Despite some interesting findings in this study, our analyses had a limitation that part of the data regarding the involvement of Sirt1/6 in the RGZ’s effects was based on the alteration of mRNA expression. In general, the mRNA expression of specific target gene corresponds to its protein levels. However, it is possible to have a discrepancy between mRNA expression and protein levels due to post-transcriptional, translational or post-translational regulations. The present study was conducted to elucidate of Sirt1 and Sirt6 on regulation of hepatic fat accumulation by RGZ. Using a rat model of moderate obesity and insulin resistance and a cell model of hepatocyte steatosis, we report upregulation of adiponectin, Sirt1/6, and downstream D-Pantothenic acid sodium targets of Sirt1/6, and also, increases in both LKB1 and AMPK activities following RGZ treatment. Additionally, we demonstrated that Sirt1/6 knockdown abolished the effects of RGZ with regard to hepatocyte fat accumulation and the Sirt1/6-AMPK pathway, suggesting that Sirt1/6 regulates RGZ-mediated metabolic processes and that the relationship between Sirt 1 and Sirt6 may be compensatory without synergistic effects. These findings indicate that Sirt1 and Sirt6 are involved in the RGZ-mediated improvement of hepatocyte steatosis, and warrant future study to identify the interaction of different sirtuins on metabolic regulation. Glaucoma is a significant cause of irreversible blindness worldwide. Primary open angle glaucoma is the most common type. Older age, a family history of POAG, myopia, central corneal thickness, and ocular hypertension are relatively consistent risk factors for POAG. Diabetes mellitus is a serious and increasingly prevalent health problem worldwide due to lifestyle changes and an aging population. DM is associated with severe acute and chronic complications, which negatively influence both the quality of life and the survival of affected individuals. Some Butenafine hydrochloride studies also found that DM is another possible risk factor for POAG. However, the relationship between DM and POAG is controversial. An earlier meta-analysis in 2004 indicated that DM is associated with an increased risk of developing POAG. However, that meta-analysis of seven cross-sectional and five case-control studies of DM and the risk of POAG did not include any cohort studies. The major drawback of cross-sectional studies is that they cannot establish clear temporal relationship between exposure and outcome. Prospective cohort studies would be a good way to assess the relationship between exposure to diabetes and development of POAG. Since then, much larger-scale epidemiological evidence, especially cohort studies, of an association between DM and POAG has been reported. However, these epidemiological studies of the relationship between DM and POAG were somewhat contradictory and inconclusive, and two studies reported discordant results. To provide a more accurate estimate of the association between DM and POAG, we conducted a meta-analysis of all case-control and cohort studies involving DM and POAG. Although several risk factors for the development of POAG have been evaluated, this is a field of ongoing investigation. DM is a possible risk factor for POAG. The current literature does not provide a definitive link between DM and POAG. Hence, the purpose of this systematic review and meta-analysis was to summarize all the available relevant evidence with reference to the relationship between DM and POAG.