Type 2 Diabetes, Fasting Glucose, Hemoglobin A1c Levels and Risk of Primary Open-Angle Glaucoma: A Mendelian Randomization Study

Abstract

Purpose To evaluate the potential causal associations between type 2 diabetes and fasting glucose and HbA1c levels and the risk of primary open-angle glaucoma (POAG) in European and East Asian populations. Methods We selected genetic variants ( P < 5 × 10 −8 ) for type 2 diabetes (898,130 Europeans; 433,540 East Asians), fasting glucose, and HbA1c (196,991 Europeans; 36,584 East Asians) from three meta-analyses of genome-wide association studies (GWAS). The GWAS for POAG provided summary statistics (192,702 Europeans; 46,523 East Asians). Mendelian randomization (MR) analysis was accomplished using the inverse variance–weighted method, weighted-median method, MR Egger method, and MR-Pleiotropy RESidual Sum and Outlier test. Results Genetically predicted type 2 diabetes was potentially positively associated with POAG in the European ancestry (body mass index [BMI]–unadjusted: odds ratio [OR] = 1.07, 95% confidence interval [CI], 1.01–1.14, P = 0.028; BMI-adjusted: OR = 1.07, 95% CI, 1.01–1.15, P = 0.035), but not in the East Asian ancestry (BMI-unadjusted: OR = 1.01, 95% CI, 0.95–1.06, P = 0.866; BMI-adjusted: OR = 1.00, 95% CI, 0.94–1.05, P = 0.882). There was no evidence to support a causal association of fasting glucose (European: OR = 1.19, P = 0.157; East Asian: OR = 0.94, P = 0.715) and HbA1c (European: OR = 1.27, P = 0.178; East Asian: OR = 0.85, P = 0.508) levels with POAG. Conclusions The causal effect of type 2 diabetes on the risk of POAG is different in European and East Asian populations. The point estimates of fasting glucose and Hb1Ac with POAG are large but not statistically significant, which prompts the question of statistical power.

Neuroprotektive Wirkungen von Antidiabetika in der Therapie von Patienten mit Diabetes und Glaukom oder hohem Glaukomrisiko

“…Epidemiologically, numerous studies have been conducted, and the majority have shown an association between glaucoma and type 2 DM 3 , 13 , 14 . Whether this is a causal relationship, i.e., whether diabetes has a causal effect on the pathogenesis and progression of POAG, is the subject of intense scientific debate.…”

“…Epidemiologisch existieren zahlreiche Untersuchungen, die in der Mehrzahl einen Zusammenhang zwischen Diabetes mellitus Typ 2 und Glaukom gezeigt haben 3 , 13 , 14 . Ob es sich hier um einen kausalen Zusammenhang handelt, d. h. der Diabetes die Entstehung und Progression des POWG ursächlich beeinflusst, ist Gegenstand intensiver wissenschaftlicher Diskussionen.…”

Blood cell traits and risk of glaucoma: A two-sample mendelian randomization study

“…Besides, MR studies avoids reverse causality because of the genetic variant used as IVs were generated earlier than most of outcomes happening ( Hingorani and Humphries, 2005 ). Recent MR studies have demonstrated that type 2 diabetes ( Hu et al, 2022 ), myopic refractive error ( Choquet et al, 2022 ), coffee consumption ( Li et al, 2022 ), and blood lipid-related metabolites ( Nusinovici et al, 2022 ) have potential causal associations with glaucoma.…”

Causal factors in primary open angle glaucoma: a phenome-wide Mendelian randomisation study

“…To date, the use of MR approaches in the context of POAG has been relatively limited. Despite this, these methods have been successfully implemented to explore the relationship between POAG and a small number of traits including brain alterations 11 , plasma lipid levels 12 , fatty acids 13 , type 2 diabetes 14 , HbA1c levels 14 , fasting glucose, coffee consumption 15 and blood pressure 16 .…”