Maternal Serum Prolactin and Prediction of Postpartum β-Cell Function and Risk of Prediabetes/Diabetes

Abstract

OBJECTIVEThe insulin resistance of mid-to late pregnancy poses a physiologic stress test for the pancreatic b-cells, which must respond by markedly increasing their secretion of insulin. This response is achieved through an expansion of b-cell mass induced by the hormones prolactin and human placental lactogen (HPL). Conversely, the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a negative regulator of b-cell function in pregnancy. Given their respective roles in the b-cell response to the stress test of gestation, we hypothesized that antepartum prolactin, HPL, and CMPF may relate to a woman's underlying glucoregulatory physiology and hence to her metabolic status after pregnancy. RESEARCH DESIGN AND METHODSThree hundred and sixty-seven women underwent measurement of fasting serum prolactin, HPL, and CMPF in the late-2nd/early-3rd trimester, followed by an oral glucose tolerance test (OGTT) at 3 months postpartum that enabled assessment of glucose tolerance, insulin sensitivity/resistance, and b-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]). RESULTSThe postpartum OGTT identified 301 women with normal glucose tolerance (NGT) and 66 with prediabetes or diabetes. Serum prolactin in pregnancy was higher in women with postpartum NGT compared with those with postpartum prediabetes/ diabetes (mean 98.2 vs. 80.2 ng/mL, P = 0.0003), whereas HPL and CMPF did not differ between the groups. On multiple linear regression analyses, antepartum prolactin was an independent determinant of postpartum ISSI-2 (b = 0.0016, t = 2.96, P = 0.003). Furthermore, higher serum prolactin in pregnancy independently predicted a lower risk of postpartum prediabetes/diabetes (odds ratio 0.50, 95% CI 0.35-0.72, P = 0.0002). CONCLUSIONSSerum prolactin in pregnancy predicts postpartum b-cell function and risk of prediabetes/diabetes.

Circulating prolactin concentrations and risk of type 2 diabetes in US women

“…Our findings were consistent with prior prospective data in pregnant and postmenopausal women with short periods of follow-up [19, 20], and were in line with crosssectional observations that higher, but physiologically normal prolactin concentrations were associated with lower type 2 diabetes prevalence [17, 18]. Furthermore, our study demonstrated that the inverse association between prolactin and type 2 diabetes risk in women remained significant after adjustment for a variety of lifestyle and reproductive factors as well as other sex and growth hormones, suggesting that prolactin may be linked to type 2 diabetes through independent pathways.…”

“…These findings suggest a potential role of prolactin in glucose homeostasis. However, long-term prospective data evaluating the relationship between prolactin and future type 2 diabetes risk remain limited, and existing evidence has been inconsistent [18–20]. Some studies reported an inverse association between prolactin and type 2 diabetes risk, particularly among women, while a few others reported null or positive associations in men and women combined [18– 21].…”

Circulating 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) levels are associated with hyperglycemia and β cell dysfunction in a Chinese population

“…A recent report by Retnakaran et al . 14 suggested that the serum CMPF levels in pregnant women do not predict postpartum insulin sensitivity, insulin resistance, or β cell function three months after delivery. In addition, Lankinen et al .…”

Histological and Metabolic State of Dams Suckling Small Litter or MSG-Treated Pups

“…As such, the histological analysis in our study confirms that SL Dams and MSG Dams present reduced MG development and, probably, milk synthesis. In this regard, studies have demonstrated that the metabolic activity of the MG is a major factor in plasma insulin regulation during the suckling period via a mechanism involving prolactin, the primary hormone in the milk synthesis, and with a known effect on insulin secretion and synthesis [31, 32]. Moreover, the sealing of all teats in dams or litter removal during lactation produces increased plasma insulin levels in lactating dams [33, 34].…”