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Open Access 16-04-2024 | Type 2 Diabetes | Review

Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities

Abstract

Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia. Similarly, intensive glucose control nested in a broader bundle of care, including blood pressure, coagulation and temperature control, can provide substantial benefit for clinical outcomes after haemorrhagic stroke. As micro- and macrovascular complications are frequent in people with diabetes, cardiovascular prevention strategies also need to consider tailored treatment. In this regard, the broader availability of sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists can allow tailored treatments, particularly for those with heart failure and chronic kidney disease as comorbidities. Here, we review the main concepts of hyperacute stroke management and CVD prevention among people with diabetes, capitalising on results from large studies and RCTs to inform clinicians on preferred treatments.

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Leon BM (2015) Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes 6(13):1246. https://doi.org/10.4239/wjd.v6.i13.1246CrossRefPubMedPubMedCentral

Mosenzon O, Cheng AYY, Rabinstein AA, Sacco S (2023) Diabetes and stroke: what are the connections? J Stroke 25(1):26–38. https://doi.org/10.5853/jos.2022.02306CrossRefPubMedPubMedCentral

Feigin VL, Stark BA, Johnson CO et al (2021) Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 20(10):795–820. https://doi.org/10.1016/s1474-4422(21)00252-0CrossRef

Kissela BM, Khoury J, Kleindorfer D et al (2005) Epidemiology of ischemic stroke in patients with diabetes: the greater Cincinnati/Northern Kentucky stroke study. Diabetes Care 28(2):355–359. https://doi.org/10.2337/diacare.28.2.355CrossRefPubMed

Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001) Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 32(10):2426–2432. https://doi.org/10.1161/hs1001.096194CrossRefPubMed

Dungan KM, Braithwaite SS, Preiser JC (2009) Stress hyperglycaemia. Lancet 373(9677):1798–1807. https://doi.org/10.1016/S0140-6736(09)60553-5CrossRefPubMedPubMedCentral

Romoli M, Vandelli L, Bigliardi G et al (2022) Fibrinogen depletion coagulopathy predicts major bleeding after thrombolysis for ischemic stroke: a multicenter study. Stroke (November) 1–8. https://doi.org/10.1161/strokeaha.122.039652

Turner R (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352(9131):837–853. https://doi.org/10.1016/S0140-6736(98)07019-6CrossRef

Ong KL, Stafford LK, McLaughlin SA et al (2023) Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 402(10397):203–234. https://doi.org/10.1016/S0140-6736(23)01301-6CrossRef

10.

Lau LH, Lew J, Borschmann K, Thijs V, Ekinci EI (2019) Prevalence of diabetes and its effects on stroke outcomes: a meta-analysis and literature review. J Diabetes Investig 10(3):780–792. https://doi.org/10.1111/jdi.12932CrossRefPubMed

11.

Banerjee C, Moon YP, Paik MC et al (2012) Duration of diabetes and risk of ischemic stroke: the Northern Manhattan Study. Stroke 43(5):1212–1217. https://doi.org/10.1161/STROKEAHA.111.641381CrossRefPubMedPubMedCentral

12.

Sarwar N, Gao P, Kondapally Seshasai SR et al (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375(9733):2215–2222. https://doi.org/10.1016/S0140-6736(10)60484-9CrossRefPubMed

13.

Janghorbani M, Hu FB, Willett WC et al (2007) Prospective study of type 1 and type 2 diabetes and risk of stroke subtypes: the Nurses’ Health Study. Diabetes Care 30(7):1730–1735. https://doi.org/10.2337/dc06-2363CrossRefPubMed

14.

Lee M, Saver JL, Hong KS, Song S, Chang KH, Ovbiagele B (2012) Effect of pre-diabetes on future risk of stroke: meta-analysis. BMJ 344(7861):e3564–e3564. https://doi.org/10.1136/bmj.e3564CrossRefPubMedPubMedCentral

15.

Cardoso CRL, Ferreira MT, Leite NC, Salles GF (2013) Prognostic impact of aortic stiffness in high-risk type 2 diabetic patients: the Rio de Janeiro type 2 diabetes cohort study. Diabetes Care 36(11):3772–3778. https://doi.org/10.2337/dc13-0506CrossRefPubMedPubMedCentral

16.

Sharif S, Visseren FLJ, Spiering W, de Jong PA, Bots ML, Westerink J (2019) Arterial stiffness as a risk factor for cardiovascular events and all-cause mortality in people with type 2 diabetes. Diabet Med 36(9):1125–1132. https://doi.org/10.1111/dme.13954CrossRefPubMedPubMedCentral

17.

Zheng M, Zhang X, Chen S et al (2020) Arterial stiffness preceding diabetes: a longitudinal study. Circ Res 127(12):1491–1498. https://doi.org/10.1161/CIRCRESAHA.120.317950CrossRefPubMed

18.

Tian X, Zuo Y, Chen S et al (2022) Hypertension, arterial stiffness, and diabetes: a prospective cohort study. Hypertension 79(7):1487–1496. https://doi.org/10.1161/HYPERTENSIONAHA.122.19256CrossRefPubMed

19.

De Oliveira Alvim R, Santos PCJL, Musso MM et al (2013) Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population. Diabetol Metab Syndr 5(1):45. https://doi.org/10.1186/1758-5996-5-45CrossRefPubMedPubMedCentral

20.

Schram MT, Henry RMA, Van Dijk RAJM et al (2004) Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes: the Hoorn study. Hypertension 43(2 I):176–181. https://doi.org/10.1161/01.HYP.0000111829.46090.92CrossRefPubMed

21.

van Sloten TT, Sedaghat S, Carnethon MR, Launer LJ, Stehouwer CDA (2020) Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression. Lancet Diabetes Endocrinol 8(4):325–336. https://doi.org/10.1016/S2213-8587(19)30405-XCrossRefPubMed

22.

Sanahuja J, Alonso N, Diez J et al (2016) Increased burden of cerebral small vessel disease in patients with type 2 diabetes and retinopathy. Diabetes Care 39(9):1614–1620. https://doi.org/10.2337/dc15-2671CrossRefPubMed

23.

Eriksson MI, Summanen P, Gordin D et al (2021) Cerebral small-vessel disease is associated with the severity of diabetic retinopathy in type 1 diabetes. BMJ Open Diabetes Res Care 9(1):e002274. https://doi.org/10.1136/bmjdrc-2021-002274CrossRefPubMedPubMedCentral

24.

Qiu C, Sigurdsson S, Zhang Q et al (2014) Diabetes, markers of brain pathology and cognitive function: the age gene/environment susceptibility-Reykjavik study. Ann Neurol 75(1):138–146. https://doi.org/10.1002/ana.24063CrossRefPubMedPubMedCentral

25.

Pofi R, Di Mario F, Gigante A et al (2016) Diabetic nephropathy: focus on current and future therapeutic strategies. Curr Drug Metab 17(5):497–502. https://doi.org/10.2174/138920021705160324165553CrossRefPubMed

26.

Pofi R, Giannetta E, Galea N et al (2021) Diabetic cardiomiopathy progression is triggered by miR122-5p and involves extracellular matrix: a 5-year prospective study. JACC Cardiovasc Imaging 14(6):1130–1142. https://doi.org/10.1016/j.jcmg.2020.10.009CrossRefPubMed

27.

Yancy CW, Jessup M, Bozkurt B et al (2013) 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 62(16):e147-239. https://doi.org/10.1016/j.jacc.2013.05.019CrossRefPubMed

28.

Lazar S, Rayner B, Lopez Campos G, McGrath K, McClements L (2020) Mechanisms of heart failure with preserved ejection fraction in the presence of diabetes mellitus. Transl Metab Syndr Res 3:1–5. https://doi.org/10.1016/j.tmsr.2020.04.002CrossRef

29.

Lejeune S, Roy C, Slimani A et al (2021) Diabetic phenotype and prognosis of patients with heart failure and preserved ejection fraction in a real life cohort. Cardiovasc Diabetol 20(1):48. https://doi.org/10.1186/s12933-021-01242-5CrossRefPubMedPubMedCentral

30.

Pofi R, Giannetta E, Feola T et al (2022) Sex-specific effects of daily tadalafil on diabetic heart kinetics in RECOGITO, a randomized, double-blind, placebo-controlled trial. Sci Transl Med 14(649):eabl8503. https://doi.org/10.1126/scitranslmed.abl8503CrossRefPubMed

31.

Kristensen SL, Preiss D, Jhund PS et al (2016) Risk related to pre-diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial. Circ Hear Fail 9(1):e002560. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002560CrossRef

32.

Jarnert C, Landstedt-Hallin L, Malmberg K et al (2009) A randomized trial of the impact of strict glycaemic control on myocardial diastolic function and perfusion reserve: a report from the DADD (Diabetes mellitus and Diastolic Dysfunction) study. Eur J Heart Fail 11(1):39–47. https://doi.org/10.1093/eurjhf/hfn018CrossRefPubMed

33.

Stratton IM, Adler AI, Neil HAW et al (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321(7258):405–412. https://doi.org/10.1136/bmj.321.7258.405CrossRefPubMedPubMedCentral

34.

Tuttle KR, Jones CR, Daratha KB et al (2022) Incidence of chronic kidney disease among adults with diabetes, 2015–2020. N Engl J Med 387(15):1430–1431. https://doi.org/10.1056/NEJMc2207018CrossRefPubMedPubMedCentral

35.

Kaze AD, Jaar BG, Fonarow GC, Echouffo-Tcheugui JB (2022) Diabetic kidney disease and risk of incident stroke among adults with type 2 diabetes. BMC Med 20(1):127. https://doi.org/10.1186/s12916-022-02317-0CrossRefPubMedPubMedCentral

36.

Rossing P, Caramori ML, Chan JCN et al (2022) KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 102(5):S1–S127. https://doi.org/10.1016/j.kint.2022.06.008CrossRef

37.

Kelly D, Rothwell PM (2020) Disentangling the multiple links between renal dysfunction and cerebrovascular disease. J Neurol Neurosurg Psychiatry 91(1):88–97. https://doi.org/10.1136/jnnp-2019-320526CrossRefPubMed

38.

Kelly DM, Rothwell PM (2020) Prevention and treatment of stroke in patients with chronic kidney disease: an overview of evidence and current guidelines. Kidney Int 97(2):266–278. https://doi.org/10.1016/j.kint.2019.09.024CrossRefPubMed

39.

Singleton JR, Smith AG, Russell JW, Feldman EL (2003) Microvascular complications of impaired glucose tolerance. Diabetes 52(12):2867–2873. https://doi.org/10.2337/diabetes.52.12.2867CrossRefPubMed

40.

Natarajan R (2021) Epigenetic mechanisms in diabetic vascular complications and metabolic memory: the 2020 Edwin Bierman Award Lecture. Diabetes 70(2):328–337. https://doi.org/10.2337/dbi20-0030CrossRefPubMedPubMedCentral

41.

Li Y, Liu Y, Liu S et al (2023) Diabetic vascular diseases: molecular mechanisms and therapeutic strategies. Signal Transduct Target Ther 8(1):152. https://doi.org/10.1038/s41392-023-01400-zCrossRefPubMedPubMedCentral

42.

Campbell BCV, De Silva DA, Macleod MR et al (2019) Ischaemic stroke. Nat Rev Dis Prim 5(1):70. https://doi.org/10.1038/s41572-019-0118-8CrossRefPubMed

43.

Thomalla G, Simonsen CZ, Boutitie F et al (2018) MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med 379(7):611–622. https://doi.org/10.1056/nejmoa1804355CrossRefPubMed

44.

Nogueira RG, Jadhav AP, Haussen DC et al (2018) Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 378(1):11–21. https://doi.org/10.1056/nejmoa1706442CrossRefPubMed

45.

Albers GW, Marks MP, Kemp S et al (2018) Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 378(8):708–718. https://doi.org/10.1056/nejmoa1713973CrossRefPubMedPubMedCentral

46.

Hacke W, Kaste M, Bluhmki E et al (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359(13):1317–1329. https://doi.org/10.1056/nejmoa0804656CrossRefPubMed

47.

Sandercock P, Wardlaw JM, Lindley RI et al (2012) The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet 379(9834):2352–2363. https://doi.org/10.1016/S0140-6736(12)60768-5CrossRefPubMed

48.

Berge E, Whiteley W, Audebert H et al (2021) European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J 6(1):I–LXII. https://doi.org/10.1177/2396987321989865CrossRefPubMedPubMedCentral

49.

Warach SJ, Dula AN, Milling TJ et al (2022) Prospective observational cohort study of tenecteplase versus alteplase in routine clinical practice. Stroke 53(12):3583–3593. https://doi.org/10.1161/STROKEAHA.122.038950CrossRefPubMed

50.

Messe SR, Khatri P, Reeves MJ et al (2016) Why are acute ischemic stroke patients not receiving IV tPA? Results from a national registry. Neurology 87(15):1565–1574. https://doi.org/10.1212/WNL.0000000000003198CrossRefPubMedPubMedCentral

51.

Westphal LP, Widmer R, Held U et al (2020) Association of prestroke metformin use, stroke severity, and thrombolysis outcome. Neurology 95(4):e362–e373. https://doi.org/10.1212/WNL.0000000000009951CrossRefPubMed

52.

Whittington HJ, Hall AR, McLaughlin CP, Hausenloy DJ, Yellon DM, Mocanu MM (2013) Chronic metformin associated cardioprotection against infarction: not just a glucose lowering phenomenon. Cardiovasc drugs Ther 27(1):5–16. https://doi.org/10.1007/s10557-012-6425-xCrossRefPubMed

53.

Kim J-T, Jahan R, Saver JL, SWIFT Investigators (2016) Impact of glucose on outcomes in patients treated with mechanical thrombectomy: a post hoc analysis of the solitaire flow restoration with the intention for thrombectomy study. Stroke 47(1):120–127. https://doi.org/10.1161/STROKEAHA.115.010753CrossRefPubMed

54.

Osei E, den Hertog HM, Berkhemer OA et al (2016) Increased admission and fasting glucose are associated with unfavorable short-term outcome after intra-arterial treatment of ischemic stroke in the MR CLEAN pretrial cohort. J Neurol Sci 371:1–5. https://doi.org/10.1016/j.jns.2016.10.003CrossRefPubMed

55.

Powers WJ, Rabinstein AA, Ackerson T et al (2019) Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 50(12):e344–e418. https://doi.org/10.1161/STR.0000000000000211CrossRefPubMed

56.

Rossi S, Romoli M, Urbinati G et al (2022) Acute stroke-like deficits associated with nonketotic hyperglycemic hyperosmolar state: an illustrative case and systematic review of literature. Neurol Sci 43(8):4671–4683. https://doi.org/10.1007/s10072-022-06088-7CrossRefPubMedPubMedCentral

57.

National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333(24):1581–1588. https://doi.org/10.1056/NEJM199512143332401CrossRef

58.

Frank B, Grotta JC, Alexandrov AV et al (2013) Thrombolysis in stroke despite contraindications or warnings? Stroke 44(3):727–733. https://doi.org/10.1161/STROKEAHA.112.674622CrossRefPubMed

59.

Ahmed N, Dávalos A, Eriksson N et al (2010) Association of admission blood glucose and outcome in patients treated with intravenous thrombolysis: results from the Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Register (SITS-ISTR). Arch Neurol 67(9):1123–1130. https://doi.org/10.1001/archneurol.2010.210CrossRefPubMed

60.

Gray CS, Hildreth AJ, Sandercock PA et al (2007) Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol 6(5):397–406. https://doi.org/10.1016/S1474-4422(07)70080-7CrossRefPubMed

61.

Johnston KC, Bruno A, Pauls Q et al (2019) Intensive vs standard treatment of hyperglycemia and functional outcome in patients with acute ischemic stroke: the SHINE randomized clinical trial. JAMA 322(4):326–335. https://doi.org/10.1001/jama.2019.9346CrossRefPubMedPubMedCentral

62.

Bain SC, Klufas MA, Ho A, Matthews DR (2019) Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: a review. Diabetes Obes Metab 21(3):454–466. https://doi.org/10.1111/dom.13538CrossRefPubMed

63.

Zhang F, Zhang S, Tao C et al (2019) Association between serum glucose level and spot sign in intracerebral hemorrhage. Medicine (Baltimore) 98(11):e14748. https://doi.org/10.1097/MD.0000000000014748CrossRefPubMed

64.

Bahadar GA, Shah ZA (2021) Intracerebral hemorrhage and diabetes mellitus: blood-brain barrier disruption, pathophysiology and cognitive impairments. CNS Neurol Disord Drug Targets 20(4):312–326. https://doi.org/10.2174/1871527320666210223145112CrossRefPubMed

65.

Wu TY, Putaala J, Sharma G et al (2017) Persistent hyperglycemia is associated with increased mortality after intracerebral hemorrhage. J Am Heart Assoc 6(8):e005760. https://doi.org/10.1161/JAHA.117.005760CrossRefPubMedPubMedCentral

66.

Qureshi AI, Huang W, Lobanova I et al (2022) Effect of moderate and severe persistent hyperglycemia on outcomes in patients with intracerebral hemorrhage. Stroke 53(4):1226–1234. https://doi.org/10.1161/STROKEAHA.121.034928CrossRefPubMed

67.

Kramer AH, Roberts DJ, Zygun DA (2012) Optimal glycemic control in neurocritical care patients: a systematic review and meta-analysis. Crit Care 16(5):R203. https://doi.org/10.1186/cc11812CrossRefPubMedPubMedCentral

68.

Ma L, Hu X, Song L et al (2023) The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial. Lancet 402(10395):27–40. https://doi.org/10.1016/S0140-6736(23)00806-1CrossRefPubMedPubMedCentral

69.

Greenberg SM, Ziai WC, Cordonnier C et al (2022) 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke 53(7):e282–e361. https://doi.org/10.1161/STR.0000000000000407CrossRefPubMed

70.

Gæde P, Oellgaard J, Kruuse C, Rossing P, Parving HH, Pedersen O (2019) Beneficial impact of intensified multifactorial intervention on risk of stroke: outcome of 21 years of follow-up in the randomised Steno-2 Study. Diabetologia 62(9):1575–1580. https://doi.org/10.1007/s00125-019-4920-3CrossRefPubMedPubMedCentral

71.

Gyldenkerne C, Kahlert J, Olesen KKW et al (2022) Twenty-year temporal trends in risk of ischemic stroke in incident type 2 diabetes: a Danish population-based cohort study. Diabetes Care 45(9):2144–2151. https://doi.org/10.2337/dc22-0440CrossRefPubMed

72.

Marx N, Federici M, Schütt K et al (2023) 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J 44(39):4043–4140. https://doi.org/10.1093/eurheartj/ehad192CrossRefPubMed

73.

Rawshani A, Rawshani A, Franzén S et al (2018) Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 379(7):633–644. https://doi.org/10.1056/NEJMoa1800256CrossRefPubMed

74.

Kleindorfer DO, Towfighi A, Chaturvedi S et al (2021) 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke 52(7):E364–E467. https://doi.org/10.1161/STR.0000000000000375CrossRefPubMed

75.

Gæde P, Oellgaard J, Carstensen B et al (2016) 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 59(11):2298–2307. https://doi.org/10.1007/s00125-016-4065-6CrossRefPubMedPubMedCentral

76.

Sattar N, Lee MMY, Kristensen SL et al (2021) Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol 9(10):653–662. https://doi.org/10.1016/S2213-8587(21)00203-5CrossRefPubMed

77.

Patoulias DI, Boulmpou A, Teperikidis E et al (2021) Cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of cardiovascular outcome trials. World J Cardiol 13(10):585–592. https://doi.org/10.4330/wjc.v13.i10.585CrossRefPubMedPubMedCentral

78.

Rados DV, Falcetta MRR, Pinto LC, Leitão CB, Gross JL (2021) All-cause mortality and cardiovascular safety of basal insulin treatment in patients with type 2 diabetes mellitus: a systematic review with meta-analysis and trial sequential analysis. Diabetes Res Clin Pract 173:108688. https://doi.org/10.1016/j.diabres.2021.108688CrossRefPubMed

79.

Benn M, Emanuelsson F, Tybjærg-Hansen A, Nordestgaard BG (2021) Impact of high glucose levels and glucose lowering on risk of ischaemic stroke: a Mendelian randomisation study and meta-analysis. Diabetologia 64(7):1492–1503. https://doi.org/10.1007/s00125-021-05436-0CrossRefPubMed

80.

Nauck MA, Meier JJ, Cavender MA, El Aziz MA, Drucker DJ (2017) Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation 136(9):849–870. https://doi.org/10.1161/CIRCULATIONAHA.117.028136CrossRefPubMed

81.

Dormandy JA, Charbonnel B, Eckland DJA et al (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial in macroVascular Events): a randomised controlled trial. Lancet 366(9493):1279–1289. https://doi.org/10.1016/S0140-6736(05)67528-9CrossRefPubMed

82.

Wilcox R, Bousser MG, Betteridge DJ et al (2007) Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04). Stroke 38(3):865–873. https://doi.org/10.1161/01.STR.0000257974.06317.49CrossRefPubMed

83.

Kernan WN, Viscoli CM, Furie KL et al (2016) Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 374(14):1321–1331. https://doi.org/10.1056/nejmoa1506930CrossRefPubMedPubMedCentral

84.

McGuire DK, Shih WJ, Cosentino F et al (2021) Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol 6(2):148–158. https://doi.org/10.1001/jamacardio.2020.4511CrossRefPubMed

85.

Puma M, Maestrini I, Altieri M, Di Piero V (2020) A neurological point of view on the European Society of Cardiology guidelines: the interactions between direct oral anticoagulants and antiepileptic drugs. Eur J Neurol 27(12):e79. https://doi.org/10.1111/ene.14428CrossRefPubMed

86.

Carnicelli AP, Hong H, Connolly SJ et al (2022) Direct oral anticoagulants versus warfarin in patients with atrial fibrillation: patient-level network meta-analyses of randomized clinical trials with interaction testing by age and sex. Circulation 145(4):242–255. https://doi.org/10.1161/circulationaha.121.056355CrossRefPubMedPubMedCentral

87.

Seyed Ahmadi S, Svensson AM, Pivodic A, Rosengren A, Lind M (2020) Risk of atrial fibrillation in persons with type 2 diabetes and the excess risk in relation to glycaemic control and renal function: a Swedish cohort study. Cardiovasc Diabetol 19(1):9. https://doi.org/10.1186/s12933-019-0983-1CrossRefPubMedPubMedCentral

88.

Kreutz R, Camm AJ, Rossing P (2020) Concomitant diabetes with atrial fibrillation and anticoagulation management considerations. Eur Heart J Suppl 22(Suppl O):O78–O86. https://doi.org/10.1093/EURHEARTJ/SUAA182

89.

Steffel J, Verhamme P, Potpara TS et al (2018) The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 39(16):1330–1393. https://doi.org/10.1093/eurheartj/ehy136CrossRefPubMed

90.

Ong HT, Teo YH, Teo YN et al (2022) Effects of sodium/glucose cotransporter inhibitors on atrial fibrillation and stroke: a meta-analysis. J Stroke Cerebrovasc Dis 31(1):106159. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106159CrossRefPubMed

91.

Scheen AJ (2023) Do SGLT2 inhibitors and GLP-1 receptor agonists modulate differently the risk of stroke? Discordance between randomised controlled trials and observational studies. Diabetes Metab 49(5):101474. https://doi.org/10.1016/j.diabet.2023.101474CrossRefPubMed

92.

Chang SN, Chen JJ, Huang PS et al (2023) Sodium-glucose cotransporter-2 inhibitor prevents stroke in patients with diabetes and atrial fibrillation. J Am Heart Assoc 12(10):e027764. https://doi.org/10.1161/JAHA.122.027764CrossRefPubMedPubMedCentral

93.

Gonzalez J, Bates BA, Setoguchi S, Gerhard T, Dave CV (2023) Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction. Cardiovasc Diabetol 22(1):54. https://doi.org/10.1186/s12933-023-01784-wCrossRefPubMedPubMedCentral

94.

Baigent C, Emberson JR, Haynes R et al (2022) Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet 400(10365):1788–1801. https://doi.org/10.1016/S0140-6736(22)02074-8CrossRef

95.

Yamada T, Wakabayashi M, Bhalla A et al (2021) Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis. Cardiovasc Diabetol 20(1):14. https://doi.org/10.1186/s12933-020-01197-zCrossRefPubMedPubMedCentral

96.

Kernan WN, Forman R, Inzucchi SE (2023) Caring for patients with diabetes in stroke neurology. Stroke 54(3):894–904. https://doi.org/10.1161/STROKEAHA.122.038163CrossRefPubMed

97.

Goldenberg RM, Cheng AYY, Fitzpatrick T, Gilbert JD, Verma S, Hopyan JJ (2022) Benefits of GLP-1 (glucagon-like peptide 1) receptor agonists for stroke reduction in type 2 diabetes: a call to action for neurologists. Stroke 53(5):1813–1822. https://doi.org/10.1161/STROKEAHA.121.038151CrossRefPubMed

98.

Marso SP, Bain SC, Consoli A et al (2016) Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 375(19):1834–1844. https://doi.org/10.1056/nejmoa1607141CrossRefPubMed

99.

Gerstein HC, Colhoun HM, Dagenais GR et al (2019) Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 394(10193):121–130. https://doi.org/10.1016/S0140-6736(19)31149-3CrossRefPubMed

100.

Spence JD, Viscoli CM, Inzucchi SE et al (2019) Pioglitazone therapy in patients with stroke and prediabetes: a post hoc analysis of the IRIS randomized clinical trial. JAMA Neurol 76(5):526–535. https://doi.org/10.1001/jamaneurol.2019.0079CrossRefPubMedPubMedCentral

Title: Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities
Publication date: 16-04-2024
Keywords: Type 2 Diabetes
Stroke
Hyperglycemia
Diabetes Therapy
Diabetes-associated Diseases
Diabetes and Cardiac Diseases
Diabetes and Cardiac Diseases
Diabetic Nephropathy
Chronic Kidney Disease
Metabolic Disease and Nutrition
Published in: Diabetologia
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-024-06146-z

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Obesity Clinical Trial Summary

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A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

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Keynote webinar | Spotlight on medication adherence

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Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials