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Dietary supplements for gestational diabetes - an upcoming study!


diabetes  & microbiome

What is my blog about this week, you wonder? GDM! Gestational diabetes! 2-7% of pregnant women in Sweden develop GDM during their ongoing pregnancy.


You might be thinking she hasn't talked about it before. Well, we discussed this as a risk when we were talking about large babies (LGA). The reason it's on the agenda again because I've been asked to participate in a large research consortium.


They've just applied for a lot of funding from the EU to finance a major international project on the treatment of GDM. This research group includes participants from Finland, Israel, and Spain who have come together to find a new and effective treatment method for GDM.


How did I end up there, you ask? Through my collaborators at CTMR at KI. You know, my microbiome friends. They've been asked to assist with analyzing the samples that will be taken, and they want to involve a Swedish clinic as well.


But let's step back a bit. What is GDM? How does the microbiome relate to GDM? Why could this lead to a new and effective method for managing all pregnant women with GDM?


Gestational Diabetes

Gestational diabetes is defined as diabetes detected during pregnancy, where glucose metabolism normalizes after childbirth.

In recent years, the focus has been on GDM and its risks for obstetric and neonatal complications.

Identifying and treating women with GDM, i.e., hyperglycemia during pregnancy, can reduce the risk of preeclampsia and the proportion of large babies (LGA).

However, there is significant disagreement nationally and internationally regarding screening and diagnostic criteria, making it difficult to compare research results.

Nevertheless, the criteria set by WHO in 2013 and the criteria by the Swedish National Board of Health and Welfare in 2015 are in agreement.


COMPLICATION RISKS in GDM

We can start by noting that GDM is not considered to increase the risk of congenital malformations in itself. However, it is known that if hyperglycemia is present in early pregnancy, it may indicate that the woman has undiagnosed type 2 diabetes, which can change the risk assessment for congenital malformations.


The risk of malformations is directly related to glucose levels. Obesity is also linked to an increased risk of malformations, and since most women with GDM have a high BMI, these two risk factors can interact.

I can point out that among my "important patients" in the Important Project, about 90% have GDM.


 What are the risks associated with GDM?

For the woman, these risks include:

  • Preeclampsia

  • Pregnancy-induced hypertension

  • Need for a cesarean section

  • Shoulder dystocia


For the newborn, there are increased risks of:

  • Macrosomia (in Sweden, ≥ 4.5 kg) or LGA (+ 2 SD adjusted for gender and gestational week; or, as it is referred to in the rest of the world, > 90th percentile, but this is not used clinically in Sweden)

  • Preterm birth

  • Traumatic birth injuries such as brachial plexus injuries

  • Neonatal hypoglycemia and the need for neonatal care

  • Respiratory issues


What is also known is that women who have had GDM have a significantly increased risk of developing primarily type 2 diabetes and cardiovascular disease in the future. If the condition normalizes postpartum, the risk of developing gestational diabetes in a subsequent pregnancy is approximately 50-70%.


How do we screen for GDM?

I was about to say, "as usual" in obstetrics, both screening criteria and diagnostic criteria for GDM vary worldwide. The choice of screening method is influenced by economic and resource constraints

However, the recommendations issued by the Swedish National Board of Health and Welfare (2015) align with the WHO's recommendations from 2013. According to these guidelines, GDM should be managed as follows:


Healthcare should offer measures to monitor and, if necessary, lower blood sugar levels in pregnant women who meet one or more of the following criteria:

  • Fasting blood sugar level >= 5.1 mmol/l

  • Values 1 hour after OGTT (oral glucose tolerance test) >= 10.0 mmol/l

  • Values 2 hours after OGTT >= 8.5 mmol/l

 

In 2018, a large Swedish multicenter study on GDM (CDC4G study) was conducted. This study led to 11 clinics in Sweden adopting common guidelines for the treatment and monitoring of GDM.


The threshold for acceptable blood sugar levels was lowered, resulting in a significantly higher number of women being diagnosed with GDM.


At Södersjukhuset in Stockholm, approximately 7,500 babies are born each year. In 2016, 46 of the pregnant women who gave birth at Södersjukhuset were diagnosed with GDM. In 2021, the number increased to 553 women. This means that approximately 12 times as many women are being diagnosed with GDM today compared to 2016.


The question is whether the outcome has improved or worsened. I don't have the answer just yet.

This fall, a student project is underway at the clinic to study the progress of women and children with GDM at Södersjukhuset after the changes in diagnostic criteria. So, stay tuned!


diabetes treatment

How is GDM treated?

The cornerstone of treating women with GDM today involves individually tailored dietary and lifestyle advice, as well as education in self-testing, including the interpretation of capillary plasma glucose.


Comprehensive information is provided about ongoing management during pregnancy and the significance of diabetes prevention measures for the woman's long-term health.


Treatment Guidelines

Blood sugar testing: Women are instructed to test themselves at least 4 times a day: fasting glucose (in the morning before breakfast) and 1 hour after starting breakfast, lunch, and dinner.


Target values for capillary plasma glucose:

  • Fasting glucose < 5.3 mmol/l

  • Before other meals < 6.0 mmol/l

  • 1 hour after starting a meal < 8.0 mmol/l

  • Before bedtime < 7.0 mmol/l

Indication for pharmacological treatment: If 3 values in a week are above the target, pharmacological treatment should be initiated.


The first approach we try today is with Metformin tablets. These tablets are gradually increased until the woman takes 2 tablets in the morning and 2 in the evening.


If this is not sufficient, insulin treatment is sometimes added, often starting with an evening injection.


However, Metformin has some side effects. Many women cannot tolerate the full dose as they experience nausea from the tablets. Injecting insulin also places a significant burden on the woman.

 

What does this have to do with the microbiome?

You have probably noticed earlier that I am interested and find the association between the microbiome and disease or health fascinating.

It is often said that the gut and its bacteria form a distinct organ system that likely influences us much more than we realize.

In a study published in 2016, researchers examined the microbiome in women with GDM and found that the microbiome in these women differed from women with normal blood sugar levels (Gestational diabetes is associated with Changes in placental microbiota and Microbiome Pediatrics Research Volume 80, pages 777–784 (2016)).

Women with GDM showed a decreased presence of certain specific bacteria in their microbiome. A reduced presence of these bacteria is associated with a lower number of a specific type of white blood cell in the blood and lower placental expression of many anti-inflammatory genes, including Interleukin (IL)-10.

These bacteria can normally have a modulating effect on the mother's immune system and create an anti-inflammatory environment in the placenta. Low levels would, in turn, be associated with a less anti-inflammatory environment and a higher risk of GDM. I find this incredibly exciting!


The upcoming major study? What does it entail?

Meta-analyses and individual randomized studies have shown that lifestyle changes (such as physical exercise and dietary regimens) and/or pharmacological interventions can improve outcomes for both the mother and the newborn in pregnancies with GDM.


Early interventions during pregnancy are considered more effective in reducing the prevalence and may also be more cost-effective. However, beyond very general instructions to improve lifestyle, there are currently no scientifically based dietary guidelines or interventions specifically tailored to reducing GDM.


The overarching goal of the current multicenter project that I have joined as a participant is to develop potential dietary supplements that can modify the composition and function of the gut microbiome in pregnant women at risk of developing GDM.


This increases the hope of ultimately reducing the high prevalence of GDM among pregnant women in Europe and in Sweden. The proposal is to use advanced microbiome and metabolome analyses to design more precise prebiotics, i.e., dietary supplements.


Imagine if you could actually prescribe something that prevents the disease, meaning the condition never develops in the best of worlds.


The idea is to combine exploratory and hypothesis-driven ideas to create a list of different dietary supplements. Then, an artificial intestinal system(?) will be used in the lab to test the effects of these substances on different microbiomes from stool samples of women with and without GDM, thus narrowing down interventions that have been validated in vitro and appear to work.


Afterward, a clinical study will be conducted to test the effect of actually giving women at increased risk of GDM this as a dietary supplement early in pregnancy before the condition develops.


Does this sound high-tech? Is it possible? Will the EU allocate funds for this massive project?

To be continued!

/Doctor Eva

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