TY - JOUR
T1 - Risk of cardiovascular events associated with pathophysiological phenotypes of type 2 diabetes
AU - Stidsen, Jacob Volmer
AU - Christensen, Diana Hedevang
AU - Henriksen, Jan Erik
AU - Højlund, Kurt
AU - Olsen, Michael Hecht
AU - Thomsen, Reimar Wernick
AU - Christensen, Lotte Brix
AU - Nielsen, Jens Steen
AU - Olesen, Thomas Bastholm
AU - Beck-Nielsen, Henning
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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.
AB - 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.
KW - Cardiovascular Diseases/complications
KW - Diabetes Mellitus, Type 2/complications
KW - Heart Failure
KW - Humans
KW - Insulin Resistance
KW - Myocardial Infarction
KW - Phenotype
KW - Prospective Studies
KW - Risk Factors
U2 - 10.1530/EJE-22-0020
DO - 10.1530/EJE-22-0020
M3 - Article
C2 - 35670619
SN - 0804-4643
VL - 187
SP - 279
EP - 291
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
IS - 2
ER -