Effect of lactation on ectopic lipid after gestational diabetes

Ut Southwestern Medical Center, Dallas TX

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Abstract

DESCRIPTION (provided by applicant): The incidence of gestational diabetes mellitus (GDM) is growing and strategies to prevent the future development of type 2 diabetes in women with previous GDM (postGDM) are needed. Lactation may be one such strategy - although, the metabolic inter-relationships between the hormonal milieu of lactation (high prolactin, low insulin), insulin resistance and its associated ectopic lipid deposition are unknown. Lactation has the potential to improve insulin resistance in postGDM by relieving excess lipid, stored in skeletal muscle and liver, through the provision of lipid to milk production. Accordingly, we hypothesize that compared to non- lactating (non-Lac) postGDM women, lactating (Lac) women will have lower ectopic lipid stores, be more insulin sensitive, and have higher adiponectin concentrations. A clinical study will be completed in 20 post- GDM women, (10 Lac and 10 non-Lac), and 12 women with nondiabetic pregnancies (6 Lac and 6 non-Lac) matched for age, ethnicity, and BMI to the post-GDM women. Data from pre-pregnancy weight and gestational weight gain will be collected. Between 5-7 wks postpartum, dietary intake will be measured by food records and 24-h recall, physical activity by accelerometer, and insulin sensitivity by two-stage clamp. These methods will be combined to accomplish the following specific aims: Aim 1: Quantitate intra-myocellular lipid and intra- hepatic TG using 7-T and 3-T MRS to test the hypothesis that ectopic lipid will be highest in non-Lac postGDM > Lac post-GDM > non-Lac healthy > Lac healthy women. Aim 2: Measure postpartum hormones (prolactin, adipokines, insulin, sex steroids, gonadotropins) to determine whether high prolactin (Lac) is significantly related to (a) higher adiponectin concentrations and (b) higher insulin sensitivity compared with normal prolactin (non-Lac) in post-GDM and healthy women. This is the first study in post-GDM and healthy postpartum women to measure prolactin and adiponectin levels, while simultaneously assessing ectopic lipids, combined with insulin sensitivity. The overall concept is that adiponectin, in the setting of postpartum-specific hormone levels, could be beneficial in the setting of GDM lactation and this concept provides a novel way to view the integration of physiology to return a postpartum mother back to insulin sensitivity. Discovering how hormonal control in lactation impacts peripheral glucose metabolism will lead to improved strategies to reduce the incidence of type 2 diabetes in post-GDM women.