Introduction and Objective: Insulin resistance (IR) significantly contributes to cardiovascular mortality in type 2 diabetes (T2D). Whether organ-specific IR (skeletal muscle, adipose tissue, liver) independently associates with structural and functional cardiac morbidity and mortality is unclear.Methods: This study included 850 Europeans with and 2243 without T2D of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) cohort undergoing echocardio- and coronary angiography for suspected acute coronary syndrome. IR was assessed at whole-body level (HOMA2-IR), adipose tissue (Adipo-IR by fasting non-esterified fatty acids and C-peptide) and liver (HIR: 0.45+0.23*log(insulin)+0.24*(AUC0-120 (insulin))-0.24*log(adiponectin)). All results were adjusted for age, sex, BMI, HbA1c and T2D status. Mortality was assessed by telephone interviews and population registers over 15 [IQR: 9, 18] yrs and Cox models also adjusted for coronary artery disease (CAD) and heart failure (HF).Results: Participants (63 [56, 70] yrs, 30% female) were mostly overweight and well-controlled (BMI 27 [25, 30] kg/m², HbA1c 6.0 [5.6, 6.4]%). HOMA2-IR, Adipo-IR and HIR were 6%, 6% and 1% higher in people with than without CAD (all p<0.001). Compared to people without HF, those with HF and preserved ejection fraction (HFpEF) and with reduced EF (HFrEF) had 8% and 11% higher HOMA2-IR (p<0.001), 17% and 16% higher Adipo-IR (p<0.001), and both 1% higher HIR (p<0.05). Adipo-IR was 4% higher in HFpEF than HFrEF (p<0.05). Higher HOMA2-IR increased mortality independent of HF by 9% (p<0.01), but not independent of CAD or HbA1c. Higher Adipo-IR increased mortality by 18% and 13% independently of CAD or HF (p<0.001). Higher HIR did not increase mortality. CAD or HF status did not interact with IR indices on mortality.Conclusion: The Adipo-IR independently predicts mortality in people at risk for cardiac diseases, emphasizing the relevance of integrating this index into clinical practice for precision medicine.
K. Bódis: None. S. Goh: None. C. Binsch: None. K. Prystupa: None. O.P. Zaharia: None. M. Schön: None. P. Wischmann: None. H. Busch: None. M. Heni: Advisory Panel; Amryt Pharma. Speaker’s Bureau; Amryt Pharma, AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker’s Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi. M. Kelm: None. A. Niessner: None. M. Roden: Research Support; Boehringer-Ingelheim. Advisory Panel; Echosens. Speaker’s Bureau; Madrigal Pharmaceuticals, Inc. Advisory Panel; MSD Life Science Foundation. Board Member; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. W. März: None. R. Wagner: Speaker’s Bureau; Boehringer-Ingelheim, Novo Nordisk. Advisory Panel; Sanofi. Speaker’s Bureau; Sanofi. Advisory Panel; Lilly Diabetes.
Source link
Leave a Reply