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Hypoglycaemia, chronic kidney disease and death in type 2 diabetes: the Hong Kong diabetes registry

Alice PS Kong1, Xilin Yang12, Andrea Luk13, Kitty KT Cheung1, Ronald CW Ma1, Wing Yee So1, Chung Shun Ho4, Michael HM Chan4, Risa Ozaki1, Chun Chung Chow1, Nicola Brown3 and Juliana CN Chan1356*

Author Affiliations

1 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China

2 Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China

3 Asia Diabetes Foundation, Shatin, China

4 Department of Chemical Pathology, Shatin, China

5 Li KaShing Institute of Health Sciences, Shatin, China

6 Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China

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BMC Endocrine Disorders 2014, 14:48  doi:10.1186/1472-6823-14-48

Published: 13 June 2014



In patients with type 2 diabetes, chronic kidney disease (CKD) is associated with increased risk of hypoglycaemia and death. Yet, it remains uncertain whether hypoglycaemia-associated mortality is modified by CKD.


Type 2 diabetic patients, with or without CKD at enrolment were observed between 1995 and 2007, and followed up till 2009 at hospital medical clinics. We used additive interaction, estimated by relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP) to examine possible synergistic effects between CKD and severe hypoglycaemia (defined as hospitalisations due to hypoglycaemia in the 12 months prior to enrolment) on the risk of death.


In this cohort of 8,767 type 2 diabetic patients [median age: 58 (interquartile range: 48 to 68) years; disease duration: 5 (1 to 11) years, men: 47.0%], 1,070 (12.2%) had died during a median follow-up period of 6.66 years (3.42-10.36) with 60,379 person-years.Upon enrolment, 209 patients had severe hypoglycaemia and 194 developed severe hypoglycaemia during follow-up (15 patients had both). In multivariable analysis and using patients without severe hypoglycaemia nor CKD as the referent group (683 deaths in 7,598 patients), severe hypoglycaemia alone (61 deaths in 272 patients) or CKD alone (267 death in 781 patients) were associated with increased risk of death [Hazard ratio, HR: 1.81(95%CI: 1.38 to 2.37) and 1.63 (1.38 to 1.93) respectively]. Having both risk factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91 (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p-values < 0.05).


Severe hypoglycaemia and CKD interact to increase risk of death in type 2 diabetes patients.