Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study

Insulin resistance and sympathetic activity are related by a positive feedback system. However, which precedes the other still remains unclear. The present study aimed to investigate the predictive role of sympathoadrenal activity in the development of insulin resistance in an 18-year follow-up study. We also examined whether reactivity to 2 different stress tests, a cold pressor test and a mental stress test, would differ in their predictive power. The 2 tests are supposed to represent different reactivity mechanisms: alpha- and beta-adrenergic responses, respectively. At entry, arterial plasma epinephrine and norepinephrine concentrations were measured in 99 healthy men (age, 19.3 +/- 0.4 years, mean +/- SD) during rest, a mental stress test, and a cold pressor test. Fasting plasma glucose concentration was measured at entry and at follow-up. Insulin resistance at follow-up was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Eighty subjects (81%) were eligible for follow-up after 18.0 +/- 0.9 years (mean +/- SD). The norepinephrine responses to cold pressor test at entry predicted plasma glucose concentration (r = 0.301, P = .010) and HOMA-IR (r = 0.383, P = .004) at follow-up in univariate analyses. In multiple regression analyses, corrected for fasting glucose at entry, family history of diabetes, blood pressure-lowering medication, body mass index at entry, and level of exercise, norepinephrine response to cold pressor test was found to be a positive predictor of future HOMA-IR (P = .010). This is the first long-term follow-up study in white subjects showing that sympathetic reactivity predicts future insulin resistance 18 years later. These findings may provide further insights into the pathophysiologic mechanisms of insulin resistance.