CE: Alpana; HCO/320407; Total nos of Pages: 8;

HCO 320407

REVIEW URRENT C OPINION

Dyslipidaemia in type 2 diabetes mellitus: bad for the heart Niki Katsiki a, Nikolaos Tentolouris b, and Dimitri P. Mikhailidis c

Purpose of review Type 2 diabetes mellitus (T2DM) is associated with increased coronary heart disease (CHD) morbidity and mortality. These patients are also more prone to heart failure, arrhythmias and sudden cardiac death. Furthermore, coronary interventions performed in such high-risk patients have worse outcomes. In this narrative review, we discuss the role of diabetic dyslipidaemia on the risk of CHD in patients with T2DM. The effects of hypolipidaemic, antihypertensive and antidiabetic drugs on lipid and glucose metabolism in T2DM are also considered. Recent findings Among CHD risk factors, diabetic dyslipidaemia characterized by moderately elevated low-density lipoprotein (LDL) cholesterol, increased triglycerides and small, dense LDL particles as well as decreased high-density lipoprotein cholesterol levels may contribute to the increased CHD risk associated with T2DM. Hypolipidaemic, antihypertensive and antidiabetic drugs can affect lipid and glucose parameters thus potentially influencing CHD risk. Such drugs may improve not only the quantity, but also the quality of LDL as well as postprandial lipaemia. Summary Current data highlight the importance of treating diabetic dyslipidaemia in order to minimize CHD risk. Both fasting and postprandial lipids are influenced by drugs in patients with T2DM; physicians should take this into consideration in clinical decision making. Keywords antidiabetic drugs, antihypertensive drugs, coronary heart disease, diabetic dyslipidaemia, hypolipidaemic drugs, postprandial lipaemia, type 2 diabetes mellitus

INTRODUCTION Type 2 diabetes mellitus (T2DM) has been linked to an increased risk for coronary heart disease (CHD) morbidity and mortality [1]. Overall, cardiovascular disease (CVD) risk is two-fold to four-fold higher in patients with T2DM compared with those without [2] and CVD is the most frequent cause of death in these patients [3]. Meta-analyses suggest that women with T2DM have a higher risk for CVD, CHD and all-cause mortality compared with men with T2DM [4,5]. With regard to myocardial infarction (MI), T2DM is associated with poor prognosis and worse outcomes following hospitalization for either ST-elevation MI (STEMI) or non-STEMI (NSTEMI) [6–8]. Percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and thrombolytic therapy are more frequently performed in diabetic compared with nondiabetic patients hospitalized for MI [9]. However, clinical outcomes and complications following these interventions are worse in patients with diabetes vs.

&

normoglycaemic patients [10 ,11]. CABG may be superior to PCI in T2DM patients with multivessel CHD [1,12]. Heart failure, arrhythmias (e.g. atrial fibrillation) and sudden cardiac death occur more frequently in patients with T2DM [13–15]. Several factors intimately linked to T2DM may contribute to the increased CVD in these patients a

Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, b First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece and cDepartment of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK Correspondence to Dimitri P. Mikhailidis, MD, FRCP, FRCPath, Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), Pond Street, London NW3 2QG, UK. Tel: +44 20 7830 2258; fax: +44 20 7830 2235; e-mail: [email protected]. Curr Opin Cardiol 2017, 32:000–000 DOI:10.1097/HCO.0000000000000407

0268-4705 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.

www.co-cardiology.com

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

CE: Alpana; HCO/320407; Total nos of Pages: 8;

HCO 320407

Lipids and emerging risk factors

KEY POINTS  T2DM is characterized by the so-called ‘atherogenic dyslipidaemia’, that is moderately increased LDL-C, elevated triglycerides and sdLDL particles as well as reduced HDL-C levels.  Diabetic dyslipidaemia contributes to the increased risk of CHD morbidity and mortality in patients with T2DM.  Glucose, glycated haemoglobin, total cholesterol, LDLC, HDL-C and triglyceride levels may be affected by hypolipidaemic, antihypertensive and antidiabetic drugs, thus influencing CHD risk in patients with T2DM.  Apart from fasting lipids, postprandial lipaemia as well as LDL quality may be improved by such drugs.

including central obesity, dyslipidaemia, hypertension, dysglycaemia, hyperuricaemia, nonalcoholic fatty liver disease (NAFLD), chronic kidney disease and hypercoagulability [16–21]. In this narrative review, we discuss the role of diabetic dyslipidaemia on the risk of CHD in patients with T2DM. The effects of hypolipidaemic, antihypertensive and antidiabetic drugs on lipid and glucose metabolism in T2DM are also considered.

DIABETIC DYSLIPIDAEMIA AND CORONARY HEART DISEASE ‘Atherogenic dyslipidaemia’ is a characteristic of lipid profiles in T2DM, that is moderately increased low-density lipoprotein cholesterol (LDL-C), elevated triglycerides and the presence of small, dense LDL (sdLDL) particles as well as reduced highdensity lipoprotein cholesterol (HDL-C) levels [22]. Higher levels of total cholesterol (TC), LDL-C and triglyceride as well as reduced HDL-C levels have been associated with CHD in T2DM patients [23–25]. Increased triglyceride levels were also shown to significantly increase CVD mortality in the Diabetes Heart Study [26]. Different lipid ratios, that is LDL-C:HDL-C, TC:HDL-C and non-HDLC:HDL-C also predict CHD risk in T2DM patients [27–29]. Furthermore, elevated LDL-C levels at admission correlated with increased in-hospital mortality in patients with T2DM after PCI for STEMI; no such relationship was found for patients without T2DM [30]. Similarly, increased non-HDL-C levels predicted periprocedural myocardial injury in T2DM patients undergoing PCI [31]. In contrast, HDL-C was inversely associated with in-stent restenosis and major adverse cardiac events post-PCI in patients with T2DM [32]. Furthermore, elevated levels of triglyceride-rich lipoproteins including very low density lipoprotein cholesterol (VLDL-C) 2

www.co-cardiology.com

levels predicted in-stent restenosis in patients with T2DM patients implanted with drug-eluting stents [33]. Interestingly, atherogenic dyslipidaemia (defined as elevated triglyceride and low HDL-C levels) was associated with silent myocardial ischaemia in patients with T2DM [34 ]. Levels of VLDL-C correlated with coronary calcification in T2DM patients in the Penn Diabetes Heart Study [35]. A recent study reported lower TC and LDL-C levels in patients with T2DM hospitalized for a first MI compared with patients without (4.4  0.9 vs. 5.4  1.2 mmol/l for TC and 2.5  0.8 vs. 3.4  1.1 mmol/l for LDL-C; P < 0.001 for both comparisons) [36]. This finding may be explained by the implementation of preventive therapeutic strategies in T2DM patients, and it also highlights the need for monitoring in these high-risk patients. Changes occur in the quality as well as quantity of lipid particles as increased levels of sdLDL have been associated with increased CVD risk [37,38]. LDL particle size was the strongest predictor for CHD in T2DM patients independent of other lipid markers [39]. In another study, patients with T2DM and CHD had significantly higher sdLDL levels than healthy controls, whereas LDL-C levels did not differ between the two groups [40]. Apart from CHD, sdLDL has been also related to subclinical atherosclerosis in patients with T2DM [39,41]. The role of triglyceride-rich lipoproteins extends to postprandial lipaemia (PPL) which occurs to a greater extent in T2DM and increases CVD risk [42]. The definition and clinical relevance of PPL has been discussed elsewhere [43,44]. CHD patients may have increased PPL [45 ,46]. A link between diabetic dyslipidaemia and glucose metabolism has been reported [47]. Insulin resistance and later insulin deficiency present in T2DM affect lipid metabolism leading not only to quantitative (elevated triglyceride and low HDL-C levels) but also to qualitative labnormalities (increased sdLDL particles and HDL dysfunction) [48]. HDL-C exhibits anti-inflammatory, antioxidant and antiapoptotic properties, protecting not only against atherosclerosis and pancreatic b-cell impairment [49]. Similarly, HDL levels and quantity are relevant as dysfunction in HDL also characterizes T2DM [50,51]. Dysfunctional HDL in T2DM may adversely affect glucose metabolism [52,53]. The ‘atherogenic’ triglyceride:HDL-C ratio has been associated with glycaemic control in patients with T2DM [54]. A positive correlation has been reported between glycaemic control (HbA1c) and sdLDL levels [55]. Furthermore, improvement of glycaemic control may lead to larger LDL particles, whereas poor glycaemic control may worsen HDL dysfunction in patients with T2DM [56,57]. &

&

Volume 32  Number 00  Month 2017

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

CE: Alpana; HCO/320407; Total nos of Pages: 8;

HCO 320407

Dysli pidaemia in type 2 diabetes mellitus Katsiki et al.

EFFECTS OF HYPOLIPIDAEMIC, ANTIHYPERTENSIVE AND ANTIDIABETIC DRUGS ON DIABETIC DYSLIPIDAEMIA AND GLYCAEMIC CONTROL Lifestyle measures including a healthy diet and physical exercise, possibly leading to weight loss, can improve diabetic dyslipidaemia [58,59]. Furthermore, a link between smoking and dyslipidaemia has been reported and smoking cessation may beneficially affect lipid disorders [60]. Bariatric surgery has also been reported to improve diabetic dyslipidaemia and glycaemic control in T2DM patients [61].

Hypolipidaemic drugs The pharmacological management of diabetic dyslipidaemia has been recently reviewed elsewhere [62 ]. Statins are the first-line choice drug therapy to achieve LDL-C targets in patients with T2DM [63]. Decreases in triglyceride and sdLDL levels as well as a slight but significant increase in HDL-C levels have been reported in statin-treated patients with T2DM [64]. Furthermore, statins significantly decrease CHD morbidity and mortality in T2DM irrespective of a prior history of CVD [65]. A meta-analysis reported that patients with T2DM benefited more than patients with T2DM in terms of CVD risk reduction [66]. Although statin-related CVD benefits outweigh any adverse event, statin therapy can lead to newonset T2DM [67,68]. Furthermore, statins may adversely affect insulin secretion and resistance, thus worsening glycaemic control [69]. Among different statins, pitavastatin was reported to significantly decrease HbA1c in poorly controlled T2DM patients [70], whereas pravastatin therapy was associated with reduced rates of new diabetes in the West of Scotland Coronary Prevention Study [71]. Ezetimibe may lead to significant improvements in TC, LDL-C, triglyceride, HDL-C, sdLDL and PPL [72–74]. Patients with T2DM on ezetimibe/simvastatin had significantly fewer major adverse cardiac events compared with statin monotherapy [75]. Similarly, in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial [76], ezetimibe/ simvastatin therapy significantly reduced LDL-C levels as well as CVD morbidity and mortality in patients with a recent acute coronary syndrome compared with simvastatin monotherapy; this benefit was more pronounced in patients with T2DM. Interestingly, ezetimibe does not impair glycaemic control and it may improve glucose metabolism and insulin resistance [77,78]. Fibrates can decrease triglyceride, sdLDL and PPL as well as increase HDL-C, thus representing a useful option in patients with T2DM [79,80]. In the &

Fenofibrate Intervention and Event Lowering in Diabetes study, fenofibrate significantly reduced nonfatal MI and coronary revascularization in patients with T2DM compared with placebo [81]. However, in the Action to Control Cardiovascular Risk in Diabetes Lipid study, simvastatin/fibrate combination did not significantly decrease cardiovascular morbidity and mortality in patients with T2DM compared with simvastatin/placebo [82] during the trial or after 10 years [83]. A benefit was observed in the prespecified subgroup of patients with elevated triglyceride and low HDL-C levels and contributes to the effects described in meta-analyses of interventions in patients with raised triglycerides [84]. Furthermore, fenofibrate prevented the angiographic progression of CHD in patients with T2DM as reported in the Diabetes Atherosclerosis Intervention Study [85]. Statin– fibrate combination is more efficient in correcting diabetic dyslipidaemia compared with either monotherapy [86]. Niacin may lower LDL-C and triglyceride, increase HDL-C and improve sdLDL and PPL [87– 89]. However, niacin was shown to increase fasting glucose levels in patients with T2DM [87,90]. On the basis of two recent negative trials, niacin was withdrawn from the European Union market (www.ema. europa.eu/ema/index. jsp?curl=pages/medicines/ human/referrals/Tre daptive,_Pelzont_and_Trevaclyn/ human_referral_prac_000014.jsp&mid=WC 0b01 ac05805c516f). However, a recent meta-regression analysis supported niacin-induced significant decreases in CVD events and revascularization [91]. Colesevelam, a second-generation bile acid sequestrant, exerts both lipid-lowering and glucose-lowering properties [92]. Its use is limited by cost and adherence to treatment. Up-to-date data show no adverse effect of Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on new-onset T2DM or on glucose metabolism in T2DM patients [93], but Mendelian randomization studies suggest that PCSK-9 inhibitors may resemble statins in their diabetogenic potential [94]. More research is needed to establish the role of PSCK9 inhibitors in the treatment of diabetic dyslipidaemia.

Antihypertensive drugs High doses of diuretics as well as b-blockers may increase the risk of T2DM, impair glucose metabolism [95] and worsen dyslipidaemia in patients with T2DM [96]. b-blockers can decrease insulin sensitivity and increase the prevalence of hypoglycaemia [97]. ‘Newer’ mixed effect b-blockers (such as carvedilol) may exert neutral or positive effects on

0268-4705 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.

www.co-cardiology.com

3

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

CE: Alpana; HCO/320407; Total nos of Pages: 8;

HCO 320407

Lipids and emerging risk factors

insulin resistance and dyslipidaemia [97]. Ramipril (an angiotensin-II converting enzyme (ACE) inhibitor) reduced TC and LDL-C as well as increased HDLC in patients with T2DM [98,99]. Angiotensin-2 receptor blockers (ARBs) decreased TC and LDL-C levels in patients with hypertension and T2DM [100–102]. Doxazosin, an adrenergic a-receptor blocker, decreased HbA1c, fasting glucose, TC, LDL-C, sdLDL and triglyceride levels, and increased HDL-C when used either as monotherapy or as addon therapy in patients with T2DM [103–105]. Among calcium channel blockers, manidipine significantly decreased HbA1c, fasting glucose, TC, triglyceride and LDL-C levels when administered either as monotherapy or as add-on therapy in patients with T2DM treated with a diuretic and an ARB or ACE inhibitor [106,107].

Antidiabetic drugs Metformin can significantly lower TC, LDL-C and triglyceride levels in patients withT2DM [108,109]. A meta-analysis of the effects of sulfonylureas reported reductions in TC and HDL-C levels (but not in triglyceride) in patients with T2DM [110]. However, other studies report increases in HDL-C and reductions in LDL-C and triglyceride levels following glimepiride therapy [111–113]. Metformin–sulfonylurea combinations (i.e. with gliclazide or glipizide) as well as glibenclamide monotherapy decrease PPL in patients with T2DM patients [114–116]. Among a-glucosidase inhibitors, acarbose improved LDL-C, triglyceride, HDL-C and PPL in patients with T2DM [110,117,118], whereas nateglinide was shown to decrease sdLDL and PPL [119,120]. Pioglitazone improves TC, triglyceride, VLDL, HDL-C and PPL levels [110,117,121,122]. Pioglitazone may raise the quantity of LDL-C, but this is counterbalanced by improvement in LDL-C particle size [123,124]. Insulin treatment can lower TC, LDL-C and triglyceride levels as well as increase HDL-C in patients with T2DM [125–127]. Overall, patients with T2DM treated with insulin had a better lipid profile (lower TC, triglyceride and LDL-C as well as higher HDL-C levels) compared with those on oral antidiabetic drugs (metformin, sulfonylurea or their combination) [128]. Dipeptidyl peptidase-4 inhibitors reduce TC, LDL-C, triglyceride and PPL [129–133]. HDL-C was increased by sitagliptin [134] and reduced by alogliptin [133]. Among glucagonlike peptide-1 receptor agonists, lixisenatide reduced TC, LDL-C and triglyceride in patients with T2DM patients [135]. Exenatide therapy was also shown to improve fasting lipids and PPL in some studies [136–139], but increases in TC and LDL-C concentrations have been also reported [137]. Once 4

www.co-cardiology.com

weekly exenatide treatment decreased TC, LDL-C and triglyceride as well as increased HDL-C levels [140,141]. Liraglutide lowered TC, LDL-C, triglyceride and TC/HDL-C ratio in patients with T2DM [142,143,144 ] and may improve PPL [145]. Highdose liraglutide (i.e. 3 mg/day) increased HDL-C levels in obese patients [146]. No data exist on the effects of dulaglutide and semaglutide. Among sodium-glucose cotransporter 2 inhibitors (SGLT2i), dapagliflozin increased TC, LDL-C and HDL-C and decreased triglyceride [41,147,148]. Similar effects have been observed with canagliflozin [149–151]. Interestingly, in patients with T2DM, canagliflozin decreased LDL-C if baseline LDL-C was at least 120 mg/dl (>3.2 mmol/l), but increased LDL-C in those with LDL-C less than 120 mg/dl [152]. Empagliflozin shows similar effects [153]. The effects of SGLT-2i on PPL and LDL particle size have not been investigated. Improvements in several CVD risk factors including body weight, glucose, blood pressure, uric acid, lipids, arterial stiffness and NAFLD as well as in renal and cardiac function may be responsible for the beneficial effects of liraglutide, semaglutide and empagliflozin in CVD endpoint trials [154– 157,158 ]. In these trials, semaglutide increased all lipid parameters (i.e. TC, LDL-C, triglyceride and HDL-C) [159 ], whereas empagliflozin slightly raised LDL-C and HDL-C [153]; whereas no data on liraglutide have been reported [160 ]. The observed CVD benefits with these drugs, despite the negative effect on LDL-C levels, may be explained by improvements in LDL (and HDL) quality and other risk factors. Further research is needed to establish such an association. &

&

&&

&&

CONCLUSION T2DM is associated with increased CHD morbidity and mortality. Coronary interventions are more frequently performed in T2DM patients with worse outcomes. T2DM has also been linked to an increased prevalence and severity of heart failure and atrial fibrillation. Diabetic dyslipidaemia contributes to the risk of CVD events in patients with T2DM. Glucose and lipid metabolism may be affected by hypolipidaemic, antihypertensive and antidiabetic drugs, thus influencing CHD risk. LDL quality and postprandial lipaemia may be improved by such drugs. Acknowledgements None. Financial support and sponsorship This review was written independently; no company or institution supported the authors financially or by Volume 32  Number 00  Month 2017

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

CE: Alpana; HCO/320407; Total nos of Pages: 8;

HCO 320407

Dysli pidaemia in type 2 diabetes mellitus Katsiki et al.

providing a professional writer. N.K. has given talks, attended conferences and participated in trials sponsored by Amgen, Angelini, Astra Zeneca, Boehringer Ingelheim, Galenica, MSD, Novartis, Novo Nordisk, Sanofi and Win Medica. D.P.M. has given talks and attended conferences sponsored by MSD, AstraZeneca and Libytec. N.T. has given talks, attended conferences and participated in trials sponsored by Novo Nordisk, Sanofi-Aventis, Novartis, AstraZeneca, Boehringer Ingelheim, MSD, GSK, Angelini, Vianex, Elli Lilly, Trigocare, Petsiavas and ELPEN. Conflicts of interest There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Naito R, Kasai T. Coronary artery disease in type 2 diabetes mellitus: recent treatment strategies and future perspectives. World J Cardiol 2015; 7:119– 124. 2. Lathief S, Inzucchi SE. Approach to diabetes management in patients with CVD. Trends Cardiovasc Med 2016; 26:165–179. 3. Go AS, Mozaffarian D, Roger VL, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation 2013; 127:143–152. 4. Lee C, Joseph L, Colosimo A, Dasgupta K. Mortality in diabetes compared with previous cardiovascular disease: a gender-specific meta-analysis. Diabetes Metab 2012; 38:420–427. 5. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ 2006; 332:73–78. 6. Savonitto S, Morici N, Cavallini C, et al. One-year mortality in elderly adults with non-ST-elevation acute coronary syndrome: effect of diabetic status and admission hyperglycemia. J Am Geriatr Soc 2014; 62:1297–1303. 7. Radomska E, Sadowski M, Kurzawski J, et al. ST-segment elevation myocardial infarction in women with type 2 diabetes. Diabetes Care 2013; 36:3469–3475. 8. Rousan TA, Pappy RM, Chen AY, et al. Impact of diabetes mellitus on clinical characteristics, management, and in-hospital outcomes in patients with acute myocardial infarction (from the NCDR). Am J Cardiol 2014; 114:1136– 1144. 9. Ahmadi A, Soori H, Sajjadi H. Modeling of in hospital mortality determinants in myocardial infarction patients, with and without type 2 diabetes, undergoing pharmaco-invasive strategy: the first national report using two approaches in Iran. Diabetes Res Clin Pract 2015; 108:216–222. 10. Li N, Yang YG, Chen MH. Comparing the adverse clinical outcomes in & patients with noninsulin treated type 2 diabetes mellitus and patients without type 2 diabetes mellitus following percutaneous coronary intervention: a systematic review and meta-analysis. BMC Cardiovasc Disord 2016; 16:238. A meta-analysis reporting worse outcomes in T2DM patients following PCI. 11. Sobel BE. Coronary revascularization in patients with type 2 diabetes and results of the BARI 2D trial. Coron Artery Dis 2010; 21:189–198. 12. Hee L, Mussap CJ, Yang L, et al. Outcomes of coronary revascularization (percutaneous or bypass) in patients with diabetes mellitus and multivessel coronary disease. Am J Cardiol 2012; 110:643–648. 13. Zhang Q, Liu T, Ng CY, Li G. Diabetes mellitus and atrial remodeling: mechanisms and potential upstream therapies. Cardiovasc Ther 2014; 32:233–2341. 14. Huxley RR, Filion KB, Konety S, Alonso A. Meta-analysis of cohort and casecontrol studies of type 2 diabetes mellitus and risk of atrial fibrillation. Am J Cardiol 2011; 108:56–62. 15. Siscovick DS, Sotoodehnia N, Rea TD, et al. Type 2 diabetes mellitus and the risk of sudden cardiac arrest in the community. Rev Endocr Metab Disord 2010; 11:53–59. 16. King RJ, Grant PJ. Diabetes and cardiovascular disease: pathophysiology of a life-threatening epidemic. Herz 2016; 41:184–192.

17. Masmiquel L, Leiter LA, Vidal J, et al. LEADER investigators. LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial. Cardiovasc Diabetol 2016; 15:29. 18. Blomster JI, Woodward M, Zoungas S, et al. The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial. BMJ Open 2016; 6:e009668. 19. Cusi K. Treatment of patients with type 2 diabetes and nonalcoholic fatty liver disease: current approaches and future directions. Diabetologia 2016; 59:1112–1120. 20. Papademetriou V, Lovato L, Doumas M, et al. ACCORD Study Group. Chronic kidney disease and intensive glycemic control increase cardiovascular risk in patients with type 2 diabetes. Kidney Int 2015; 87:649–659. 21. Katsiki N, Papanas N, Fonseca VA, et al. Uric acid and diabetes: is there a link? Curr Pharm Des 2013; 19:4930–4937. 22. Szalat A, Durst R, Leitersdorf E. Managing dyslipidaemia in type 2 diabetes mellitus. Best Pract Res Clin Endocrinol Metab 2016; 30:431–444. 23. Sone H, Tanaka S, Tanaka S, et al. Japan Diabetes Complications Study Group. Serum level of triglycerides is a potent risk factor comparable to LDL cholesterol for coronary heart disease in Japanese patients with type 2 diabetes: subanalysis of the Japan Diabetes Complications Study (JDCS). J Clin Endocrinol Metab 2011; 96:3448–3456. 24. Pereira EC, Bertolami MC, Faludi AA, et al. Predictive potential of twenty-two biochemical biomarkers for coronary artery disease in type 2 diabetes mellitus. Int J Endocrinol 2015; 2015:146816. 25. Haffner SM. Lipoprotein disorders associated with type 2 diabetes mellitus and insulin resistance. Am J Cardiol 2002; 90 (8A):55i–61i. 26. Raffield LM, Hsu FC, Cox AJ, et al. Predictors of all-cause and cardiovascular disease mortality in type 2 diabetes: Diabetes Heart Study. Diabetol Metab Syndr 2015; 7:58. 27. Park GM, An H, Lee SW, et al. Risk score model for the assessment of coronary artery disease in asymptomatic patients with type 2 diabetes. Medicine (Baltimore) 2015; 94:e508. 28. Fujihara K, Suzuki H, Sato A, et al. Carotid artery plaque and LDL-to-HDL cholesterol ratio predict atherosclerotic status in coronary arteries in asymptomatic patients with type 2 diabetes mellitus. J Atheroscler Thromb 2013; 20:452–464. 29. Eliasson B, Cederholm J, Eeg-Olofsson K, et al., National Diabetes Register. Clinical usefulness of different lipid measures for prediction of coronary heart disease in type 2 diabetes: a report from the Swedish National Diabetes Register. Diabetes Care 2011; 34:2095–2100. 30. Pres D, Gasior M, Lekston A, et al. Relationship between low-density lipoprotein cholesterol level on admission and in-hospital mortality in patients with ST-segment elevation myocardial infarction, with or without diabetes, treated with percutaneous coronary intervention. Kardiol Pol 2010; 68:1005–1012. 31. Zeng RX, Li XL, Zhang MZ, et al. Non-HDL cholesterol is a better target for predicting periprocedural myocardial injury following percutaneous coronary intervention in type 2 diabetes. Atherosclerosis 2014; 237:536–543. 32. Sukhija R, Aronow WS, Sureddi R, et al. Predictors of in-stent restenosis and patient outcome after percutaneous coronary intervention in patients with diabetes mellitus. Am J Cardiol 2007; 100:777–780. 33. Qin Z, Zheng F, Zeng C, et al. Elevated very low density lipoprotein cholesterol levels are independently associated with in-stent restenosis in diabetic patients after drug-eluting stent implantation. Angiology 2017; In press. 34. Valensi P, Avignon A, Sultan A, et al. Atherogenic dyslipidemia and risk of & silent coronary artery disease in asymptomatic patients with type 2 diabetes: a cross-sectional study. Cardiovasc Diabetol 2016; 15:104. A study showing that T2DM patients may suffer from silent CHD. 35. Prenner SB, Mulvey CK, Ferguson JF, et al. Very low density lipoprotein cholesterol associates with coronary artery calcification in type 2 diabetes beyond circulating levels of triglycerides. Atherosclerosis 2014; 236:244– 250. 36. Kasteleyn MJ, Vos RC, Jansen H, Rutten GE. Differences in clinical characteristics between patients with and without type 2 diabetes hospitalized with a first myocardial infarction. J Diabetes Complications 2016; 30:830– 833. 37. Mikhailidis DP, Elisaf M, Rizzo M, et al. European panel on low density lipoprotein (LDL) subclasses’: a statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses: executive summary. Curr Vasc Pharmacol 2011; 9:531–532. 38. Mikhailidis DP, Elisaf M, Rizzo M, et al. European panel on low density lipoprotein (LDL) subclasses’: a statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses. Curr Vasc Pharmacol 2011; 9:533–571. 39. Berneis K, Jeanneret C, Muser J, et al. Low-density lipoprotein size and subclasses are markers of clinically apparent and nonapparent atherosclerosis in type 2 diabetes. Metabolism 2005; 54:227–234. 40. Huang YC, Chang PY, Hwang JS, Ning HC. Association of small dense low density lipoprotein cholesterol in type 2 diabetics with coronary artery disease. Biomed J 2014; 37:375–379.

0268-4705 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.

www.co-cardiology.com

5

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

CE: Alpana; HCO/320407; Total nos of Pages: 8;

HCO 320407

Lipids and emerging risk factors 41. Rizzo M, Al-Busaidi N, Rizvi AA. Dapagliflozin therapy in type-2 diabetes: current knowledge and future perspectives. Expert Opin Pharmacother 2015; 16:281–284. 42. Katsiki N, Athyros VG, Karagiannis A. Achieving lipid targets in primary care settings. Curr Med Res Opin 2014; 30:1971–1974. 43. Kolovou GD, Mikhailidis DP, Kovar J, et al. Assessment and clinical relevance of nonfasting and postprandial triglycerides: an expert panel statement. Curr Vasc Pharmacol 2011; 9:258–270. 44. Kolovou GD, Mikhailidis DP, Nordestgaard BG, et al. Definition of postprandial lipaemia. Curr Vasc Pharmacol 2011; 9:292–301. 45. Perez-Martinez P, Alcala-Diaz JF, Kabagambe EK, et al. Assessment of & postprandial triglycerides in clinical practice: validation in a general population and coronary heart disease patients. J Clin Lipidol 2016; 10:1163– 1171. Assessed the prevalence of PPL in CHD patients and the general population. 46. Pirillo A, Norata GD, Catapano AL. Postprandial lipemia as a cardiometabolic risk factor. Curr Med Res Opin 2014; 30:1489–1503. 47. Parhofer KG. Interaction between glucose and lipid metabolism: more than diabetic dyslipidemia. Diabetes Metab J 2015; 39:353–362. 48. Verge`s B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia 2015; 58:886–899. 49. Kruit JK, Brunham LR, Verchere CB, Hayden MR. HDL and LDL cholesterol significantly influence beta-cell function in type 2 diabetes mellitus. Curr Opin Lipidol 2010; 21:178–185. 50. Otocka-Kmiecik A, Mikhailidis DP, Nicholls SJ, et al. Dysfunctional HDL: a novel important diagnostic and therapeutic target in cardiovascular disease? Prog Lipid Res 2012; 51:314–324. 51. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. Characteristics other than the diagnostic criteria associated with metabolic syndrome: an overview. Curr Vasc Pharmacol 2014; 12:627–641. 52. Van Linthout S, Spillmann F, Schultheiss HP, Tscho¨pe C. High-density lipoprotein at the interface of type 2 diabetes mellitus and cardiovascular disorders. Curr Pharm Des 2010; 16:1504–1516. 53. Kostapanos MS, Elisaf MS. High density lipoproteins and type 2 diabetes: emerging concepts in their relationship. World J Exp Med 2014; 4:1–6. 54. Quispe R, Martin SS, Jones SR. Triglycerides to high-density lipoproteincholesterol ratio, glycemic control and cardiovascular risk in obese patients with type 2 diabetes. Curr Opin Endocrinol Diabetes Obes 2016; 23:150–156. 55. Esteghamati A, Asnafi S, Eslamian M, et al. Associations of small dense lowdensity lipoprotein and adiponectin with complications of type 2 diabetes. Endocr Res 2015; 40:14–19. 56. Sa´nchez-Quesada JL, Vinagre I, de Juan-Franco E, et al. Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size, electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution. Am J Cardiol 2012; 110:67–71. 57. Gomez Rosso L, Lhomme M, Meron˜o T, et al. Poor glycemic control in type 2 diabetes enhances functional and compositional alterations of small, dense HDL3c. Biochim Biophys Acta 2017; 1862:188–195. 58. Manfredini F, D’Addato S, Laghi L, et al. Influence of lifestyle measures on hypertriglyceridaemia. Curr Drug Targets 2009; 10:344–355. 59. Del Pilar Solano M, Goldberg RB. Management of diabetic dyslipidemia. Endocrinol Metab Clin North Am 2005; 34:1–25. 60. Athyros VG, Katsiki N, Doumas M, et al. Effect of tobacco smoking and smoking cessation on plasma lipoproteins and associated major cardiovascular risk factors: a narrative review. Curr Med Res Opin 2013; 29:1263– 1274. 61. Kalyvas AV, Vlachos K, Abu-Amara M, et al. Bariatric surgery as metabolic surgery for diabetic patients. Curr Pharm Des 2014; 20:3631–3646. 62. Filippatos TD, Florentin M, Georgoula M, Elisaf MS. Pharmacological man& agement of diabetic dyslipidemia. Expert Rev Clin Pharmacol 2017; 10:187–200. A review summarizing therapeutic options for diabetic dyslipidaemia. 63. Halcox J, Misra A. Type 2 diabetes mellitus, metabolic syndrome, and mixed dyslipidemia: how similar, how different, and how to treat? Metab Syndr Relat Disord 2015; 13:1–21. 64. Chang YH, Lin KD, Shin SJ, Lee YJ. Changes in high-density-lipoprotein cholesterol upon statin treatment in type 2 diabetic patients: a meta-analysis. Nutr Metab Cardiovasc Dis 2014; 24:1067–1073. 65. Cholesterol Treatment Trialists’ (CTT) Collaborators. Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008; 371:117–125. 66. Costa J, Borges M, David C, Vaz Carneiro A. Efficacy of lipid lowering drug treatment for diabetic and nondiabetic patients: meta-analysis of randomized controlled trials. BMJ 2006; 332:1115–1124. 67. Katsiki N, Rizzo M, Mikhailidis DP, Mantzoros CS. New-onset diabetes and statins: throw the bath water out, but, please, keep the baby! Metabolism 2015; 64:471–475. 68. Athyros VG, Mikhailidis DP. Pharmacotherapy: statins and new-onset diabetes mellitus – a matter for debate. Nat Rev Endocrinol 2012; 8:133–134. 69. Muscogiuri G, Sarno G, Gastaldelli A, et al. The good and bad effects of statins on insulin sensitivity and secretion. Endocr Res 2014; 39:137–143.

6

www.co-cardiology.com

70. Huang CH, Huang YY, Hsu BR. Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes. J Diabetes Investig 2016; 7:769–776. 71. Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001; 103:357–362. 72. Sakamoto K, Kawamura M, Kohro T, et al., RESEARCH Study Group. Effect of ezetimibe on LDL-C lowering and atherogenic lipoprotein profiles in type 2 diabetic patients poorly controlled by statins. Plos One 2015; 10:e0138332. 73. Hiramitsu S, Miyagishima K, Ishii J, et al. Effect of ezetimibe on lipid and glucose metabolism after a fat and glucose load. J Cardiol 2012; 60:395– 400. 74. Katsiki N, Theocharidou E, Karagiannis A, et al. Ezetimibe therapy for dyslipidemia: an update. Curr Pharm Des 2013; 19:3107–3114. 75. Chang SH, Wu LS, Lee CH, et al. Simvastatin-ezetimibe combination therapy is associated with a lower rate of major adverse cardiac events in type 2 diabetics than high potency statins alone: a population-based dynamic cohort study. Int J Cardiol 2015; 190:20–25. 76. Cannon CP, Blazing MA, Giugliano RP, et al., IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372:2387–2397. 77. Tsunoda T, Nozue T, Yamada M, et al. Effects of ezetimibe on atherogenic lipoproteins and glucose metabolism in patients with diabetes and glucose intolerance. Diabetes Res Clin Pract 2013; 100:46–52. 78. Saito I, Azuma K, Kakikawa T, et al. A randomized, double-blind, placebocontrolled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia. Lipids Health Dis 2015; 14:40. 79. Steinmetz A. Treatment of diabetic dyslipoproteinemia. Exp Clin Endocrinol Diabetes 2003; 111:239–245. 80. Rizzo M, Berneis K. Who needs to care about small, dense low-density lipoproteins? Int J Clin Pract 2007; 61:1949–1956. 81. Keech A, Simes RJ, Barter P, et al., FIELD study investigators. Effects of longterm fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005; 366:1849–1861. 82. Study Group ACCORD. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010; 362:1563–1574. 83. Elam MB, Ginsberg HN, Lovato LC, et al., ACCORDION Study Investigators. Association of fenofibrate therapy with long-term cardiovascular risk in statintreated patients with type 2 diabetes. JAMA Cardiol 2016. [Epub ahead of print] 84. Maki KC, Guyton JR, Orringer CE, et al. Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia. J Clin Lipidol 2016; 10:905–914. 85. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001; 357:905–910. 86. Jones PH, Cusi K, Davidson MH, et al. Efficacy and safety of fenofibric acid co-administered with low- or moderate-dose statin in patients with mixed dyslipidemia and type 2 diabetes mellitus: results of a pooled subgroup analysis from three randomized, controlled, double-blind trials. Am J Cardiovasc Drugs 2010; 10:73–84. 87. Ding Y, Li Y, Wen A. Effect of niacin on lipids and glucose in patients with type 2 diabetes: a meta-analysis of randomized, controlled clinical trials. Clin Nutr 2015; 34:838–844. 88. Florentin M, Tselepis AD, Elisaf MS, et al. Effect of nonstatin lipid lowering and antiobesity drugs on LDL subfractions in patients with mixed dyslipidaemia. Curr Vasc Pharmacol 2010; 8:820–830. 89. Usman MH, Qamar A, Gadi R, et al. Extended-release niacin acutely suppresses postprandial triglyceridemia. Am J Med 2012; 125:1026–1035. 90. Collins PD, Sattar N. Glycaemic effects of nonstatin lipid-lowering therapies. Curr Cardiol Rep 2016; 18:133. 91. Siniawski D, Santos-Gallego CG, Badimon JJ, Masson WM. Niacin is still beneficial. Implications from an updated meta-regression analysis. Acta Cardiol 2016; 71:463–472. 92. Sandhu S, Moosavi M, Golmohammadi K, Francis GA. Colesevelam as an add-on treatment for control of dyslipidemia and hyperglycemia in type 2 diabetes. Can J Diabetes 2016; 40:112–114. 93. Athyros VG, Tziomalos K, Doumas M, et al. The effect of proprotein convertase subtilisin-kexin type 9 and its inhibition on glucose metabolism and cardiovascular risk. We should do better the second time after statins. Curr Pharm Des 2017. [Epub ahead of print] 94. Schmidt AF, Swerdlow DI, Holmes MV, et al. PCSK9 genetic variants and risk of type 2 diabetes: a Mendelian randomisation study. Lancet Diabetes Endocrinol 2017; 5:97–105. 95. Karagiannis A, Tziomalos K, Anagnostis P, et al. The effect of antihypertensive agents on insulin sensitivity, lipids and haemostasis. Curr Vasc Pharmacol 2010; 8:792–803. 96. Palmer BF. Metabolic complications associated with use of diuretics. Semin Nephrol 2011; 31:542–552.

Volume 32  Number 00  Month 2017

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

CE: Alpana; HCO/320407; Total nos of Pages: 8;

HCO 320407

Dysli pidaemia in type 2 diabetes mellitus Katsiki et al. 97. Fonarow GC. Managing the patient with diabetes mellitus and heart failure: issues and considerations. Am J Med 2004; 116 (Suppl 5A):76S–88S. 98. Koulouris S, Symeonides P, Triantafyllou K, et al. Comparison of the effects of ramipril versus telmisartan in reducing serum levels of high-sensitivity Creactive protein and oxidized low-density lipoprotein cholesterol in patients with type 2 diabetes mellitus. Am J Cardiol 2005; 95:1386–1388. 99. Janka HU, Nuber A, Mehnert H. Metabolic effects of ramipril treatment in hypertensive subjects with noninsulin-dependent diabetes mellitus. Arzneimittelforschung 1990; 40:432–435. 100. Kintscher U, Marx N, Martus P, et al. Effect of high-dose valsartan on inflammatory and lipid parameters in patients with Type 2 diabetes and hypertension. Diabetes Res Clin Pract 2010; 89:209–215. 101. Derosa G, Fogari E, D’Angelo A, et al. Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone. J Clin Pharm Ther 2007; 32:261–268. 102. Appel GB, Radhakrishnan J, Avram MM, et al. RENAAL Study Analysis of metabolic parameters as predictors of risk in the RENAAL study. Diabetes Care 2003; 26:1402–1407. 103. Derosa G, Cicero AF, Gaddi A, et al. Effects of doxazosin and irbesartan on blood pressure and metabolic control in patients with type 2 diabetes and hypertension. J Cardiovasc Pharmacol 2005; 45:599–604. 104. Pessina AC, Ciccariello L, Perrone F, et al. Clinical efficacy and tolerability of alpha-blocker doxazosin as add-on therapy in patients with hypertension and impaired glucose metabolism. Nutr Metab Cardiovasc Dis 2006; 16:137–147. 105. Tamasawa N, Matsui J, Ogawa Y, et al. Effect of doxazosin on the size of LDL particle in the type 2 diabetic patients with hypertension. J Diabetes Complications 2000; 14:135–139. 106. Luque Otero M, Martell Claros N; Study Investigators Group. Manidipine versus enalapril monotherapy in patients with hypertension and type 2 diabetes mellitus: a multicenter, randomized, double-blind, 24-week study. Clin Ther 2005; 27:166–173. 107. Martell-Claros N, de la Cruz JJ. Manidipine for hypertension not controlled by dual therapy in patients with diabetes mellitus: a noncomparative, open-label study. Clin Drug Investig 2011; 31:427–434. 108. Xu T, Brandmaier S, Messias AC, et al. Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes. Diabetes Care 2015; 38:1858–1867. 109. Ma J, Liu LY, Wu PH, et al. Comparison of metformin and repaglinide monotherapy in the treatment of new onset type 2 diabetes mellitus in China. J Diabetes Res 2014; 2014:294017. 110. Monami M, Vitale V, Ambrosio ML, et al. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: metaanalysis of placebo-controlled trials. Adv Ther 2012; 29:736–746. 111. Araki T, Emoto M, Konishi T, et al. Glimepiride increases high-density lipoprotein cholesterol via increasing adiponectin levels in type 2 diabetes mellitus. Metabolism 2009; 58:143–148. 112. Derosa G, Gaddi AV, Piccinni MN, et al. Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial. Diabetes Obes Metab 2006; 8:197–205. 113. Umpierrez G, Issa M, Vlajnic A. Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial. Curr Med Res Opin 2006; 22:751–759. 114. Emral R, Ko¨seog˘lulari O, Tonyukuk V, et al. The effect of short-term glycemic regulation with gliclazide and metformin on postprandial lipemia. Exp Clin Endocrinol Diabetes 2005; 113:80–84. 115. Jeppesen J, Zhou MY, Chen YD, Reaven GM. Effect of metformin on postprandial lipemia in patients with fairly to poorly controlled NIDDM. Diabetes Care 1994; 17:1093–1099. 116. Skrapari I, Perrea D, Ioannidis I, et al. Glibenclamide improves postprandial hypertriglyceridaemia in type 2 diabetic patients by reducing chylomicrons but not the very low-density lipoprotein subfraction levels. Diabet Med 2001; 18:781–785. 117. Buse JB, Tan MH, Prince MJ, Erickson PP. The effects of oral antihyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes. Diabetes Obes Metab 2004; 6:133–156. 118. Ogawa S, Takeuchi K, Ito S. Acarbose lowers serum triglyceride and postprandial chylomicron levels in type 2 diabetes. Diabetes Obes Metab 2004; 6:384–390. 119. Onishi Y, Fujisawa T, Sakaguchi K, Maeda M. Effect of nateglinide on the size of LDL particles in patients with type 2 diabetes. Adv Ther 2006; 23:549– 555. 120. Ju-Ming L, Xiao-Hui G, Xiao-Feng L, et al. Effects of nateglinide on postprandial plasma glucose excursion and metabolism of lipids in Chinese patients with type 2 diabetes: a 4-week, randomized, active-control, openlabel, parallel-group, multicenter trial. Curr Med Res Opin 2012. [Epub ahead of print] 121. Nakano K, Hasegawa G, Fukui M, et al. Effect of pioglitazone on various parameters of insulin resistance including lipoprotein subclass according to particle size by a gel-permeation high-performance liquid chromatography in newly diagnosed patients with type 2 diabetes. Endocr J 2010; 57:423–430.

122. Sharma SK, Verma SH. A study of effects of pioglitazone and rosiglitazone on various parameters in patients of type-2 diabetes mellitus with special reference to lipid profile. J Assoc Physicians India 2016; 64: 24–28. 123. Perez A, Khan M, Johnson T, Karunaratne M. Pioglitazone plus a sulphonylurea or metformin is associated with increased lipoprotein particle size in patients with type 2 diabetes. Diab Vasc Dis Res 2004; 1:44–50. 124. Deeg MA, Buse JB, Goldberg RB, et al. Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia. Diabetes Care 2007; 30:2458–2464. 125. Zeng L, Lu H, Deng H, et al. Noninferiority effects on glycemic control and bcell function improvement in newly diagnosed type 2 diabetes patients: basal insulin monotherapy versus continuous subcutaneous insulin infusion treatment. Diabetes Technol Ther 2012; 14:35–42. 126. Lindstro¨m T, Olsson AG, von Schenck H, et al. Insulin treatment improves microalbuminuria and other cardiovascular risk factors in patients with type 2 diabetes mellitus. J Intern Med 1994; 235:253–261. 127. Fukui T, Hirano T. High-density lipoprotein subspecies between patients with type 1 diabetes and type 2 diabetes without /with intensive insulin therapy. Endocr J 2012; 59:561–569. 128. Habib SS, Aslam M, Naveed AK, Razi MS. Comparison of lipid profiles and lipoprotein a levels in patients with type 2 diabetes mellitus during oral hypoglycemic or insulin therapy. Saudi Med J 2006; 27:174–180. 129. Duvnjak L, Blaslov K. Dipeptidyl peptidase-4 inhibitors improve arterial stiffness, blood pressure, lipid profile and inflammation parameters in patients with type 2 diabetes mellitus. Diabetol Metab Syndr 2016; 8:26. 130. Scheen AJ. Cardiovascular effects of gliptins. Nat Rev Cardiol 2013; 10:73– 84. 131. Derosa G, Ragonesi PD, Fogari E, et al. Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2-year study evaluation. Fundam Clin Pharmacol 2014; 28:221–229. 132. Takeda H, Sasai N, Ito S, et al. Efficacy and safety of alogliptin in patients with type 2 diabetes: analysis of the ATTAK-J Study. J Clin Med Res 2016; 8:130–140. 133. Tai H, Wang MY, Zhao YP, et al. The effect of alogliptin on pulmonary function in obese patients with type 2 diabetes inadequately controlled by metformin monotherapy. Medicine (Baltimore) 2016; 95:e4541. 134. Fan M, Li Y, Zhang S. Effects of sitagliptin on lipid profiles in patients with type 2 diabetes mellitus: a meta-analysis of randomized clinical trials. Medicine (Baltimore) 2016; 95:e2386. 135. Roca-Rodrı´guez MM, Muros de Fuentes MT, Pie´drola-Maroto G, et al. Lixisenatide in patients with type 2 diabetes and obesity: beyond glycaemic control. Aten Primaria 2016. [Epub ahead of print] 136. Ojo O. The use of exenatide in managing markers of cardiovascular risk in patients with type 2 diabetes: a systematic review. Int J Environ Res Public Health 2016; 13:E941. 137. Simo´ R, Guerci B, Schernthaner G, et al. Long-term changes in cardiovascular risk markers during administration of exenatide twice daily or glimepiride: results from the European exenatide study. Cardiovasc Diabetol 2015; 14:116. 138. Tokuda M, Katsuno T, Ochi F, et al. Effects of exenatide on metabolic parameters/control in obese Japanese patients with type 2 diabetes. Endocr J 2014; 61:365–372. 139. Bunck MC, Corne´r A, Eliasson B, et al. One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress. Atherosclerosis 2010; 212:223–229. 140. Blonde L, Pencek R, MacConell L. Association among weight change, glycemic control, and markers of cardiovascular risk with exenatide once weekly: a pooled analysis of patients with type 2 diabetes. Cardiovasc Diabetol 2015; 14:12. 141. Bergenstal RM, Li Y, Porter TK, et al. Exenatide once weekly improved glycaemic control, cardiometabolic risk factors and a composite index of an HbA1c < 7%, without weight gain or hypoglycaemia, over 52 weeks. Diabetes Obes Metab 2013; 15:264–271. 142. Rizzo M, Rizvi AA, Patti AM, et al. Liraglutide improves metabolic parameters and carotid intima-media thickness in diabetic patients with the metabolic syndrome: an 18-month prospective study. Cardiovasc Diabetol 2016; 15:162. 143. Hermansen K, Bækdal TA, D€ uring M, et al. Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial. Diabetes Obes Metab 2013; 15:1040–1048. 144. Katsiki N, Christou GA, Kiortsis DN. Liraglutide and cardiometabolic effects: & more than just another antiobesity drug? Curr Vasc Pharmacol 2016; 14:76–79. A review that highlights the cardiometabolic benefits of liraglutide. 145. Lorenz M, Lawson F, Owens D, et al. Differential effects of glucagon-like peptide-1 receptor agonists on heart rate. Cardiovasc Diabetol 2017; 16:6. 146. Giannoglou GD, Chatzizisis YS, Zamboulis C, et al. Elevated heart rate and atherosclerosis: an overview of the pathogenetic mechanisms. Int J Cardiol 2008; 126:302–312.

0268-4705 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.

www.co-cardiology.com

7

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

CE: Alpana; HCO/320407; Total nos of Pages: 8;

HCO 320407

Lipids and emerging risk factors 147. Matthaei S, Bowering K, Rohwedder K, et al., Study 05 Group. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care 2015; 38:365–372. 148. Matthaei S, Bowering K, Rohwedder K; Study 05 Group. Durability and tolerability of dapagliflozin over 52weeks as add-on to metformin and sulphonylurea in type 2 diabetes. Diabetes Obes Metab 2015; 17:1075– 1084. 149. Xiong W, Xiao MY, Zhang M, Chang F. Efficacy and safety of canagliflozin in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Medicine (Baltimore) 2016; 95:e5473. 150. Bode B, Stenlo¨f K, Harris S, et al. Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55-80 years with type 2 diabetes. Diabetes Obes Metab 2015; 17:294–303. 151. Stenlo¨f K, Cefalu WT, Kim KA, et al. Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: findings from the 52-week CANTATA-M study. Curr Med Res Opin 2014; 30:163– 175. 152. Inagaki N, Goda M, Yokota S, et al. Effects of baseline blood pressure and low-density lipoprotein cholesterol on safety and efficacy of canagliflozin in Japanese patients with type 2 diabetes mellitus. Adv Ther 2015; 32:1085– 1103. 153. Zinman B, Wanner C, Lachin JM, et al., EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373:2117–2128.

8

www.co-cardiology.com

154. Mamakou V, Eleftheriadou I, Katsiki N, et al. Antidiabetic drugs as antihypertensives: new data on the horizon. Expert Opin Pharmacother 2017; In press. 155. Athyros VG, Katsiki N, Karagiannis A. Editorial: can glucagon like peptide 1 (GLP1) agonists or sodium-glucose co-transporter 2 (SGLT2) inhibitors ameliorate non-alcoholic steatohepatitis in people with or without diabetes? Curr Vasc Pharmacol 2016; 14:494–497. 156. Athyros VG, Katsiki N, Tentolouris N. Editorial: do some glucagon-likepeptide-1 receptor agonists (GLP-1 RA) reduce macrovascular complications of type 2 diabetes mellitus a commentary on the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) Trial. Curr Vasc Pharmacol 2016; 14:469–473. 157. Katsiki N, Athyros VG, Mikhailidis DP. Nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: effects of statins and antidiabetic drugs. J Diabetes Complications 2017; 31:521–522. 158. Katsiki N, Mikhailidis DP, Theodorakis MJ. Sodium-glucose cotransporter 2 & inhibitors (SGLT2i): their role in cardiometabolic risk management. Curr Pharm Des 2017; Jan 13. [Epub ahead of print] A review discussing the cardiometabolic effects of all available SGLT-2i. 159. Marso SP, Bain SC, Consoli A, et al., SUSTAIN-6 Investigators. Semaglutide && and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375:1834–1844. This trial reported significant reductions in CVD risk with semaglutide. 160. Marso SP, Daniels GH, Brown-Frandsen K, et al., LEADER Steering Com&& mittee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375:311–322. The LEADER trial reported significant reductions in CVD risk with liraglutide.

Volume 32  Number 00  Month 2017

Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Dyslipidaemia in type 2 diabetes mellitus: bad for the heart.

Type 2 diabetes mellitus (T2DM) is associated with increased coronary heart disease (CHD) morbidity and mortality. These patients are also more prone ...
302KB Sizes 0 Downloads 15 Views