Increased Risk of Ischemic Stroke after Hyperosmolar Hyperglycemic State: A Population-Based Follow-Up Study

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Abstract

Background

Although much attention has been focused on the association between chronic hyperglycemia and cerebrovascular diseases in type 2 diabetes mellitus (DM) patients, there is no data regarding the risk of ischemic stroke after a hyperosmolar hyperglycemic state (HHS) attack. The objective of this study was to investigate the risk of ischemic stroke in type 2 DM patients after an HHS attack.

Methods

From 2004 to 2008, this retrospective observational study was conducted on a large cohort of Taiwanese using Taiwan’s National Health Insurance Research Database (NHIRD). We identified 19,031 type 2 DM patients who were discharged with a diagnosis of HHS and 521,229 type 2 DM patients without an HHS diagnosis. Using the propensity score generated from logistic regression models, conditional on baseline covariates, we matched 19,031 type 2 DM patients with an HHS diagnosis with the same number from the comparison cohort. The one-year cumulative rate for ischemic stroke was estimated using the Kaplan-Meier method. After adjusting covariates, Cox proportional hazard regression was used to compute the adjusted one-year rate of ischemic stroke.

Results

Of the patients sampled, 1,810 (9.5%) of the type 2 DM patients with HHS and 996 (5.2%) of the comparison cohort developed ischemic stroke during the one-year follow-up period. After adjusting for covariates, the adjusted HR for developing ischemic stroke during the one-year follow-up period was 1.8 (95% C.I., 1.67 to 1.95, P<0.001) for type 2 DM patients with HHS compared with those without HHS.

Conclusion

Although DM is a well-recognized risk factor for atherosclerosis, type 2 DM patients that have suffered a HHS attacks are at an increased risk of developing ischemic stroke compared with those without HHS.

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Most cited references 20

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Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.

J Stamler, O Vaccaro, J Neaton … (1993)

To assess predictors of CVD mortality among men with and without diabetes and to assess the independent effect of diabetes on the risk of CVD death. Participants in this cohort study were screened from 1973 to 1975; vital status has been ascertained over an average of 12 yr of follow-up (range 11-13 yr). Participants were 347,978 men aged 35-57 yr, screened in 20 centers for MRFIT. The outcome measure was CVD mortality. Among 5163 men who reported taking medication for diabetes, 1092 deaths (603 CVD deaths) occurred in an average of 12 yr of follow-up. Among 342,815 men not taking medication for diabetes, 20,867 deaths were identified, 8965 ascribed to CVD. Absolute risk of CVD death was much higher for diabetic than nondiabetic men of every age stratum, ethnic background, and risk factor level--overall three times higher, with adjustment for age, race, income, serum cholesterol level, sBP, and reported number of cigarettes/day (P < 0.0001). For men both with and without diabetes, serum cholesterol level, sBP, and cigarette smoking were significant predictors of CVD mortality. For diabetic men with higher values for each risk factor and their combinations, absolute risk of CVD death increased more steeply than for nondiabetic men, so that absolute excess risk for diabetic men was progressively greater than for nondiabetic men with higher risk factor levels. These findings emphasize the importance of rigorous sustained intervention in people with diabetes to control blood pressure, lower serum cholesterol, and abolish cigarette smoking, and the importance of considering nutritional-hygienic approaches on a mass scale to prevent diabetes.

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Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview.

K. Malmberg, Kevin Hunt, Arvind Pathak … (2001)

"Stress" hyperglycemia may be associated with increased mortality and poor recovery in diabetic and nondiabetic patients after stroke. A systematic review and meta-analysis of the literature relating acute poststroke glucose levels to the subsequent course were done to summarize and quantify this relationship. A comprehensive literature search was done for cohort studies reporting mortality and/or functional recovery after stroke in relation to admission glucose level. Relative risks in hyperglycemic compared with normoglycemic patients with and without diabetes were calculated and meta-analyzed when possible. Thirty-two studies were identified; relative risks for prespecified outcomes were reported or could be calculated in 26 studies. After stroke of either subtype (ischemic or hemorrhagic), the unadjusted relative risk of in-hospital or 30-day mortality associated with admission glucose level >6 to 8 mmol/L (108 to 144 mg/dL) was 3.07 (95% CI, 2.50 to 3.79) in nondiabetic patients and 1.30 (95% CI, 0.49 to 3.43) in diabetic patients. After ischemic stroke, admission glucose level >6.1 to 7.0 mmol/L (110 to 126 mg/dL) was associated with increased risk of in-hospital or 30-day mortality in nondiabetic patients only (relative risk=3.28; 95% CI, 2.32 to 4.64). After hemorrhagic stroke, admission hyperglycemia was not associated with higher mortality in either diabetic or nondiabetic patients. Nondiabetic stroke survivors whose admission glucose level was >6.7 to 8 mmol/L (121 to 144 mg/dL) also had a greater risk of poor functional recovery (relative risk=1.41; 95% CI, 1.16 to 1.73). Acute hyperglycemia predicts increased risk of in-hospital mortality after ischemic stroke in nondiabetic patients and increased risk of poor functional recovery in nondiabetic stroke survivors.

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Mortality and causes of death in a national sample of diabetic patients in Taiwan.

Chin-Hsiao Tseng (2004)

To determine the mortality rate, causes of death, and standardized mortality ratio (SMR) in Taiwanese diabetic patients. A cohort of 256036 diabetic patients (118855 men and 137181 women, aged 61.2 +/- 15.2 years) using the National Health Insurance were assembled during the years 1995-1998 and followed up to the end of 2001. Deaths were verified by indexing to the National Register of Deaths. Underlying causes of death were determined from death certificates coded according to the ninth revision of the International Classification of Diseases. The general population of Taiwan was used as reference for SMR calculation. With a total of 1124348.4 person-years of follow-up, 43888 patients died and the crude mortality rate was 39.0/1000 person-years. Mortality rates increased with age, and diabetic men had a significantly higher risk of death than women. However, mortality rate ratio for men versus women attenuated with increasing age. The overall SMR was 1.63 (1.62-1.65), and SMRs also attenuated in the elderly. Causes of death ascribed to diabetes; cancer; cardiopulmonary disease; stroke; disease of arteries, arterioles, and capillaries; nephropathy; infection; digestive diseases; accidents; and suicide were 28.8, 18.5, 9.0, 10.5, 0.3, 4.8, 6.4, 7.9, 3.2, and 0.8%, respectively. Approximately 71.2% of the diabetes-related deaths would not be ascribed to diabetes on death certificates in Taiwan. The diabetic men have higher risk of dying than women, and diabetic patients have excess mortality when compared with the general population. For underlying causes of death not listed as diabetes, total cardiovascular death, including cardiopulmonary disease, stroke, and disease of arteries, arterioles, and capillaries, is the most common cause of death, followed by cancer.

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Author and article information

Contributors

Xiaoying Wang: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 8 April 2014

Volume: 9

Issue: 4

Electronic Location Identifier: e94155

Affiliations

[1 ]Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

[2 ]Division of Neurology, Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

[3 ]Division of Metabolism and Endocrinology, Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

[4 ]School of Medicine, Tzu Chi University, Hualian, Taiwan

[5 ]Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

[6 ]Community Medicine Research Center and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan

[7 ]Department of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

[8 ]Department of Education, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

[9 ]Center for Clinical Epidemiology and Biostatistics, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

Massachusetts General Hospital, United States of America

Author notes

* E-mail: hematcd2@ 123456hotmail.com (WCL); hematcd@ 123456hotmail.com (CCL)

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: JYW CYW YSH PFC KYH PC WCL CCL. Analyzed the data: PC WCL CCL. Wrote the paper: JYW CYW.

Article

Publisher ID: PONE-D-13-40567

DOI: 10.1371/journal.pone.0094155

PMC ID: 3979762

PubMed ID: 24714221

SO-VID: b6f54463-f33a-4e2d-9066-788b96873f6d

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 3 October 2013

Date accepted : 11 March 2014

Page count

Pages: 6

Funding

The authors have no support or funding to report.

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Increased Risk of Ischemic Stroke after Hyperosmolar Hyperglycemic State: A Population-Based Follow-Up Study

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Abstract

Background

Methods

Results

Conclusion

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PLOS: COVID-19 pandemic

Most cited references 20

Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.

Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview.

Mortality and causes of death in a national sample of diabetic patients in Taiwan.

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