Prediabetes, Type 2 Diabetes, Obesity
Conditions
Keywords
type 2 diabetes, prediabetes, obesity, gastric banding, metformin
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.
Interventions
DRUGMetformin
metformin 1000 mg bid
DEVICEgastric banding
LAP-BAND
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady State Beta Cell Compensation | 24 months | mean plasma C-peptide concentration during clamp steady state, adjusted for mean clamp insulin sensitivity |
Other
| Measure | Time frame | Description |
|---|---|---|
| Glycemia | 24 months | fasting and 2-hour OGTT glucose levels |
Countries
United States
Participant flow
Recruitment details
Recruited from Kaiser Permanente Southern California
Pre-assignment details
Five participants randomized to metformin and six participants randomized to gastric banding refused to initiate treatment
Participants by arm
| Arm | Count |
|---|---|
| Metformin subjects receiving metformin
Metformin: metformin 1000 mg bid | 44 |
| Gastric Banding subjects receiving LAP-BAND
gastric banding: LAP-BAND | 44 |
| Total | 88 |
Baseline characteristics
| Characteristic | Total | Metformin | Gastric Banding |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 88 Participants | 44 Participants | 44 Participants |
| Body Mass Index | 35.53 kilograms per meters squared STANDARD_DEVIATION 2.9 | 35.0 kilograms per meters squared STANDARD_DEVIATION 2.9 | 35.7 kilograms per meters squared STANDARD_DEVIATION 2.9 |
| Body weight | 96.8 kilograms STANDARD_DEVIATION 11.8 | 96.1 kilograms STANDARD_DEVIATION 10.9 | 97.5 kilograms STANDARD_DEVIATION 12.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 40 Participants | 21 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 23 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1C | 5.87 percent of hemoglobin STANDARD_DEVIATION 0.06 | 5.82 percent of hemoglobin STANDARD_DEVIATION 0.06 | 5.92 percent of hemoglobin STANDARD_DEVIATION 0.06 |
| Hyperglycemic clamp | 3.52 nmol/l adjusted for insulin sensitivity | 3.37 nmol/l adjusted for insulin sensitivity | 3.67 nmol/l adjusted for insulin sensitivity |
| Oral Glucose Tolerance Test 2-hour glucose | 10.45 mmol/l STANDARD_DEVIATION 2.65 | 10.5 mmol/l STANDARD_DEVIATION 2.6 | 10.4 mmol/l STANDARD_DEVIATION 2.7 |
| Oral Glucose Tolerance Test fasting glucose | 6.2 mmol/l STANDARD_DEVIATION 0.75 | 6.2 mmol/l STANDARD_DEVIATION 0.8 | 6.2 mmol/l STANDARD_DEVIATION 0.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 65 Participants | 31 Participants | 34 Participants |
| Region of Enrollment United States | 88 participants | 44 participants | 44 participants |
| Sex: Female, Male Female | 69 Participants | 34 Participants | 35 Participants |
| Sex: Female, Male Male | 19 Participants | 10 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 38 |
| other Total, other adverse events | 18 / 39 | 3 / 38 |
| serious Total, serious adverse events | 2 / 39 | 4 / 38 |
Outcome results
Primary
Steady State Beta Cell Compensation
mean plasma C-peptide concentration during clamp steady state, adjusted for mean clamp insulin sensitivity
Time frame: 24 months
Population: Participants completing 24-month hyperglycemic clamp
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Metformin | Steady State Beta Cell Compensation | 3.01 (nmol/L) adjusted for M/I |
| Gastric Banding | Steady State Beta Cell Compensation | 3.19 (nmol/L) adjusted for M/I |
Comparison: We selected a sample size that would allow detection of an effect size of \~0.6 or greater between gastric band and metformin groups for measures of β-cell function after two years, hypothesizing greater function in the gastric band group.p-value: 0.05General Linear Models
Other Pre-specified
Glycemia
fasting and 2-hour OGTT glucose levels
Time frame: 24 months
Population: participants completing 24 months of interventions
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin | Glycemia | fasting glucose | 5.95 mmol/l | Standard Error 0.11 |
| Metformin | Glycemia | 2-hour glucose | 10.87 mmol/l | Standard Error 0.57 |
| Gastric Banding | Glycemia | fasting glucose | 5.85 mmol/l | Standard Error 0.18 |
| Gastric Banding | Glycemia | 2-hour glucose | 9.92 mmol/l | Standard Error 0.54 |
Other Pre-specified
Glycemia
HbA1C
Time frame: 24 months
Population: participants completing 24 months of interventions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Glycemia | 5.84 percent of hemoglobin | Standard Error 0.09 |
| Gastric Banding | Glycemia | 5.73 percent of hemoglobin | Standard Error 0.09 |