Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes—A Double-Blind, Randomized Controlled Trial

Abstract

Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

Vitamin D in Reproductive Health and Pregnancy

“…As mentioned above, VDD has been associated with impaired glucose tolerance, insulin resistance, and risk of developing type 2 diabetes. 13 Similarly, gestational diabetes mellitus (GDM) is a condition of glucose intolerance with onset or first recognition in pregnancy, characterized by insulin resistance and impaired β-cell function, 40 and high risk of progression to type 2 diabetes. 41 The incidence of GDM is increasing in line with increased maternal age and obesity, with an estimated worldwide prevalence of 15-20%.…”

Effects of antidiabetic agents on pancreatic beta-cell function in gestational diabetes: is there enough evidence?

“…[11][12][13] In the study by Mozaffari-Khosravi et al, [11] 45 postpartum women with previous GDM were divided into an intervention and a control group (24 and 21, respectively). Women in the intervention group received an injection of 300,000 IU of vitamin D. Three months after the intervention, they were revaluated, and it was found that beta-cell function (assessed by HOMA beta-cell index) was slightly increased only in the control group.…”

“…On the other hand, when comparing beta-cell function in the two groups, it was neither different before nor after the intervention. In the study by Yeow et al, [12] a double-blind, randomized controlled trial was performed on 26 women with a previous history of GDM, which were randomized to receive either daily 4,000 IU vitamin D or placebo for 6 months. Beta-cell function was evaluated at baseline and at the end of the treatment period through a 75-g oral glucose tolerance test (OGTT), with several empirical indices: the difference between one hour and fasting insulin normalized to the same difference in glucose (sort of insulinogenic index), the area under the curve (AUC) of insulin during the OGTT normalized to glucose AUC, a similar index with C-peptide, an OGTT-based acute insulin response index, and the oral disposition index (insulin to glucose AUC ratio, multiplied by an index of insulin sensitivity).…”

“…As regards the remaining women, 9 of them required insulin during the pregnancy; also, 9 of them developed impaired glucose tolerance or diabetes after delivery. Beta-cell function was evaluated with three indices: the 1 hour to fasting insulin difference over the same glucose difference, the insulin to glucose AUC ratio, and the oral disposition index (though computed slightly differently than in study [12]). Results were presented with women stratified into the two groups indicated above, i.e., women who at mid-pregnancy reverted to normal glucose tolerance, versus those women whose GDM condition remained.…”

“…Yeow et al TP [12] 26 women, studied postpartum Vitamin D Empirical indices (disposition, insulinogenic-like, and acute insulin response indices, based on OGTT) Samimi et al [13] 28 women Omega-3 fatty acid Empirical index (HOMA beta-cell) Horie et al [14] 41 women Nutrition therapy Empirical indices (disposition, and insulinogenic-like indices, based on OGTT) Cao et al [15] 81 women Nutrition therapy and possibly insulin…”