title: Hypoglycaemia, chronic kidney disease and death in type 2 diabetes: the Hong Kong diabetes registry.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Severe hypoglycaemia and CKD interact to increase risk of death in type 2 diabetes patients.
authors.forename: Alice P S
authors.initials: AP
authors.lastname: Kong
authors.forename: Xilin
authors.initials: X
authors.lastname: Yang
authors.forename: Andrea
authors.initials: A
authors.lastname: Luk
authors.forename: Kitty K T
authors.initials: KK
authors.lastname: Cheung
authors.forename: Ronald C W
authors.initials: RC
authors.lastname: Ma
authors.forename: Wing Yee
authors.initials: WY
authors.lastname: So
authors.forename: Chung Shun
authors.initials: CS
authors.lastname: Ho
authors.forename: Michael H M
authors.initials: MH
authors.lastname: Chan
authors.forename: Risa
authors.initials: R
authors.lastname: Ozaki
authors.forename: Chun Chung
authors.initials: CC
authors.lastname: Chow
authors.forename: Nicola
authors.initials: N
authors.lastname: Brown
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China. jchan@cuhk.edu.hk.
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003643:Death; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006723:Hong Kong; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000401:mortality*; D012189:Retrospective Studies; D012307:Risk Factors