Prediabetes, Type 2 Diabetes
Conditions
Keywords
Prediabetes, Vitamin D
Brief summary
The goal of the Vitamin D and type 2 diabetes (D2d) study is to determine if vitamin D supplementation works to delay the onset of type 2 diabetes in people at risk for the disease and to gain a better understand how vitamin D affects glucose (sugar) metabolism.
Detailed description
The goal of the Vitamin D and type 2 diabetes (D2d) study is to determine if vitamin D supplementation works to delay the onset of type 2 diabetes in people at risk for the disease and to gain a better understand how vitamin D affects glucose (sugar) metabolism. Researchers at US sites will enroll people with pre-diabetes (people who have higher than normal blood glucose level but not high enough to meet the diagnosis of diabetes). The study will enroll participants over approximately 2 years and participants will be followed for approximately 3 years. Participants will receive either Vitamin D or a placebo by chance. Participants will take 1 pill a day for the duration of the study.
Interventions
DIETARY_SUPPLEMENTVitamin D (Cholecalciferol)
Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
OTHERPlacebo
Administered as one soft-gel pill daily by mouth
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Office of Dietary Supplements (ODS)
American Diabetes Association
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pre-diabetes (at increased risk for diabetes) defined by meeting 2-out-of-3 of the following glycemic criteria at the baseline visit: 1. Fasting plasma glucose (FPG) 100-125 mg/dL 2. 2-hour plasma glucose (2hPG) 140-199 mg/dL 3. Hemoglobin A1c (HbA1c) 5.7-6.4% 2. Age ≥ 30 years .(≥25 years for people of the following races: American-Indian, Alaska Native, Native Hawaiian or Other Pacific Islander). 3. Body Mass Index ≥ 24.0 (22.5 for Asians) and ≤ 42.0 kg/m2 4. Provision of signed and dated written informed consent prior to any study procedures. Major
Exclusion criteria
1. Diabetes based on either of the following criteria: 1. History (past 1 year) of hypoglycemic pharmacotherapy (oral or injectable medication approved by the FDA for type 2 diabetes), used for any condition (e.g. pre-diabetes, diabetes, polycystic ovarian syndrome. 2. Meeting the diagnosis criteria for diabetes 2. History (past 3 years) of hyperparathyroidism, nephrolithiasis or hypercalcemia. 3. Pregnancy (past 1 year by report or positive pregnancy test at screening), intent to become pregnant in the next 4 years or unprotected intercourse. History of gestational diabetes is not an exclusion criterion. 4. Currently breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Development of Diabetes | Approximately 48 months | New-onset diabetes was based on annual glycemic testing of fasting plasma glucose, glycated hemoglobin, and 2-hour post-load plasma glucose and semiannual testing of fasting plasma glucose and glycated hemoglobin. If two or three of the glycemic measures met the 2010 ADA thresholds for diabetes, the participant was considered to have met the diabetes outcome. When only the measure for fasting plasma glucose or glycated hemoglobin met the threshold, confirmatory testing was performed for the positive measure within 8 weeks. If only the measure for 2-hour post-load plasma glucose met the threshold, then a 75-g oral glucose tolerance test to reassess all three glycemic measures was repeated. If the repeat measure was positive or both fasting plasma glucose and glycated hemoglobin were positive (in the case of a repeat oral glucose tolerance test), than the participant was considered to have met the diabetes outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Identification of Characteristics Associated With the Variability in Achieved 25OHD Concentration. | Every 12 months for approximately 48 months | — |
| Number of Participants With Adverse Events. | Approximately 48 months | — |
| Change in Blood Pressure as a Continuous Variable. | Approximately 48 months | — |
| Number of Participants Who Discontinue Study Pills. | Approximately 48 months | — |
| Change in FPG as a Continuous Variable. | Every 12 months for approximately 48 months | — |
| Change in 2hPG as a Continuous Variable. | Every 12 months for approximately 48 months. | — |
| Change in HbA1c as a Continuous Variable. | Every 6 months for approximately 48 months | — |
| Measurement of Insulin Resistance (Derived From the OGTT). | Every 12 months for approximately 48 months | — |
| Measurement of Beta Cell Secretion (Derived From the OGTT) | Every 12 months for approximately 48 months | — |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 25OHD Concentration | Approximately 48 months | — |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Approximately 48 months | Race and ethnic group were reporting by the participant. The category other includes American Indian or Alaska Native; Native Hawaiian or other Pacific Islander; and other race. Ethnic group includes any race. |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria) | Approximately 48 months | Participants met at least two of three glycemic criteria for prediabetes: fasting plasma glucose level, 100 to 125 mg per deciliter (5.6 to 6.9 mmol per liter); plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter (7.8 to 11.0 mmol per liter) (impaired glucose tolerance); and glycated hemoglobin level, 5.7 to 6.4% (39 to 47 mmol per mole). |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI | Approximately 48 months | — |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference | Approximately 48 months | — |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age | Approximately 48 months | — |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure) | Approximately 48 months | — |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements | Approximately 48 months | — |
| Blood Plasma 25OHD Concentration. | Approximately 48 months | — |
Other
| Measure | Time frame |
|---|---|
| Time to Development of Cancer. | Approximately 48 months. |
| Time to Development of Cardiovascular Event. | Approximately 48 months. |
| Incidence of Cancer in a Pre-diabetes Population Defined by the Modern American Diabetes Association Criteria. | Approximately 48 months. |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Sex | Approximately 48 months. |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Ethnicity | Approximately 48 months. |
| Incidence of Cardiovascular Disease in a Pre-diabetes Population Defined by the Modern American Diabetes Association Criteria. | Approximately 48 months. |
| Quality of Life and Mood Scores in Pre-diabetes Population Using a Validated Instrument (PROMIS-29 Profile v2.0 and a General Question on Perception of Overall Health From the PROMIS Scale 1.2). | One time assessment at the month 24 visit. |
| Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 2 Hour Plasma Glucose | Approximately 48 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo One pill daily
Placebo: Administered as one soft-gel pill daily by mouth | 1,212 |
| Vitamin D (Cholecalciferol) One vitamin D pill daily
Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth. | 1,211 |
| Total | 2,423 |
Baseline characteristics
| Characteristic | Total | Vitamin D (Cholecalciferol) | Placebo |
|---|---|---|---|
| 2-Hr post-load plasma glucose (mg/dl) | 137.2 mg/dl STANDARD_DEVIATION 34.3 | 136.9 mg/dl STANDARD_DEVIATION 34.3 | 137.6 mg/dl STANDARD_DEVIATION 34.3 |
| Age, Continuous | 60.0 years STANDARD_DEVIATION 9.9 | 59.6 years STANDARD_DEVIATION 9.9 | 60.4 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 225 Participants | 120 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2198 Participants | 1091 Participants | 1107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting plasma glucose (mg/dl) | 107.9 mg/dl STANDARD_DEVIATION 7.4 | 108.0 mg/dl STANDARD_DEVIATION 7.4 | 107.8 mg/dl STANDARD_DEVIATION 7.4 |
| Glycated hemoglobin (%) | 5.9 % STANDARD_DEVIATION 0.2 | 5.9 % STANDARD_DEVIATION 0.2 | 5.9 % STANDARD_DEVIATION 0.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 13 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 130 Participants | 66 Participants | 64 Participants |
| Race (NIH/OMB) Black or African American | 616 Participants | 301 Participants | 315 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 43 Participants | 24 Participants | 19 Participants |
| Race (NIH/OMB) White | 1616 Participants | 810 Participants | 806 Participants |
| Region of Enrollment United States | 2423 participants | 1211 participants | 1212 participants |
| Serum 25-hydroxyvitamin D (ng/ml) | 28.0 ng/ml STANDARD_DEVIATION 10.2 | 27.7 ng/ml STANDARD_DEVIATION 10.2 | 28.2 ng/ml STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 1086 Participants | 541 Participants | 545 Participants |
| Sex: Female, Male Male | 1337 Participants | 670 Participants | 667 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 1,212 | 5 / 1,211 |
| other Total, other adverse events | 26 / 1,212 | 31 / 1,211 |
| serious Total, serious adverse events | 153 / 1,212 | 173 / 1,211 |
Outcome results
Primary
Time to Development of Diabetes
New-onset diabetes was based on annual glycemic testing of fasting plasma glucose, glycated hemoglobin, and 2-hour post-load plasma glucose and semiannual testing of fasting plasma glucose and glycated hemoglobin. If two or three of the glycemic measures met the 2010 ADA thresholds for diabetes, the participant was considered to have met the diabetes outcome. When only the measure for fasting plasma glucose or glycated hemoglobin met the threshold, confirmatory testing was performed for the positive measure within 8 weeks. If only the measure for 2-hour post-load plasma glucose met the threshold, then a 75-g oral glucose tolerance test to reassess all three glycemic measures was repeated. If the repeat measure was positive or both fasting plasma glucose and glycated hemoglobin were positive (in the case of a repeat oral glucose tolerance test), than the participant was considered to have met the diabetes outcome.
Time frame: Approximately 48 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Time to Development of Diabetes | 323 Participants |
| Vitamin D (Cholecalciferol) | Time to Development of Diabetes | 293 Participants |
Secondary
Blood Plasma 25OHD Concentration.
Time frame: Approximately 48 months
Secondary
Change in 2hPG as a Continuous Variable.
Time frame: Every 12 months for approximately 48 months.
Secondary
Change in Blood Pressure as a Continuous Variable.
Time frame: Approximately 48 months
Secondary
Change in FPG as a Continuous Variable.
Time frame: Every 12 months for approximately 48 months
Secondary
Change in HbA1c as a Continuous Variable.
Time frame: Every 6 months for approximately 48 months
Secondary
Identification of Characteristics Associated With the Variability in Achieved 25OHD Concentration.
Time frame: Every 12 months for approximately 48 months
Secondary
Measurement of Beta Cell Secretion (Derived From the OGTT)
Time frame: Every 12 months for approximately 48 months
Secondary
Measurement of Insulin Resistance (Derived From the OGTT).
Time frame: Every 12 months for approximately 48 months
Secondary
Number of Participants Who Discontinue Study Pills.
Time frame: Approximately 48 months
Secondary
Number of Participants With Adverse Events.
Time frame: Approximately 48 months
Secondary
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 25OHD Concentration
Time frame: Approximately 48 months
Secondary
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age
Time frame: Approximately 48 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age | 25-44 | 103 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age | 45-59 | 439 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age | ≥ 60 | 670 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age | 25-44 | 106 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age | 45-59 | 468 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age | ≥ 60 | 637 Participants |
Secondary
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI
Time frame: Approximately 48 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI | <30 | 429 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI | ≥30 | 783 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI | <30 | 435 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI | ≥30 | 776 Participants |
Secondary
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements
Time frame: Approximately 48 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements | No intake | 793 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements | Any intake | 419 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements | No intake | 826 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements | Any intake | 385 Participants |
Secondary
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure)
Time frame: Approximately 48 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure) | At or above 37° north latitude | 898 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure) | Below 37° north latitude | 314 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure) | At or above 37° north latitude | 892 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure) | Below 37° north latitude | 319 Participants |
Secondary
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria)
Participants met at least two of three glycemic criteria for prediabetes: fasting plasma glucose level, 100 to 125 mg per deciliter (5.6 to 6.9 mmol per liter); plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter (7.8 to 11.0 mmol per liter) (impaired glucose tolerance); and glycated hemoglobin level, 5.7 to 6.4% (39 to 47 mmol per mole).
Time frame: Approximately 48 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria) | Met all three criteria | 429 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria) | Met two criteria | 783 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria) | Met all three criteria | 427 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria) | Met two criteria | 784 Participants |
Secondary
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation)
Race and ethnic group were reporting by the participant. The category other includes American Indian or Alaska Native; Native Hawaiian or other Pacific Islander; and other race. Ethnic group includes any race.
Time frame: Approximately 48 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Race: Black | 315 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Ethnic Group: Hispanic | 105 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Race: Other | 91 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Ethnic Group: Non-Hispanic | 1107 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Race: White | 806 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Ethnic Group: Non-Hispanic | 1091 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Race: White | 810 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Race: Black | 301 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Race: Other | 100 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) | Ethnic Group: Hispanic | 120 Participants |
Secondary
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference
Time frame: Approximately 48 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference | <Median of 104.2 cm | 585 Participants |
| Placebo | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference | ≥Median of 104.2 cm | 627 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference | <Median of 104.2 cm | 620 Participants |
| Vitamin D (Cholecalciferol) | Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference | ≥Median of 104.2 cm | 591 Participants |
Other Pre-specified
Incidence of Cancer in a Pre-diabetes Population Defined by the Modern American Diabetes Association Criteria.
Time frame: Approximately 48 months.
Other Pre-specified
Incidence of Cardiovascular Disease in a Pre-diabetes Population Defined by the Modern American Diabetes Association Criteria.
Time frame: Approximately 48 months.
Other Pre-specified
Quality of Life and Mood Scores in Pre-diabetes Population Using a Validated Instrument (PROMIS-29 Profile v2.0 and a General Question on Perception of Overall Health From the PROMIS Scale 1.2).
Time frame: One time assessment at the month 24 visit.
Other Pre-specified
Time to Development of Cancer.
Time frame: Approximately 48 months.
Other Pre-specified
Time to Development of Cardiovascular Event.
Time frame: Approximately 48 months.
Other Pre-specified
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 2 Hour Plasma Glucose
Time frame: Approximately 48 months
Other Pre-specified
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Ethnicity
Time frame: Approximately 48 months.
Other Pre-specified
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Sex
Time frame: Approximately 48 months.