Inclusion Criteria:
1. High-risk prediabetes ("at high risk for type 2 diabetes") defined by meeting the following 2 prediabetes criteria established by the American Diabetes Association (ADA) in the 2010 clinical practice guidelines:
1. Fasting plasma glucose (FPG) 100-125 mg/dL, inclusive
2. Hemoglobin A1c (HbA1c) 5.7-6.4%, inclusive
2. Age 30-74 years, inclusive
3. Body Mass Index ≥ 23.0 and ≤ 35.0 kg/m2
4. Provision of signed and dated written informed consent prior to any study procedures.
Exclusion Criteria:
5. History of diabetes (ICD10 diabetes code E08.X through E13.X) or meeting a diabetes glycemic criterion at screening, as defined by the ADA guidelines (FPG ≥ 126 mg/dL or HbA1c ≥ 6.5%).
6. History (past 2 years) of hyperparathyroidism, symptomatic or asymptomatic (i.e., radiographic) nephrolithiasis or hypercalcemia.
7. Any medical condition (past 2 years) that in the opinion of the site investigator may increase risk for nephrolithiasis or hypercalcemia during the trial (e.g., sarcoidosis).
8. If older than 70 years, history (past 1 year) of a fall.
9. Use of tanning devices within 12 weeks of the baseline visit and unwilling to stop use of tanning devices for the duration of the study.
Medications and Supplements
10. Use (past 6 months) of hypoglycemic pharmacotherapy (oral or injectable medication approved by the FDA for type 2 diabetes) for any condition (e.g., prediabetes, diabetes, polycystic ovarian syndrome, MASLD, sleep apnea) or any other medication that may affect glycemia (e.g., hydroxychloroquine)
11. Current use of medications approved by the FDA for weight management (e.g., incretin receptor agonists) or planned use during the study.
12. Use of supplements containing vitamin D at total doses higher than 1000 IU/day within 8 weeks of the baseline visit and unwillingness to limit vitamin D supplementation dosage to no higher than 1000 IU/day during the study. Because supplements vary widely in vitamin D content (e.g., may include cod liver or cod liver oi), participants will bring all supplements to the site for a review by the research team.
13. Use of supplements containing calcium at total doses higher than 600 mg/day within 1 week of the baseline visit and unwillingness to limit calcium supplementation dosage to no higher than 600 mg/day during the study.
14. Current use of medications or conditions (e.g., untreated celiac disease) that would interfere with the absorption or metabolism of vitamin D.
15. Use of an anticonvulsant drug started within 6 months of screening. Stable regimen of anticonvulsants is allowed.
16. History of intolerance to vitamin D supplements, allergic to any content of the study drug or unwilling to take vitamin D supplements (e.g., someone who eats a vegan diet and would object to the cholecalciferol ingredient which is produced from cholesterol extracted from sheep wool harvested from healthy living sheep).
Other Medical History
17. Severe symptomatic cardiovascular disease based on history (unstable angina, dyspnea on exertion, paroxysmal nocturnal dyspnea, arrhythmia, congestive heart failure NYHA class II or higher, claudication)
18. History (past 1 year) of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass graft.
19. History (past 1 year) of cerebrovascular disease (stroke, transient ischemic attack).
20. Any type of cancer (past 5 years) except for basal cell skin cancer. Prostate cancer (for men over age 55) or well-differentiated thyroid cancer not expected to require treatment (except for suppression with thyroid hormone) over the next 3 years, are not exclusions. People with history of squamous cell cancer of the skin, which was completely excised and with no evidence of metastases, are eligible.
21. History (past 6 months) of treatment with oral (for \> 7 days) or intravenous glucocorticoids or disease likely to require oral or intravenous glucocorticoid therapy during the study. Inhaled glucocorticoid use is not an exclusion. Epidural or intra-articular glucocorticoid injections are not exclusions, but study visits need to be conducted at least two weeks after the injection. Persons with adrenal insufficiency treated with physiologic doses of glucocorticoids who are otherwise stable are not excluded.
22. History (past 1 year) of substance abuse or unstable psychiatric disorder that in the opinion of the site investigator would impede competence or adherence with study procedures or hinder completion of the study or increase risk.
23. History of bariatric surgery (e.g., Roux-en-Y gastric bypass, gastric sleeve) or planned bariatric surgery in the next 2 years.
24. Extreme (over 18 hours) intermittent fasting diets because prolonged fasting downregulates CYP2R1 activity.
25. A life-threatening event within 30 days of screening or currently planned major surgery.
26. Any other active medical condition (including but not limited to liver disease, wasting illness, HIV, tuberculosis, oxygen-dependent chronic obstructive pulmonary disease, organ transplant, Cushing's syndrome) that in the opinion of the site investigators would interfere with the study objectives, impede competence or adherence with study procedures or increase risk.
27. Uncontrolled hypertension (systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 100 mm Hg).
28. Poor venous access.
Laboratory Evaluation
29. Serum liver transaminase higher than 3 times the normal range for the clinical site's laboratory, within 18 months of screening.
30. Anemia (hematocrit \< 32 for women, \< 36 for men), whole blood transfusion (within 18 months of screening) or chronic requirement, whole blood donation (within 3 months of screening) or other condition (hemolysis, hemoglobinopathy) rendering HbA1c results unreliable as indicator of chronic glycemia. Participants who donate platelets are not excluded.
31. Low platelet count (\< 100,000) within 18 months of screening.
32. Chronic kidney disease, defined as estimated glomerular filtration rate \[GFR\] \< 50 mL/min per 1.73 m2 from creatinine level and GFR calculated by the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations that omit race within 18 months of screening.
33. Hypercalcemia, defined as serum calcium concentration ≥ upper limit of normal within 18 months of screening.
34. Hypercalciuria, defined as spot urine (morning void) calcium-creatinine ratio \> 0.275 within 18 months of screening.
35. Baseline serum 25(OH)D level greater than 100 ng/mL.
Other
36. Participation (within 30 days of screening) in another interventional research study, and unwillingness to refrain from participating in another intervention study during the study.
37. Previous randomization in the study. Participants who did not qualify after screening may be screened again if the prior reason for exclusion has been addressed (e.g., high blood pressure is treated).
38. Any other reason that in the opinion of the site investigator would interfere with the study objectives, impede adherence with study procedures or hinder completion of the study or increase risk.
Women only
39. Pregnancy (past 1 year by report or positive pregnancy test at screening), intent to become pregnant in the next 2 years. History of gestational diabetes is not an exclusion criterion.
40. Currently breastfeeding.
41. Use of oral contraceptives or menopausal hormone therapy started within 3 months of baseline. .
Continuous Glucose Monitoring specific
42. Regular use of personal CGM and unwillingness to refrain from using personal CGM for the duration of the study.
43. Use of hydroxyurea or regular use of high doses of acetaminophen (may impact CGM).
44. Extensive skin changes (e.g., skin breakdown, rash) making CGM sensor use problematic.
45. Significant skin sensitivity to adhesive (making CGM sensor unfeasible).
