RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.
INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.
METHODS: We analysed data from 4101 adults (Malay, n = 1901 and Indian, n = 2200) who participated in the baseline (2004-2009) and 6-year follow-up (2011-2015) of two independent population-based studies with similar methodology in Singapore. BMI was categorised into normal (<25 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). DM was diagnosed as random plasma glucose ≥200 mg/dL, HbA1c ≥6.5% or self-reported physician diagnosed DM. DR was assessed from retinal photographs graded using a standard protocol. The associations of baseline BMI with incident DM and DR was examined using multivariable poisson regression models adjusting for potential confounders including duration of DM, family history of DM and HbA1c.
RESULTS: The incidence of DM was 12.8% and among 1586 participants with DM, the incidence of DR was 17.6% over a median follow-up period of 6.2 years. Compared to those with BMI
DESIGN: A questionnaire containing 47 questions was developed which encompassed clinical scenarios such as treatment response to anti-vascular endothelial growth factor and steroid, treatment side effects, as well as cost and compliance/reimbursement in the management of DME using a Dephi questionnaire as guide.
METHODS: An expert panel of 12 retinal specialists from Singapore, Malaysia, Philippines, India and Vietnam responded to this questionnaire on two separate occasions. The first round responses were compiled, analyzed and discussed in a round table discussion where a consensus was sought through voting. Consensus was considered achieved, when 9 of the 12 panellists (75%) agreed on a recommendation.
RESULTS: The DME patients were initially profiled based on their response to treatment, and the terms target response, adequate response, nonresponse, and inadequate response were defined. The panellists arrived at a consensus on various aspects of DME treatment such as need for classification of patients before treatment, first-line treatment options, appropriate time to switch between treatment modalities, and steroid-related side effects based on which recommendations were derived, and a treatment algorithm was developed.
CONCLUSIONS: This consensus article provides comprehensive, evidence-based treatment guidelines in the management of DME in Asian population. In addition, it also provides recommendations on other aspects of DME management such as steroid treatment for stable glaucoma patients, management of intraocular pressure rise, and recommendations for cataract development.