Diet, nutrient status and gestational diabetes

Gestational diabetes mellitus (GDM) is one of the most common metabolic complications during pregnancy and prevalence has continued to increase worldwide. As BMI is one of the most important risk factors for development of GDM, prevention of GDM has focused on modifiable factors including diet. A range of dietary factors has been investigated, but results per dietary factor are limited and inconclusive (chapter 1). This thesis aims to provide more insight into dietary intake and nutrient status before and during pregnancy and into the association of dietary intake and nutrient status with risk of GDM. In addition, two methodological topics are addressed: the development of an index reflecting adherence to the Dutch dietary guidelines of 2015 and the effect of combining food frequency questionnaire (FFQ) and 24-hour recall (24hR) data on bias in diet-disease associations. In chapter 2, the development and evaluation of the Dutch Healthy Diet 2015 (DHD15) index score is described. The DHD15 index score assesses adherence to the Dutch dietary guidelines of 2015 and consists of 15 components representing the 15 food-based dietary guidelines. Per component the score ranges between zero and ten, resulting in a total score between zero (no adherence) and 150 (complete adherence). We evaluated the DHD15 index based on data from two 24hR and one FFQ from 885 men and women, aged 20-70 years, participating in the longitudinal NQplus study. A higher DHD15 index score was inversely associated with BMI, smoking, and intakes of energy, total fat, and saturated fat and positively associated with energy-adjusted micronutrient intakes. We concluded that the DHD15 index is a good marker of diet quality. Measurement error in dietary intakes leads to biased diet-disease associations. If dietary intake is assessed with a second method, regression calibration (RC) or enhanced regression calibration (ERC) can be used to combine dietary intakes. This could result in less biased associations. In chapter 3, we investigated the effect of combining dietary intakes obtained with two methods (24hR and FFQ) on diet-disease associations using data from 236 participants of the NQplus study. We observed that combining FFQ and 24hR data with RC and ERC for protein and potassium resulted in empirical attenuation factors approaching 1, indicating less biased diet-disease associations. In chapter 4, the prevalence of common delivery-related adverse pregnancy outcomes was compared between women with normal glucose tolerance during pregnancy (NGT), women with treated GDM and women with untreated borderline GDM (BGDM). BGDM was defined as women with an abnormal 50-grams glucose challenge test and a normal 75-grams oral glucose tolerance test. Medical file data were used from 1049 women who had undergone GDM screening and had given birth in hospital Gelderse Vallei Ede in the period 2010-2014. Women with treated GDM had a higher risk of laceration and women with untreated BGDM had a higher risk of laceration and (unscheduled) Caesarean section as compared to women with NGT. Furthermore, we observed that associations between glucose tolerance and adverse pregnancy outcomes were not mediated by macrosomia (birth weight >4000 gram). In chapter 5, the associations between pre-pregnancy dietary carbohydrate quantity and quality with risk of GDM were investigated in women of reproductive age in an Australian cohort. A total of 3,607 women aged 25-30 years were followed-up for self-reported GDM development from 2003 till 2015. Pre-pregnancy dietary intake was assessed with a FFQ in 2003 and 2009. Carbohydrate quantity was assessed based on total carbohydrate intake and the low-carbohydrate diet (LCD) score. Carbohydrate quality was assessed by studying fibre intake, total sugar intake, glycaemic index, glycaemic load and intake of carbohydrate-rich food groups. A relatively low carbohydrate and high fat and protein intake as expressed by the LCD score and a higher cereal intake were significantly associated with higher risk of GDM, whereas higher fibre, fruit and fruit juice intakes were associated with lower risk of GDM. Chapter 6 describes the prevalence of inadequate micronutrient intakes and the association of pre-pregnancy micronutrient adequacy with risk of GDM in the same Australian cohort of women of reproductive age. We used a summary measure of adequate micronutrient intake across 13 micronutrients, i.e. the mean adequacy ratio (MAR). Prevalence of inadequate dietary micronutrient intake was more than 50% for the micronutrients calcium, potassium, magnesium, vitamin E and folate, indicating suboptimal pre-pregnancy micronutrient intakes. A higher overall micronutrient adequacy (i.e. MAR) was associated with a lower risk of developing GDM. In chapter 7, changes in folate, vitamin B6, vitamin B12, vitamin D and iron intake, their status markers and diet quality from preconception to the second trimester of pregnancy are described. In addition, associations of these micronutrient intakes, their status markers and diet quality with glucose tolerance during pregnancy were examined. Data from 91 Dutch women at increased risk of GDM, aged 18-40 years, and with either a wish to get pregnant or less than 24 weeks pregnant was collected longitudinally. Data was collected at preconception (n=67), 12 weeks of pregnancy (n=47) and 24 weeks of pregnancy (n=55). At each time point women underwent a fasting venipuncture and a 75-grams oral glucose tolerance test. Dietary intake was assessed at each time point with a validated FFQ and two non-consecutive 24hR. We observed significant changes in total micronutrient intakes throughout pregnancy, due to changes in supplemental intakes, whereas dietary micronutrient intakes and diet quality remained stable. Nutrient status levels changed significantly from preconception to the second trimester of pregnancy. For folate, vitamin B6 and vitamin D this could be partly explained by changes in intake. In general, no associations between fasting and 2-hour glucose levels and HbA1c levels with diet quality, micronutrient intake or status levels were observed; except for a weak inverse association of folate intake with 2-hour glucose levels, and a weak positive association between ferritin and 2-hour glucose levels. Diet quality was inversely associated with fasting glucose in a sensitivity analysis, excluding data from participants with only one measurement. Using data from the same study collected at preconception from the same study (n=66), main dietary sources of folate, vitamin D, and the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were determined in chapter 8. Additionally, associations of these intakes with their blood levels were examined. A large proportion of women did not meet the Dutch recommended intakes of folate (50%), vitamin D (67%), and EPA+DHA (52%). Vegetables were the main contributor of dietary folate intake (25%), oils and fats of dietary vitamin D intake (39%), and fish of dietary EPA and DHA intake (69%). Fourteen percent had an inadequate folate status and 23% an inadequate vitamin D status. Supplemental folate intake, supplemental and dietary vitamin D intake and dietary EPA+DHA intake were significantly associated with their blood levels. In chapter 9, the main findings of this thesis were summarized and a reflection on methodological aspects was given. Considering results described in this thesis and associations reported by other studies, it is probable that a healthy diet can reduce risk of developing GDM. Most convincing evidence was observed for diet in the pre-pregnancy period. More research is needed to understand which foods and nutrients drive diet-GDM associations, and to unravel underlying mechanisms. Diet in the pre-pregnancy period was considered suboptimal and intakes of several vital micronutrients, including folate, were below recommended intakes for a large proportion of women in two different studies. Although the Health Council of the Netherlands already called upon the provision of proper and adequate preconception care a decade ago, more action is needed to improve intake and status of essential micronutrients in the preconception period.