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J Diabetes Investig. 2019 Oct 3. doi: 10.1111/jdi.13153. [Epub ahead of print]

Absolute Risk of Acute Coronary Syndrome after Severe Hypoglycemia: A Population-Based 2-year Cohort Study Using the National Database in Japan.

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Department of Public Health, Health Management and Policy, Nara Medical University, Nara, 634-8521, Japan.
Department of Diabetology, Nara Medical University, Nara, 634-8521, Japan.
Division of Medical Information Technology and Administration Planning, Kyoto University Hospital, Kyoto, Japan.
Solutions Center for Health Insurance Claims, Kyoto University Hospital, Kyoto, Japan.



Although the epidemiologic relationship between hypoglycemia and increased risk of acute coronary syndrome (ACS) has been well established, the time period for increased risk of ACS following a severe hypoglycemic episode remains unknown. This study aimed to determine the ACS risk following a severe hypoglycemic episode.


We performed a retrospective population-based cohort study based on national claims data in Japan. We retrieved data of diabetes patients aged ≥35 years collected from April 2014 to March 2016. The absolute risk of ACS was defined as the occurrence of an emergency percutaneous coronary intervention after a severe hypoglycemic episode.


In total, data of 7,909,626 patients were included in the analysis. The absolute risk of ACS was 2.7/1000 person-years in all patients. ACS risk in patients with severe hypoglycemic episodes was 3.0/1000 person-years. Severe hypoglycemic episodes increased the absolute risk of ACS in patients aged ≥70 years, but not in patients aged <70 years. The absolute risk of ACS was 10.6/1000 person-years within 10 days of a severe hypoglycemic episode. There was a significant trend between shorter duration after an episode and higher ACS risk.


Severe hypoglycemia was associated with an increased risk of ACS in elderly diabetes patients. ACS risk increased with a shorter period after a severe hypoglycemic episode, suggesting that severe hypoglycemia leads to an increased risk of ACS in diabetes patients. These findings indicate that it is important to avoid severe hypoglycemia while treating diabetes, particularly in elderly patients.


acute coronary syndrome; cardiovascular disease; diabetes; hypoglycemia

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