Discussion
We found that the total concentrations of plasma FAs, as well as total MUFA and MUFA ratio measured at 11th–14th week of pregnancy, were significantly higher and PUFA n-6 ratios lower in women who were later diagnosed with GDM, independent of the women’s BMI. The fact that stratifying by BMI did not alter our results is important to note because obesity, IR and FA profiles in GDM are strongly inter-related.12
In most previous studies on FA profiles in pregnancy cohorts, FA analysis was performed during or after GDM diagnoses.12 These studies found that SFA concentrations appeared to be higher in women diagnosed with GDM when compared with a control group and that PUFA n-6 and PUFA n-3 concentrations were both lower in women with GDM.12 A recent meta-analysis similarly reported that women with GDM had higher total concentrations of FFAs in the second and third trimester compared with women without GDM, with concentrations decreasing as pregnancy progressed.35
The results of the few studies that have investigated FA concentrations in early pregnancy, prior to GDM diagnosis, agree with the present study’s findings, showing higher total concentrations of SFA13–15 and MUFA13 15 as well as PUFA n-616 and PUFA n-313 in women who were later diagnosed with GDM compared with those who were not. On the other hand, some of these studies reported lower PUFA n-613 15 and PUFA n-315–17 concentrations in women who later received a GDM diagnosis.
FA profiles have been proposed as a means of predicting later T2D diagnosis in non-pregnant populations, where higher relative concentrations of FFA,36 PUFA n-6,37 MUFA36 37 and SFA36 37 have been associated with an increased risk of impaired glucose tolerance and T2D risk. These studies have reported similar results as observed for circulating FA in the pregnant population in our study. Associations between higher PUFA n-6 relative to total FA and increased insulin sensitivity have also been found in previous studies in non-pregnant populations,36 which is in accordance with the results seen in the present pregnancy cohort.
The FA profiles may be a result of differences in intake or absorption of both carbohydrates and fat.12 Plasma MUFA and SFA concentrations do not only represent dietary intake as FAs can be synthesized endogenously, mainly from carbohydrates, which is then referred to as de novo lipogenesis.38 39 Other factors that could influence FA profile are FA synthesis and incorporation of FA into cell membranes. It remains unclear how the plasma total FA profile is physiologically associated with diabetes. Lipogenesis is stimulated by insulin and suppressed by the hormones glucagon and epinephrine. Some studies have suggested that higher FFA may alter insulin signalling, secretion and glucose production.40 41 It is, therefore, possible that an abnormal increase of insulin in the blood may lead to higher FA concentrations and vice versa.
Some differences were found in food consumption in the first trimester between women with and without GDM diagnoses, and it is not clear how this difference might be reflected in the plasma FA profile. It could have been expected to see a difference in EPA and DHA concentrations between the two groups because women who later were diagnosed with GDM had a less frequent intake of both fatty fish and omega-3 supplements. However, because FA can be synthesized endogenously from excess carbohydrates, the overall quality of the diet, including carbohydrate quality and amount consumed, might explain some of the difference observed in FA concentration between the two groups, overall carbohydrate quality being one.19 21 42
As we have previously reported in this cohort, the women who were later diagnosed with GDM had lower quality of carbohydrate intake as they had a lower intake of wholegrains (estimated by biomarkers).19 Intake of soft drinks also tended to be greater for women diagnosed with GDM as well as use of saturated fat for cooking, even though the difference was not statistically significant. This could suggest that the overall diet quality in early pregnancy was lower among the women later diagnosed with GDM.
In summary, a stronger association has been observed between plasma FA and diabetes risk compared with dietary intake estimates.37 It is important to note that different sources of FA measurements can represent varying dietary intake periods, such as adipose tissue (long-term FA intake 1–1.5 years), skeletal muscle cells, erythrocytes (120 days), serum, total plasma, phospholipids (1–2 weeks12), cholesteryl esters and FFAs.37 Erythrocytes have been claimed as a preferable option to evaluate differences in recent FA intake, at least regarding PUFA n-3.39 However, FA from erythrocytes and plasma have been found to correlate.37 In our study, we analyzed total plasma FA, which includes the FAs from cholesteryl esters, phospholipids, triacyclglycerols and FFA thought to represent very recent intake (1–2 weeks), whereas the answers in the FFQ covered intake during the previous 3 months.
It might be considered a limitation that our participants were not fasting. This might have resulted in lower concentrations of FFA because they are reduced in response to higher insulin levels postmeals43 and makes a comparison with other studies challenging. However, comparisons of our results with other studies may be affected by the non-fasting state of our participants and by the difference in methodology used when analysing FA profiles. Another limitation is that we did not have exact information on date of diagnoses, thereby part of our GDM cases may have received their diagnosis at or close to drawing of the blood sample in which FA profiles were quantified. However, we did see a similar trend in the results (online supplemental 4) when we ran our analysis excluding all women with known risk factors that prompt early GDM screening (BMI, age and previous GDM/macrosomia). We therefore believe that this limitation did not majorly affect our main results.
The strength of our study is that we analyzed plasma FA early in pregnancy, in addition to acquiring subjective data on dietary intake. Our study also features prospectively collected data from a large sample size of 853 pregnant women with high participation rate (75%). We report both total concentrations of all FA subgroups as well as their ratios. We adjusted for BMI, and stratified our FA results by BMI, a process that, to our knowledge, has not been previously performed in a pregnancy cohort.
In conclusion, we found that women who were later diagnosed with GDM had a higher concentration of total plasma FA, total MUFA and MUFA ratios as well as lower PUFA n-6 ratios in early pregnancy, independent of the women’s BMI, compared with women who remained free of GDM. The women who were not diagnosed with GDM also tended to have better diet quality in early pregnancy. These results suggest that FA biomarkers in early pregnancy may predict GDM. However, further studies are required to confirm this hypothesis.