ADA: Statins for Young T1D Patients, Too?

Heart risk in 30s might warrant statin use, observational data suggest

BOSTON -- Type 1 diabetes patients younger than 40 may be candidates for statin use, as guidelines recommend after age 40, researchers suggested.

Under the American Heart Association/American College of Cardiology definition, the 10-year cardiovascular risk was about 5% for type 1 diabetes patients ages 30 to 39 and about 13% in those ages 40 to 44, Rachel G. Miller, MD, of the University of Pittsburgh, and colleagues found.

Adding coronary revascularization to that definition -- which also included cardiovascular death or nonfatal stroke or myocardial infarction -- brought the 10-year risk to nearly 7% for type 1 diabetes patients in their 30s, the group reported here at the American Diabetes Association meeting.

Although still a little shy of the 7.5% 10-year risk threshold recommended for statin treatment in the guidelines, the 20% of the cohort already on a statin before age 40 was excluded along with a number of events that happened before the start of follow-up.

"We conclude that young adults aged 30 to 39 years with 20 or less years' type 1 diabetes duration are at sufficiently high atherosclerotic cardiovascular disease risk to merit statin therapy," the group concluded in their poster presentation.

Both the AHA/ACC and the American Diabetes Association guidelines recommend statins after 40 for essentially all diabetes patients and support possible use for younger people with cardiovascular disease risk factors.

"We've been comfortable with the concept that anybody over the age of 40 with type 2 should be on a statin and by extrapolation anybody who has type 1 over the age of 40 should be recommended for statins," commented Naveed Sattar, MD, a metabolic medicine specialist at the University of Glasgow, Scotland.

"What we now need is good guidance: Who are these people under 40 with type 1 who should get a statin, and how do we recognize them?"

There isn't enough data to develop a risk score for type 1 diabetes yet, he noted. Lifetime risk might be a better criterion in that population than the 10-year risks, which are heavily predicated upon age and which underpin current guidelines, Sattar noted.

"I think in the next 2 or 3 years either from national databases within Scandinavia or Scotland we're going to have a type 1 diabetes risk score that might allow us to look at this question," he suggested.

Comparisons with the general population in the surrounding county showed huge elevations in risk with type 1 diabetes even at these early ages, but absolute event numbers were small in Miller's study.

Among the 517 people under age 45 without pre-existing atherosclerotic cardiovascular disease followed from 1996 to 2011 in the Pittsburgh Epidemiology of Diabetes Complications study (a prospective group of childhood-onset cases seen at a single center soon after diagnosis):

• One event occurred in 20- to 29-year-olds
• 18 accrued in those in their 30s
• 22 occurred in participants in their early 40s

The fatal coronary artery event and nonfatal stroke or MI rates were 134 per 100,000 in the cohort ages 20 to 29, 502 per 100,000 people in their 30s, and 1,336 per 100,000 in the 40 to 44 age range.

Sattar cautioned against overinterpreting the "very crude analysis."

Miller disclosed no relevant relationships with industry. A co-author disclosed relationships with Eli Lilly and Company and Profil Institute for Clinical Research.

Sattar disclosed relationships with Amgen, AstraZeneca, and Sanofi.

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Study Questions Statin, Memory Loss Connection

Statin and nonstatin use both associated with increased complaints of memory loss

Beginning treatment with a statin was associated with a nearly fourfold increased risk of developing acute memory loss within 30 days in a retrospective cohort study, but a similar increase in risk was seen in patients starting non-statin lipid-lowering drugs.

Compared with non-users, both statin and non-statin lipid-lowering drug (LLD) use was found to be associated with acute memory loss in the weeks following treatment initiation, but there was no difference in memory loss when statins and non-statins were compared with each other, researcher Brian L. Strom, MD, of Rutgers University in Newark, N.J., and colleagues wrote online June 8 in JAMA Internal Medicine.

The observation that all LLDs were associated with memory loss suggests that either all drugs used to lower lipid levels cause acute memory loss or that the observed memory loss in the study was due to detection bias, Strom said.

In a telephone interview with MedPage Today, Strom said it makes sense that patients on a new drug would be more likely to notice symptoms and attribute them to the drug, and they are also more likely to report such symptoms to their physician.

"Patients might report a memory loss to me that they would otherwise pay little attention to because I am seeing them more often and I ask them about it," he said.

Earlier Statin, Memory Studies Mixed

Several previous studies have shown acute memory loss associated with the use of statins, but others have not shown the association or have even shown improved memory in long-term statin users compared with non-users.

Strom noted that without the non-statin LLD control group in his study, the findings would have shown a strong association between statin initiation and short-term memory loss.

"In the absence of this control group, the finding would have been completely misleading," he said.

The study included data obtained between early 1987 through late 2013 from The Health Improvement Network (THIN), which is a comprehensive database of medical records from general practitioners in the U.K. Patients were excluded from the analysis if they had a diagnosis of Alzheimer's disease or dementia, if they had received medications used for dementia, or if they had other conditions affecting cognition, such as Parkinson's disease, Huntington's disease, or vascular dementia.

The analysis compared 482,543 statin users with 482,543 matched non-users of any lipid-lowering drug (control group 1) and with 26,484 users of non-statin LLDs, such as cholestyramine, colestipol hydrochloride, colesevelam, clofibrate, gemfibrozil, and niacin (control group 2).

A secondary case-crossover analysis was performed that included 68,028 patients with incident acute memory loss whose exposure to statins was evaluated during the period immediately before the outcome versus three earlier periods (31 to 60 days prior, 150 to 180 days prior, and 270 to 300 days prior).

Non-statin LLD Users Had 3.6-Fold Risk Increase

The analysis revealed that:

• When compared with matched non-users of any LLDs, there was a strong association between first exposure to statins and acute memory loss within 30 days immediately following exposure (fully adjusted odds ratio 4.40, 95% CI 3.01-6.41).
• The association was not seen in the comparison of statin versus non-statin LLDs (fully adjusted OR 1.03, 95% CI 0.63-1.66).
• The association was seen in the first 30 days following exposure in non-statin LLD users compared with matched non-user controls (adjusted OR 3.60, 95% CI 1.34-9.70).
• Both atorvastatin and simvastatin showed an increased OR within the first 30 days after exposure compared with non-users (adjusted OR 2.40, 95% CI 1.42-4.04 and 3.53, 95% CI 2.79 -4.48, respectively).
• The case-crossover analysis showed a weak negative association, which was not found to be clinically meaningful.

A potential study limitation cited by the researchers involved a substantial difference in baseline characteristics between users of statins and users of non-statin LLDs, and differences among users of the various statin drugs.

"Bias from confounding by indication is the most serious potential problem in this study, even though we attempted to control for indication variables and a large number of other underlying conditions," the researchers wrote.

The case-crossover analysis was conducted to address this issue because each patient served as his or her own control.

Statin, Memory Issue 'Tempest in Teapot'

The researchers also noted that potential confounding could exist for variables not recorded in the medical records database.

Strom said the study findings should reassure both patients and physicians who prescribe statins.

"This whole issue of short-term memory loss with statins is really a tempest in a teapot," he said. "Statins are very effective drugs, and people should not veer away from them for fear of a short-term memory effect, especially given the data suggesting that long-term statin use improves memory."

The research was funded by the National Institutes of Health.

Strom reported receiving research funding from AstraZeneca and Bristol-Myers Squibb and serving as a consultant to Abbott, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, Novartis and Pfizer. A co-author reported receiving research funding from AstraZeneca and Bristol-Myers Squibb and serving as a consultant to AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, and Merck.

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Study finds increased risk of type 2 diabetes with statin use

A new study published in the journal Diabetologia finds the use of statins - drugs commonly used to lower cholesterol - may significantly increase the risk of type 2 diabetes, and that this risk remains even after accounting for confounding factors, including age, smoking status and body mass index.

The researchers found statin therapy was associated with a 46% increased risk of type 2 diabetes, even after adjustment for confounding factors.

The link between statin use and higher risk of diabetes is not new. Back in 2013, for example, Medical News Today reported on a study published in The BMJ that found certain statins - particularly atorvastatin (Lipitor),rosuvastatin (Crestor) and simvastatin (Zocor) - raised the risk of diabetes by up to 22%.

But according to the researchers of this latest study - including Prof. Markku Laakso of the Institute of Clinical Medicine at the University of Eastern Finland and Kuopio University Hospital in Finland - such studies have had numerous limitations.

The team explains that many of these studies have included selective populations, such as those at high risk of cardiovascular disease. As a result, findings may not be applicable to the general population.

The researchers also note that these studies have often included participants whose diabetes has been self-reported or based on their fasting glucose measurements, which may underestimate the actual number of incident diabetes cases.

Increased risk 'most likely linked to statins that reduce insulin sensitivity and secretion'

For their study, Prof. Laakso and colleagues analyzed the effects of statin use on 8,749 nondiabetic Caucasian men aged 45-73 years who were part of the Finland-based Metabolic Syndrome in Men (METSIM) study.

During the 5.9-year follow-up, 625 men were diagnosed with type 2 diabetes, as determined by either an oral glucose tolerance test (OGTT), an HbA1c level of at least 6.5%, or the commencement of antidiabetic medication.

The results of the analysis revealed that men who were treated with statins were at 46% higher risk of diabetes than men who were not treated with statins.

This 46% increased diabetes risk was present even after adjusting for the men's age, body mass index (BMI), waist circumference, physical activity levels, smoking status, alcohol intake, family history of diabetes and treatment with beta-blockers and diuretic medications.

The researchers also assessed changes in insulin resistance and insulin secretion among men who were treated with statins. They found that statins led to a 24% reduction in insulin sensitivity during follow-up, as well as a 12% reduction in insulin secretion.

For two statins - simvastatin and atorvastatin - the researchers found the associated risk of type 2 diabetes was dose-dependent, as were the reductions in insulin sensitivity and insulin secretion among the men taking these statins.

After accounting for the aforementioned confounding factors, the team found high-dose simvastatin was linked to a 44% higher risk of type 2 diabetes, while a lower dose was linked to a 28% increased risk. High-dose atorvastatin was associated with a 37% increased risk of type 2 diabetes.

Of the study participants, 53% were taking atorvastatin and 29% were taking simvastatin.

Based on their results, the researchers say:

"Statin therapy was associated with a 46% increased risk of type 2 diabetes after adjustment for confounding factors, suggesting a higher risk of diabetes in the general population than previously reported.

The association of statin use with increased risk of developing diabetes is most likely directly related to statins decreasing both insulin sensitivity and secretion."

Prof. Laakso and colleagues say that while one strength of this study is its large size, the fact that all participants were male and Caucasian means the findings may not be generalizable to women or those of other ethnicities.

In February, Medical News Today reported on a study claiming - contrary to previous findings - statins may not protect against Parkinson's disease.

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