By Inna Lutsenko, MD,neurologist and specialist, Center for Distance Learning and Advanced Training, Kyrgyz State Medical Academy after I.K.Akhunbaev; twitter: @inna_lutsenko
In 2013, 382 million people had diabetes, and this number is expected to rise to 592 million by 2035 [3]. It’s well known that diabetes mellitus is an independent risk factor for ischemic stroke [1-8]. Diabetes also increases the risk of stroke-related dementia by more than threefold [4]. Hence, an urgent global healthcare priority is preventing heart attacks and strokes in diabetic patients.
Pathogenically, the diabetic milieu is characterised by a chronic state of low-grade inflammation, endothelial dysfunction, hypercoagulability, dyslipidemia and insulin resistance [5]. So, the hyperglycaemia specifically affects vascular structure and function by four mechanisms: it increases the oxidative stress and free radical-mediated damage, induces the formation of advanced glycosylation end products, promotes diversion of glucose into the aldose reductase pathway and activates isozymes of protein kinase C.
Hyperglycaemia in the acute phase of stroke has been established as a predictor of poor outcome in all patients, but particularly more so in those not previously known to have diabetes – stress hyperglycemia [7]. Chronic hyperglycemia leads to intima media changes of the thinnest vessels of the Willis circle, e.g.thalamic and lenticulostriate arteries, which can result in cerebral small vessel disease, including white matter changes, cerebral microbleeds, and acute ischemic stroke, with the latter being mostly the lacunar subtype. Ischaemic strokes can also be of the posterior circulation of the brain. In some patients, chronic hyperglycemia is not diagnosed prior to the stroke event and regrettably stroke may be the first manifestation.
Fortunately, with many developments in primary prevention, we now have several ways to prevent stroke in patients with diabetes. Recent ESC guidelines [4], updated in 2019, recommend that patients with diabetes mellitus at high risk of cerebrovascular events maintain systolic arterial pressure during treatment to at 130 mmHg and <130 mmHg if tolerated but not <120mmHg. Antiplatelet agents (aspirin) at a dose of 75–100 mg / day for primary prevention may be considered in very high / high risk patients with diabetes mellitus in the absence of clear contraindications. Metformin is indicated for overweight patients with T2DM with moderate cardiovascular risk of CVD, and for patients with diabetes and atrial fibrillation, NOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) are recommended. SGLT2 inhibitors are recommended for patients with T2DM with very high / high cardiovascular risk to reduce cardiovascular events, and the GLP-1 receptor agonist is recommended for patients with T2DM and CVD or very high / high risk of CVD in order to reduce the risk of fatal CVD complications. A meta-analysis including 18 686 patients with DM demonstrated that a statin-induced reduction of LDL-C by 1.0 mmol/L (40 mg/dL) was associated with a 9% reduction in all-cause mortality and a 21% reduction in the incidence of major CV events, so regular therapy with statins is highly recommended as well.
In addition to medication, it has been suggested that patients with both insulin resistance and diabetes mellitus should engage in regular aerobic exercise, which not only decreases the secretion of pro-inflammatory cytokines, such as TNF-alpha and IL-1-beta, but also increases antioxidant levels, which in turn improve insulin sensitivity. In other words, in addition to drug therapy, lifestyle management also plays a key role in the prevention stroke in patients with diabetes mellitus
References:
- Adrià Arboix, Antoni Rivas, Luis García-Eroles, Lourdes de Marcos, Joan Massons and Montserrat Oliveres. Cerebral infarction in diabetes: Clinical pattern, stroke subtypes, and predictors of in-hospital mortality. BMC Neurology 2005, 5:9 doi:10.1186/1471-2377-5-9. http://www.biomedcentral.com/1471-2377/5/9
- Chih-Cheng Hsu, Pai-Feng Hsu, Shih-Hsien Sung, Shih-Te Tu, Ben-Hui Y, Chi-Jung Huang, Hao-Min Cheng. Is There a Preferred Stroke Prevention Strategy for Diabetic Patients with Non-Valvular Atrial Fibrillation? Comparing Warfarin, Dabigatran and Rivaroxaban. Anticoagulation for Diabetic Atrial Fibrillation. DOI https://doi.org/10.1160/TH17-02-0095. ISSN 0340-6245.
- Guariguata L,Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014;103(02): 137–149
- Francesco Cosentino et al. 2019 ESC Guidelines on diabetes, prediabetes, and cardiovascular diseases developed in collaboration with the EASD. The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). European Heart Journal (2019) 00, 169 ESC GUIDELINES doi:10.1093/eurheartj/ehz486
- Luchsinger JA, Tang MX, Stern Y et al. Diabetes mellitus and risk of Alzheimer’s disease and dementia with stroke in multiethnic cohort. Am J Epidemiol 2001; 154: 635–41.
- Idris I, Gray S, Donnelly R. Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes. Diabetologia 2001; 44: 659–73.
- Capes SE, Hunt D, Malmberg K et al. Stress hyperglycemia and prognosis of stroke on nondiabetic and diabetic patients. A systematic overview. Stroke 2001; 32: 2426–32.
