Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial

Abstract

Background: Vitamin D (VD) may increase sirtuin 1 (SIRT1) and subsequently PPAR-γ coactivator 1α (PGC-1α) and irisin levels and these improvements may reduce insulin resistance (IR). The aim was to assess the effects of vitamin D supplementation on SIRT1, irisin, and IR in overweight/obese type 2 diabetes (T2D) patients. Methods: Ninety T2D males and females were recruited as a clinical trial study (mean of age and body mass index (BMI) of intervention and placebo groups were 50.05 ± 10.17 and 50.36 ± 10.2 yrs. and 31.37 ± 3.4 and 30.43 ± 3.2 kg/m 2 , respectively). The inclusion criteria were T2D, VD deficient, BMI > 25 kg/m 2 , and serum HbA1c < 8.5%. The exclusion criteria were using vitamin and mineral supplements, having any acute disease, recent modifying dose or type of drugs. The supplementation was 50,000 IU/week VD or placebo for 8 weeks. The demographic characteristics, anthropometrics, dietary intakes and physical activity status, sun exposure status, fasting blood sugar (FBS) and insulin, glycosylated hemoglobin (HbA1c), irisin, SIRT1, 25-hydroxy D3 (25(OH)VD), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were determined. The significant P-value was ≤0.05. Results: The increase of serum VD, SIRT1, and irisin in the intervention group was significant (p < 0.001). HbA1c was decreased significantly by 1%. The changes in the other glucose indices (FBS, insulin, and IR) were non-significant. Conclusions: VD supplementation may improve T2D by decreasing HbA1c and increasing SIRT1 and irisin in VD deficient T2D patients. Further trials are suggested. Trial registration: Iranian Registry of Clinical Trials, IRCT201604202365N11. Registered 21/08/2016, http://en.irct. ir/trial/2019.

Role of Vitamin D in the Metabolic Syndrome

“…In their work, Lemieux et al demonstrated that supplementation with 5000 IU daily of vitamin D for 6 months increased insulin sensitivity and pancreatic β-cell activity [ 48 ]. Other authors showed the benefits of supplementation with 50,000 IU/week of vitamin D for 8 weeks in patients with type 2 diabetes, with a reduction in glycosylated hemoglobin and an increase in sirtuin 1, which appears to be related to increased insulin secretion by pancreatic β-cells [ 50 ]. In their study on diabetic patients, Farrokhian et al also observed that an administration pattern of 50,000 IU every 2 weeks for 6 months reduces basal glycemia, increasing insulin sensitivity [ 51 ].…”

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions

“…In diabetic animal models, vitamin D increases irisin expression [160]. In overweight and obese patients, depletion of vitamin D is associated with worsened inflammatory state in obese [161], whereas vitamin D stimulus upregulated PGC-1α expression and consequently irisin secretion [162] Moreover, Safarpour et al have demonstrated that in obese and diabetic subjects vitamin D supplementation counteracts impaired insulin signaling and increased irisin signaling pathway [163]. Then, the relationship between irisin and vitamin D should be further investigated.…”

The Effect of Daily Intake of Vitamin D-Fortified Yogurt Drink, With and Without Added Calcium, on Serum Adiponectin and Sirtuins 1 and 6 in Adult Subjects with Type 2 Diabetes

“…following adjustment for changes of serum SIRT1 indicates a SIRT1-mediated effect of vitamin D on adiponectin secretion. Thus, vitamin D up-regulates SIRT1, as demonstrated in both animal model [51] and randomized clinical trial [21] and then SIRT1 in turn regulates adiponectin secretion. This nding is in accord with the report of regulation of adiponectin secretion by SIRT1 and endoplasmic reticulum oxidoreductase Ero1-Lα [52].…”

“…The ameliorating effects of raising vitamin D status of subjects with T2D on glycemic status as well as parathyroid hormone, some antioxidative and in ammatory biomarkers have been already documented [10,13,14,[17][18][19]. Though the regulating effect of vitamin D on pancreatic β-cell function and insulin signaling has been described [20], there is evidence suggesting an indirect effect of vitamin D in T2D through other mediators including adiponectin and sirtuins [13,21].…”