5. Prise en charge du diabète et de l’AVC

Le diabète est un important facteur de risque des maladies cardiovasculaires et est reconnu comme un facteur indépendant de risque de l’AVC ischémique. Le risque d’AVC est 50 % plus élevé chez les personnes diabétiques. La plupart des adultes atteints de diabète de type 1 ou de type 2 doivent être considérés comme étant exposés à un risque élevé de maladie vasculaire. Les exceptions à cette règle sont les jeunes adultes atteints de diabète de type 1 ou de type 2 chez qui la maladie est présente depuis moins de temps, et qui ne souffrent pas de complications liées au diabète (dont les maladies cardiovasculaires confirmées) et qui n’ont pas d’autres facteurs de risque cardiovasculaire. Le diabète augmente le risque d’AVC et ce facteur de risque est particulièrement déterminant chez les jeunes : chez certains sous-groupes de jeunes, des études semblent même indiquer un risque d’AVC multiplié par dix. Globalement, le diabète est considéré comme un facteur de risque important de nombreux problèmes de santé, et est abordé ici dans le contexte d’un ensemble exhaustif de mesures de prévention et de prise en charge du mode de vie. 

Dans le cas de patients qui subissent un AVC et qui reçoivent en même temps un nouveau diagnostic de diabète, une formation relative à leur diabète est considérée comme une priorité incontournable. Les personnes ayant des antécédents de diabète ont fait état d’un manque de connaissance des risques d’AVC chez les personnes diabétiques, ajoutant souvent qu’ils ne connaissaient que les risques cardiaques, sans savoir qu’il y a un risque vasculaire plus général. Plusieurs personnes ayant subi un AVC et souffrant d’une maladie du cœur ont mentionné que leur glycémie ne faisait l’objet d’analyses et de discussions que lors des rendez-vous à ce sujet; ils se demandaient pourquoi il n’en était pas de même dans le cadre des soins relatifs à leur AVC. Parmi les préoccupations exprimées par les personnes qui ont subi un AVC, mentionnons les suivantes : la question de savoir si elles ont subi un test de dépistage du diabète, et le cas échéant, quels en avaient été les résultats, quelles étaient les précautions à prendre dorénavant, et, en cas de détection d’un diabète, comment, quand et par qui se ferait le suivi. Les commentaires des personnes qui ont subi un AVC et de leur famille ont mis en évidence les cloisonnements qui existent dans le réseau actuel de la santé, de même que la nécessité de fournir des soins coordonnés et ininterrompus après un AVC, compte tenu notamment du nombre de personnes aux prises avec de multiples affections comorbides.

1. Programmes concertés de sensibilisation au diabète aux échelons provinciaux et communautaires, auxquels participent les groupes communautaires, les prestataires de soins de première ligne (médecins, infirmières praticiennes, pharmaciens, etc.) et les autres partenaires pertinents.
2. Programmes concertés de formation et de soutien des personnes diabétiques en vue d’améliorer l’observance du traitement et de réduire les risques de complications cardiovasculaires.
3. Disponibilité et facilité d’accès accrues à des programmes de formation sur la prise en charge des patients diabétiques ayant subi un AVC pour les professionnels de la santé à toutes les étapes du continuum de soins.
4. Harmonisation constante avec les recommandations et les lignes directrices de Diabète Canada.
5. Accès universel et équitable à des médicaments efficaces et peu coûteux pour tous les habitants du pays, sans égard à la géographie, à l’âge ou à la capacité de payer.

1. Proportion de la population avec un diagnostic confirmé de diabète (de type 1 et de type 2).
2. Proportion des personnes atteintes de diabète parmi les cas de nouvel AVC observés dans un hôpital.
3. Proportion des patients traités dans un hôpital pour un AVC, pour lesquels un diagnostic de diabète est ensuite établi durant leur hospitalisation.

Notes sur la mesure des indicateurs

• Indicateur de rendement n^o 1 : Pour le Canada, les données peuvent être extraites du Système national de surveillance du diabète de l’Agence de santé publique du Canada. 
• Il faut normaliser les indicateurs de rendement 1 et 2 en fonction de l’âge et du sexe.
• Sources de données : Ordonnances des médecins, notes des médecins et du personnel infirmier, résumés produits au moment du congé ou copies des ordonnances données aux patient.
• Les valeurs sériques devraient être tirées, dans la mesure du possible, des rapports officiels des laboratoires.
• Il est possible de suivre les tendances et les points de référence dans la base de données du Système national de surveillance du diabète.

Renseignements destinés aux dispensateurs de soins de santé

• Cœur + AVC – Liste de vérification après un AVC 
• Lignes directrices de pratique clinique de Diabète Canada 
• Ressources de Diabète Canada à l’intention des professionnels 

Informations destinées au patient

• Cœur + AVC – Liste de vérification après un AVC 
• Cœur + AVC – Votre cheminement après un AVC  
• Cœur + AVC – Soutien en ligne et par les pairs 
• Cœur + AVC – Ressources sur le diabète 
• Diabète Canada 
• Ressources pour les patients de Diabète Canada (en anglais seulement) 

Diabetes Management Evidence Table and Reference List 

In persons with diabetes, the risk of stroke, particularly ischemic stroke is increased. Estimates from the InterStroke 1 study (O’Donnell et al. 2010) suggested that the odds of any stroke were increased by 36% among those with diabetes (60% for ischemic stroke). More recent estimates from the Interstroke 2 study (O’Donnell et al. 2016), are lower at 16% and 33% for any and ischemic stroke, respectively, although the population attributable risks (PAR) are similar between studies.  The PAR for ischemic stroke was 7.9% in Interstroke 1 and was 7.5% in the Interstroke 2 study. The independent contribution of diabetes is difficult to determine, since many risk factors for stroke, including hypertension, dyslipidemia and atrial fibrillation, are found more frequently in those with diabetes. The higher stroke risk may be due to the complex interplay between the various hemodynamic and metabolic components of the diabetes syndrome. In addition to the traditional risk factors, those specifically associated with the metabolic syndrome (insulin resistance, central obesity, impaired glucose tolerance and hyperinsulinemia), which are common in diabetes, also contribute to the increased risk. In persons with diabetes, stroke outcomes are worse, and are associated with increased mortality, more residual neurologic and functional disability and longer hospital stays. Lifestyle changes, tight glycemic control, antiplatelet drugs, such as aspirin and control of lipid levels with statins can all have beneficial effects. Blood pressure control is another vital aspect in reducing risk, and a number of recent studies have provided evidence supporting the use of angiotensin converting enzyme (ACE) inhibitors as first-line treatment in patients with diabetes. 

Intensive blood glucose management to reduce stroke and cardiovascular risk has been studied in several large RCTs. The Action to Control Cardiovascular Risk in Diabetes Study (ACCORD, glucose-lowering arm) investigators (Gerstein et al. 2008) assessed whether intensive therapy to target normal glycated hemoglobin (HbA1c) levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. In this study, 10,251 patients with a median HbA1c level of 8.1% were randomly assigned to receive intensive therapy using multiple drugs including insulins and oral hypoglycemia agents, (targeting an HbA1c level <6.0%) or standard therapy (targeting a level from 7.0%-7.9%). The trial was stopped early due to mortality trends suggesting an increased rate of death from any cause associated with intensive therapy (HR=1.22, 95% CI 1.01-1.46, p=0.04).  Although at 4 months, mean HbA1c values had fallen to 6.7% (intensive group) and 7.5% (control group), there was no reduction in the risk of the primary outcome (nonfatal MI, nonfatal stroke or death from cardiovascular causes) associated with intensive glucose lowering (6.9% vs. 7.2%, HR=0.90, 95% CI 0.78-1.04, p=0.16). Patients in the intensive group required medical assistance for hypoglycemia more frequently (10.5% vs. 3.5%), and greater proportions gained >10 kg from baseline (27.8% vs. 14.1%) and experienced a serious nonhypoglycemic adverse event (2.2% vs. 1.6%). Another trial that examined intensive glucose control in persons with poorly-controlled diabetes was the Veterans Affairs Diabetes Trial (Duckworth et al. 2009). After a median duration of follow-up of 5.6 years, HbA1c values were significantly lower in the intensive glucose control group; however, there were no significant differences between groups on any of the primary or secondary outcomes, including the risk of stroke (26 vs. 36 events, HR=0.78, 95% CI 0.48-1.28) or TIA (19 vs. 13, HR=1.48, 95% CI 0.73-2.99). There were significantly more hypoglycemic events in the intensive therapy group. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (Patel et al. 2008) randomly assigned patients (n = 11,140) with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve an HbA1c value of 6.5% or less. After a median of 5 years of follow- up, the mean HbA1c level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1% v. 20.0% with standard control; HR 0.90, 95% CI 0.82–0.98; p=0.01), as well as that of major microvascular events (9.4% v. 10.9%; HR 0.86, 95% CI 0.77–0.97; p=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% v. 5.2%; HR 0.79, 95% CI 0.66–0.93; p=0.006), with no significant effect on retinopathy (p=0.50). There was no significant difference between groups in the risk of death from any cause (HR=0.93, 95% CI 0.83-1.06, p=0.28) or in the risk of fatal or nonfatal stroke or all cerebrovascular events associated with intensive intervention. Severe hypoglycemia was significantly more frequent in the intensive treatment group (HR=1.86, 95% CI 1.42-2.40, p<0.001).  The results of these three trials and UK Prospective Diabetes Studies 33 and 34 were included in a meta-analysis (Marso et al. 2010) which examined the benefit of intensive glycemic control for the prevention of vascular events, among persons with type 2 diabetes. At the end of follow-up (mean of 5 years), the mean HbA1c values were 6.6% (intensive) and 7.4% (control). There was no reduction in the risk of all-cause mortality, stroke or cardiovascular mortality associated with intensive glycemic treatment; however, there was a significant 14% reduction in nonfatal myocardial infarction (RR=0.86, 95% CI 0.77-0.97, p=0.015).

Additional agents can also be added to standard regimens to improve glycemic control in patients with type 2 diabetes who have trouble achieving their blood glucose targets. One such agent is selective inhibitor of sodium glucose cotransporter (SGLT-2), which has been shown to reduce glycated hemoglobin levels and improve cardiovascular outcomes. Recent RCTs include CREDENCE (Perkovic et al. 2019, Mahaffey et al. 2019), DECLARE–TIMI 58 (Wiviott et al. 2019), CANVAS (Neal et al. 2017, Zhou et al. 2019) and EMPA-REG OUTCOME (Zinman et al. 2015). The proportion of patients with established atherosclerotic cardiovascular disease in these trials was 50% (CREDENCE), 40.6% (DECLARE), 65.6% (CANVAS) and 100% (EMPA-REG). A systematic review & meta-analysis including the results from three of these trials (EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58), which compared empagliflozin, canagliflozin and dapagliflozin vs. placebo, reported SGLT2 reduced the risk of a major adverse cardiac event by 11% (HR=0·89, 95% CI 0·83–0·96, p=0·0014); however, the benefit was only seen in persons with established atherosclerotic CVD. The overall risk of ischemic stroke was not reduced significantly in the SGLT2 group (HR=0.97, 95% CI 0.86-1.10), nor was the risk reduced significantly in persons with established atherosclerotic CVD, or in those with multiple risk factors (Zelniker et al. 2018). The CREDENCE trial was stopped prematurely due to efficacy.  After a median of 2.6 years of follow-up, the event rate of the primary outcome (a composite of end stage kidney disease, doubling of the serum creatinine level, or renal or cardiovascular death) was significantly lower in the canagliflozin group (43.2 vs. 61.2 per 1000 patient-years; HR= 0.70; 95% CI 0.59 to 0.82). The risk was reduced significantly in both the primary and secondary prevention groups. The risk of cardiovascular death, myocardial infarction or stroke was also reduced significantly by 20%. 

The glucagon-like peptide 1 receptor (GLP-1), liraglutide, is another example of an agent that may be added to standard regimes. Many large, RCTs have evaluated their effectiveness within the past 5 years, including REWIND (Gerstein et al. 2019), PIONEER 6, (Husain et al. 2019), HARMONY (Hernandez et al. 2018), EXCEL (Holman et al. 2017), SUSTAIN-6 (Marso et al. 2016) and LEADER (Marso et al. 2016). All of these trials included persons with type 2 diabetes, with established cardiovascular risk factors +/- a previous cardiovascular event who were treated with various GLP-1 agents (albiglutide, liraglutide, semaglutide, exenatide, dulaglutide) or placebo for a duration of 2.1 to 5.4 years. The risk of the primary outcome, major cardiovascular event, was reduced significantly from 8% to 24%. When the results of these trials were included in two systematic reviews, the risk of nonfatal and total stroke were significantly lower in the treatment group, with no significant reduction in the risk of fatal stroke (Barkas et al. 2019, Bellastella et al. 2019). 

Insulin resistance, while widespread in persons with type 2 diabetes, is also present in persons who have suffered a stroke or TIA. Treatment with Pioglitazone has recently been investigated (Kernan et al. 2016). In the Insulin Resistance After Stroke (IRIS) study, 3,876 patients, ≥40 years with stroke or TIA within previous 6 months, with insulin resistance were randomized to receive pioglitazone with a target dose of 45 mg daily or placebo for 5 years. The risk of the primary outcome (fatal or non-fatal myocardial infarction or fatal or non-fatal stroke) was significantly lower for patients in the pioglitazone group (9.0% vs. 11.8%, HR=0.76, 95% CI 0.62-0.93, p=0.007), as was the risk of the development of diabetes over the study period (3.8% vs. 7.7%, HR=0.48, 95% CI 0.33-0.69, p<0.001). The risk of stroke was not significantly reduced for patients in the pioglitazone group (6.5% vs. 8.0%, HR=0.82, 95% CI 0.61-1.10, p=0.19) and the frequency of adverse events including bone fracture, weight gain, edema, shortness of breath and liver enzyme abnormalities was significantly higher in the pioglitazone group. In another trial (PROspective pioglitAzone Clinical Trial In macroVascular Events), treatment with pioglitazone for persons with type 2 diabetes and extensive macrovascular disease did not reduce the risk of the primary outcome (HR=0.90, 95% CI 0.80-1.02, p=0.095) or the risk of stroke (HR=0.81, 95% CI 0.61-1.07), after an average of 32 months (Dormandy et al. 2005).