Abstract
Despite decades of research into risk-reduction strategies, cardiovascular disease
and renal disease remain leading causes of morbidity and mortality among patients
with type 2 diabetes mellitus. Given the tight clustering of cardiovascular and renal
disease with the metabolic abnormalities of type 2 diabetes mellitus, we can think
of these conditions together as cardiovascular-renal-metabolic disease states. A holistic
view of cardiovascular-renal-metabolic disease states is critical to provide integrated
patient-centered care to individuals with these disease states. Here, we explore the
cardiovascular and renal risks associated with type 2 diabetes mellitus and highlight
the importance of reducing cardiovascular-renal-metabolic disease risk in a comprehensive
manner. We advocate a cross-disciplinary, team-based model to manage cardiovascular-renal-metabolic
disease risk among patients with type 2 diabetes mellitus.
Keywords
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References
- 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2020.Diabetes Care. 2020; 43: S111-S134
- Economic costs of diabetes in the U.S. in 2017.Diabetes Care. 2018; 41: 917-928
- Diabetes mellitus, fasting glucose, and risk of cause-specific death.N Engl J Med. 2011; 364: 829-841
- Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus - mechanisms, management, and clinical considerations.Circulation. 2016; 133: 2459-2502
- Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people.Lancet Diabetes Endocrinol. 2015; 3: 105-113
- Temporal trends in the prevalence of diabetic kidney disease in the United States.JAMA. 2011; 305: 2532-2539
- Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis.Lancet. 2012; 380: 1662-1673
- Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.Lancet. 2010; 375: 2215-2222
- Is diabetes a coronary risk equivalent? Systematic review and meta-analysis.Diabet Med. 2009; 26: 142-148
- Diabetes and prior coronary heart disease are not necessarily risk equivalent for future coronary heart disease events.J Gen Intern Med. 2016; 31: 387-393
- Coronary heart disease in patients with diabetes.N Engl J Med. 2000; 342: 1040-1042
- Diabetes and long-term outcomes of ischaemic stroke: findings from Get With The Guidelines-Stroke.Eur Heart J. 2018; 39: 2376-2386
- Diabetes and poor outcomes within 6 months after acute ischemic stroke: the China National Stroke Registry.Stroke. 2011; 42: 2758-2762
- Role of diabetes in congestive heart failure: the Framingham study.Am J Cardiol. 1974; 34: 29-34
- Diabetic cardiomyopathy.Diabetes Care. 2003; 26: 2949-2951
- Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored.Lancet Diabetes Endocrinol. 2014; 2: 843-851
- The incidence of congestive heart failure in type 2 diabetes: an update.Diabetes Care. 2004; 27: 1879-1884
- Excess risk of hospitalisation for heart failure among people with type 2 diabetes.Diabetologia. 2018; 61: 2300-2309
- Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis.Diabetes Care. 2017; 40: 1597-1605
- Epidemiology of peripheral artery disease.Circ Res. 2015; 116: 1509-1526
- Peripheral arterial disease in patients with diabetes.J Am Coll Cardiol. 2006; 47: 921-929
- Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease.Arterioscler Thromb Vasc Biol. 2020; 40: 1808-1817
- 11. Microvascular complications and foot care: standards of medical care in diabetes-2020.Diabetes Care. 2020; 43: S135-S151
- Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014.JAMA. 2016; 316: 602-610
- Cardiovascular disease and diabetic kidney disease.Semin Nephrol. 2018; 38: 217-232
- Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: the CHOICE Study.J Am Soc Nephrol. 2002; 13: 1918-1927
- 5. Facilitating behavior change and well-being to improve health outcomes: standards of medical care in diabetes-2020.Diabetes Care. 2020; 43: S48-S65
- 8. Obesity management for the treatment of type 2 diabetes: standards of medical care in diabetes-2020.Diabetes Care. 2020; 43: S89-S97
- Physical activity/exercise and diabetes: a position statement of the American Diabetes Association.Diabetes Care. 2016; 39: 2065-2079
- 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD.Eur Heart J. 2020; 41: 255-323
- 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines.J Am Coll Cardiol. 2019; 74: e177-e232
- Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis.JAMA. 2015; 313: 603-615
- Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis.Lancet. 2016; 387: 957-967
- Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses.BMJ. 2016; 352: i717
- 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
- 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines.Circulation. 2019; 139: e1082-e1143
- 10-year follow-up of intensive glucose control in type 2 diabetes.N Engl J Med. 2008; 359: 1577-1589
- Intensive glucose control and cardiovascular outcomes in type 2 diabetes.Heart Lung Circ. 2011; 20: 647-654
- Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials.Lancet. 2009; 373: 1765-1772
- Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials.Lancet Diabetes Endocrinol. 2017; 5: 431-437
- Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N Engl J Med. 2008; 358: 2560-2572
- Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes.N Engl J Med. 2018; 379: 633-644
- Secondary prevention of cardiovascular disease in patients with type 2 diabetes mellitus: international insights from the TECOS Trial (trial evaluating cardiovascular outcomes with sitagliptin).Circulation. 2017; 136: 1193-1203
- Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study.Lancet. 1999; 353: 617-622
- Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.N Engl J Med. 2003; 348: 383-393
- Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the STENO-2 randomised trial.Diabetologia. 2016; 59: 2298-2307
- Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.N Engl J Med. 2015; 373: 2117-2128
- Empagliflozin and progression of kidney disease in type 2 diabetes.N Engl J Med. 2016; 375: 323-334
- Canagliflozin and cardiovascular and renal events in type 2 diabetes.N Engl J Med. 2017; 377: 2099
- Dapagliflozin and cardiovascular outcomes in type 2 diabetes.N Engl J Med. 2019; 380: 347-357
- Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.N Engl J Med. 2019; 380: 2295-2306
- Cardiovascular outcomes with ertugliflozin in type 2 diabetes.N Engl J Med. 2020; 383: 1425-1435
- Sotagliflozin in patients with diabetes and recent worsening heart failure.N Engl J Med. 2021; 384: 117-128
- Sotagliflozin in patients with diabetes and chronic kidney disease.N Engl J Med. 2021; 384: 129-139
- Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis.JAMA Cardiol. 2021; 6: 148-158
- Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis.Ann Intern Med. 2013; 159: 262-274
- Emerging role of SGLT-2 inhibitors for the treatment of obesity.Drugs. 2019; 79: 219-230
- Dapagliflozin in patients with heart failure and reduced ejection fraction.N Engl J Med. 2019; 381: 1995-2008
- Cardiovascular and renal outcomes with empagliflozin in heart failure.N Engl J Med. 2020; 383: 1413-1424
- Dapagliflozin in patients with chronic kidney disease.N Engl J Med. 2020; 383: 1436-1446
- The potential for improving cardio-renal outcomes by sodium-glucose co-transporter-2 inhibition in people with chronic kidney disease: a rationale for the EMPA-KIDNEY study.Clin Kidney J. 2018; 11: 749-761
- Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial.Eur J Heart Fail. 2019; 21: 1279-1287
ClinicalTrials.gov, U.S. National Library of Medicine. Dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction heart failure (DELIVER). Available at: https://clinicaltrials.gov/ct2/show/NCT03619213. Accessed June 9, 2021.
- GLP-1 receptor agonists: a review of head-to-head clinical studies.Ther Adv Endocrinol Metab. 2015; 6: 19-28
- Lixisenatide in patients with type 2 diabetes and acute coronary syndrome.N Engl J Med. 2015; 373: 2247-2257
- Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial.Lancet Diabetes Endocrinol. 2018; 6: 859-869
- Liraglutide and cardiovascular outcomes in type 2 diabetes.N Engl J Med. 2016; 375: 311-322
- Liraglutide and renal outcomes in type 2 diabetes.N Engl J Med. 2017; 377: 2197-2198
- Semaglutide and cardiovascular outcomes in patients with type 2 diabetes.N Engl J Med. 2016; 375: 1834-1844
- Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes.N Engl J Med. 2017; 377: 1228-1239
- Microvascular and cardiovascular outcomes according to renal function in patients treated with once-weekly exenatide: insights from the EXSCEL trial.Diabetes Care. 2020; 43: 446-452
- Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.Lancet. 2018; 392: 1519-1529
- Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial.Lancet. 2019; 394: 131-138
- Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.Lancet. 2019; 394: 121-130
- Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes.N Engl J Med. 2019; 381: 841-851
- Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.Lancet Diabetes Endocrinol. 2019; 7: 776-785
- 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of Cardiology Solution Set Oversight Committee.J Am Coll Cardiol. 2020; 76: 1117-1145
- Management of hyperglycemia in type 2 diabetes, 2018. a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetes Care. 2018; 41: 2669-2701
- Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials.Diabetes Metab. 2019; 45: 409-418
- GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus.Nat Rev Endocrinol. 2012; 8: 728-742
- GLP-1 effects on islets: hormonal, neuronal, or paracrine?.Diabetes Care. 2013; 36: S145-S148
- Cardiorenal protection with the newer antidiabetic agents in patients with diabetes and chronic kidney disease: a scientific statement from the American Heart Association.Circulation. 2020; 142: e265-e286
- Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999 to 2010: comparison by prevalent cardiovascular disease status.Diab Vasc Dis Res. 2013; 10: 505-513
- Gaps in evidence-based therapy use in insured patients in the united states with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.J Am Heart Assoc. 2021; 10e016835
Article info
Publication history
Published online: May 21, 2021
Footnotes
Funding: None.
Conflicts of Interest: NJP reports research grants from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Regeneron, Sanofi, Verily Life Sciences, and Novartis; consulting fees from Boehringer Ingelheim, Eli Lilly, AstraZeneca, and Novo Nordisk; and being on a study board for Novo Nordisk. PD reports research grants from Boehringer Ingelheim, Novartis, and Sanofi.
Authorship: Both authors drafted and critically revised the manuscript.
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