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More recently, it was determined that adipocytokines also play an important role in regulating insulin sensitivity in both the nonpregnant and pregnant states. These proinflammatory cell-signaling proteins are normally produced by maternal adipose tissue, but during pregnancy, the placenta also contributes large amounts of some adipokines.

Leptin is secreted by adipocytes and was initially noted to suppress hunger at the hypothalamic level. Circulating leptin levels in the nonpregnant state are directly proportional to fat cell mass, so that appetite suppression is favored when increased energy storage in fat occurs; obese individuals appear to be resistant to this appetite-suppressing effect of leptin. It has many other functions, some of which significantly impact maternal metabolism [27]. Leptin can inhibit insulin secretion and release, while insulin can increase leptin production. Leptin can increase peripheral insulin sensitivity but may enhance hepatic insulin resistance. Leptin also has effects on the hypothalamic-pituitary axis, the adrenal and thyroid axes, and the growth hormone axis. During pregnancy, maternal circulating leptin levels increase markedly and are significantly higher in the first and second trimester in women who develop gestational diabetes compared to controls [28–30]. The placenta is a major source of leptin, as evidenced by the rapid fall in circulating leptin levels after delivery [31] as well as the lack of correlation between leptin levels and maternal fat accretion. Serum leptin levels at term are approximately 50% higher than prior to pregnancy [32]. Serum leptin levels were significantly correlated with insulin resistance (insulin sensitivity index) at 24–28 weeks in 80 normal gravidas whose body mass indexs (BMIs) were on average overweight [23]. It appears that pregnancy induces a state of leptin resistance, since in the latter half of pregnancy leptin levels rise despite increased energy intake. It is likely that increases in serum leptin levels, primarily of placental origin, contribute to the insulin resistance of pregnancy. hPL induces CNS leptin resistance, and this effect may constitute one of the mechanisms responsible for the association between hPL and insulin resistance in pregnancy [33].