Which of the following is a risk factor for developing Cushing's syndrome?

Long-term use of prednisone is identified as a significant risk factor for developing Cushing's syndrome because this condition can result from prolonged exposure to glucocorticoids, which are compounds similar to cortisol, the hormone that is typically elevated in Cushing's syndrome. Prednisone is a synthetic glucocorticoid used to treat various inflammatory and autoimmune conditions. When taken over an extended period, it can lead to symptoms associated with Cushing's syndrome, such as weight gain, thinning of the skin, and elevated blood sugar levels.

The other options, while they may have their own health implications, are not direct causative factors for the hormonal imbalances characteristic of Cushing's syndrome. Obesity can be a symptom rather than a cause, high cholesterol is more associated with metabolic syndrome rather than Cushing's specifically, and family history of diabetes does not inherently influence the development of Cushing's syndrome directly. Thus, the long-term use of prednisone stands out clearly as a direct risk factor for this condition.