The association of basal insulin treatment versus standard care with outcomes in anti-GAD positive and negative subjects: A post-hoc analysis of the ORIGIN trial

Kåre I Birkeland; Valdemar Grill; Cecilie Wium; Matthew J McQueen; Patricio Lopez-Jaramillo; Shun Fu Lee; Hertzel C Gerstein

doi:10.1111/dom.13528

The association of basal insulin treatment versus standard care with outcomes in anti-GAD positive and negative subjects: A post-hoc analysis of the ORIGIN trial

Diabetes Obes Metab. 2019 Feb;21(2):429-433. doi: 10.1111/dom.13528. Epub 2018 Oct 3.

Authors

Kåre I Birkeland¹, Valdemar Grill^{2

3}, Cecilie Wium⁴, Matthew J McQueen⁵, Patricio Lopez-Jaramillo⁶, Shun Fu Lee⁷, Hertzel C Gerstein⁸

Affiliations

¹ Department of Transplantation Medicine, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
² Department of Endocrinology, St. Olav's Hospital, Trondheim, Norway.
³ Institute of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
⁵ Department of Pathology and Molecular Medicine, Population Health Research Institute, McMaster University Hamilton Health Sciences, Hamilton, Ontario, Canada.
⁶ Research Institute, FOSCAL, Bucaramanga, Colombia and Universidad Tecnológica Equinoccial, Facultad de Ciencias de la Salud Eugenio Espejo, Quito, Ecuador.
⁷ Department of Statistics, Population Health Research institute, McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada.
⁸ Department of Medicine, Population Health Research institute, McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada.

PMID: 30203580
DOI: 10.1111/dom.13528

Abstract

We compared cardiovascular and other outcomes in patients with dysglycaemia with or without anti-glutamic acid dehydrogenase (GAD) antibodies participating in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. Of the 12 537 participants, 8162 had anti-GAD measured at baseline and 267 were anti-GAD positive. The effects of insulin glargine versus standard care and of n-3 fatty acids supplements versus placebo were compared by testing the interaction of the treatment effects and anti-GAD status. The effect of glargine on development of new diabetes was assessed in participants without previous diabetes at baseline. The overall incidence of outcomes did not differ between anti-GAD positive and anti-GAD negative subjects. The incidence of the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke did not differ between anti-GAD positive participants randomized to insulin glargine or to standard care, with a hazard ratio (HR) (95% confidence interval [CI]) of 0.80 (0.44-1.44) or in anti-GAD negative participants with a HR of 1.07 (0.96-1.20) (P for interaction = 0.20).

Trial registration: ClinicalTrials.gov NCT00069784.

Keywords: CVD; anti-GAD; type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Autoantibodies / blood*
Blood Glucose / analysis
Blood Glucose / metabolism
Diabetes Mellitus, Type 2 / blood*
Diabetes Mellitus, Type 2 / diagnosis
Diabetes Mellitus, Type 2 / drug therapy*
Diabetes Mellitus, Type 2 / mortality
Female
Glutamate Decarboxylase / immunology*
Glycated Hemoglobin / analysis
Glycated Hemoglobin / metabolism
Humans
Insulin / standards
Insulin / therapeutic use*
Insulin Glargine / therapeutic use*
Male
Middle Aged
Prognosis
Randomized Controlled Trials as Topic / statistics & numerical data
Retrospective Studies
Standard of Care* / statistics & numerical data
Treatment Outcome

Substances

Autoantibodies
Blood Glucose
Glycated Hemoglobin A
Insulin
Insulin Glargine
Glutamate Decarboxylase

Associated data

ClinicalTrials.gov/NCT00069784