Clinical Trial Summary
Background Gestational diabetes mellitus (GDM) is defined as a defect of glucose tolerance
with its onset or its first recognition during pregnancy and that usually disappears, at
least temporarily, after delivery. Its prevalence generally ranges between 3 and 6%, but may
reach 12 to 15% in high-risk populations or specific ethnic groups. GDM increases the risk of
potentially severe maternal, fetal and neonatal complications (gestational hypertension,
pre-eclampsia, caesarean delivery; macrosomia; shoulder dystocia). These risks are linearly
correlated with the level of maternal hyperglycaemia. GDM is due to a failure of pancreatic
beta cells to sustain compensatory insulin secretion for insulin resistance that is
physiological in pregnancy but can be much more pronounced in some women, especially in case
of overweight or obesity. Maternal obesity is a major risk factor of GDM. Yet, micronutrient
deficiencies are frequently reported in obese patients. Some nutritional deficiencies,
concerning particularly some lipophilic micronutrients (vitamin A, vitamin D, vitamin E,
carotenoids) may be associated with diseases linked to insulin resistance. Numerous studies
show an inverse relationship between plasma concentrations and/or dietary intake of these
micronutrients and incidence of type 2 diabetes. Vitamin D deficiency could be involved in
the pathogenesis of type 2 diabetes through an alteration of insulin secretion and
sensitivity. Deficiencies in vitamin A, vitamin E or carotenoids (in particular lycopene and
beta carotene) increase oxidative stress and pro-inflammatory status, and could thus be
implied in the physiopathology of insulin resistance and glucose intolerance.
Some case-control studies find an inverse correlation between the plasma concentrations of
vitamin D during pregnancy and the incidence of GDM, independently of age, ethnic origin and
of body mass index. Data are scarce for vitamin A and vitamin E, and are lacking for
carotenoids. Besides, the few available studies are mainly descriptive ones, without clear
explanations on underlying mechanisms. The favourable effects of these micronutrients on
insulin sensitivity could be partially mediated by adipokines and/or pro-inflammatory
cytokines secreted at the level of the adipose tissue. Numerous studies showed that women
developing GDM during their pregnancy presented with a significant decrease in the
circulating rates of adiponectin, (that is an adipokine with anti-inflammatory and
insulin-sensitizing properties) and a significant increase in the secretion of the
pro-inflammatory cytokines implied in the physiopathology of insulin resistance. In our
laboratory (INRA unit 1260), we showed in experimental works conducted in vitro in human
adipocytes and in vivo in mice that vitamin E could induce the transcription and the
secretion of adiponectin; we also showed that vitamin D or lycopene could modulate the
inflammatory reaction in the adipose tissue, which is involved in the physiopathology of
insulin resistance.
Aims and methods We hypothesise that, in pregnant women, there is a link between plasma
concentrations and dietary intakes of lipophilic micronutrients (mainly vitamins A, D, E and
carotenoids), secretion of adipokines and pro-inflammatory cytokines, and risk of developing
a GDM; we also hypothesise that this relationship is independent of age, body mass index,
ethnic origin and other main risk factors of GDM. To test this hypothesis, we aim to lead a
transversal monocentric study, within a population of 500 pregnant women submitted to a
systematic screening of GDM by an oral glucose tolerance test (OGTT) in the Hôpital Nord of
Marseilles.
The main criterion of evaluation of the link between lipophilic micronutrients and GDM will
be a nutritional score calculated as follows: for each micronutrient (vitamin A, D, E,
lycopene, beta carotene, alpha carotene, lutein), we will attribute 0 point if the patient is
situated in the lowest quartile, 1 or 2 points in the following quartiles, and 3 points in
the highest quartile. At the end, each patient will thus have a score between 0 and 21
reflecting the global status of these micronutrients.
The main secondary objectives will be to define the relationships between the plasma
concentrations and dietary intakes of these micronutrients and 1/the value of glycemia and
insulinemia during OGTT 2/the degree of insulin sensitivity estimated by the measure of HOMA
index, 3/the circulating rates of some adipokines (mainly adiponectin, leptin, chemerin) and
pro-inflammatory cytokines (TNF alpha, IL-1, IL-6), and 4/the children's birth weight.
