Lipoatrophic diabetes is a syndrome characterized by insulin resistance in association with a paucity of adipose tissue. Patients with severe lipoatrophy die prematurely, typically from the complications of diabetes or liver disease. Experiments with lipoatrophic mice suggest that the insulin resistance is caused by the lack of adipose tissue. Adipose tissue normally produces leptin, a hormone that increases insulin action. To what extent does leptin deficiency cause diabetes in lipoatrophic patients? In one mouse model of lipoatrophy, leptin administration reversed the diabetes and liver disease. In a different, more severely adipose-deficient mouse, the effects of leptin treatment were detectable, but more modest.