CoChat
Sign Up
Cited by 223Chronic Kidney Disease and DiabetesDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Treatment and Management

Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study

Open access
Birkeland, Kåre I., Bodegard, Johan, Eriksson, Jan W., Norhammar, Anna, Haller, Hermann, Linssen, Gerard C.M., Banerjee, Amitava, Thuresson, Marcus +8 more·2020·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.14074PMC PMC7496468
Open this paper in CoChat — free accountOpen PDF

Abstract

Aims: To examine the manifestation of cardiovascular or renal disease (CVRD) in patients with type 2 diabetes (T2D) initially free from CVRD as well as the mortality risks associated with these diseases. Methods: Patients free from CVRD were identified from healthcare records in England, Germany, Japan, the Netherlands, Norway and Sweden at a fixed date. CVRD manifestation was defined by first diagnosis of cardiorenal disease, or a stroke, myocardial infarction (MI) or peripheral artery disease (PAD) event. The mortality risk associated with single CVRD history of heart failure (HF), chronic kidney disease (CKD), MI, stroke or PAD was compared with that associated with CVRD‐free status. Results: Of 1 177 896 patients with T2D, 772 336 (66%) were CVRD‐free and followed for a mean of 4.5 years. A total of 137 081 patients (18%) developed a first CVRD manifestation, represented by CKD (36%), HF (24%), stroke (16%), MI (14%) and PAD (10%). HF or CKD was associated with increased cardiovascular and all‐cause mortality risk: hazard ratio (HR) 2.02 (95% confidence interval [CI] 1.75–2.33) and HR 2.05 (95% CI 1.82–2.32), respectively. HF and CKD were separately associated with significantly increased mortality risks, and the combination was associated with the highest cardiovascular and all‐cause mortality risk: HRs 3.91 (95% CI 3.02–5.07) and 3.14 (95% CI 2.90–3.40), respectively. Conclusion: In a large multinational study of >750 000 CVRD‐free patients with T2D, HF and CKD were consistently the most frequent first cardiovascular disease manifestations and were also associated with increased mortality risks. These novel findings show these cardiorenal diseases to be important and serious complications requiring improved preventive strategies.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/dom.14074

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In a large multinational cohort of 750,000 people with diabetes without established cardiovascular disease, heart failure and CKD were the most frequent first manifestations of cardiovascular or kidney disease.

    “In a large multinational cohort of 750,000 people with diabetes without established cardiovascular disease, heart failure and CKD were the most frequent first manifestations of cardiovascular or kidney disease (218).”

    From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [218]

  • In a large multinational cohort of 750,000 people with diabetes without established CVD, heart failure and CKD were the most frequent first manifestations of cardiovascular or kidney disease.

    “In a large multinational cohort of 750,000 people with diabetes without established CVD, heart failure and CKD were the most frequent first manifestations of cardiovascular or kidney disease (207).”

    From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [207]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 58 · Cited by 223

Research works printed but not linked: 50

  1. [2]Birkeland KI, Bodegard J, Norhammar A, et al. How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study. Diabetes Obes Metab. 2018; 24: 968‐ 974. PMC6590461 30537226
  2. [3]Thrainsdottir IS, Aspelund T, Thorgeirsson G, et al. The association between glucose abnormalities and heart failure in the population‐based Reykjavik study. Diabetes Care. 2005; 28(3): 612‐ 616. 15735197
  3. [4]Collaboration GBDCKD. Global, regional, and national burden of chronic kidney disease, 1990‐2017: a systematic analysis for the global burden of disease study 2017. Lancet. 2020; 395(10225): 709‐ 733. 32061315 PMC7049905
  4. [5]Braunwald E. Diabetes, heart failure, and renal dysfunction: the vicious circles. Prog Cardiovasc Dis. 2019; 62(4): 298‐ 302. 31377223
  5. [6]Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev. 2017; 3(1): 7‐ 11. 28785469 PMC5494150
  6. [8]Bertoni AG, Hundley WG, Massing MW, Bonds DE, Burke GL, Goff DC Jr. Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care. 2004; 27(3): 699‐ 703. 14988288
  7. [9]Bruck K, Stel VS, Gambaro G, et al. CKD prevalence varies across the european general population. J Am Soc Nephrol. 2016; 27(7): 2135‐ 2147. 26701975 PMC4926978
  8. [10]Gansevoort RT, Correa‐Rotter R, Hemmelgarn BR, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013; 382(9889): 339‐ 352. 23727170
  9. [11]Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351(13): 1296‐ 1305. 15385656
  10. [12]Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10‐year follow‐up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359(15): 1577‐ 1589. 18784090
  11. [13]Kerr M, Bray B, Medcalf J, O'Donoghue DJ, Matthews B. Estimating the financial cost of chronic kidney disease to the NHS in England. Nephrol Dial Transplant. 2012; 27(Suppl 3): iii73‐ iii80. 22815543 PMC3484716
  12. [14]Seuring T, Archangelidi O, Suhrcke M. The economic costs of type 2 diabetes: a global systematic review. Pharmacoeconomics. 2015; 33(8): 811‐ 831. 25787932 PMC4519633
  13. [15]van der Velde M, Matsushita K, Coresh J, et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with all‐cause and cardiovascular mortality. A collaborative meta‐analysis of high‐risk population cohorts. Kidney Int. 2011; 79(12): 1341‐ 1352. 21307840
  14. [16]Ismail Y, Kasmikha Z, Green HL, McCullough PA. Cardio‐renal syndrome type 1: epidemiology, pathophysiology, and treatment. Semin Nephrol. 2012; 32(1): 18‐ 25. 22365158
  15. [17]Rangaswami J, Bhalla V, Blair JEA, et al. Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement From the American Heart Association. Circulation. 2019; 139(16): e840‐ e878. 30852913
  16. [19]Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013; 24(2): 302‐ 308. 23362314 PMC3559486
  17. [20]de Boer IH, Rue TC, Hall YN, Heagerty PJ, Weiss NS, Himmelfarb J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA. 2011; 305(24): 2532‐ 2539. 21693741 PMC3731378
  18. [21]Gregg EW, Li Y, Wang J, et al. Changes in diabetes‐related complications in the United States, 1990‐2010. N Engl J Med. 2014; 370(16): 1514‐ 1523. 24738668
  19. [22]Greene SJ, Butler J. Primary prevention of heart failure in patients with type 2 diabetes mellitus. Circulation. 2019; 139(2): 152‐ 154. 30615507 PMC6834062
  20. [24]Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377(7): 644‐ 657. 28605608
  21. [25]Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2018; 380(4): 347‐ 357. 30415602
  22. [28]Mosenzon O, Wiviott SD, Cahn A, et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomised trial. Lancet Diabetes Endocrinol. 2019; 7(8): 606‐ 617. 31196815
  23. [29]Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016; 375(4): 323‐ 334. 27299675
  24. [30]Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019; 380(4): 347‐ 357. 30415602
  25. [31]Mahaffey KW, Jardine MJ, Bompoint S, et al. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes and chronic kidney disease in primary and secondary cardiovascular prevention groups: results from the randomized CREDENCE trial. Circulation. 2019; 140: 739‐ 750. 31291786 PMC6727954
  26. [33]Birkeland KI, Bodegard J, Norhammar A, et al. How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study. Diabetes Obes Metab. 2018; 21(4): 968‐ 974. PMC6590461 30537226
  27. [34]Kosiborod M, Lam CSP, Kohsaka S, et al. Cardiovascular Events Associated with SGLT‐2 inhibitors versus other glucose‐lowering drugs: the CVD‐REAL 2 study. J Am Coll Cardiol. 2018; 71(23): 2628‐ 2639. 29540325
  28. [35]Tanabe M, Motonaga R, Terawaki Y, Nomiyama T, Yanase T. Prescription of oral hypoglycemic agents for patients with type 2 diabetes mellitus: a retrospective cohort study using a Japanese hospital database. J Diabetes Investig. 2017; 8(2): 227‐ 234. PMC5334304 27549920
  29. [36]Tanabe M, Nomiyama T, Motonaga R, Murase K, Yanase T. Reduced vascular events in type 2 diabetes by biguanide relative to sulfonylurea: study in a Japanese hospital database. BMC Endocr Disord. 2015; 15: 49. 26382923 PMC4574461
  30. [37]Herings RM, Pedersen L. Pharmacy‐based medical record linkage systems In: Kimmel S, Hennessey S, eds. Pharmacoepidemiology. 5th ed. Oxford, United Kingdom: John Wiley & Sons, Ltd; 2012: 270‐ 286.
  31. [38]van Herk‐Sukel MP, van de Poll‐Franse LV, Lemmens VE, et al. New opportunities for drug outcomes research in cancer patients: the linkage of the Eindhoven Cancer Registry and the PHARMO Record Linkage System. Eur J Cancer. 2010; 46(2): 395‐ 404. 19811904
  32. [39]Birkeland KI, Jorgensen ME, Carstensen B, et al. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium‐glucose co‐transporter‐2 inhibitors versus other glucose‐lowering drugs (CVD‐REAL Nordic): a multinational observational analysis. Lancet Diabetes Endocrinol. 2017; 5(9): 709‐ 717. 28781064
  33. [40]Persson F, Nystrom T, Jorgensen ME, et al. Dapagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in people with type 2 diabetes (CVD‐REAL Nordic) when compared with dipeptidyl peptidase‐4 inhibitor therapy: a multinational observational study. Diabetes Obes Metab. 2018; 20(2): 344‐ 351. 28771923 PMC5811811
  34. [41]Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people. Lancet Diabetes Endocrinol. 2015; 3(2): 105‐ 113. 25466521 PMC4303913
  35. [42]Avery CL, Loehr LR, Baggett C, et al. The population burden of heart failure attributable to modifiable risk factors: the ARIC (Atherosclerosis Risk in Communities) study. J Am Coll Cardiol. 2012; 60(17): 1640‐ 1646. 23021327 PMC3653309
  36. [43]Nichols GA, Gullion CM, Koro CE, Ephross SA, Brown JB. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care. 2004; 27(8): 1879‐ 1884. 15277411
  37. [45]Levelt E, Mahmod M, Piechnik SK, et al. Relationship between left ventricular structural and metabolic remodeling in type 2 diabetes. Diabetes. 2016; 65(1): 44‐ 52. 26438611 PMC4890658
  38. [46]Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004; 63(4): 582‐ 592. 15306213
  39. [47]Fang ZY, Yuda S, Anderson V, Short L, Case C, Marwick TH. Echocardiographic detection of early diabetic myocardial disease. J Am Coll Cardiol. 2003; 41(4): 611‐ 617. 12598073
  40. [48]Lebeche D, Davidoff AJ, Hajjar RJ. Interplay between impaired calcium regulation and insulin signaling abnormalities in diabetic cardiomyopathy. Nat Clin Pract Cardiovasc Med. 2008; 5(11): 715‐ 724. 18813212
  41. [49]Waddingham MT, Edgley AJ, Tsuchimochi H, Kelly DJ, Shirai M, Pearson JT. Contractile apparatus dysfunction early in the pathophysiology of diabetic cardiomyopathy. World J Diabetes. 2015; 6(7): 943‐ 960. 26185602 PMC4499528
  42. [52]Johansson I, Dahlstrom U, Edner M, Nasman P, Ryden L, Norhammar A. Prognostic implications of type 2 diabetes mellitus in ischemic and nonischemic heart failure. J Am Coll Cardiol. 2016; 68(13): 1404‐ 1416. 27659462
  43. [54]Cherney DZI, Repetto E, Wheeler DC, et al. Impact of cardio‐renal‐metabolic comorbidities on cardiovascular outcomes and mortality in type 2 diabetes mellitus. Am J Nephrol. 2020; 51(1): 74‐ 82. 31812955
  44. [55]Garcia‐Carro C, Vergara A, Agraz I, et al. The new era for reno‐cardiovascular treatment in type 2 diabetes. J Clin Med. 2019; 8(6). 1‐ 16. PMC6617211 31212945
  45. [56]Braunwald E. Diabetes, heart failure, and renal dysfunction: the vicious circles. Prog Cardiovasc Dis. 2019; 62: 298‐ 302. 31377223
  46. [57]Ronco C, Ronco F, McCullough PA. A call to action to develop integrated curricula in cardiorenal medicine. Blood Purif. 2017; 44(4): 251‐ 259. 29065398
  47. [58]Verma S, Juni P, Mazer CD. Pump, pipes, and filter: do SGLT2 inhibitors cover it all? Lancet. 2019; 393(10166): 3‐ 5. 30424891
  48. [59]Connelly KA, Bhatt DL, Verma S. Can we declare a victory against cardio‐renal disease in diabetes? Cell Metab. 2018; 28(6): 813‐ 815. 30517896
  49. [60]Brynildsen J, Hoiseth AD, Nygard S, et al. [ Diagnostic accuracy for heart failure ‐ data from the Akershus Cardiac Examination 2 Study]. Tidsskr Nor Laegeforen. 2015; 135(19): 1738‐ 1744. 26486668
  50. [61]Ingelsson E, Arnlov J, Sundstrom J, Lind L. The validity of a diagnosis of heart failure in a hospital discharge register. Eur J Heart Fail. 2005; 7(5): 787‐ 791. 15916919

Authors
Birkeland, K. I., Bodegard, J., Eriksson, J. W., Norhammar, A., Haller, H., Linssen, G. C. M., Banerjee, A., Thuresson, M., Okami, S., Garal‐Pantaler, E., Overbeek, J., Mamza, J. B., Zhang, R., Yajima, T., Komuro, I., & Kadowaki, T.
Affiliations
  • Oslo University Hospital (NO)
  • AstraZeneca Oslo Norway
  • Uppsala University (SE)
  • Karolinska Institutet (SE)
  • Medizinische Hochschule Hannover (DE)
  • Ziekenhuis Groep Twente (NL)
  • University College Hospital (GB)
  • Statisticon (Sweden) (SE)
  • AstraZeneca (Japan) (JP)
  • Team Gesundheit GmbH Essen Germany
  • Pharmo Institute (NL)
  • AstraZeneca (United Kingdom) (GB)
  • The University of Tokyo (JP)
  • Teikyo University Hospital, Mizonokuchi (JP)
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2020-06-03
Volume
22
Issue
9
Pages
1607-1618
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.14074
PMC
PMC7496468
OpenAlex
W3021757681
Cited by
223
References
58
Citations by year
2026: 25 · 2025: 39 · 2024: 35 · 2023: 47 · 2022: 43 · 2021: 29 · 2020: 5
FWCI
19.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc)
Funders
AstraZeneca
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
type 2 diabetes, heart failure, chronic kidney disease, mortality risk, cardiovascular disease, stroke, myocardial infarction, peripheral arterial disease, cardiorenal disease, disease progression
MeSH terms
Diabetes Mellitus, Type 2, England, Germany, Heart Failure, Humans, Japan, Netherlands, Norway, Risk Factors, Sweden, Cohort Studies, Renal Insufficiency, Chronic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review