Vitamin D is a fat-soluble vitamin, regulating calcium and phosphorus metabolism in vivo. The serum 25-hydroxyvitamin concentrations are the best index to measure the nutritional status of vitamin D in vivo[9]. Vitamin D, regulating bone metabolism and calcium management in bone health processes, is widely confirmed, however, its extraskeletal effects such as the immune system, regulation of cell proliferation and differentiation, and glucose metabolism got more attention either[5].
The research abroad has reported that the serum 25-hydroxyvitamin D concentration in gestational diabetes patients is lower than that of normal pregnant women, and there is an maternal elevated risk of GDM patients with vitamin D deficiency at the first trimester of pregnancy [11]. Interestingly the demand of vitamin D could be higher in pregnant women than in that without pregnant[12], which may aggravate the relative deficiency of vitamin D. In fact, 40–100% pregnant women in both the developing or developed countries, still suffer from vitamin D deficiency [11]. Some research showed vitamin D may be a potential candidate for the prevention of gestational diabetes mellitus (GDM), despite conflicting current opinions[11].
The pathogenesis of gestational diabetes,referring to the fact of vitamin D deficiency, has attracted increasingly attention. The researches show the relationship between low vitamin D status and the risk of GDM. A meta-analysis of 12 studies with 5,615 patients found a moderate correlation between 25(OH)D concentrations below 50 nmol/L of pregnant women and an increased risk of GDM (OR 1.38, 95% CI: 1.12–1.70)[13]. Moreover, Zhang found similar conclusions in a meta-analysis of 20 studies conducted in Europe, Australia, North America, and Asia with different study design including cross-sectional, case-control, nested case-control, and cohort studies including 9209 participants[1]. Vitamin D supplementation for patients with GDM seems to ameliorate different metabolic markers including blood glucose levels, insulin resistance, and inflammatory biomarkers[14] [7]. Supplementation with 50,000 International Units (IU) twice monthly has been shown to improve insulin resistance significantly, while 5000 IU daily has failed to improve blood glucose in another trial[15]. Low vitamin D status is recognized to be correlated with fasting blood glucose in prediabetes patients [16]. However, as far as we know༌the information on the effect and mechanism of vitamin D on fasting glucose is limited.
In our study, 60.61% of the subjects showed vitamin D deficiency, accounting for more than half of the subjects, indicating that vitamin D deficiency was prevalent in patients with gestational diabetes. In the multiple linear regression analysis, 25(OH)D concentration is negatively correlated to FBG ( β = -0.587, p = 0.001), adjusted to eGFR, gestational age, and age. In the multiple linear regression analysis, 25(OH)D concentration is negatively correlated to HbA1c ( β = -0.408, p = 0.018 ), adjusted to eGFR, gestational age, and age. As 25(OH) D concentration decreased, fasting blood glucose and HbA1c increased, and 25(OH) D concentration was negatively correlated with fasting blood glucose and HbA1c. Vitamin D is probably a protective factor of glucose metabolism in Chinese women with gestational diabetes.
Vitamin D binds to the corresponding receptor of human islet β cells to promote insulin secretion and plays an important role in inhibiting the progression of diabetes [4]. The vitamin D status may affect blood glucose and islet function in patients with obesity [17]. Vitamin D can bind to the corresponding receptors of islet β cells or act directly on β cells to promote insulin transcription and synthesis. Consider that vitamin D deficiency may affect insulin secretion and cause insulin resistance, leading to increased fasting blood glucose and HbA1c. Vitamin D receptors (VDRs), expressed in different extra-bones peripheral tissues, were found the action on insulin receptor that promotes insulin sensitivity and insulin secretion[18] .
In the multiple linear regression analysis) of our study, vitamin D status was a predictor of HOMA-IR (β = -0.481, p = 0.007), as the dependent variable, but not eGFR, gestational age or age, as independent variable. In the 33 subjects, eGFR, gestational age, and age, HOMA β is independent variables, 25(OH) D concentration as dependent variable, serum 25(OH)D concentration was objectively correlated to HOMA β ( β = 0.235, p = 0.206), however, the relationship is not significant.
There is growing evidence that inflammation plays an important role in the pathogenesis of gestational diabetes. Vitamin D may also play an important role in the inflammatory reaction, autoimmune injury, insulin secretion, and insulin resistance of islet β cells and then affect the body's glucose metabolism [19]. Inflammation in the form of immune cells infiltrating among glandular cells can result in functional pancreatic alterations [20]. Vitamin D that can recover the physiological insulin secretion by exerting anti-inflammatory properties [21].The neutrophil to lymphocyte ratio (neutrophil-to-lymphocyte ratio, NLR) as a new inflammatory index, the value in the diagnosis and treatment of coronary heart disease, tumor, endometriosis [22]. And other diseases has attracted attention. NLR is a new inflammatory marker proposed in recent years, which is the ratio of neutrophils to lymphocytes in blood routine and can reflect the inflammatory state of the body. At present, a large number of studies have been carried out abroad on the ratio of neutrophils to lymphocytes, mainly aimed at the prognosis of tumor[23], coronary heart disease grade[22] and so on, it is found that the ratio of neutrophils to lymphocytes has a significant prognosis for the above diseases. Yilmaz, et al.[22]found a significant association with gestational diabetes. As multiple linear regression analysis can only prove the negative correlation, not further prove its causality.
Our study found that with the decrease of 25(OH) D concentrations, the NLR level increased, suggesting that with the decrease of vitamin D status may probably lead to the enhancement of inflammatory response, which may increase the fasting blood glucose level in patients with GDM. 25(OH)D concentration and NRL were negatively related ( β = -0.389, p = 0.035), adjusted to eGFR, gestational age, and age. It is interesting that the negative relationship is found between 25(OH) D concentration and HOMA-IR, but not between 25(OH) D concentration and HOMA-β, which may lead to a hypothesis of vitamin D affecting glucose metabolism via insulin sensitivity, not islet function. Further research is needed to give more evidence and proof. In all, vitamin D may affect blood glucose in patients with gestational diabetes by participating in the inflammatory response.