Risk of cardiovascular events associated with pathophysiological phenotypes of type 2 diabetes. Issue 2 (27th June 2022)

• Record Type: Journal Article
• Authors: Stidsen, Jacob Volmer; Christensen, Diana Hedevang; Henriksen, Jan Erik; Højlund, Kurt; Olsen, Michael Hecht; Thomsen, Reimar Wernick; Christensen, Lotte Brix; Nielsen, Jens Steen; Olesen, Thomas Bastholm; Beck-Nielsen, Henning
• Is Part Of: European journal of endocrinology. Volume 187:Issue 2(2022)
• Page Start: 279
• Page End: 291
• Publication Date: 2022-06-27
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/EJE-22-0020
• Languages: English
• ISSNs: 0804-4643

Abstract

Abstract: Objective: Hyperglycaemia in type 2 diabetes is caused by varying degrees of two defects: low insulin sensitivity and beta-cell dysfunction. We assessed if subgrouping of patients into three pathophysiological phenotypes according to these defects could identify individuals with high or low risk of future cardiovascular events. Design: This is a prospective cohort study. Methods: We assessed estimates of insulin sensitivity and beta-cell function from the homeostasis model assessment-2 in 4209 individuals with recently diagnosed type 2 diabetes enrolled from general practitioners and outpatient clinics in Denmark. Individuals were followed for a composite cardiovascular endpoint (either atherosclerotic outcomes (myocardial infarction, unstable angina pectoris, stroke, coronary or peripheral revascularization), heart failure, or cardiovascular death) and all-cause mortality. Results: Totally 417 individuals with the insulinopenic phenotype (high insulin sensitivity and low beta-cell function) had substantially lower risk of cardiovascular events (5-year cumulative incidence: 4.6% vs 10.1%; age-/sex-adjusted hazard ratio (aHR): 0.49; 95% CI: 0.30–0.82) compared with 2685 individuals with the classical phenotype (low insulin sensitivity and low beta-cell function), driven by atherosclerotic events. Conversely, 1107 individuals with the hyperinsulinaemic phenotype (low insulin sensitivity and high beta-cell function) had more cardiovascular events (5-year cumulative incidence: 12.6%; aHR: 1.33; 95% CI: 1.05–1.69), primarily driven by increased heart failure and cardiovascular death and increased all-cause mortality. Conclusions: Simple phenotyping based on insulin sensitivity and beta-cell function predicts distinct future risks of cardiovascular events and death in patients with type 2 diabetes. These results suggest that precision medicine according to underlying type 2 pathophysiology potentially can reduce diabetes complications.