Impaired Fasting Glucose, Impaired Glucose Tolerance, Vitamin D Insufficiency
Conditions
Keywords
Vitamin D, Glucose intolerance, African American men
Brief summary
This study will supplement African American male (AAM) veterans at risk for diabetes and newly diagnosed T2DM with vitamin D (low or higher dose) and evaluate whether vitamin D helps to improve early markers of diabetes. The study will be done at Veteran Administration Medical Center in Chicago.
Detailed description
The goal of this randomized clinical trial (RCT) is to determine vitamin D efficacy and safety for improving early markers of T2DM in African American male (AAM) veterans at risk for T2DM (n=205, duration 12 months). The primary outcome will be change in oral glucose insulin sensitivity (OGIS). The secondary outcomes will include various parameters of glucose metabolism and other biomarkers. Analysis based on primary and secondary goal as well as predetermined levels of A1C, OGTT and 25OHD at the end of the study.
Interventions
DRUGPlacebo
Supplement of vitamin D 400 units provided to all subjects, in addition Arm 1 will get placebo and Arm 2 will get D2 50K
DRUG50K vitamin D2
Supplement of vitamin D 400 units provided to all subjects, in addition Arm 1 will get placebo and Arm 2 will get D2 50K
Sponsors
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
35 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Veterans at Jesse Brown VA Medical Center (JBVAMC) only * Male * African American race * Age 35-85 years * BMI 28-39.9 kg/m2 * Stable weight (+/- 10%) for at least 3 months prior to study entry * FPG 95 - 125 mg/dl * A1C 5.7 - 6.4% * Circulating 25OHD 5.0 - 29.9 ng/ml * Subjects who take ergocalciferol are allowed in the study after a washout period 1 3 month. * Subjects who take vitamin D supplements other than ergocalciferol are allowed in the study as long as total dose is no more than 600 IU/day (including MVI and calcium plus D supplements). * Non-diabetic subjects who are diagnosed with T2DM during screening (A1C 6.5-7%) or after randomization are allowed to continue if they follow lifestyle intervention and do not need to take anti-diabetic medications.
Exclusion criteria
* Subjects with T2DM * Weight gain or loss of more than 10% within 3 months prior to the study entry * History of kidney stones, hyperparathyroidism, sarcoidosis or hypercalcemia * A1C \>7%. * Very low 25OHD levels (\<5 ng/ml) and/or the presence of a physical consequence of very low vitamin D levels (hypocalcemia, hypophosphatemia, proximal muscle weakness) * Chronic kidney disease (CKD) stage 4 and 5 * Problems that in the judgment of PI may be associated with the risk to the subject or non-compliance * Subjects who take vitamin D supplements and not willing to go through washout period for ergocalciferol or to take no more than 600 IU/day of total vitamin D supplements * History, clinical manifestations or medications of significant metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, psychiatric/ psychological disorders, or social circumstances which in the opinion of the investigator would be expected to interfere with the study or increase risk to the subject * Non-diabetic subjects who are diagnosed with T2DM after randomization and need to take anti-diabetic medications are brought for the final visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oral Glucose Insulin Sensitivity (OGIS) | 12 months | Oral glucose insulin sensitivity = index of insulin sensitivity, higher index means higher insulin sensitivity. Low insulin sensitivity means high insulin resistance and high risk of type 2 diabetes mellitus. It is calculated by a special formula using insulin and glucose measured in Oral Glucose Tolerance test. The primary outcome was the change in oral glucose insulin sensitivity (OGIS, from oral glucose tolerance test) after 12 months of treatment calculated as OGIS at 12-months minus OGIS baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline at 12 Months | Baseline and 12 Months | — |
| Insulin Sensitivity by Matsuda Composite | 12 Months | Insulin Sensitivity by Matsuda Composite - index of insulin sensitivity, higher index means higher insulin sensitivity. Low insulin sensitivity means high insulin resistance and high risk of type 2 diabetes mellitus. It is calculated by a special formula using insulin and glucose measured in Oral Glucose Tolerance test. The formula is different from a formula for OGIS. Matsuda composite calculated based on formula 10\^4/Square Root of \[(fasting glucose x fasting insulin) x (mean glucose x mean insulin)\] (Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic glucose clamp. Diabetes Care. 1999;22:1462-1470) Unit of measure is 10000/√\[(µU/mL)/(mg/dL)\]x\[(µU/mL)/(mg/dL)\]. |
| Insulinogenic Index-30 | 12 Month | Index of insulin secretion, higher index means higher insulin secretion. It is calculated by a special formula using insulin and glucose measured at 0 min and at 30 min (hence 30 in the name) in Oral Glucose Tolerance test. Insulin secretion was assessed based on formula Insulinogenic index-30 \[(insulin at 30 min - fasting insulin)/(glucose at 30 min - fasting glucose)\] (Kosaka K, Hagura R, Kuzuya T. Insulin responses in equivocal and definite diabetes, with special reference to subjects who had mild glucose intolerance but later developed definite diabetes. Diabetes. 1977;26:944-952) |
| C-Peptidogenic Index-30 | 12 Month | Index of insulin secretion, higher index means higher insulin secretion. C-peptide circulates in blood in amounts equal to insulin because insulin and C-peptide are linked when first made by the pancreas. C-peptide is more stable in blood than insulin; therefore it can be reliably used to evaluate insulin secretion. It is calculated by a special formula using C-peptide and glucose measured at 0 min and at 30 min (hence 30 in the name) in Oral Glucose Tolerance test. Insulin secretion was assessed based on formula C-Peptidogenic index-30 \[(C-Peptide at 30 min - fasting C-peptide)/(glucose at 30 min - fasting glucose)\]Bergstrom RW, Wahl PW, Leonetti DL, Fujimoto WY. Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance. J Clin Endocrinol Metab. 1990;71:1447-1453.) |
| Incident Diabetes | 12 Months | — |
Countries
United States
Participant flow
Recruitment details
Participants were recruited among African American Male veterans coming for medical care to Jesse Brown VA Medical Center in Chicago between May 2011 and December 2012.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Supplement of vitamin D 400 units provided to all subjects in addition to placebo. | 86 |
| 50K Vitamin D2 Supplement of vitamin D 400 units provided to all subjects in addition to D2 50K. | 87 |
| Total | 173 |
Baseline characteristics
| Characteristic | Total | Placebo | 50K Vitamin D2 |
|---|---|---|---|
| Age, Customized 35-85 Years | 173 participants | 86 participants | 87 participants |
| BMI | 31.9 Kg/m2 STANDARD_DEVIATION 2.65 | 31.5 Kg/m2 STANDARD_DEVIATION 2.4 | 32.4 Kg/m2 STANDARD_DEVIATION 2.9 |
| HbA1c | 6.1 Percentage of A1C STANDARD_DEVIATION 0.26 | 6.1 Percentage of A1C STANDARD_DEVIATION 0.2 | 6.1 Percentage of A1C STANDARD_DEVIATION 0.26 |
| Race/Ethnicity, Customized African American Male Veterans | 173 participants | 86 participants | 87 participants |
| Region of Enrollment United States | 173 participants | 86 participants | 87 participants |
| Sex/Gender, Customized Male | 173 participants | 86 participants | 87 participants |
| Vit D | 14.3 ng/ml STANDARD_DEVIATION 4.8 | 14.0 ng/ml STANDARD_DEVIATION 4.8 | 14.7 ng/ml STANDARD_DEVIATION 4.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 86 | 0 / 87 |
| serious Total, serious adverse events | 0 / 86 | 0 / 87 |
Outcome results
Primary
Oral Glucose Insulin Sensitivity (OGIS)
Oral glucose insulin sensitivity = index of insulin sensitivity, higher index means higher insulin sensitivity. Low insulin sensitivity means high insulin resistance and high risk of type 2 diabetes mellitus. It is calculated by a special formula using insulin and glucose measured in Oral Glucose Tolerance test. The primary outcome was the change in oral glucose insulin sensitivity (OGIS, from oral glucose tolerance test) after 12 months of treatment calculated as OGIS at 12-months minus OGIS baseline.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Oral Glucose Insulin Sensitivity (OGIS) | -16.0 ml/min/m^2 of body surface area | Standard Deviation 55.83 |
| 50K Vitamin D2 | Oral Glucose Insulin Sensitivity (OGIS) | 7.8 ml/min/m^2 of body surface area | Standard Deviation 56.02 |
p-value: 0.026ANOVA
Secondary
Change in HbA1c From Baseline at 12 Months
Time frame: Baseline and 12 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in HbA1c From Baseline at 12 Months | 0.01 percentage of A1C | Standard Deviation 0.21 |
| 50K Vitamin D2 | Change in HbA1c From Baseline at 12 Months | -0.01 percentage of A1C | Standard Deviation 0.18 |
p-value: 0.6ANOVA
Secondary
C-Peptidogenic Index-30
Index of insulin secretion, higher index means higher insulin secretion. C-peptide circulates in blood in amounts equal to insulin because insulin and C-peptide are linked when first made by the pancreas. C-peptide is more stable in blood than insulin; therefore it can be reliably used to evaluate insulin secretion. It is calculated by a special formula using C-peptide and glucose measured at 0 min and at 30 min (hence 30 in the name) in Oral Glucose Tolerance test. Insulin secretion was assessed based on formula C-Peptidogenic index-30 \[(C-Peptide at 30 min - fasting C-peptide)/(glucose at 30 min - fasting glucose)\]Bergstrom RW, Wahl PW, Leonetti DL, Fujimoto WY. Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance. J Clin Endocrinol Metab. 1990;71:1447-1453.)
Time frame: 12 Month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | C-Peptidogenic Index-30 | -0.64 (ng/mL)/(mg/dL) | Standard Deviation 15.84 |
| 50K Vitamin D2 | C-Peptidogenic Index-30 | 5.32 (ng/mL)/(mg/dL) | Standard Deviation 17.47 |
p-value: 0.22ANOVA
Secondary
Incident Diabetes
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incident Diabetes | 9 participants |
| 50K Vitamin D2 | Incident Diabetes | 9 participants |
p-value: 0.869Chi-squared
Secondary
Insulinogenic Index-30
Index of insulin secretion, higher index means higher insulin secretion. It is calculated by a special formula using insulin and glucose measured at 0 min and at 30 min (hence 30 in the name) in Oral Glucose Tolerance test. Insulin secretion was assessed based on formula Insulinogenic index-30 \[(insulin at 30 min - fasting insulin)/(glucose at 30 min - fasting glucose)\] (Kosaka K, Hagura R, Kuzuya T. Insulin responses in equivocal and definite diabetes, with special reference to subjects who had mild glucose intolerance but later developed definite diabetes. Diabetes. 1977;26:944-952)
Time frame: 12 Month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Insulinogenic Index-30 | -0.03 (µU/mL)/(mg/dL) | Standard Deviation 1.1 |
| 50K Vitamin D2 | Insulinogenic Index-30 | 0.26 (µU/mL)/(mg/dL) | Standard Deviation 1.03 |
p-value: 0.34ANOVA
Secondary
Insulin Sensitivity by Matsuda Composite
Insulin Sensitivity by Matsuda Composite - index of insulin sensitivity, higher index means higher insulin sensitivity. Low insulin sensitivity means high insulin resistance and high risk of type 2 diabetes mellitus. It is calculated by a special formula using insulin and glucose measured in Oral Glucose Tolerance test. The formula is different from a formula for OGIS. Matsuda composite calculated based on formula 10\^4/Square Root of \[(fasting glucose x fasting insulin) x (mean glucose x mean insulin)\] (Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic glucose clamp. Diabetes Care. 1999;22:1462-1470) Unit of measure is 10000/√\[(µU/mL)/(mg/dL)\]x\[(µU/mL)/(mg/dL)\].
Time frame: 12 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Insulin Sensitivity by Matsuda Composite | 0.13 10^4/√[(µU/mL)/(mg/dL)x(µU/mL)/(mg/dL)] | Standard Deviation 1.43 |
| 50K Vitamin D2 | Insulin Sensitivity by Matsuda Composite | 0.44 10^4/√[(µU/mL)/(mg/dL)x(µU/mL)/(mg/dL)] | Standard Deviation 1.51 |
p-value: 0.389ANOVA
Post Hoc
Change in Glycemia
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Change in Glycemia | 8.3 percentage of participants |
| 50K Vitamin D2 | Change in Glycemia | 31.6 percentage of participants |
p-value: 0.13Chi-squared