LEP and hyperinsulinemic hypoglycemia, familial, 4: Perry et al. 49 demonstrated that peripheral leptin diminishes hypothalamic-pituitary-adrenal (HPA) axis activity to reduce gluconeogenesis and glycemia, but this mechanism is specific to conditions of severe insulin deficiency because an increase in the magnitude of residual levels in insulin-deficient diabetes diminishes the ability of leptin to lower circulating glucose50,51.