Determinants of serious health outcome-free status in middle-aged and older people with dysglycaemia: Exploratory analysis of the ORIGIN trial

Kamel Mohammedi; Sibylle Hess; Matthew McQueen; Marie Pigeyre; Shun Fu Lee; Guillaume Pare; Hertzel C Gerstein

doi:10.1111/dom.15654

Determinants of serious health outcome-free status in middle-aged and older people with dysglycaemia: Exploratory analysis of the ORIGIN trial

Diabetes Obes Metab. 2024 May 15. doi: 10.1111/dom.15654. Online ahead of print.

Authors

Kamel Mohammedi^{1

2}, Sibylle Hess³, Matthew McQueen¹, Marie Pigeyre¹, Shun Fu Lee¹, Guillaume Pare¹, Hertzel C Gerstein¹

Affiliations

¹ Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.
² Université de Bordeaux, INSERM, BMC, U1034, Avenue de Magellan, Pessac, France.
³ Sanofi, Global Medical Diabetes, Frankfurt, Germany.

PMID: 38747213
DOI: 10.1111/dom.15654

Abstract

Aim: To assess clinical and biochemical measurements that can identify people with dysglycaemia (i.e. diabetes or pre-diabetes) who remain free of serious outcomes during follow-up.

Materials and methods: We conducted exploratory analyses using data from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) study to identify independent determinants of outcome-free status in 12 537 middle-aged and older adults with prediabetes and early type 2 diabetes from 40 countries. Serious outcome-free status was defined as the absence of major cardiovascular outcomes, kidney or retinal outcomes, peripheral artery disease, dementia, cancer, any hospitalization, or death during follow-up.

Results: In total, 3328 (26.6%) participants remained free of serious outcomes during a median follow-up of 6.2 years (IQR 5.8, 6.7). Independent clinical determinants of outcome-free status included younger age, female sex, non-White ethnicity, shorter diabetes duration, absence of previous cardiovascular disease, current or former smokers, higher grip strength, Mini-Mental State Examination score, and ankle-brachial index, lower body mass index and kidney disease index, and non-use of renin-angiotensin system drugs and beta-blockers. In a subset of 8401 people with baseline measurements of 238 biomarkers, growth differentiation factor 15, kidney injury molecule-1, N-terminal pro-brain natriuretic peptide, uromodulin, C-reactive protein, factor VII and ferritin were independent determinants. The combination of clinical determinants and biomarkers best identified participants who remained outcome-free (C-statistics 0.71, 95% confidence interval 0.70-0.73; net reclassification improvement 0.55, 95% confidence interval 0.48-0.58).

Conclusions: A set of routinely measured clinical characteristics and seven protein biomarkers identify middle-aged and older people with prediabetes or early type 2 diabetes as least likely to experience serious outcomes during follow-up.

Keywords: cancer; cardiovascular disease; dysglycaemia; kidney disease; retinopathy; type 2 diabetes.