Association of Insulin Analogue and Antihypertensive Drug Use with Sight-Threatening Diabetic Retinopathy in Type 2 Diabetes

Autor: Jen-Chieh Lin, 林人傑
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
Objectives: The aims of the study are to estimate age- and sex-specific prevalence and incidence of sight-threatening diabetic retinopathy in Taiwan and evaluate the effect of systemic drugs on prevention of diabetic retinopathy progression, focusing on antihypertensive drugs and long-acting insulin analogues. Materials and Methods: Data was collected from a representative database, Longitudinal Health Insurance Database (LHID) 2005, during 2005, on a total of 222 incident cases of patients with sight-threatening diabetic retinopathy (STDR) among 29,165 type 2 diabetic patients. Sight-threatening diabetic retinopathy was defined as clinically significant macular edema or severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy according to the classification of the Early Treatment Diabetic Retinopathy Study Research Group. Gender-specific and age-adjusted incidence and prevalence rates of STDR were analyzed for the patients with type 2 diabetes and STDR identified using ICD-9-CM codes and procedure codes. Type 2 diabetic patients aged 20-100 years, with at least one prescription for antihypertensive drugs between 2000 and 2011 were identified from Longitudinal Health Insurance Database (LHID) 2005. The incidence rates of STDR were followed and Cox proportional hazards models were used to analyze the risk associated with antihypertensive drugs. A retrospective cohort consisting of patients with type 2 diabetes aged &;#8805; 20 years and newly initiated on long-acting insulin analogues (glargine and detemir) and intermediate-acting human insulin were identified from the National Health Insurance database between January 2004 and December 2006 and categorized into different cohorts. Risk of developing STDR was determined by Cox proportional hazards models and compared between different cohorts. Results: The number of incident cases of STDR increased in line with the increasing diabetic population during 2005-2011. During 2005, no gender differences in the age-adjusted incidence and prevalence rates were observed. The prevalence of sight-threatening DR was significantly higher when patients were aged 40-59 and 60-79. The crude incidence rates of STDR among patients received thiazide diuretics, alpha-blockers, beta-blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB) were 16.45, 9.49, 12.81, 19.19, 17.63, and 18.15 per 1,000 person-years. Users of ACEI and ARB were associated with a significantly higher risk than CCB users, independent of baseline characteristics. After adjusting time-varying use of concomitant medications for propensity score (PS) matched or unmatched cohorts, the results showed that patients receiving ACEI, ARB and CCB were associated with a significantly greater risk compared with beta-blocker users. The hazard ratio varied from 1.18 to 1.55 with statistical significance. Of the 32,395 eligible patients, initiators of insulin glargine, insulin detemir and NPH insulin were identified for comparison through propensity score matching. Long-acting insulin analogue, glargine, was not associated with changed risk for STDR by intention-to-treat and time-varying use approaches between either matched or unmatched cohorts. However, patients treated with insulin detemir, were associated with significantly changed risk for sight-threatening DR while analyses were performed by different approach for matched and unmatched cohort. Conclusions: There was no significant difference in the incidence between genders. Our findings provide the evidence that the incident cases of STDR increased among identified type 2 diabetic patients, but the overall prevalence of STDR was in a declining trend in Taiwan, suggesting that decreased mortality rate, better diabetes management, and early detection of treatable DR might contribute to the prevalence patterns. Our study did not support a superiority of ACEI, ARB and CCB over beta-blockers for lowering the progression of DR over 11-year follow-up. While comparing long-acting insulin analogue, glargine, with NPH insulin, no significant difference in the risk of sight-threatening DR was found. However, significantly increased risk was detected in insulin detemir initiators compared with NPH insulin initiators. The strategies that aim at preventing DR by treating type 2 diabetic patients with long-acting insulin analogues remain further prospective studies with longer follow-up period to validate our observations within an appropriate dosage range and to further evaluate the safety of long-acting insulin analogues on reducing the progression of DR.
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