Association of long-term insulin variability before the onset of diabetes with cardiovascular outcomes in later life: Findings from the coronary artery risk development in young adults (CARDIA) study.

Background: The important effects of variability of some physiological/biological characteristics (such as LDL cholesterol, blood pressure) on cardiovascular outcomes have been elucidated, while the role of insulin variability is undefined. Objectives: To investigate the associations of long-term fasting insulin variability during young adulthood before the onset of diabetes with subsequent cardiovascular outcomes in middle age. Methods: We included 3,983 CARDIA (Coronary Artery Risk Development Study in Young Adults) participants aged 18 to 30 years with at least three fasting insulin measurements. Intra-individual fasting insulin variability was defined by the average real variability (ARV) of insulin and standard deviation (SD) of insulin during 30-year follow-up. The presence and the degree of coronary artery calcification (CAC) were assessed by computed tomography at year 25. Incident cardiovascular disease (CVD) and all-cause mortality were adjudicated. Results: After multivariable adjustment, comparing high versus low tertile of insulin ARV, the hazard of CVD increased by 65 % (HR, 1.65; 95 % CI, 1.13-2.39) and all-cause mortality by 97 % (HR, 1.97; 95 % CI, 1.38-2.82). Higher tertile of insulin ARV was associated with significantly worse degree of CAC (β =0.1; 95 % CI, 0.03-0.18) but not with the presence of CAC ( Conclusion: High long-term insulin variability in young adulthood before the onset of diabetes was associated with an increased risk of CVD and all-cause mortality in later life, independent of average FG, HOMA-IR and other established cardiovascular risk factors. Long-term insulin variability was associated with the degree but not the presence of CAC.