Hypoglycemia and Incident Cognitive Dysfunction: A Post Hoc Analysis From the ORIGIN Trial

Diabetes Care. 2019 Jan;42(1):142-147. doi: 10.2337/dc18-0690. Epub 2018 Nov 13.

Abstract

Objective: Epidemiological studies have reported a relationship between severe hypoglycemia, cognitive dysfunction, and dementia in middle-aged and older people with type 2 diabetes. However, whether severe or nonsevere hypoglycemia precedes cognitive dysfunction is unclear. Thus, the aim of this study was to analyze the relationship between hypoglycemia and incident cognitive dysfunction in a group of carefully followed patients using prospectively collected data in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial.

Research design and methods: This prospective cohort analysis of data from a randomized controlled trial included individuals with dysglycemia who had additional cardiovascular risk factors and a Mini-Mental State Examination (MMSE) score ≥24 (N = 11,495). Severe and nonsevere hypoglycemic events were collected prospectively during a median follow-up time of 6.2 years. Incident cognitive dysfunction was defined as either reported dementia or an MMSE score of <24. The hazard of at least one episode of severe or nonsevere hypoglycemia for incident cognitive dysfunction (i.e., the dependent variable) from the time of randomization was estimated using a Cox proportional hazards model after adjusting for baseline cardiovascular disease, diabetes status, treatment allocation, and a propensity score for either form of hypoglycemia.

Results: This analysis did not demonstrate an association between severe hypoglycemia and incident cognitive impairment either before (hazard ratio [HR] 1.16; 95% CI 0.89, 1.52) or after (HR 1.00; 95% CI 0.76, 1.31) adjusting for the severe hypoglycemia propensities. Conversely, nonsevere hypoglycemia was inversely related to incident cognitive impairment both before (HR 0.59; 95% CI 0.52, 0.68) and after (HR 0.58; 95% CI 0.51, 0.67) adjustment.

Conclusions: Hypoglycemia did not increase the risk of incident cognitive dysfunction in 11,495 middle-aged individuals with dysglycemia.

Trial registration: ClinicalTrials.gov NCT00069784.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology*
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / epidemiology*
  • Educational Status
  • Female
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / drug therapy
  • Hypoglycemia / epidemiology*
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Insulin Glargine / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors

Substances

  • Hypoglycemic Agents
  • Insulin Glargine
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT00069784