**6. Weight gain and lipodystrophy**

GCs have reciprocal effects on adipose tissue metabolism, promoting both lipolysis and lipogenesis/adipogenesis, inducing irregularity of adipose tissue distribution (i.e. lipodystrophy). These effects are shown in **Figure 2** (adapted from [69]). About 60–70% of patients treated with GCs for a long-term period report weight gain. This is different from classical weight gain. A central hypertrophy of adipose tissue develops. Characteristic findings are facial adipose tissue (moon face), truncal obesity and dorsocervical adipose tissue (buffalo hump). In contrast, peripheral and subcutaneous adipose tissues get thinner. This specific changes are called Cushingoid features and related with lipodystrophy induced by GCs. Weight gain is the most common self-reported side effect. About two-thirds of patients exhibit Cushingoid features within the

**Figure 2.** Mechanisms of glucocorticoid-induced weight gain and lipodystrophy.

first 2 months of therapy with GCs. These side effects are dependent on both the dose and duration of GCs. The risk of weight gain increases from the use of 5 to 7.5 mg per day of prednisone (or an equivalent). The risk of these side effects are higher in younger patients, females, those with a higher baseline body mass index, those with a higher initial caloric intake (>30 kcal/kg/ day), and those with a baseline higher leptin and lower resistin levels. More importantly, these side effects are related with high blood pressure, blood glucose and triglyceride levels, and low high-density lipoprotein cholesterol levels (cardiovascular risk factors). Therefore, treatment with GCs increases the risk of coronary heart disease, cardiac insufficiency, and stroke [70–74].
