September 20, 2012
*Minor revisions for 2012
Patients with diabetes who have had an ischemic stroke or transient ischemic attack should have their diabetes assessed and optimally managed [Evidence level A].
2.4.1 Diabetes assessment
- For patients with diabetes and either ischemic stroke or transient ischemic attack, glycated hemoglobin (HbA1C ) should be measured as part of a comprehensive stroke assessment [Evidence Level B].
- In all patients with stroke or TIA, fasting lipid levels (total cholesterol, high-density lipoprotein cholesterol, total glycerides and calculated low-density lipoprotein cholesterol) should be measured at the time of diagnosis and at appropriate intervals if therapy initiated [Evidence Level C].
- Blood pressure should be measured at every diabetes visit in patients with stroke or at risk of stroke [Evidence Level C].
2.4.2 Diabetes management
- Glycemic targets must be individualized; however, therapy in most patients with type 1 or type 2 diabetes and stroke or TIA should be treated to achieve a glycated hemoglobin (HbA1C) level ≤7.0 percent to reduce the risk of microvascular complications [Evidence Level A] and, in individuals with type 1 diabetes, macrovascular complications [Evidence Level C].
- To achieve an HbA1C ≤7.0%, patients with type 1 or type 2 diabetes should aim for a fasting plasma glucose or preprandial plasma glucose target of 4.0 to 7.0 mmol/L [Evidence Level B].
- The 2-hour postprandial plasma glucose target is 5.0 to 10.0 mmol/L [Evidence Level B]. If HbA1C targets cannot be achieved with a postprandial target of 5.0 to 10.0 mmol/L, further postprandial blood glucose lowering, to 5.0 to 8.0 mmol/L, can be considered [Evidence Level C].
- Adults with diabetes and ischemic stroke are at high risk of further vascular events and should also be treated with a statin to achieve a low-density lipoprotein cholesterol ≤2.0 mmol/L [Evidence Level A].
- Unless contraindicated, low dose acetylsalicylic acid therapy (81 to 325 mg/day) is recommended in all patients with diabetes with evidence of cardiovascular disease such as stroke [Evidence Level A].
Diabetes is a major risk factor for cardiovascular disease and is recognized as an independent risk factor for ischemic stroke.86 Most adults with type 1 or type 2 diabetes should be considered at high risk for vascular disease. The exceptions are younger adults with type 1 and type 2 diabetes with shorter duration of disease and without complications of diabetes (including established cardiovascular disease) and without other cardiovascular disease risk factors. Diabetes increases the risk of stroke and is a particularly potent risk factor in younger individuals, with studies suggesting an increase in stroke risk of as much as 10-fold in some younger subgroups. Overall, diabetes is considered a major risk factor for many conditions and is considered here as part of a comprehensive package supporting prevention and lifestyle management.
- Coordinated diabetes awareness programs at the provincial and community levels that involve community groups, primary care providers (including physicians, nurse practitioners and pharmacists), and other relevant partners.
- Coordinated education and support programs for persons with diabetes to increase compliance and reduce ongoing risks for cardiovascular complications.
- Increased availability and access to education programs for healthcare providers across the continuum of care on management of patients with diabetes and stroke
- Continued alignment with recommendations and guidelines developed by the Canadian Diabetes Association.
- Proportion of persons with diabetes presenting to hospital with a new stroke event.
- Proportion of the population with a confirmed diagnosis of diabetes (type 1 and type 2).
- Proportion of patients presenting to hospital with a stroke who receive a subsequent diagnosis of diabetes while in hospital for stroke care.
- Data sources may include physician order sheets, physicians’ or nurses’ notes, discharge summaries, or copies of prescriptions given to patients.
- Blood values should be taken from official laboratory reports where possible.
- Trends and benchmarks may be monitored and tracked through the National Diabetes Surveillance System data.
- Performance measure 2: Rates may be obtained for Canada from the Public Health Agency of Canada Diabetes Surveillance database.
- Canadian Diabetes Association - http://www.diabetes.ca/
- Canadian Diabetes Association Clinical Practice Guidelines http://www.diabetes.ca/for-professionals/resources/2008-cpg/
Diabetes is an important modifiable risk factor for a first ischemic stroke. In a review of stroke and diabetes, Idris and colleagues stated that the combination of diabetes and stroke is a major cause of morbidity and mortality worldwide.87 Evidence from large clinical trials performed in patients with diabetes supports the need for aggressive and early intervention to target patients’ cardiovascular risks to prevent the onset, recurrence and progression of acute stroke. They describe the epidemiology of diabetes and stroke, and report an estimate that the risk of stroke is increased 1.5- to three-fold for patients with diabetes. Diabetes also doubles the risk of stroke recurrence, and stroke outcomes are significantly worse among patients with diabetes, with increased hospital and long-term stroke mortality, more residual neurologic and functional disability and longer hospital stays. From a clinical perspective, diabetes increases the risk of ischemic stroke more than hemorrhagic stroke, resulting in a greater ischemic to hemorrhagic stroke ratio in people with diabetes compared with the general population. Idris and colleagues further reported that although strokes in patients with diabetes are associated with a worse outcome, there is no evidence to suggest that diabetes induces a larger area of cerebral infarction.
The high stroke risk in diabetes may be due to the complex interplay between the various hemodynamic and metabolic components of the diabetes syndrome. Other than the many recognized risk factors associated with acute stroke (e.g., hypertension, dyslipidemia and atrial fibrillation), specific risk factors attributable to diabetes have also been reported. Components of the metabolic syndrome such as insulin resistance, central obesity, impaired glucose tolerance and hyperinsulinemia, both individually and collectively, are associated with an excess risk of stroke disease.87
Many diabetes patients exhibit metabolic syndrome and these additional risk factors, such as raised hypertension and cholesterol, multiply the overall risk. Reducing these risk factors to target levels is essential and requires a multifactor approach. Lifestyle changes, tight glycemic control, antiplatelet drugs (ASA) and control of lipid levels, (e.g., using statins), can all have significant 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 ACE inhibitors as first-line treatment in patients with diabetes.
Karapanayiotides and collaborators reported that the Framingham Study found a 2.5-fold incidence of ischemic stroke in diabetic men and a 3.6-fold incidence in diabetic women.88 In the largest case–control study with adjustment for multiple known risk factors, the risk of ischemic stroke for diabetic individuals was increased 2.3-fold. Two other large studies reported similar findings with odds ratios (ORs) of 2.12 and 2.47. However, it is difficult to determine the level of association between diabetes and ischemic stroke, as diabetes is also associated with a two-fold higher incidence of hypertension and cardiac disease and with an increased incidence of asymptomatic carotid artery disease and hyperlipidemia. Karapanayiotides and collaborators concluded that other risk factors for stroke such as hypertension, hypercholesterolemia, cardiac ischemic disease and vascular claudication are significantly more frequent in diabetic individuals, confirming that diabetic patients have high cerebral and cardiovascular risk.
Lehto and coworkers conducted a seven-year follow-up study on diabetic patients and nondiabetic controls to assess risk for stroke.89 They found diabetic men had a two- to three-fold higher risk, and diabetic women a five-fold higher risk for stroke than corresponding nondiabetic subjects (men: OR 2.4, 95% CI 1.2–4.9 in East Finland; OR 3.3, 95% CI 1.6–6.9 in West Finland; women: OR 5.5, 95% CI 2.4–12.9 in East Finland; OR 5.4, 95% CI 2.3–12.6 in West Finland).133 Ischemic stroke was the most common cause of stroke in nondiabetic subjects and type 2 diabetes patients in both areas. High fasting plasma glucose was a risk factor for stroke even after adjustment for other variables. In addition to fasting plasma glucose, glycemic control was also assessed by HbA1c, which reflects hyperglycemia during the preceding two months. There was a dose–response relationship between HbA1c and risk of stroke. The duration of diabetes was also an important risk factor for stroke events in type 2 subjects In addition, low levels of HDL cholesterol (less than 0.90 mmol/L), high levels of total triglyceride (more than 2.30 mmol/L) and the presence of hypertension were associated with a 2-fold increase in the risk of stroke mortality or morbidity.
The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary artery disease.90 A total of 1501 patients with diabetes and coronary artery disease, with LDL cholesterol levels of < 3.36 mmol/L, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from coronary heart disease, nonfatal non–procedure related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke. The results found end-of-treatment mean LDL cholesterol levels were 2.55 mmol/L with atorvastatin 10 mg and 1.99 mmol/L with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (HR 0.75, 95% CI 0.58–0.97; p = 0.026). Significant differences between the groups in favour of atorvastatin 80 mg were also observed for time to cerebrovascular event (HR 0.69, 95% CI 0.48–0.98; p = 0.037) and any cardiovascular event (HR 0.85, 95% CI 0.73–1.00; p = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes. The researchers concluded that among patients with clinically evident coronary artery disease and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25 percent compared with atorvastatin 10 mg.
The Action to Control Cardiovascular Risk in Diabetes Study (ACCORD) investigators assessed whether intensive therapy to target normal HbA1c levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.91 Patients (n = 10 251) with a median HbA1c level of 8.1 percent were randomly assigned to receive intensive therapy (targeting an HbA1c level below 6.0 percent) or standard therapy (targeting a level from 7.0 percent to 7.9 percent). The finding of higher mortality in the intensive- therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. During follow- up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard- therapy group (HR 0.90, 95% CI 0.78–1.04; p = 0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard therapy group (HR 1.22, 95% CI 1.01–1.46; p = 0.04).135 These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes.
The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial 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.92 After a median of 5 years of follow- up, the mean glycated hemoglobin 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).