Pre-diabetes
Conditions
Keywords
pre-diabetes, minorities, oral glucose tolerance test, disposition index, insulin secretion, insulin sensitivity, diabetes
Brief summary
Vitamin D supplementation in minority subjects with both pre-diabetes and low vitamin D levels will delay the development of diabetes.
Detailed description
Low vitamin D levels 1) are associated with abnormalities in insulin secretion and insulin action, 2) predict the development of diabetes in those without diabetes, and 3) are more common in people with diabetes. Minority populations (African-Americans and Latinos) are more likely to have both low levels of vitamin D and diabetes. This study will identify minority individuals who are at increased risk for diabetes (those with central obesity, family history of diabetes in first degree relatives and either with hypertension or being treated for hypertension), and determine if they have both pre-diabetes, ie, impaired fasting glucose and/or impaired glucose tolerance, and low levels of vitamin D. Those that have both will be randomized to either high doses of vitamin D or placebo and insulin secretion and action as well as changes in the oral glucose tolerance test (reversion to normal, maintenance of pre-diabetes or development of diabetes) will be monitored at 3 month intervals for one year. This study will test the hypothesis that the increased amount of diabetes in minority populations may be due in part to low levels of vitamin D and whether supplementing this vitamin may delay the development of diabetes.
Interventions
DRUGvitamin D
liquid vitamin D3 dissolved in medium chain triglyceride once a week
DRUGplacebo
medium chain triglyceride given once per week
Sponsors
American Diabetes Association
Charles Drew University of Medicine and Science
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Age greater than 40. 2. Impaired fasting glucose (FPG level greater than 100 and less than 126 mg/dl); and/or 3. Impaired glucose tolerance (2-h plasma glucose concentration after 75 gram glucose load greater than 140 and less than 200 mg/dl) 4. Serum 25-OHD less than 30 ng/ml 5. Able and willing to provide informed consent
Exclusion criteria
1. FPG greater than 126 mg/dl or 2-hour-OGTT plasma glucose greater than 200 mg/dl 2. Major psychiatric disorder on medication (excluding successfully treated depression) 3. Diagnosed diabetes mellitus 4. HIV/AIDS 5. Major hematological, hepatic (AST/ALT levels greater than or equal to 2 times normal) or renal eGFR less than 60 ml/min) disorder 6. History of carcinoma, except skin basal cell or squamous cell skin carcinomas 7. Heart failure, unstable angina or history of a myocardial infarction 8. Alcohol or substance abuse 9. Current treatment with glucocorticoids 10. Current treatment with diabetes medications, including metformin 11. Cushing's syndrome 12. Primary hyperparathyroidism 13. Nephrolithiasis 14. Pregnancy or breast-feeding 15. Regular visits to a tanning salon (unlikely in this minority population)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects Who Develop Diabetes | one year | Diabetes defined by a FPG\>=126 mg/dl or a 2-hr glucose concentration on an OGTT of \>=200 mg/dl |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disposition Index | Baseline, 3, 6, 9, 12 months | Measure of insulin secretion multiplied by measure of insulin sensitivity,both derived from oral glucose tolerance test; higher values are better |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects with low vitamin D levels and pre-diabetes | 56 |
| Vitamin D Subjects with low vitamin D levels and pre-diabetes | 61 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Hypokalemia-affects insulin secretion | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 5 |
Baseline characteristics
| Characteristic | Vitamin D | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 52 Participants | 107 Participants |
| Age Continuous | 52.3 Years STANDARD_DEVIATION 8 | 52.5 Years STANDARD_DEVIATION 7 | 52.4 Years STANDARD_DEVIATION 7.5 |
| Region of Enrollment United States | 61 participants | 56 participants | 117 participants |
| Sex: Female, Male Female | 43 Participants | 36 Participants | 79 Participants |
| Sex: Female, Male Male | 18 Participants | 20 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 53 | 0 / 56 |
| serious Total, serious adverse events | 0 / 53 | 0 / 56 |
Outcome results
Primary
Percent of Subjects Who Develop Diabetes
Diabetes defined by a FPG\>=126 mg/dl or a 2-hr glucose concentration on an OGTT of \>=200 mg/dl
Time frame: one year
Population: Minorities with pre-diabetes and hypovitaminosis D
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Subjects Who Develop Diabetes | 9 percentage of participants |
| Vitamin D | Percent of Subjects Who Develop Diabetes | 12 percentage of participants |
Comparison: Null hypothesis is that there is no effect of vitamin D on the development of diabetes in people with pre-diabetes and hypovitaminosis D. There were no published data when this trial was started on the effect of vitamin D in pre-diabetes making a power calculation difficult.p-value: 0.6195% CI: [8, 12]Chi-squared
Secondary
Disposition Index
Measure of insulin secretion multiplied by measure of insulin sensitivity,both derived from oral glucose tolerance test; higher values are better
Time frame: Baseline, 3, 6, 9, 12 months
Population: modified intent to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Disposition Index | Disposition Index at 3 months | 1.5 Unitless | Standard Deviation 0.8 |
| Placebo | Disposition Index | Disposition Index at 9 months | 1.3 Unitless | Standard Deviation 0.6 |
| Placebo | Disposition Index | Disposition Index at 6 months | 1.4 Unitless | Standard Deviation 0.6 |
| Placebo | Disposition Index | Disposition Index at 12 months | 1.6 Unitless | Standard Deviation 1.6 |
| Placebo | Disposition Index | Dispostion Index at baseline | 1.4 Unitless | Standard Deviation 0.5 |
| Vitamin D | Disposition Index | Disposition Index at 12 months | 1.3 Unitless | Standard Deviation 0.5 |
| Vitamin D | Disposition Index | Dispostion Index at baseline | 1.3 Unitless | Standard Deviation 0.4 |
| Vitamin D | Disposition Index | Disposition Index at 3 months | 1.3 Unitless | Standard Deviation 0.5 |
| Vitamin D | Disposition Index | Disposition Index at 6 months | 1.2 Unitless | Standard Deviation 0.5 |
| Vitamin D | Disposition Index | Disposition Index at 9 months | 1.3 Unitless | Standard Deviation 0.4 |
Comparison: The null hypothesis is that there would be no difference in the changes in the Disposition Index between the 2 groups over the year.p-value: 0.39ANOVA