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

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. 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. 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. 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 (P = 0.197). Similar results were also observed in insulin SD. 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.