Hemoglobin glycation index, calculated from a single fasting glucose value, as a prediction tool for severe hypoglycemia and major adverse cardiovascular events in DEVOTE

Klara R. Klein, Edward Franek, Steven Marso, Thomas R. Pieber, Richard E. Pratley, Amoolya Gowda, Kajsa Kvist, John B. Buse

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Introduction Hemoglobin glycation index (HGI) is the difference between observed and predicted glycated hemoglobin A1c (HbA 1c), derived from mean or fasting plasma glucose (FPG). In this secondary, exploratory analysis of data from DEVOTE, we examined: whether insulin initiation/titration affected the HGI; the relationship between baseline HGI tertile and cardiovascular and hypoglycemia risk; and the relative strengths of HGI and HbA 1c in predicting these risks. Research design and methods In DEVOTE, a randomized, double-blind, cardiovascular outcomes trial, people with type 2 diabetes received once per day insulin degludec or insulin glargine 100 units/mL. The primary outcome was time to first occurrence of a major adverse cardiovascular event (MACE), comprising cardiovascular death, myocardial infarction or stroke; severe hypoglycemia was a secondary outcome. In these analyses, predicted HbA 1c was calculated using a linear regression equation based on DEVOTE data (HbA 1c =0.01313 FPG (mg/dL) (single value)+6.17514), and the population data were grouped into HGI tertiles based on the calculated HGI values. The distributions of time to first event were compared using Kaplan-Meier curves; HRs and 95% CIs were determined by Cox regression models comparing risk of MACE and severe hypoglycemia between tertiles. Results Changes in HGI were observed at 12 months after insulin initiation and stabilized by 24 months for the whole cohort and insulin-naive patients. There were significant differences in MACE risk between baseline HGI tertiles; participants with high HGI were at highest risk (low vs high, HR: 0.73 (0.61 to 0.87) 95% CI; moderate vs high, HR: 0.67 (0.56 to 0.81) 95% CI; p<0.0001). No significant differences between HGI tertiles were observed in the risk of severe hypoglycemia (p=0.0911). With HbA 1c included within the model, HGI no longer significantly predicted MACE. Conclusions High HGI was associated with a higher risk of MACE; this finding is of uncertain significance given the association of HGI with insulin initiation and HbA 1c. Trial registration number NCT01959529.

Original languageEnglish (US)
Article numbere002339
JournalBMJ Open Diabetes Research and Care
Volume9
Issue number2
DOIs
StatePublished - Nov 24 2021
Externally publishedYes

Keywords

  • diabetes mellitus
  • type 2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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