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

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2024-08, Vol.26 (8), p.3272-3280
• Main Authors: Mohammedi, Kamel, Hess, Sibylle, McQueen, Matthew, Pigeyre, Marie, Lee, Shun Fu, Pare, Guillaume, Gerstein, Hertzel C.
• Format: Article
• Language: English
• Subjects: Aged; Angiotensin; Ankle; Ankle Brachial Index; Biomarkers; Biomarkers - blood; Body mass index; Brain injury; Brain natriuretic peptide; C-Reactive Protein - analysis; C-Reactive Protein - metabolism; cancer; cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Coagulation factors; Dementia disorders; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; dysglycaemia; Early experience; Female; Ferritin; Follow-Up Studies; Human health and pathology; Humans; Hypoglycemic Agents - therapeutic use; kidney disease; Kidney diseases; Life Sciences; Male; Middle Aged; Natriuretic Peptide, Brain; Older people; Peptide Fragments - blood; Prediabetic State - blood; Prediabetic State - diagnosis; Prediabetic State - epidemiology; Renin; retinopathy; Statistical analysis; type 2 diabetes; Vascular diseases
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.15654

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.