Statin therapy lowers risk of coronary artery disease in young patients with Type 1 diabetes
UC Davis researchers have found that low doses of simvastatin, part of a class of medications widely used to lower cholesterol, reduced the major risk factors for coronary artery disease in young patients with Type 1 diabetes, indicating that the use of these drugs could reduce their risk later in life for this condition, the main cause of death in these patients.
Results of the study appeared in a published, online edition of The Journal of Clinical Endocrinology & Metabolism. The principal investigator of the study is Ishwarlal Jialal, director of the UC Davis Laboratory for Atherosclerosis and Metabolic Research.
Coronary artery disease
Coronary artery disease is the main cause of death among people with Type 1 diabetes. The incidence of coronary artery disease among young, asymptomatic individuals with Type 1 diabetes is 1-2 percent a year, but by their mid-40s, more than 70 percent of men and 50 percent of women with the disease develop coronary artery calcium, a marker of the fatty deposits known as plaque, which build up in the inner lining of an artery. This condition is called atherosclerosis, commonly called "hardening of the arteries." When plaques become fragile and rupture, they cause blood clots that can block blood flow or break off and travel to another part of the body, causing a heart attack, limb loss or stroke.
By age 55, 35 percent of people with Type 1 diabetes die of coronary artery disease, in contrast to 8 percent of nondiabetic men and 4 percent of nondiabetic women.
Previous research has established the benefit of managing the level of low-density lipoprotein, also known as "bad" cholesterol, as the major contributor to plaque, in patients with Type 2 diabetes.
— Ishwarlal Jialal, director of the UC Davis Laboratory for Atherosclerosis and Metabolic Research
Testing the effect of simvastatin
However, there is scant information on lipid management in patients with Type 1 diabetes, or the use of statins for that purpose. Jialal and Sridevi Devaraj, associate professor of pathology, tested the effect of simvastatin on biomarkers of vascular inflammation, including circulating markers such as C-reactive protein and biomolecules released from monocytes, the pivotal cells involved in plaque formation in patients with Type 1 diabetes.
The study involved 52 patients with Type 1 diabetes, men and women with an average age of 23.4 years, who took either 20 milligrams of simvastatin or a placebo daily for three months. After that period, the researchers found that the simvastatin had significantly reduced the levels of LDL. LDL carries most of the cholesterol in the body, and an excess of LDL can clog the arteries with cholesterol buildup.
In addition, the group that took simvastatin had lower levels of other substances regarded as evolving risk factors for coronary artery disease, including C-reactive protein and monocyte function, including the "master switch" that regulates inflammation, a protein called nuclear factor-kappa B.
The levels of this protein were reduced by more than 50 percent in participants who took simvastatin. Study participants who took the placebo did not experience similar reductions.
Although there are clear guidelines for statin therapy for Type 2 diabetes, similar guidelines for such therapy do not exist for patients in North America with Type 1 diabetes. However, for the young, North American participants in the UC Davis study, statin therapy appears to have beneficial effects on the lipid profile and on inflammation, both of which are critical contributors to premature atherosclerosis. Because the subjects who took simvastatin experienced no significant side effects, the researchers endorse a multicenter clinical trial investigating the safety and efficacy of statin therapy on surrogates of cardiovascular disease.
"However, while such studies are being undertaken," the authors state, "it is not unreasonable to propose that statin therapy be used for the prevention of premature atherosclerosis in this high-risk population."
The UC Davis researchers note that the recently published Joint British Societies' guidelines on cardiovascular disease prevention in clinical practice suggest that statin therapy be used in patients with both Type 1 and Type 2 diabetes who are in specific age groups and have certain medical conditions, such as high blood pressure, diabetic kidney or eye complications, LDL cholesterol higher than 130 mg/dl, and poor diabetes control.
"Given the important role of inflammation in the genesis of premature cardiovascular disease," Jialal states, "serious consideration should be given to statin therapy as recommended by the British guidelines in Type1 diabetes patients. While it may not be appropriate to institute statin therapy in all young Type 1 diabetes patients, it is not unreasonable to consider statin therapy in patient with moderate to high risk as recommended."
Steven C. Griffen, assistant professor of endocrinology, and Eric Miguelino, a postdoctoral scholar in the Department of Pathology, assisted with patient recruitment. The study was funded by grants from the Juvenile Diabetes Research Foundation and the National Institutes of Health.