Type 2 diabetes (T2D) is a prevalent metabolic disease with a projected increase in cases globally. While weight management and healthy lifestyles are crucial for T2D management, research explores alternative therapies, including dietary supplements. Vitamin D has shown potential benefits in diabetes, possibly through indirect effects on adiponectin and sirtuins. Adiponectin, an adipokine, improves insulin resistance, while sirtuins, NAD+-dependent enzymes, play a role in insulin resistance, inflammation, and oxidative stress. SIRT1 and SIRT6 are particularly relevant to glucose homeostasis in T2D. This study aimed to investigate the effects of daily vitamin D-fortified yogurt, with and without added calcium, on serum adiponectin, SIRT1, and SIRT6 levels in adults with T2D, examining whether added calcium influences these effects.

Existing literature suggests a link between vitamin D and T2D, with studies demonstrating the ameliorating effects of increased vitamin D status on glycemic status, parathyroid hormone, and inflammatory biomarkers in T2D patients. While the direct effect of vitamin D on pancreatic β-cell function and insulin signaling is acknowledged, evidence suggests indirect effects through adiponectin and sirtuins. Adiponectin, primarily secreted by adipose tissue, regulates blood glucose and lipids, improving insulin resistance. Sirtuins, involved in aging and longevity, influence insulin resistance, inflammation, and oxidative stress in diabetes, making them potential therapeutic targets. SIRT1 and SIRT6 specifically are highlighted for their role in glucose homeostasis.

This study utilized serum samples and data from a previously conducted clinical trial (NCT01229891). 75 adults (30 men, 45 women) aged 30-60 years with confirmed T2D were randomly allocated to one of three groups: (i) D-fortified yogurt drink (DY; 1000 IU vitamin D, 300 mg calcium), (ii) Ca+D-fortified yogurt drink (CDY; 1000 IU vitamin D, 500 mg calcium), and (iii) plain yogurt drink (PY; no vitamin D, 300 mg calcium). The intervention lasted 12 weeks. Assessments, including dietary intake (24-hour recall), anthropometrics (weight, height, BMI), and serum concentrations of 25(OH)D (HPLC), HbA1c, adiponectin, and total body fat mass (FM) were performed at baseline and after 12 weeks. Serum SIRT1 and SIRT6 were measured using EIA. Statistical analyses included ANOVA, chi-square test, Pearson correlation, and multiple linear regression. A p-value < 0.05 was considered significant.

No significant between-group differences in dietary intake were observed at baseline. Both DY and CDY groups showed significant within-group increases in serum adiponectin (+60.4 ± 8.6 µg/L and +57.5 ± 6.4 µg/L, respectively, p < 0.001 for both). Significant within-group increases in SIRT1 and SIRT6 were observed only in the CDY group (p = 0.003 and p = 0.001, respectively). Being in the CDY group was a more favorable predictor of SIRT6 improvement. Changes in 25(OH)D were significant predictors of changes in adiponectin, but this association disappeared after adjusting for SIRT1 changes. However, the association between 25(OH)D and HbA1c remained significant even after adjusting for SIRT1. Multiple regression analysis indicated that daily intake of D-fortified yogurt (with or without added calcium) significantly increased SIRT1 compared to PY. CDY intake significantly increased SIRT6 compared to PY. Both D-fortified groups showed significant decreases in BMI and FM.

The findings support the hypothesis that vitamin D supplementation increases circulating SIRT1 and SIRT6 levels in T2D individuals. The observed increase in adiponectin in both D-fortified yogurt groups suggests a potential role for vitamin D in improving insulin sensitivity, possibly mediated by SIRT1. The greater impact of CDY on SIRT6 suggests that calcium may play a synergistic role in regulating sirtuin expression. The persistence of the association between 25(OH)D and HbA1c after adjusting for SIRT1 suggests that vitamin D's effect on glycemic control may be partly independent of SIRT1. The reduction in BMI and FM in both D-fortified groups implies additional mechanisms beyond SIRT1 and SIRT6 involvement in vitamin D’s impact on weight management.

Daily consumption of vitamin D-fortified yogurt for 12 weeks increased circulating SIRT1 and SIRT6 in T2D subjects, with CDY showing greater benefit for SIRT6. Vitamin D's impact on adiponectin appears SIRT1-dependent, while its effect on HbA1c seems SIRT1-independent. Further research is needed to explore the long-term effects of vitamin D and calcium supplementation on T2D management, investigate the role of other sirtuins, and clarify the intricate interplay between vitamin D, sirtuins, and metabolic parameters in T2D.

The study's short duration (12 weeks) limits the assessment of long-term effects. The study did not evaluate other sirtuins that might affect pancreatic β-cell function (e.g., SIRT3). The relatively small sample size may affect the generalizability of findings. The study design relied on self-reported dietary intake, which can be subject to recall bias.