Cardiometabolic Syndrome and Increased Risk of Heart Failure

Current Heart Failure Reports

Volumn 13, Issue 5, 2016, Pages 219-229

  von Bibra, Helene ^a   Paulus, Walter ^b   St John Sutton, Martin ^c  

^a KLINIKUM BOGENHAUSEN   (Germany)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Carbohydrate restriction; Diastolic dysfunction; HFPEF; Insulin resistance; Metabolic syndrome

Indexed keywords

ANTIDIABETIC AGENT; BIGUANIDE DERIVATIVE; EMPAGLIFLOZIN; GLITAZONE DERIVATIVE; GLUCOSE; GLUCOSE TRANSPORTER 4; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIRAGLUTIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METFORMIN; MITOGEN ACTIVATED PROTEIN KINASE; MONOUNSATURATED FATTY ACID; PHOSPHATIDYLINOSITOL 3 KINASE; PIOGLITAZONE; PROTEIN KINASE B; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; TETRAHYDROLIPSTATIN; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL;

ACUTE CORONARY SYNDROME; BARIATRIC SURGERY; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CHRONIC OBSTRUCTIVE LUNG DISEASE; CORONARY ARTERY DISEASE; DIASTOLIC DYSFUNCTION; DIET SUPPLEMENTATION; ECHOCARDIOGRAPHY; EXERCISE; HEART FAILURE; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART FUNCTION; HEART MUSCLE FIBROSIS; HUMAN; HYPERGLYCEMIA; HYPERTENSION; INSULIN RESISTANCE; META ANALYSIS (TOPIC); METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; OXIDATIVE STRESS; PREVALENCE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK FACTOR; SLEEP DISORDERED BREATHING; AGE; CARDIAC MUSCLE; CARDIOVASCULAR DISEASE; COMPLICATION; DIASTOLIC HEART FAILURE; ENERGY METABOLISM; HEART STROKE VOLUME; METABOLISM; OBESITY; SEDENTARY LIFESTYLE;

AGE FACTORS; CARDIOVASCULAR DISEASES; ENERGY METABOLISM; HEART FAILURE; HEART FAILURE, DIASTOLIC; HUMANS; MYOCARDIUM; OBESITY; RISK FACTORS; SEDENTARY LIFESTYLE; STROKE VOLUME;

EID: 84982241914     PISSN: 15469530     EISSN: 15469549     Source Type: Journal    
DOI: 10.1007/s11897-016-0298-4     Document Type: Review

References (100)

1. Reaven GM. Insulin resistance: the link between obesity and cardiovascular disease. Med Clin North Am. 2011;95:875–92.
2. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association /National Heart, Lung and Blood Institute Scientific Statement. Circulation. 2005;112:2735–52.
3. Alberti KG, Eckel RH, Grundy SM, et al. International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society and International Association for the Study of Obesity. Circulation. 2009;120:1640–5.
4. Redfield MM, Jacobsen SJ, Burnett Jr JC, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289:1994–202.
5. Wong C, Marwick TH. Obesity cardiomyopathy: pathogenesis and pathophysiology. Nat Clin Pract Cardiovasc Med. 2007;4:436–43.
6. Witteles RM, Fowler MB. Insulin-resistant cardiomyopathy. Clinical evidence, mechanisms and treatment options. J Am Coll Cardiol. 2008;51:93–102.
7. Boudina S, Dale Abel E. Diabetic cardiomyopathy revisited. Circulation. 2007;115:3213–23.
8. von Bibra H, St. John Sutton M. DD in diabetes and metabolic syndrome—diagnostic and prognostic potential. Diabetologia. 2010;53:1033–45.
9. Thrainsdottir IS, Aspelund T, Gudnason V, et al. Increasing glucose levels and BMI predict future heart failure. Experience from the Reykjavik study. Eur J Heart Fail. 2007;9:1051–7.
10. Vardeny O, Gupta DK, Claggett B, Burke S, Shah A, Loehr L, et al. Insulin resistance and incident heart failure: the ARIC study (Atherosclerosis Risk in Communities). JACC Heart Fail. 2013;1:531–6.
11. Banerjee D, Biggs ML, Mercer L, Mukamal K, Kaplan R, Barzilay J, et al. Insulin resistance and incident heart failure; cardiovascular health study. Circ Heart Fail. 2013;6:364–70.
12. Ingelsson E, Sundstrom J, Arnlov J, et al. Insulin resistance and risk of congestive heart failure. JAMA. 2005;294:334–41.
13. Aroor AR, Mandavia CH, Sowers JR. Insulin resistance and heart failure: molecular mechanisms. Heart Fail Clin. 2012;8:609–17.
14. Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation. 2007;116:434–8.
15. Mamas MA, Deaton C, Rutter MK, et al. Impaired glucose tolerance and insulin resistance in heart failure: underrecognized and undertreated? J Card Fail. 2010;16:761–8.
16. Borlaug BA, Paulus WJ. Heart failure preserved ejection fraction: pathophysiology, diagnosis and treatment. Eur Heart J. 2011;32:670–9.
17. Paulus WJ, Tschope C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal ejection fraction by the heart failure and echocardiography associations of the european society of cardiology. Eur Heart J. 2007;28:2539–50.
18. Schocken DD, Benjamin EJ, Fonarow GC, et al. Prevention of heart failure: a scientific statement of the American heart association councils. Circulation. 2008;117:2544–65.
19. Paulus W, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62:263–71.
20. Wan SH, Vogel MW, Chen HH. Pre-clinical diastolic dysfunction. J Am Coll Cardiol. 2014;63:407–16. Thorough epidemiologic and etiologic discussions of DD, the preceding abnormality of HFPEF.
21. von Bibra H, Paulus W, St John Sutton M, Leclerque C, Schuster T, Schumm-Draeger PM. Quantification of DD via the age dependence of diastolic function—impact of insulin resistance with and without type 2 diabetes. IJC. 2015;182:368–74. The dominant dependence of age on diastolic function has important biomathematical consequences: dysfunction can be quantified by the difference of the actually measured E’ to the age related normal value from a regression equation derived from healthy individuals. Furthermore, risk factors need to be assessed in relation to this difference, so that the error is avoided to “identify” risk factors that also heavily depend on age.
22. Kelli HM, Kassas I, Lattouf O. Cardio metabolic syndrome: a global epidemic. J Diabet Metab. 2015;6:513–26. Broad epidemiologic insight into the cardiometabolic syndrome.
23. von Bibra H, Paulus W. Diastolic dysfunction—echocardiographic detection, etiology and therapy. Kardiologe. 2016;10:47–55.
24. Serizawa T, Vogel WM, Apstein CS, Grossman W. Comparison of acute alterations in left ventricular relaxation and diastolic chamber stiffness induced by hypoxia and ischemia. J Clin Invest. 1980;68:91–102.
25. Phan TT, Abozguia K, Shivu G, et al. Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency. J Am Coll Cardiol. 2009;54:4002–9.
26. Fontes-Carvalho R, Ladeiras-Lopes R, Bettencourt P, et al. DD in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes. Cardiovasc Diabetol. 2015;14:4–12. This review resets diastolic dysfunction in diabetes from a glucose centered view into the close link to insulin resistance, i.e. the key problem of metabolic syndrome.
27. Hwang YC, Jee JH, Kang M, et al. Metabolic syndrome and insulin resistance are associated with abnormal left ventricular diastolic function and structure independent of blood pressure and fasting plasma glucose level. Int J Cardiol. 2012;179:107–11.
28. Ritchie R. Evidence for a causal role of oxidative stress in the myocardial complications of insulin resistance. Heart Lung Circ. 2009;18:11–8.
29. Lam CS. HFpEF: invasive solution to diagnostic confusion? J Am Coll Cardiol. 2010;55:1711–2.
30. von Bibra H, Wulf G, St John Sutton M, Schuster T, Pfützner A, Heilmeyer P. Low-carbohydrate/high-protein diet improves diastolic cardiac function and the metabolic syndrome in overweight-obese patients with type 2 diabetes. IJC Metab Endoc. 2014;2:11–8. This hypothesis creating study with partial cross-over design assesses the therapeutic effects of either a traditional low-fat or a low carbohydrate diet, i.e. low GI and GL, on cardiac function and cardiovascular risk factors and glucose/insulin metabolism in obese type-2-diabetics, given an identical moderate aerobic training in any dietary intervention.
31. Edelmann F, Gelbrich G, Düngen HD, et al. Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction. J Am Coll Cardiol. 2011;58:1781–92.
32. Siri-Tarino PW, Chiu S, Bergeron N, Krauss RM. Saturated fats versus polyunsaturated fats versus carbohydrates for cardiovascular disease prevention and treatment. Annu Rev Nutr. 2015;35:517–43. The effects of saturated fatty acids on cardiovascular risk factors are profoundly modulated by the macronutrients that replace them, meaning that replacement by PUFAs has shown beneficial effects but replacement with carbohydrates did not or did worsen cardiovascular risk.
33. Mozaffarian D, Ludwig DS. The 2015 US dietary guidelines: lifting the ban on total dietary fat. JAMA. 2015;313:2421–2. Based on the Dietary Guidelines Advisory Committee’s recent recommendations, the ban on total dietary fat is lifted.
34. Ströhle A, Worm N. Metabolisches syndrom. Pathophysiologische grundlagen und rationale empfehlungen zur ernährungstherapie. Deutsche Apotheker Zeitung. 2012;152:50–67.
35. Reaven GM. The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr. 2005;25:391–406.
36. Franz MJ, Vanwormer JJ, Crain AL, et al. Weight-loss outcomes: a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc. 2007;107:1755–67.
37. Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr. 2013;97:505–16. A meta-analysis of 20 RCTs about the effects of various diets on glycemic control, lipids and weight loss in type 2 diabetes demonstrating that low-carbohydrate, low GI, Mediterranean and high protein diets effectively improve various markers of cardiovascular risk.
38. Astrup A, Grunwald GK, Melanson EL, et al. The role of low fat diets in body weight control: a meta-analysis of ad libidum dietary intervention studies. Intern Obes Relat Metab Disord. 2000;24:1545–52.
39. Howard BV, Manson JE, Stefanick MI, et al. Low-fat dietary pattern and weight change over 7 years: the womens health initiative dietary modification trial. Jama. 2006;295:39–49.
40. Pirozzo S, Summerbell C, Cameron C, et al. Should we recommend low-fat diets for obesity? Obes Rev. 2003;4:83–90.
41. Marantz PR, Bird ED, Alderman MH. A call for higher standards of evidence for dietary guidelines. Am J Prev Med. 2008;34:234–40.
42. Yang Q, Zhang Z, Gregg EW, et al. Added sugar intake and cardiovascular diseases mortality among US adults. JAMA Intern Med. 2014;174:516–24.
43. Hession M, Rolland C, Kulkarni U, et al. Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obes Rev. 2009;10:36–50.
44. Nordmann AJ, Nordmann A, Briel M, et al. Effects of low-carbohydrate vs. low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Arch Int Med. 2006;166:285–93.
45. Feinstein RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015;31:11–3. A prudent discussion about the present need for a reappraisal of dietary guidelines given the epidemic of obesity, diabetes and cardiovascular risk. The benefits of carbohydrate restriction are presented in 12 points of evidence as opposed to the conjectural concerns about the respective efficacy and safety.
46. Shikany JM, Desmond R, Mc Cubrey R, et al. Meta-analysis of studies of a specific delivery mode for a modified carbohydrate diet. J Hum Nutr Diet. 2011;24:525–35.
47. Thomas De, Elliott EJ, Baur L. Low gycemic index or low glycemic load diets for overweight and obesity. Cochrane Database Syst Rev. 2007;(3):CD005105
48. Worm N. Ernährungsempfehlungen beim metabolischen syndrom. Schweiz Z Ernährungsmed. 2007;5:29–34.
49. Ebbeling CB, Leidig MM, Sinclair KB, et al. Effects of an ad libitum low-glycemic load diet on cardiovascular disease risk factors in obese young adults. Am J Clin Nutr. 2005;81:976–82.
50. Accurso A, Bernstein RK, Dahlqvist A, et al. Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal. Nutr Metab. 2008;5:9–17.
51. Frisch S, Zittermann A, Berthold HK, et al. A randomized controlled trial on the efficacy of carbohydrate-reduced or fat-reduced diets in patients attending a telemedically guided weight loss program. Cardiovasc Diabetol. 2009;8:36–45.
52. Pereira MA, Swain J, Goldfine AB, et al. L low-glycemic load diet on resting energy expenditure and heart disease risk factors during weight loss. JAMA. 2004;292:2482–90.
53. Mendoza JA, Drewnowski A, Chistakis DJ. Dietary energy density is associated with obesity and the metabolic syndrome in U.S. adults. Diabetes Care. 2007;30:974–9.
54. Abete I, Astrup A, Martinez JA, et al. Obesity and the metabolic syndrome: role of different dietary macronutrient distribution patterns and specific nutritional components on weight loss and maintenance. Nutr Rev. 2010;68:214–31.
55. Larsen TM, Dalskov SM, van Baak M, et al. For the diets obesity and genes (Diogenes) project. Diets with high or low protein content and glycemic index for weight-loss maintenance. N Eng J Med. 2010;363:2102–13.
56. Santos FL, Esteves SS, da Costa PA, et al. Systematic review and meta-analysis of the effects of low carbohydrate diets on cardiovascular risk factors. Ob Rev. 2012;13:1048–66.
57. Ceriello A, Colagiuri S. International diabetes federation guideline for management of postmeal glucose: a review of recommendations. Diab Med. 2008;25:1151–6.
58. Monnier L, Mas E, Ginet C, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295:1681–7.
59. Hwalla N, Shakera L, Torbaya N, et al. Postprandial glycemic and insulinemic responses to high-carbohydrate vs. high-protein meals in obese normoglycemic subjects with varied insulin sensitivity. Nutr Res. 2005;25:535–48.
60. Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index and glycemic load values: 2002. Am J Clin Nutr. 2002;76:56.
61. Micha R, Nelson M. Glycemic index and glycemic load used in combination to characterize metabolic responses of mixed meals in healthy, lean, young adults. J Am Coll Nutr. 2011;30:113–25.
62. Te Morenga LA, Howatson AJ, Jones RM, et al. Dietary sugars and cardiometabolic risk: systemativ review and meta-analysis of randomized controlled trials of the effects on blood pressure and lipids. Am J Clin Nutr. 2014;100:165–79.
63. Dong JY, Zhang JH, Wang P, et al. Meta-analysis of dietary glycemic load and glycemic index in relation to risk of coronary heart disease. Am J Cardiol. 2012;109:1608–13.
64. Gerstein HC, Me M, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.
65. Executive Summary. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(1):120–43.
66. Heilmeyer P, von Bibra H. Diastolic heart failure treated by diet. Dtsch Med Wochenschr. 2016;141:121–4.
67. Joslin Diabetes Center & Clinic. Clinical nutrition guideline for overweight and obese adults with type 2 diabetes or those at higher risk for developing type 2 diabetes. http://www.joslin.org/bin_from_cms/Nutrition_Guidelines-8.22.11%281%29.pdf
68. Kodama S, Saito K, Tanaka S, et al. Influence of fat and carbohydrate proportions on the metabolic profile in patients with type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32:959–65.
69. Mensink RP, Zock PL, Kester AD, et al. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77:1146–55.
70. Krauss RM, Blanche RJ, Rawlings RS, et al. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr. 2006;83:1025–31.
71. Cao Y, Mauger DJ, Pelkman CL, et al. Effects of moderate (MF) versus lower fat (LF) diets on lipids and lipoproteins: a meta-analysis of clinical trials in subjects with and without diabetes. J Clin Lipidol. 2009;3:19–32.
72. Eslick GD, Howe PR, Smith C, et al. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. 2009;136:4–16.
73. Appel LJ, Sacks FM, Carey VJ, et al. Effects of protein, nonsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the Omni-heart randomized trial. JAMA. 2005;294:2455–64.
74. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure: DASH Collaborative Research Group. N Engl J Med. 1997;336:1117–24.
75. Chiu S, Bergeron N, Williams PT, et al. Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial. Am J Clin Nutr. 2016. doi:10.3945/ajcn.115.123281.
76. Fung TT, van Dam RM, Hankinson SE, et al. Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies. Ann Intern Med. 2010;153:289–98.
77. Lin X, Zhang X, Guo J, et al. Effects of exercise training on cardiorespiratory fitness and biomarkers of cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2015;4:e002014. doi:10.1161/JAHA.115.002014.
78. Hanson S, Jones A. Is there evidence that walking groups have health benefits? a systematic review and meta-analysis. Br J Sports Med. 2015;0:1–7.
79. Strasser B, Strasser B, Siebert U, Schobersberger W. Resistance training in the treatment of the metabolic syndrome: a systematic review and meta-analysis of the effect of resistance training on metabolic clustering in patients with abnormal glucose metabolism. Sports Med. 2010;40:397–E.
80. Wen C, Wai JP, Tsai MK, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort. Lancet. 2011;378:1244–53.
81. Mechanik JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient—2013 update: cosponsored by american association of clinical endocrinologists, the obesity society, and American society for metabolic & bariatric surgery$. Surg Obes Relat Dis. 2013;9:159–91.
82. Batsis JA, Romera-Corral A, Collazo-Clavell ML, Sarr MG, Somers VK, Lopez-Jimenez F. Effect of bariatric surgery on the metabolic syndrome: a population-based, long-term controlled study. Mayo Clin Proc. 2008;83:897–907.
83. Hammer S, Snel M, Lamb HJ, et al. Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function. J Am Coll Cardiol. 2008;52:1006–12.
84. Rider OJ, Francis JM, Ali MK, et al. Beneficial cardiovascular effects of bariatric surgical and dietary weight loss in obesity. J Am Coll Cardiol. 2009;54:718–26.
85. von Bibra H, St. John Sutton M. Impact of diabetes on post-infarction heart failure and left ventricular remodelling. Curr Heart Fail Rep. 2011;8:242–51.
86. Hummel SL, Seymour EM, Brook RD, et al. Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fraction. Circ Heart Fail. 2013;6:1165–71.
87. Hordern MD, Coombes JS, Cooney LM, et al. Effects of exercise intervention on myocardial function in type 2 diabetes. Heart. 2008;95:1343–9.
88. Kosmala W, O’Moore-Sullivan T, Plaksej R, et al. Improvement of left ventricular function by lifestyle intervention in obesity: contributions of weight loss and reduced insulin resistance. Diabetologia. 2009;52:2306–11.
89. von Bibra H, St John Sutton M, Schuster T, Ceriello A, Siegmund T, Schumm-Draeger PM. Oxidative stress after a carbohydrate meal contributes to the deterioration of diastolic cardiac function in non-hypertensive insulin-treated patients with moderately well controlled type 2 diabetes. Horm Met Res. 2013;45:449–55. This prospective interventional study compared the effects of a single carbohydrate meal on oxidative stress and cardiac function in type-2-diabetes and non-diabetic controls, demonstrating an association of increased oxidative stress with decreased diastolic function postpranidally especially in diabetic individuals.
90. Pandey S, Parashar A, Kumbhani DJ, et al. Exercise training in patients with heart failure and preserved ejection fraction. Meta-analysis of randomized control trials. Circ Heart Fail. 2015;8:33–40.
91. Anderson C, Sogaard P, Hoffmann S, et al. Metformin is associated with improved left ventricular diastolic function measured by tissue Doppler imaging in patients with diabetes. Eur J Endocrin. 2010;163:593–9.
92. van der Meer RW, Rijzewijk LJ, de Jong HW, et al. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation. 2009;119:2069–77.
93. Marso SP, Daniels GH, Brown-Frandsen K, et al. for the LEADER steering committee on behalf of the LEADER investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.
94. Pfeffer NA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373:2247–57.
95. Oe H, Nakamura K, Kihara H, et al. Comparison of sitagliptin and voglibose on left ventricular DD in patients with type 2 diabetes: results of the 3D trial. Cardiovasc Diabet. 2015;14:83–96.
96. Fadini GP, Avogaro A, Degli Esposti L, et al. Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: a retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database. Eur Heart J. 2015;36:2454–62.
97. Fitchett D, Zinman B, Wanner C et al., EMPA REG OUTCOME Investigators.Heart Failure Outcomes with Empagliflozin in Patients with Type 2 Diabetes at High Cardiovascular Risk: Results of the EMPA-REG OUTCOME® Trial. Eur Heart J. 2016;37:1526–34. In patients with type 2 diabetes and high cardiovascular risk, the most recently developed SGLT2 inhibitor empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure as compared to placebo
98. De Caterina R, Madonna R, Sourij H, et al. Glycemic control in acute coronary syndromes: prognostic value and therapeutic options. Eur Heart J. 2010;31:1557–64.
99. Von Bibra H, Siegmund T*, Kingreen I, Riemer M, Schuster T, Schumm-Draeger PM. Analogue insulin in multiple daily injection therapy of type 2 diabetes improves postprandial glucose control compared to human insulin, associated with beneficial effects on cardiac function—a randomized controlled long-term study. Cardiovasc Diabetol. 2016;15:7–17. The improvement of post-prandial glucose matters for the improvement of diastolic dysfunction and may be achieved in insulin dependent type 2 diabetes by MDI with analogue insulins as compared to MDI with human insulins.
100. Scognamiglio R, Negut C, de Kreutzenberg S, Tiengo A, Avogaro A. Effects of different insulin regimens on postprandial myocardial perfusion defects in type 2 diabetic patients. Diabetes Care. 2006;29:95–100.