Although it has been suggested that selenium (Se) increases the risk of T2DM, most evidence comes from observational studies that cannot prove causality. A systematic review assessed randomized clinical trials and found that the risk of T2DM was not greater in those randomized to Se supplementation than in those randomized to placebo. Se is a toxic element in animals and humans, and overexposure to Se has also been linked to detrimental health effects in humans. Previous studies were mostly conducted in Se-sufficient areas. Moreover, the effectiveness of low-dose Se supplementation on participants with elevated glycemic status was unknown. This cross-over, double blinded, randomized controlled trail aimed to investigate the effectiveness of Se supplementation for glucose control among participants with diabetes or prediabetes. Moreover, we also aimed to examine whether selenoprotein P genotypes, Se-related gut microbiota and their related metabolite modified the effectiveness.

Inclusion Criteria:

1. FPG ≥ 5.6 mmol/L;
2. HbA1c ≥ 5.7%;
3. OGTT 2h or postprandial blood glucose ≥ 7.8 mmol/L.
4. T2D patients with stable anti-diabetic medication and blood glucose controlled well for 4 weeks prior.

Exclusion Criteria:

1. Under 30 years old or above 70 years old;
2. Pregnancy;
3. Major surgery in the previous 6 months or planned to occur during the trail;
4. Insulin injection for diabetes;
5. Suffering from severe obesity (BMI > 40 kg/m2), immunodeficiency syndrome, thyroid disease, coronary heart disease, stroke, malignant neoplasm, kidney or liver disease, or other serious diseases, such as mental illness;
6. Reduced kidney function (GFR < 60 mL/min/1.73m2, creatinine > 1.2 times the normal upper limit [male, > 133.2 μmol/L; female > 100 μmol/L]);
7. Systolic or diastolic blood pressure greater than 160 or 100 mmHg;
8. Taking dietary supplements (e.g., selenium, vitamin, fish oil, etc.) for nearly one month before the intervention;
9. Taking antibiotics or probiotics within 12 weeks of screening.