiliation: University of Southern California
name: Thomas A Buchanan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: RISE Consortium. Restoring Insulin Secretion (RISE): design of studies of beta-cell preservation in prediabetes and early type 2 diabetes across the life span. Diabetes Care. 2014;37(3):780-8. doi: 10.2337/dc13-1879. Epub 2013 Nov 5.
citation: Xiang AH, Trigo E, Martinez M, Katkhouda N, Beale E, Wang X, Wu J, Chow T, Montgomery C, Nayak KS, Hendee F, Buchanan TA; RISE Consortium; RISE Collaborators. Impact of Gastric Banding Versus Metformin on beta-Cell Function in Adults With Impaired Glucose Tolerance or Mild Type 2 Diabetes. Diabetes Care. 2018 Dec;41(12):2544-2551. doi: 10.2337/dc18-1662. Epub 2018 Oct 3.
citation: RISE Consortium. Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic Clamp. Diabetes Care. 2018 Aug;41(8):1696-1706. doi: 10.2337/dc18-0244. Epub 2018 Jun 25.
citation: Utzschneider KM, Ehrmann DA, Arslanian SA, Barengolts E, Buchanan TA, Caprio S, Edelstein SL, Hannon TS, Kahn SE, Kozedub A, Mather KJ, Nadeau KJ, Sam S, Tripputi M, Xiang AH, El Ghormli L; RISE Consortium. Weight loss and beta-cell responses following gastric banding or pharmacotherapy in adults with impaired glucose tolerance or type 2 diabetes: a randomized trial. Obesity (Silver Spring). 2022 Aug;30(8):1579-1588. doi: 10.1002/oby.23475.
citation: Kahn SE, Edelstein SL, Arslanian SA, Barengolts E, Caprio S, Ehrmann DA, Hannon TS, Marcovina S, Mather KJ, Nadeau KJ, Utzschneider KM, Xiang AH, Buchanan TA; RISE Consortium; Rise Consortium Investigators:. Effect of Medical and Surgical Interventions on alpha-Cell Function in Dysglycemic Youth and Adults in the RISE Study. Diabetes Care. 2021 Sep;44(9):1948-1960. doi: 10.2337/dc21-0461. Epub 2021 Jun 16.
citation: Kahn SE, Mather KJ, Arslanian SA, Barengolts E, Buchanan TA, Caprio S, Ehrmann DA, Hannon TS, Marcovina S, Nadeau KJ, Utzschneider KM, Xiang AH, Edelstein SL; RISE Consortium; Rise Consortium Investigators:. Hyperglucagonemia Does Not Explain the beta-Cell Hyperresponsiveness and Insulin Resistance in Dysglycemic Youth Compared With Adults: Lessons From the RISE Study. Diabetes Care. 2021 Sep;44(9):1961-1969. doi: 10.2337/dc21-0460. Epub 2021 Jun 15.
citation: Arslanian SA, El Ghormli L, Kim JY, Tjaden AH, Barengolts E, Caprio S, Hannon TS, Mather KJ, Nadeau KJ, Utzschneider KM, Kahn SE; RISE Consortium. OGTT Glucose Response Curves, Insulin Sensitivity, and beta-Cell Function in RISE: Comparison Between Youth and Adults at Randomization and in Response to Interventions to Preserve beta-Cell Function. Diabetes Care. 2021 Mar;44(3):817-825. doi: 10.2337/dc20-2134. Epub 2021 Jan 12.
citation: RISE Consortium. Obesity and insulin sensitivity effects on cardiovascular risk factors: Comparisons of obese dysglycemic youth and adults. Pediatr Diabetes. 2019 Nov;20(7):849-860. doi: 10.1111/pedi.12883. Epub 2019 Jul 29.
citation: RISE Consortium. Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose Tolerance Test. Diabetes Care. 2018 Aug;41(8):1707-1716. doi: 10.2337/dc18-0243. Epub 2018 Jun 25.
citation: Hannon TS, Kahn SE, Utzschneider KM, Buchanan TA, Nadeau KJ, Zeitler PS, Ehrmann DA, Arslanian SA, Caprio S, Edelstein SL, Savage PJ, Mather KJ; RISE Consortium. Review of methods for measuring beta-cell function: Design considerations from the Restoring Insulin Secretion (RISE) Consortium. Diabetes Obes Metab. 2018 Jan;20(1):14-24. doi: 10.1111/dom.13005. Epub 2017 Jun 22.