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Statins before diabetes diagnosis did not increase microvascular disease risk
Patients treated with statins before being diagnosed with diabetes are not at increased risk for microvascular disease, according to data published in The Lancet Diabetes & Endocrinology.
The possibility raised in a study conducted by Danish researchers that statins could actually protect against the small vessel disease requires further investigation, according to the study researchers.
“Our findings show that statin use before diabetes diagnosis was not associated with increased risk of microvascular diseases in people that developed diabetes,” they wrote. “The protective effect of statins against some forms of microvascular disease should be addressed in similar studies to ours and, preferably, in randomized controlled trials.”
Sune F. Nielsen, PhD, and Børge G. Nordestgaard, MD, both of the University of Copenhagen in Herlev, Denmark, identified all patients in the country aged at least 40 years who received a diabetes diagnosis between 1996 and 2009.
Using data from the Danish Patient Registry and the Danish Registry of Medicinal Product Statistics, the researchers randomly selected 15,679 individuals treated with statins regularly until their diabetes diagnosis. The group was matched in a 1:3 ratio with 47,037 individuals who had never used statins before diagnosis.
The researchers analyzed data with Cox regression models to compare the cumulative incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy or gangrene of the foot between cohorts. Adjustments were made for covariates, including sex, age at diabetes diagnosis and diagnosis method; a propensity score was also added to address potential biases between statin users and non-statin users.
At an average 2.7 years of follow-up, 2,866 patients developed diabetic retinopathy; 1,406 diabetic neuropathy; 1,248 diabetic nephropathy; and 2,392 gangrene of the foot. Statin users demonstrated a lower cumulative incidence of diabetic retinopathy (HR=0.6; 95% CI,
0.54-0.66), diabetic neuropathy (HR=0.66; 95% CI, 0.57-0.75) and gangrene of the foot (HR=0.88; 95% CI, 0.8-0.97) compared with non-statin users. This was not the case for diabetic nephropathy (HR=0.97; 95% CI, 0.85-1.1).
Similar results were observed with adjustments for the competing risk of death, visits to a family doctor, covariate stratification and matching propensity score. The corresponding multivariable adjusted HR for diabetes in the total population was 1.17 (95% CI, 1.14-1.21).
The researchers acknowledged several limitations, including potential selection bias, limited availability and completeness of information, missing records for diabetes control after diagnosis and missing blood pressure data. However, they said the study’s strengths were its size and that patients were never treated for hyperglycemia.
Future studies should include genetic variants “associated with lifelong reduced amounts of LDL cholesterol, with or without effects on 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR)” and ideally in a randomized controlled trial, according to researchers.
In an accompanying commentary, David Preiss, MD, PhD, of the University of Glasgow, questioned how conclusive data could be obtained in this area of study.
“Large placebo-controlled trials with robust microvascular outcomes are unlikely to be undertaken because of ethical constraints,” Preiss wrote.
Preiss also noted that investigation of HMGCR polymorphisms would entail huge populations with thorough records of diabetic retinopathy, diabetic nephropathy and diabetic neuropathy outcomes, but conceded suitable studies are developing.
“A further possibility is to gather information about laser treatment for diabetic retinopathy across all major statin trials,” Preiss wrote.
Disclosure: This work was supported by Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital. One researcher reports consultancy fees or lecture honoraria from AstraZeneca, Merck and Pfizer.