Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons With Diabetes Mellitus.
Lin Hsien-Chang,Stein Joshua D,Nan Bin,Childers David,Newman-Casey Paula Anne,Thompson Debra A,Richards Julia E
IMPORTANCE:Caloric restriction mimetic drugs have geroprotective effects that delay or reduce risks for a variety of age-associated systemic diseases, suggesting that such drugs might also have the potential to reduce risks of blinding ophthalmologic conditions for which age is a major risk factor. OBJECTIVE:To determine whether the caloric restriction mimetic drug metformin hydrochloride is associated with reduced risk of open-angle glaucoma (OAG) in persons with diabetes mellitus. DESIGN, SETTING, AND PATIENTS:Retrospective cohort study of patients aged 40 years or older with diabetes mellitus and no preexisting record of OAG in a large US managed care network from January 1, 2001, through December 31, 2010. EXPOSURES:Quantity of metformin and other prescribed diabetes medications as captured from outpatient pharmacy records. MAIN OUTCOMES AND MEASURES:Risk of developing OAG. RESULTS:Of 150 016 patients with diabetes mellitus, 5893 (3.9%) developed OAG. After adjusting for confounding factors, those prescribed the highest quartile of metformin hydrochloride (>1110 g in 2 years) had a 25% reduced OAG risk relative to those who took no metformin (hazard ratio = 0.75; 95% CI, 0.59-0.95; P = .02). Every 1-g increase in metformin hydrochloride use was associated with a 0.16% reduction in OAG risk (adjusted hazard ratio = 0.99984; 95% CI, 0.99969-0.99999; P = .04), which predicts that taking a standard dose of 2 g of metformin hydrochloride per day for 2 years would result in a 20.8% reduction in risk of OAG. After accounting for potential confounders, including metformin and diabetic medications, the risk of developing OAG was increased by 8% (hazard ratio = 1.08; 95% CI, 1.03-1.13; P = .003) for each unit of increase in glycated hemoglobin level. CONCLUSIONS AND RELEVANCE:Metformin use is associated with reduction in risk of developing OAG, and risk is reduced even when accounting for glycemic control in the form of glycated hemoglobin level. Other diabetes medications did not confer a similar OAG risk reduction. This study suggests that metformin may be affecting OAG risk on multiple levels, some involving improved glycemic control and some involving mechanisms outside glycemic control such as neurogenesis, inflammatory systems, or longevity pathways targeted by caloric restriction mimetic drugs. If confirmed by prospective clinical trials, these findings could lead to novel treatments for this sight-threatening disease.
Type 2 diabetes mellitus and risk of open-angle glaucoma development in Koreans: An 11-year nationwide propensity-score-matched study.
Jung Y,Han K,Park H-Y L,Park C K
Diabetes & metabolism
PURPOSE:To evaluate the risk of primary open-angle glaucoma (POAG) development in type 2 diabetes mellitus (T2DM) patients. METHODS:In this 11-year longitudinal study based on the Korean National Health Insurance research database, the data collected comprised 1,025,340 (2.2%) participants who were randomly selected from 46,605,433 Korean residents in 2002. The database was analyzed to identify participants with an initial diagnosis of T2DM in 2003-2004. The control group was composed of participants without T2DM who were propensity-score-matched, five controls per T2DM patient, according to age, gender, household income, residential area and underlying diseases, including hypertension, dyslipidaemia, coronary heart disease, cerebrovascular disease and thyroid disease. Cox proportional-hazards regression was used to calculate the overall hazard ratios (HRs) in participants with and without T2DM for development of POAG before and after adjusting for confounding factors. RESULTS:There were 12,657 participants with T2DM and 63,285 propensity-score-matched controls without T2DM. POAG developed in 413 (3.3%) and 1188 (1.9%) participants in the T2DM and control groups, respectively. T2DM was associated with an increased risk of POAG development [HR: 1.80; 95% confidence interval (CI): 1.58-2.04] after adjusting for age, gender, household income and other potential confounders. CONCLUSION:T2DM was significantly associated with the development of POAG after adjusting for potential confounders in the Korean population.
Increased risk of open-angle glaucoma among patients with diabetes mellitus: a 10-year follow-up nationwide cohort study.
Rim Tyler Hyungtaek,Lee Sang Yeop,Bae Hyoung Won,Seong Gong Je,Kim Sung Soo,Kim Chan Yun
PURPOSE:To evaluate the risk of open-angle glaucoma among patients with diabetes. METHODS:This retrospective propensity score-matched cohort study included patients with diabetes and a matched comparison group from the Korean National Health Insurance Service National Health Screening Cohort, which includes approximately 500 000 adults aged ≥40 years. Nondiabetes group was matched to diabetes group in a 1:1 ratio using a propensity score based on age, sex, comorbidities, antihypertensive medication use and medical care visits. Each group was followed from January 1, 2004 to either the date of developing open-angle glaucoma or the date of last follow-up in 2013. RESULTS:Incidence of open-angle glaucoma was 20.0/10 000 person-years in diabetes group (n = 58 358) and 17.0/10 000 person-years in nondiabetes group (n = 58 358). Age- and sex- adjusted hazard ratio (HR) was 1.19 (95% confidence interval [CI], 1.09-1.30). In the subgroup analyses, diabetes was associated with an increased risk of open-angle glaucoma in both younger and older age groups (HR = 1.20 for those aged 40-59 years and HR = 1.18 for those aged 60-79 years) and in both sexes (men, HR = 1.13; women, HR = 1.27). CONCLUSION:Patients diagnosed with diabetes were more likely to develop open-angle glaucoma compared with patients without diabetes.