Hypoglycemia & Incident Cognitive Dysfunction: A Post-Hoc Analysis from the Origin Trial

Presentation Number: OR11-2
Date of Presentation: April 1st, 2017

Tali Cukierman-Yaffe*1, Jung Hyejung2, Jackie Bosch3, Zubin Punthakee4 and Hertzel C Gerstein5
1Sheba Medical Center, Tel-Aviv university, Israel, Population Health Research Institute, McMcaster university, Canada, 2Population Health Research Institute, McMaster university, Hamilton, Canada, 3Population Health Research Institute, McMaster university, Hamilton Canada, 4Population Health Research Institute, McMaster university, Hamilton, ON, CANADA, 5Population Health Research Institute, McMaster University

Abstract

Epidemiological studies have reported that recurrent severe hypoglycemia is associated with dementia and cognitive dysfunction in middle-aged and older people with type 2 diabetes. Cognitive dysfunction may precede or follow severe hypoglycemia in people with type 2 diabetes who are at risk for both conditions. The relationship between incident hypoglycemia and incident cognitive dysfunction was therefore analyzed using prospectively collected data in the outcome reduction with an initial glargine intervention (ORIGIN) trial. Methods:This prospective cohort analysis of data from a randomized controlled trial included individuals with dysglycemia (88% diabetes) who all had additional cardiovascular risk and a Mini Mental State Examination (MMSE) score equal to or above 24/30 (N=11495). Hypoglycemia (severe and non-severe) events were collected prospectively through-out the study (median follow-up 6.2 years). Non-severe hypoglycemia was defined as an event associated with symptoms of hypoglycemia, confirmed by a capillary glucose of <=54 mg/dl (3 mmol/L) and not requiring assistance from another person. Severe hypoglycemia was defined as a symptomatic hypoglycemic event requiring the assistance of another person and either 1) prompt recovery after oral carbohydrate, IV glucose, or glucagon and/or 2) documented self- measured or lab measured plasma glucose of <= 36mg-dl (2mmol/L). Incident cognitive dysfunction was defined as either newly reported dementia or a MMSE score of below 24 during follow-up. The relationship between severe and non-severe hypoglycemia (included as time-varying covariates) and incident cognitive dysfunction was determined using Cox proportional hazard models after adjusting for several variables and a propensity score for hypoglycemia.

Results: There was no relationship between severe hypoglycemia and incident cognitive impairment after adjusting for baseline CVD, diabetes status, treatment allocation, a propensity score for severe hypoglycemia and the interaction of treatment allocation and severe hypoglycemia (HR 1.28, 95% 0.8, 2.05). Those individuals who experienced at least one episode of non-severe hypoglycemia were less likely to develop cognitive dysfunction than were those that did not, after adjustment for baseline CVD, diabetes status, treatment allocation, a propensity score for non-severe hypoglycemia and the interaction of treatment allocation and hypoglycemia (HR 0.71, 95% 0.56, 0.9).

To conclude: Among 11,495 individuals ~63 years of age with dysglycemia, after accounting for the risk factors of hypoglycemia, hypoglycemia itself was not associated with an increased incidence of cognitive dysfunction over 6.2 years.

 

Disclosure: TC: Speaker, Eli Lilly & Company, Speaker, Astra Zeneca, Speaker, Merck & Co., Speaker, Novo Nordisk, Speaker, Sanofi, Speaker, BI, Advisory Group Member, Sanofi. ZP: Investigator, Amgen, Advisory Group Member, Animas, Advisory Group Member, Astra Zeneca, Speaker, Astra Zeneca, Speaker, Astra Zeneca, Investigator, Astra Zeneca, Advisory Group Member, BI, Speaker, BI, Investigator, BI, Advisory Group Member, Bristol-Myers Squibb, Speaker, Bristol-Myers Squibb, Investigator, Bristol-Myers Squibb, Advisory Group Member, Eli Lilly & Company, Speaker, Eli Lilly & Company, Investigator, Eli Lilly & Company, Investigator, Lexicon Pharmaceuticals, Inc., Advisory Group Member, Merck & Co., Speaker, Merck & Co., Investigator, Merck & Co., Advisory Group Member, Novo Nordisk, Speaker, Novo Nordisk, Investigator, Novo Nordisk, Advisory Group Member, Pfizer, Inc., Speaker, Pfizer, Inc., Advisory Group Member, Serono, Speaker, Serono, Advisory Group Member, Sanofi, Consultant, Sanofi, Investigator, Sanofi. HCG: Ad Hoc Consultant, Sanofi, Principal Investigator, Sanofi, Speaker, Sanofi, Advisory Group Member, Eli Lilly & Company, Advisory Group Member, Astra Zeneca, Advisory Group Member, Merck & Co., Advisory Group Member, Amgen, Advisory Group Member, Novo Nordisk, Advisory Group Member, Abbott Laboratories, Advisory Group Member, Berlin Chemie, Advisory Group Member, BI, Advisory Group Member, Kaneq Bioscience, Principal Investigator, Eli Lilly & Company, Principal Investigator, Astra Zeneca, Principal Investigator, Merck & Co.. Nothing to Disclose: JH, JB