How to treat diabetic dyslipidaemia
EAS Academy. Zambon A. 04/25/17; 175533 Topic: Therapy
Prof. Alberto Zambon
Prof. Alberto Zambon

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Professor Alberto Zambon in his presentation discussed the characteristics of the dyslipidemia observed in patients with diabetes mellitus (DM) and noticed that optimal management of atherogenic dyslipidaemias in patients with diabetes should focus on LDL-C. He explained that diabetic patients have a cluster of abnormalities including elevation of both fasting and postprandial TG, apoB, and sdLDL as well as low HDL-C and ApoA1. He emphasized that statins are recommended for lowering LDL-C, irrespective of the baseline LDL-C levels.
Subsequently, he presented the 2016 ESC/EAS guidelines for the management of dyslipidaemias in diabetic patients and briefly discussed the recommended goals of LDL-C in type 1 DM and type 2 DM with or without additional risk factors. Prof Zambon also presented the recommended hypolipidemic drug interventions, including statins as monotherapy or in combination with ezetimibe or with bile acid sequestrant or with PSCK9 inhibitors. Furthermore, he presented the ADA 2017 recommendations for statin and combination treatment in diabetic patients as a function of the age and the existence of various cardiovascular disease (CVD) risk factors.
 
Subsequently, Prof. Zambon, presented data form clinical trials demonstrating the efficacy of cholesterol-lowering therapy in diabetic population, including data from the more recent IMPROVE –IT trial related to the subpopulation of diabetic patients participated in the trial. He also discussed the beneficial effect of ezetimibe on fasting and postprandial triglyceride-rich lipoproteins in type-2 diabetes. He next presented an overview of statin-related side effects, such as muscle-related side effects, hepatic dysfunction, gastrointestinal side effects, proteinuria as well as  new onset of diabetes (use of some statins is associated with small but significant risk of type 2 DM, however overall risk is outweighed by benefit in CVD risk reduction). Prof. Zambon also presented data from the ACCORD lipid trial on the beneficial effect of the combination of simvastatin with fenofibrate compared with simvastatin monotherapy in lowering the triglyceride (TG) levels and also discussed the lack of any difference between the 2 patient groups in serious adverse events during follow-up from the same trial. He also presented new data on the selective PPAR modulator (SPPARM) model of PPARα ligand action and was focused on the lowering effect of pemafibrate (K-877) on TG levels and on the elevation of plasma HDL-C concentration. Next, Prof Zambon presented new data form 2 randomized, double-blind placebo controlled clinical trials showing the TG-lowering effect of pemafibrate in combination with statins including pitavastatin. Finally, he discussed the lipid-lowering efficacy concerning the LDL-C, Non-HDL-C and TG of the PCSK9 inhibitor evolocumab in type 2 DM patients and he also discussed future lipid-lowering therapeutic options and ongoing clinical trials (omega-3-fatty acids, new PPAR modulators, andisense oligolnucleotides, monoclonal antibodies, various inhibitors (MTP inhibitor, DGAT-1 CETP inhibitors), and bempedoic acid (affects the adenosine triohisphate citrate lyase and AMPK – fatty acids metabolism). He closed his lecture presenting an algorithm form the EAS consensus on how to estimate the CVD risk and how to treat type 2 DM patients with very high or high CVD risk.

 
Professor Alberto Zambon in his presentation discussed the characteristics of the dyslipidemia observed in patients with diabetes mellitus (DM) and noticed that optimal management of atherogenic dyslipidaemias in patients with diabetes should focus on LDL-C. He explained that diabetic patients have a cluster of abnormalities including elevation of both fasting and postprandial TG, apoB, and sdLDL as well as low HDL-C and ApoA1. He emphasized that statins are recommended for lowering LDL-C, irrespective of the baseline LDL-C levels.
Subsequently, he presented the 2016 ESC/EAS guidelines for the management of dyslipidaemias in diabetic patients and briefly discussed the recommended goals of LDL-C in type 1 DM and type 2 DM with or without additional risk factors. Prof Zambon also presented the recommended hypolipidemic drug interventions, including statins as monotherapy or in combination with ezetimibe or with bile acid sequestrant or with PSCK9 inhibitors. Furthermore, he presented the ADA 2017 recommendations for statin and combination treatment in diabetic patients as a function of the age and the existence of various cardiovascular disease (CVD) risk factors.
 
Subsequently, Prof. Zambon, presented data form clinical trials demonstrating the efficacy of cholesterol-lowering therapy in diabetic population, including data from the more recent IMPROVE –IT trial related to the subpopulation of diabetic patients participated in the trial. He also discussed the beneficial effect of ezetimibe on fasting and postprandial triglyceride-rich lipoproteins in type-2 diabetes. He next presented an overview of statin-related side effects, such as muscle-related side effects, hepatic dysfunction, gastrointestinal side effects, proteinuria as well as  new onset of diabetes (use of some statins is associated with small but significant risk of type 2 DM, however overall risk is outweighed by benefit in CVD risk reduction). Prof. Zambon also presented data from the ACCORD lipid trial on the beneficial effect of the combination of simvastatin with fenofibrate compared with simvastatin monotherapy in lowering the triglyceride (TG) levels and also discussed the lack of any difference between the 2 patient groups in serious adverse events during follow-up from the same trial. He also presented new data on the selective PPAR modulator (SPPARM) model of PPARα ligand action and was focused on the lowering effect of pemafibrate (K-877) on TG levels and on the elevation of plasma HDL-C concentration. Next, Prof Zambon presented new data form 2 randomized, double-blind placebo controlled clinical trials showing the TG-lowering effect of pemafibrate in combination with statins including pitavastatin. Finally, he discussed the lipid-lowering efficacy concerning the LDL-C, Non-HDL-C and TG of the PCSK9 inhibitor evolocumab in type 2 DM patients and he also discussed future lipid-lowering therapeutic options and ongoing clinical trials (omega-3-fatty acids, new PPAR modulators, andisense oligolnucleotides, monoclonal antibodies, various inhibitors (MTP inhibitor, DGAT-1 CETP inhibitors), and bempedoic acid (affects the adenosine triohisphate citrate lyase and AMPK – fatty acids metabolism). He closed his lecture presenting an algorithm form the EAS consensus on how to estimate the CVD risk and how to treat type 2 DM patients with very high or high CVD risk.

 
2016 ESC/EAS Guidelines…..
ADA Standards of Care in Diabetes 2017. Diabetes care 2017; 40, Suppl 1
Preiss D, et al. JAMA 2011;305:2556-2564
Ishibashi S, eta al Atherosclerosis 2016
Harai H et al. Atherosclerosis 2017
Sattar N, et al. Lancet Diabetes Endocrinol 2016 4:403-410
Chapman MJ   EAS consensus Eur Heart J 2011
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