TABLE 2.
Leptin deficiency and leptin resistance states1
| Disease state | Estimated prevalence | Associated features |
| Leptin deficiency | ||
| Hypothalamic amenorrhea | 3–8.5% in women aged 13–44 y | Strenuous exercise, stress, energy deficit, neuroendocrine dysfunction |
| Lipoatrophy (congenital) | Rare | Insulin resistance, impaired glucose tolerance, dyslipidemia |
| Anorexia nervosa | 1–3% of college-age subjects | Disturbed body image, severe restriction of food intake, loss of body weight, neuroendocrine disturbances |
| HIV-lipodystrophy | ≤50% of antiretroviral-treated patients | Insulin resistance, impaired glucose tolerance or type 2 diabetes, dyslipidemia, increased risk of cardiovascular disease |
| Obesity as a manifestation of leptin deficiency | ||
| Complete congenital leptin deficiency | Rare | Hypogonadotrophic hypogonadism, hyperphagia, advanced bone age, hyperinsulinemia, immune dysfunction in the context of early onset morbid obesity |
| Heterozygous leptin deficiency | ≤5–6% of the obese | Garden-variety obesity with low leptin concentrations relative to fat mass |
| Obesity as a manifestation of leptin resistance (involving leptin and molecular pathways downstream of the leptin receptor) | ||
| Leptin receptor gene mutations | Rare | Hypogonadotrophic hypogonadism, abnormal growth hormone, and TSH secretion |
| POMC mutations | Rare | ACTH deficiency, red hair, pale skin |
| Prohormone convertase deficiency | Rare | Hypogonadotrophic hypogonadism, hypocortisolemia, postprandial hypoglycemia |
| MC4R mutations | 5–8% of childhood obesity | Increased fat and lean body mass, increased linear growth and bone density |
| Mutations of other molecules downstream of leptin receptor | Rare | Obesity with onset in childhood |
| Mechanism to be discovered | >90% of obese subjects | Garden-variety obesity |