Abstract
BackgroundPatients with type 2 diabetes are at high risk for cardiovascular disease. Although hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular events, residual risk remains even after target low-density lipoprotein cholesterol (LDL-C) levels have been achieved. Lipoprotein particle size and fraction changes are thought to contribute to such risks. The purpose of this study was to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid and docosahexaenoic acid, on lipoprotein particle size, concentration, and glycemic control in Japanese patients with type 2 diabetes and hypertriglyceridemia.MethodsThis was a multicenter, prospective, open-label, single arm study. We enrolled 14 patients with type 2 diabetes and hypertriglyceridemia treated with statins and dipeptidyl peptidase-4 inhibitors with glycated hemoglobin (HbA1c) < 8.0%, LDL-C < 120 mg/dL, and fasting triglyceride ≥150 mg/dL. After a 12-week observation period, they were treated with 4 g/day n-3 PUFAs for 12 weeks. Lipoprotein particle sizes, concentrations, lipoprotein insulin resistance (LPIR) scores, lipid profiles, HbA1c, and fasting plasma glucose (FPG) were measured before and after treatment. Lipoprotein profiles were measured by nuclear magnetic resonance spectroscopy. Data were analyzed using Wilcoxon signed-rank tests.ResultsConcentrations of total cholesterol (P < 0.001), LDL-C (P = 0.003), and triglyceride (P < 0.001) decreased following n-3 PUFA administration. N-3 PUFAs decreased the size of very low-density lipoprotein (VLDL; P < 0.001) particles, but did not affect LDL or high-density lipoprotein (HDL) particles. The concentration of large LDL increased, whereas small LDL decreased, causing the large to small LDL ratio to increase significantly (P = 0.042). Large VLDL and chylomicron concentrations significantly decreased, as did the large to small VLDL ratio (all P < 0.001). FPG levels unchanged, whereas HbA1c levels slightly increased. LPIR scores improved significantly (P = 0.001).ConclusionsN-3 PUFAs partly improved atherogenic lipoprotein particle size and concentration, and produced less atherogenic lipoprotein subclass ratios in patients that achieved target LDL-C levels and glycemic control. These results suggest that n-3 PUFAs may reduce residual cardiovascular risk factors in statin-treated patients with type 2 diabetes and hypertriglyceridemia.Trial registrationThe study was registered at UMIN-ID: UMIN000013776.
Highlights
Patients with type 2 diabetes are at high risk for cardiovascular disease
There were no significant differences in body mass index (BMI) or blood pressure before and after treatment
In this study, we found that n-3 n-3 polyunsaturated fatty acids (PUFAs) could reduce the ratio of atherogenic lipoprotein particles and reduce the lipoprotein insulin resistance (LPIR) score in patients with type 2 diabetes, whereas there were no marked changes in LDL particle size and concentration
Summary
Patients with type 2 diabetes are at high risk for cardiovascular disease. Hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular events, residual risk remains even after target low-density lipoprotein cholesterol (LDL-C) levels have been achieved. Numerous clinical trials have demonstrated that LDL-C-lowering therapy with hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular (CV) events [2, 3], significant CV risks remain after achieving target LDL-C levels. Residual risk factors include hypertriglyceridemia, a low level of high-density lipoprotein (HDL) cholesterol, and increased small dense LDL or oxidized LDL. In the ACCORD lipid trial including 5518 patients with diabetes and high CV risk, the addition of fenofibrate [5] to simvastatin failed to reduce CV events, with significant risk reduction only in patients with hypertriglyceridemia and low HDL. Lipid-lowering therapies that can be used safely and effectively in statin-treated patients with diabetes are required
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