Lipid metabolism in normal pregnancy - a magnetic resonance spectroscopy pilot study

Background

Gestational diabetes mellitus (GDM) affects 5% of pregnancies and is associated with poor obstetric outcome. The mechanism of insulin resistance in pregnancy is unclear but may be due to increased fat deposition in liver and muscle, as seen in type 2 diabetes. Magnetic resonance spectroscopy (MRS) quantifies tissue metabolites without the need for biopsy.

Hypothesis

Insulin resistance in normal pregnancy is associated with higher concentrations of intramyocellular lipid (IMCL).

Methods

11 nulliparous women (27–34 years) with normal body mass index and no history or family history of diabetes were studied at 34 weeks gestation. To date, six women have been studied at 12 weeks postpartum. At each visit, women were fasted and underwent MRS of the soleus muscle to quantify IMCL followed by a standardized meal test to determine insulin sensitivity.

Results

IMCL was 20% higher in pregnancy compared to the postpartum period (18.6±8.4 vs 15.5±6.9 mmol/g). Consistent with this, insulin resistance fell by 44% (homeostasis model assessment: 1.2±0.5 at 34 weeks to 0.7±0.3 following delivery). Simultaneously, insulin secretion fell 2.3 fold to maintain glucose homeostasis (area under curve: 9220±1747 vs 3919±1365, p=0.005).

Conclusion

These findings demonstrate that during normal pregnancy the pancreas up regulates insulin secretion to overcome insulin resistance related to increased fatty acid availability in skeletal muscle. Women with GDM may be expected to demonstrate more profound insulin resistance and exaggerated organ lipid deposition. This pilot study confirms that MRS is both acceptable and feasible during pregnancy and has the potential to identify the true pathophysiology of GDM.