The Effects of Lipid Lowering on Diabetic Retinopathy

Gordon, Bruce R.; Kavanagh, Mary; Robertson, Carolyn; Drexler, Andrew; Chang, Stanley; Berrocal, María H.; Yannuzzi, Lawrence A.

doi:10.1016/s0002-9394(14)76244-0

Cited by 122 publications

(69 citation statements)

References 17 publications

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“…An interaction was noted between the method of diabetes diagnosis and statin use, with respect to diabetic retinopathy and gangrene, but risk estimates for individuals diagnosed via hospital or prescription records pointed in the same direction (appendix pp [19][20][21]. Other possible interactions were not consistent among several endpoints and, therefore, could represent chance fi ndings.…”

Section: Resultsmentioning

confidence: 98%

“…Diabetic retinopathy was a primary outcome in some randomised trials of statins in individuals with diabetes, in which lipid abnor ma lities were also targeted. [19][20][21][22] In one trial (n=30), a signifi cant reduction in the severity of hard exudates (p=0·007) and subfoveal lipid migration in macular oedema (p=0·04) were noted. 19 In a second trial (n=133), fl uorescein angiography and colour fundus photography worsened in patients allocated to placebo, but not in those allocated to a statin (p=0·009); 20 a similar result was reported in a study of six individuals with type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…19 In a second trial (n=133), fl uorescein angiography and colour fundus photography worsened in patients allocated to placebo, but not in those allocated to a statin (p=0·009); 20 a similar result was reported in a study of six individuals with type 1 diabetes. 21 Finally, in a randomised trial of 166 individuals with type 2 diabetes who received multifactorial interven tion, including statin use versus placebo, 22 secondary outcomes included a reduced risk of diabetic retinopathy (hazard ratio 0·57, 95% CI 0·37-0·88), neuropathy (0·53, 0·34-0·81), and nephropathy (0·44, 0·25-0·77). These results accord with our fi ndings in the total population of 186 295 individuals with diabetes, except we were unable to detect any reduction in risk for development of nephropathy unless we adjusted for use of antihypertensives before the diagnosis of diabetes.…”

Section: Discussionmentioning

confidence: 99%

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Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study

Nielsen

Nordestgaard

2014

The Lancet Diabetes & Endocrinology

103

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SummaryBackground The role of statins in the development of microvascular disease in patients with diabetes is unknown. We tested the hypothesis that statin use increases the risk of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and gangrene of the foot in individuals with diabetes. MethodsWe identifi ed all patients living in Denmark who were aged 40 years or older and were diagnosed with incident diabetes between Jan 1, 1996, and Dec 31, 2009. We obtained patients' data from the Danish Patient Registry and information on drug use from the Danish Registry of Medicinal Product Statistics. We randomly selected 15 679 individuals from the database who had used statins regularly until their diagnosis of diabetes (statin users) and matched them in a 1:3 ratio with 47 037 individuals who had never used statins before diagnosis (non-statin users). Our primary outcome was to compare the cumulative incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, or gangrene of the foot in statin users versus non-statin users. We analysed data with Cox regression models, adjusted for covariates including sex, age at diabetes diagnosis, and method of diabetes diagnosis. To address potential biases between statin users and non-statin users, we made adjustments to our analysis with a propensity score and with other factors. Median follow-up was 2·7 years (range 0-13).Findings During 215 725 person-years of follow-up, 2866 patients developed diabetic retinopathy, 1406 developed diabetic neuropathy, 1248 developed diabetic nephropathy, and 2392 developed gangrene of the foot. Compared with non-statin users, statin users had a lower cumulative incidence of diabetic retinopathy (hazard ratio 0·60, 95% CI 0·54-0·66; p<0·0001), diabetic neuropathy (0·66, 0·57-0·75; p<0·0001), and gangrene of the foot (0·88, 0·80-0·97; p=0·010), but not diabetic nephropathy (0·97, 0·85-1·10; p=0·62). These results were similar after adjusting for the competing risk of death, after matching for a propensity score, after adjusting for visits to a family doctor, and by stratifi cation on covariates. The corresponding multivariable adjusted hazard ratio for risk of diabetes in the total population was 1·17 (95% CI 1·14-1·21; p<0·0001).Interpretation Use of statins before diagnosis of incident diabetes was not associated with an increased risk of microvascular disease. Whether statins are protective against some forms of microvascular disease-a possibility raised by these data-will need to be addressed in other studies similar to ours, in mendelian randomisation studies, and preferably in randomised controlled trials. Funding

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study

Nielsen

Nordestgaard

2014

The Lancet Diabetes & Endocrinology

103

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“…The study noted that statin users had lower cumulative incidence of diabetic retinopathy (HR 0.60; 95 % CI 0.54-0.66) and Two small trials reported that statins were associated with an improvement in diabetic retinopathy in diabetic patients. 67,68 For example, in one of the studies, which was a randomized controlled trial (50 patients with diabetic retinopathy), simvastatin was associated with improved ophthalmologic fundus examination. 68 On the other hand, several observational and experimental studies have noted that statin use was associated with high blood glucose levels.…”

Section: Discussionmentioning

confidence: 99%

Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults

et al. 2015

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BACKGROUND: Statin use is associated with increased incidence of diabetes and possibly with increased body weight and reduced exercise capacity. Data on the longterm effects of these associations in healthy adults, however, are very limited. In addition, the relationship between these effects and diabetic complications has not been adequately studied. OBJECTIVE: To examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in a cohort of healthy adults. RESEARCH DESIGN: This was a retrospective cohort study. PARTICIPANTS: Subjects were Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012. Patients were divided into statin users and nonusers. INTERVENTION: We excluded patients who, at baseline, had a preexisting disease indicative of cardiovascular diseases, any positive element of the Charlson comorbidity index (including diabetes mellitus), or life-limiting chronic diseases. Using 42 baseline characteristics, we generated a propensity score to match statin users and nonusers. MAIN MEASURES: Outcomes assessed included newonset diabetes, diabetic complications, and overweight/ obesity. KEY RESULTS: A total of 25,970 patients (3982 statin users and 21,988 nonusers) were identified as healthy adults at baseline. Of these, 3351 statins users and 3351 nonusers were propensity score-matched. Statin users had higher odds of new-onset diabetes (odds ratio [OR] 1.87; 95 % confidence interval [95 % CI] 1.67-2.01), diabetes with complications (OR 2.50; 95 % CI 1.88-3.32), and overweight/obesity (OR 1.14; 95 % CI 1.04-1.25). Secondary and sensitivity analyses demonstrated similar findings. CONCLUSIONS: Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use for primary prevention.

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“…Two small pilot studies have used statin therapy in diabetic retinopathy. 46,47 In one pilot study, six patients with exudative maculopathy were treated with pravastatin, which lowered their total and LDL cholesterol by 40%. Over one year, an improvement in hard exudates in all six patients, with reduced microaneurysms in four patients was observed, and acuity improved in one patient.…”

Section: Lipid Lowering Therapy In Exudative Maculopathymentioning

confidence: 99%

The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid lowering therapy?

Chowdhury

Hopkins

Dodson

et al. 2002

Eye

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The treatment for diabetic maculopathy is laser photocoagulation of the pigment epithelium. With the advent of systemic lipid lowering therapy over the last decade, there may be potential for medical therapy also. There is some anecdotal evidence of the effect of lipid lowering agents (particularly statins) in reducing exudate, and a number of studies have shown that lipid lowering therapy may reduce macular exudates, but numbers in these trials are small. A randomised controlled trial is now required to investigate whether the use of systemic lipid lowering therapy is of benefit in patients with exudative maculopathy, even in the absence of dyslipidaemia.

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The Effects of Lipid Lowering on Diabetic Retinopathy

Cited by 122 publications

References 17 publications

Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study

Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study

Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults

The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid lowering therapy?

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