What Does Diabetes Have to do With Patients with Stroke?

Q. Are persons with diabetes at risk for stroke?

A. The risk of stroke is increased 2.9-fold among persons with diabetes, accounting for 15% to 27% of all incident strokes.¹ Stroke risk is limited to ischemic, not hemorrhagic, events. In a separate systematic review and meta-analysis of 64 cohorts including 775,385 individuals, the relative risk of diabetes-related stroke was calculated at 2.28 in women and 1.83 in men.²

In a review of 5 cohort studies on people with prediabetes (defined as HA1c 6.1%-6.9%),³ there is a 21% increase in stroke risk after adjusting for other cardiovascular risk factors. In contrast, there is a reduced incidence of transient ischemic attacks (TIA) among people with diabetes. A person with diabetes with a TIA has a 2.1 to 5.6-fold greater risk of subsequent stroke.^{1
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Q. If a patient admitted with a stroke and has hyperglycemia, does this mean they have diabetes?

A. In a systematic review of 33 studies, 8% to 63% of patients without diabetes were admitted with a glucose level of >6.1 mmol/L (>110 mg/dL) versus 39% to 83% of patients who had diabetes.⁴ Glucoses declined within the first 24 hours and increased again after 48 hours.

Among hyperglycemic patients without diabetes, 27% to 37% developed impaired glucose tolerance within 3 months after discharge and one-third of these individuals went on to develop overt diabetes.

Q. Does admission for hyperglycemia pose any additional risk to patients with stroke? 

A. The risk of death among patients with diabetes and a blood glucose level of >140 mg/dL is increased 2.7-fold; the risk of death among patients without diabetes and a blood glucose level of >140 mg/dL is increased 18.3-fold.⁵ Among such persons with “stress-related” hyperglycemia, the degree of hyperglycemia is proportional to infarct size and progression, as well as 30-day and 1-year mortality rates.¹ The degree of hyperglycemia in persons with diabetes has no correlation with short-term mortality, except among women age 55 and older.⁶ 

In contrast, hyperglycemia in people without diabetes is associated with an 18-fold increase of in-hospital mortality and this is limited to cortical, not lacunar, stroke.⁴ Data from this study show that treatment with tissue plasminogen activator (rtPA) results in a greater risk of hemorrhagic complications. Note: In animal studies, rtPA activity is decreased in the setting of hyperglycemia and hyperinsulinemia.

Q. Does insulin treatment improve outcomes in persons with hyperglycemia and acute stroke?

A. Small trials, such as the Treatment of Hyperglycemia in Ischemic Stroke (THIS)⁷ in the United States and the Glucose in Insulin in Stroke Trial (GIST-UK) in the United Kingdom,⁴ failed to show benefits from aggressive insulin therapy as compared to usual care, despite theoretical physiologic benefits.⁸ In THIS,⁷ 11 of 31 patients who received aggressive therapy experienced hypoglycemia.

Q. What special considerations need to be considered among patients with acute stroke?

A. Patients with neurocritical illness may not experience usual warning symptoms of hypoglycemia.⁴ The risk of cerebral damage may be enhanced and standard ICU insulin protocols may therefore not be appropriate in the stroke unit. Sliding scale insulin, although often used based on convenience, is associated with an increased risk of hypoglycemia. Patients with acute stroke may have impairments in mobility, vision, and manual dexterity, making rehabilitation more difficult.⁹

Q. What glucose targets are appropriate with patients with hyperglycemia and acute stroke?

A. There are no established, evidence-based glucose targets for persons with acute stroke.⁸ However, the American Heart Association and European Stroke Organization guidelines recommend insulin therapy if the blood glucose level is >7.8 mmol/L (140 mg/dL)⁴ and the American Stroke Association recommends insulin therapy if the blood glucose level is >7.8 mmol/L to 10 mmol/L (140 mg/dL-180 mg/dL).¹⁰ There are no reported guidelines on optimal treatment regimens but there is global consensus that it is imperative to avoid hypoglycemia. ■

Kim A. Carmichael, MD, is an associate professor of medicine, department of internal medicine, division of endocrinology, diabetes, and lipid research at Washington University School of Medicine in St Louis, MO.

References:

1.Air EL, Kissela BM. Diabetes, the metabolic syndrome, and ischemic stroke: epidemiology and possible mechanisms. Diabetes Care. 2007;30:3131-3140.

2. Peters SAE, Huxley RR, Woodward M. Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events. Lancet. 2014;
383(9933):1973-1980.

3. Lee M, Saver JL, Hong KS, et al. Effect of pre-diabetes on future risk of stroke: meta-analysis. Brit Med J. 2012;344:
e3564.

4. Kruyt ND, Biessels GJ, DeVries JH, Roos YB. Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management. Nat Rev Neurol. 2010;6:145-155.

5. May AK, Kauffmann RM, Collier BR. The place for glycemic control in the surgical patient. Surg Infections. 2011;
12:405-418.

6. Zhao W, Katzmarzyk PT, Horswell R, et al. HbA1c and coronary heart disease risk among diabetic patients. Diabetologia. 2014;37(2):428-435. 

7. Bruno A, Kent TA, Coull BM, et al. Treatment of hyperglycemia in ischemic stroke (THIS). A randomized pilot trial. Stroke. 2008;39(2):348-349.

8. Godoy DA, DiNapoli M, Rabinstein AA. Treating hyperglycemia in neurocritical patients: benefits and perils. Neurocrit Care. 2010;13(3):425-438.

9. Golden SH, Hill-Briggs F, Williams K,
et al. Management of diabetes during acute stroke and inpatient stroke rehabilitation. Arch Phys Med Rehabil. 2005;86:2377-2384.

10. Radermecker RP, Scheen AM. Management of blood glucose in patients with stroke. Diabetes Metab. 2010;
36(suppl 3):S94-S99.