The incredible connection between vitamin D & gestational diabetes

Last month, I wrote a blog on the importance of vitamin D during preconception, pregnancy, and postpartum.

In that blog, we touched on the importance of vitamin D in preventing gestational diabetes mellitus (GDM)—vitamin D deficiency poses a higher risk of GDM (1).

Outside of pregnancy, vitamin D deficiency is associated with increased insulin resistance and increased risk of metabolic syndrome (2) and type 2 diabetes (3). Additionally, vitamin D has an inverse relationship with HbA1c values in type 1 diabetes (4).

In this blog, I’ll expand on vitamin D and GDM.

To begin, let’s take a look at the relationship between vitamin D and glucose control, and then we’ll review what the science says about vitamin D and GDM.

How does vitamin D impact glucose regulation?

The relationship between vitamin D and glycemic control is complicated and multifaceted. In the simplest terms, vitamin D influences glucose regulation by affecting the beta cells’ insulin production and cellular sensitivity to insulin (5, 6).

Vitamin D regulates the concentration of intracellular calcium ions (Ca2+) in the beta cells of the pancreas, which has a domino effect on multiple processes related to insulin production.

“It was reported that 1,25(OH)2D3 reduced the expression of the L-type Ca2+ channels causing a decrease in intracellular Ca2+ concentration and thereby altering calcium signaling. In turn, rapid, non-genomic 1,25(OH)2D3 action was found to be responsible for the increase of cytoplasmic Ca2+ level that activates exocytosis of insulin in the pancreatic β-cells. Two vitamin D-mediated signaling pathways are involved in this process” (5).

Outside of the pancreas, vitamin D influences insulin sensitivity and reduces the effect of insulin resistance. Similar to its action on beta cells, the effect that vitamin D has on Ca2+ regulates cellular sensitivity to insulin in skeletal muscle and adipose tissue (7). Intracellular Ca2+ is tightly controlled, and levels falling outside the ideal range affect the expression of glucose transporters GLUT-1 and GLUT-4 (5).

Additionally, Maestro et al. (2003) have demonstrated the importance of the vitamin D receptor on the expression of insulin receptor genes (8).

Finally, the role of vitamin D in managing systemic inflammation must be acknowledged when considering metabolic health and glucose regulation. Vitamin D is an anti-inflammatory agent, inhibiting nuclear factor kappa beta (NF-κB), reducing pro-inflammatory gene expression, and circulating inflammatory cytokines (5). Heightened states of inflammation and chronically elevated pro-inflammatory cytokines have been implicated in the loss of insulin sensitivity (9).

Understanding these complex mechanisms by which vitamin D regulates insulin production and sensitivity is foundational to grasping vitamin D’s importance in the entire glucose regulation system.

Thus, seeing these mechanisms reflected in many observational and clinical studies is unsurprising.

A 2022 cross-sectional study of over 9,000 individuals demonstrated a significant inverse relationship between serum vitamin D and insulin resistance. More specifically, there was an 18% decrease in the risk of developing insulin resistance for each additional unit of supplemental D3 (OR 0.82, 95% CI 0.72–0.93) (10).

However, it’s important to note that this effect varied based on race. The protective effect of vitamin D supplementation was true for ”Mexican-American,” “Non-Hispanic White,” and “other races (including multi-racial).” Notably, vitamin D supplementation appeared to be linked to a slight but noteworthy increased risk of insulin resistance for those identifying as “Other-Hispanic” and “Non-Hispanic Black” (OR: 1.05, 95%CI: 0.66-1.67 and OR: 1:05, 95%CI: 0.82-1.34, respectively) (10). It is not clear why these variations occur in these ethnicities, and further studies may clarify whether the underlying issue has to do with certain missing cofactors or some other reason.

The evidence around the therapeutic use of vitamin D for glycemic control is mixed, but supplementing with vitamin D to increase serum 25(OH)D levels effectively reduces insulin resistance (11). Recently, several RCTs have shown supplemental vitamin D to be effective in improving insulin sensitivity and slowing the progression toward type 2 diabetes (12, 13).

Vitamin D and GDM

It’s clear that vitamin D is essential for glucose regulation, and the effects above are likely why it appears to protect against gestational diabetes.

The study of vitamin D status as a risk factor for GDM is rather new, and a clear guideline for the optimal dosage of vitamin D to prevent GDM or the lab value corresponding with the least risk of GDM has yet to be established. Additionally, it’s important to note that vitamin D status is only one risk factor for GDM; however, it’s relatively easy to modify.

A 2020 meta-analysis of 53 articles comparing the serum vitamin D levels of women with GDM to those without found that those with GDM had much lower vitamin D levels than their healthy counterparts (1).

Achieving optimal vitamin D status before conception is ideal. However, Yue & Ying (2020) found that vitamin D sufficiency before 20 weeks of gestation protects against the development of GDM (14). Notably, their results suggested that serum vitamin D of 20 ng/mL (50 nmol/L) or greater was able to protect against GDM. It’s worthwhile to note that 20 ng/mL is low—the Vitamin D Council considers 40 ng/mL (100 nmol/L) to be the bare minimum of sufficiency.

Another 2020 observational study reported similar results.

For women with serum vitamin D of 10 ng/mL (25 nmol/L), the prevalence of GDM was 21%; for those in the range of 20-30 ng/mL (50-75 nmol/L), the prevalence dropped to 15%. Not surprisingly, the risk was even lower for those with values >30 ng/mL (75 nmol/L), with the prevalence of GDM dropping to 9.2% (15).

These combined results show us that even low but improved vitamin D levels may help prevent GDM significantly, and 20 ng/mL (50 nmol/L) appears to be the threshold for improved glycemic control (15).

“We found that 50 nmol/L might be the threshold concentration of 25(OH)D that could determine the significance of the association of 25(OH)D concentrations with GDM and glucose metabolism. Only when 25(OH)D concentrations were >50 nmol/L were they significantly and negatively correlated with GDM risk, FPG, and glucose AUC” (15).

Furthermore, this effect was only significant in women taking a daily vitamin D supplement (15).

A 2016 randomized placebo-controlled trial found that supplementing with 5,000 IU of D3 daily protected against GDM in high-risk women (16).

The beneficial effect of vitamin D goes beyond GDM prevention alone.

For women with GDM and vitamin D deficiency (<20 ng/mL), supplementing with vitamin D to raise serum levels above 20 ng/mL has been shown to reduce fasting glucose, HbA1c, and HOMA-IR (17).

Additionally, results of a 2021 meta-analysis indicated that women with GDM who supplement with vitamin D may significantly reduce the risk of material and neonatal complications such as C-section, postpartum hemorrhage, fetal distress, hyperbilirubinemia, and polyhydramnios (18).

Other considerations: don’t forget about vitamin D’s cofactors!

The absorption and function of vitamin D rely on other micronutrients, commonly known as cofactors. These cofactors include magnesium, vitamin K2, and vitamin A.

These cofactors are crucial for optimizing vitamin D and protecting health. For example, magnesium deficiency leads to lower levels of active vitamin D (19), and vitamins K2 and A may protect against vitamin D toxicity (20, 21).

In my practice, I consider the importance of each of these micronutrients. I typically have clients take a prenatal or multivitamin/mineral with K2, magnesium, vitamin A, and vitamin D, and suggest foods rich in these nutrients, as well.

And, of course, monitoring vitamin D levels is key for optimizing D status and preventing GDM.

You can learn more about supplementing with vitamin D during pregnancy here.

If you’d like to learn more about the importance of other blood markers during preconception and pregnancy, click here to sign up for my pregnancy and postpartum-specific blood chemistry masterclass!

References