Since the ATM axis is associated with altered hepatic insulin sensitivity and atherosclerosis in mice, we translated these rodent data to humans with metabolic syndrome in two exploratory clinical trials: (1) A dose escalation study with a primary endpoint of insulin sensitivity and pre-specified secondary endpoints including serum lipids and blood pressure; and (2) Placebo or chloroquine treatment for 1 year with a primary endpoint of carotid intima-media thickness, a noninvasive predictor of cardiovascular events [10]. Here, INS is linked to metabolic syndrome.