Gestation and Birth
Links Between Gestation and Birth Factors and Diabetes/Obesity
A number of environmental influences that occur during gestation and birth may be involved in the development of diabetes, especially type 1 diabetes, although further studies would need to confirm these associations. For example, the increasing use of medically unnecessary C-sections may be a concern. Other factors are linked to diabetes are out of our control, like family history or birth order (as well as genetics, which is beyond the scope of this website).
A number of additional factors may influence the development of type 1 diabetes during gestation or in early life, which are discussed on other pages (e.g., Breastfeeding, Nutrition, Wheat and Dairy. The Diet and the Gut page contains information on taking antibiotics while pregnant or in early life. The Viruses and Bacteria page discusses infections during pregnancy. The Height and Weight page considers growth in early life and type 1 diabetes. Vitamin D Deficiency during pregnancy has been associated with type 1 diabetes in the offspring. Prenatal and childhood exposure to famine is associated with later diabetes in offspring; see the Nutrition page for more on that topic.
And, exposure to environmental chemicals is another important environmental factor to consider during gestation and early life, since many contaminants can cross the placenta. Chemicals that are toxic to the developing immune system are addressed on the Autoimmunity page. These chemicals may affect the risk of type 1 diabetes in the child. Some chemicals have also been linked to the development of gestational diabetes in the mother, such as Air Pollution and Pesticides.
In fact, a relatively new area of research is the study of early-life exposure to environmental chemicals and the later development of diabetes and obesity (Haugen et al. 2015), discussed throughout this website. The development of type 2 diabetes in children, for example, is influenced by a number of early-life environmental exposures; a review concludes, "The key period for intervention to prevent type 2 diabetes is within the first 1000 days of life." (Rughani et al. 2020).
There is an entire field of research devoted to the study of early-life environmental exposures and later life disease, called the Developmental Origins of Health and Disease (DOHaD).
Is the Risk of Type 1 Diabetes Affected by Factors Even Before Birth?
Perhaps. There is some evidence that even the prenatal environment can affect the risk of type 1 diabetes development later in life (Stene and Gale, 2013). Certain immune system markers are sometimes already present at birth in people who go on to develop type 1 diabetes during childhood or even adolescence (Thorsen et al. 2017). In fact, some markers may even be present in mid-pregnancy (Vistnes et al. 2018). A new study, the ENDIA study is now looking at environmental factors beginning in pregnancy that may be linked to type 1 diabetes development (Phillips et al. 2017). For a free full text review of various early-life exposures and type 1 diabetes, see Craig et al. 2019.
The Antibodies That Precede Type 1 Diabetes Can Be Present at Birth
While generally, type 1 diabetes does not appear at birth, but develops later in life, the autoimmune antibodies that often precede type 1 development may already be present at birth or in very early life, implying that fetal or early life environmental exposures may determine the development of autoimmunity (Hummel and Zeigler, 2011; Knip et al. 2017).
Scandinavian studies have found that babies born with these antibodies are at an increased risk of developing type 1 diabetes later in life (Eising et al. 2011; Lundgren et al. 2015). In Sweden, children under 15 who developed type 1 diabetes had an increased prevalence of these antibodies in their umbilical cord blood. However, those who developed type 1 at older ages did not (Elfving et al. 2003).
However, the antibodies present in cord blood may be transferred by the mother to the fetus, and have been found to disappear by the time the baby is 1 year of age (Ludvigsson and Wahlberg, 2002). So it is not entirely clear how important these antibodies are.
Month of Birth
People with type 1 tend to be born more often during certain months-- for example, in the U.S., children born in the spring had a higher risk of type 1, especially in northern vs southern areas (Kahn et al. 2009). Sweden shows a similar pattern of spring birth for children with an increased risk of autoantibodies or type 1 diabetes (Lewy et al. 2008; Wahlberg et al. 2005). However other authors noted that this pattern held only in homogeneous populations, not heterogeneous populations (Laron et al. 2005).
In fact, even type 2 diabetes may be "programmed" during the prenatal period. I didn't know this, but fingerprints are permanently fixed by the 19th week of gestation. A study of Dutch women found that markers of their offspring's fingerprints varied by the season in which they were conceived, implying that the prenatal environment may influence fingerprints (Kahn et al. 2008). These fingerprint markers, in turn, were associated with the offspring's development of diabetes as well as their beta cell function later in life Kahn et al. 2009, Kahn et al. 2010). However, the season of birth is not associated with type 2 diabetes development in Denmark (Jensen et al. 2015).
Maternal and Paternal Age
An analysis of the data from 30 studies found that on average, there is a 5% increased risk of type 1 diabetes for every 5 year increase in maternal age. That is, children of older mothers have a slightly increased risk of developing type 1 diabetes. Children of older fathers, on the other hand, do not appear to have an increased risk of type 1 diabetes. The authors argue that increasing maternal age can only explain a very small percentage ("hardly any") of the increasing incidence of type 1 diabetes in children. Why might a higher maternal age increase the risk of type 1? We do not know. The chromosomal changes that are more common in children of older mothers are not thought to be involved in the development of type 1 diabetes (Cardwell et al. 2010a).
Family Members With Type 1 Diabetes
As a mother with type 1 diabetes, who has a child with type 1 diabetes, I first have to mention that the fact that more people with type 1 diabetes are now having babies than before does NOT explain the increased incidence of type 1 diabetes (Atkinson et al. 2014). Thank you.
The risk of type 1 developing in offspring is higher if the father has type 1 than if the mother has type 1, especially if the father was diagnosed at a young age. If you want the numbers, in one study, 7.8% of the offspring of fathers with type 1 developed type 1 by age 20, and 5.3% of the women (both higher than the general population) (Harjutsalo et al. 2006). This study was from Finland, where type 1 rates are high, but the father vs. mother finding holds in other populations as well (Stene and Gale, 2013). This does not bode well for my future grandchildren. A meta-analysis found that the offspring of fathers with type 1 had a 1.5 times higher risk of developing childhood-onset type 1 than offspring of mothers with type 1 (Hidayat et al. 2019). Scientists are trying to figure out why the children of mothers with type 1 have a lower risk than the children of fathers with type 1 (e.g., Knoop et al. 2020).
If a child has type 1 diabetes, the risk of type 1 diabetes in a sibling is 4.1% by age 20, and 6.9% by age 50 (Harjutsalo et al. 2005). These numbers again are from Finland, and may be higher than found in other countries. However, in the U.S. (Colorado), the overall risk of type 1 by age 20 was 4.4% (and highest if the sibling was diagnosed early)-- so comparable to European rates (Steck et al. 2005).
Overall, the risk of developing type 1 varies from 1 to 15% in siblings, parents and children of people with type 1, while the risk of developing the disease in the general population ranges from 0.12 to 0.4%. Identical twins have about a 23-50% chance of developing type 1 if their twin has it (Chiarelli et al. 2019). The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) found that The risk of developing multiple autoantibodies was lower in children with maternal type 1 diabetes, compared to those with fathers or siblings with type 1 (Pacaud et al. 2020).
Among siblings, those with high genetic risk of type 1 had similar rates of diabetes. Yet those with low genetic risk of type 1 had very different rates. That means that other environmental factors play a role especially in people at low genetic risk of type 1 (Hippich et al. 2019).
If you have a mother AND a sibling with type 1 diabetes, as my oldest son does, well, I don't know what the risk is, but I keep my eye on him.
It is also worth noting that most people who develop type 1 diabetes have no family members with the disease. Even in Finland, of those diagnosed with type 1, only 24% had first- or second-degree relatives with type 1 diabetes (Parkkola et al. 2013). Why am I citing so many studies from Finland? Mainly because the disease is well studied there, and they have some of the best type 1 diabetes data in the world.
Genetics or Epigenetics?
If we have a parent with diabetes, we assume that the higher risk of diabetes is due to genetics. But environmental factors may also play a role, via epigenetic mechanisms. Via epigentics, the environment can affect genes, and these changes can even be passed down from one generation to the next. For example, researchers have found that if a father has pre-diabetes, he has changes in his sperm, which lead to an increased susceptibility to diabetes in his offspring. In fact, these epigenetic changes can affect the pancreatic islets for two generations (Wei et al. 2015). Epigenetic changes in mothers with diabetes may play a role as well (Ge et al. 2014). Maternal diabetes is associated with numerous epigenetic changes in the offspring-- even in subsequent generations-- and epigenetic mechanisms may underlie these effects (Ma et al. 2015).
Maternal Smoking During Pregnancy
Type 2 Diabetes and Obesity
In 2011, the National Institutes of Environmental Health Sciences (NIEHS) convened an expert workshop to examine the role of environmental chemicals in the development of diabetes and obesity. One of the factors they evaluated was maternal smoking during pregnancy (cigarettes contain not only the chemical nicotine, but thousands of others as well). They concluded that, "Current epidemiological data support a positive association between maternal smoking and increased risk of obesity or overweight in offspring. The data strongly suggest a causal relation..." which is a pretty strong statement from a group of scientists. (Paternal smoking may also be a contributing factor). (Behl et al. 2013). Maternal smoking may also affect the infant's gut microbiota, which could be one mechanism involved (McLean et al. 2019). Even smoking by grandparents may affect the weight status of granddaughters, although in general the risk may largely not persist past the first generation, and be mostly due to maternal smoking (Dougan et al. 2016).
So, smoking during pregnancy can increase a child's risk of obesity. What about diabetes? The evidence on type 2 diabetes was too limited to draw a conclusion, according to the NIEHS review. However, some subsequent studies have found that maternal smoking during pregnancy is linked to an increased risk of type 2 diabetes in the offspring (La Merrill et al. 2015).
Type 1 Diabetes
The NIEHS review (Behl et al. 2013) did not support an association between maternal smoking during pregnancy and later type 1 diabetes in the offspring-- some studies actually show a decreased risk (or no association) (e.g., Begum et al. 2020; Hidayat et al. 2019; Magnus et al. 2018; Metsälä et al. 2020).
But additional data on type 1 found that maternal smoking during pregnancy was linked to an increased risk of type 1 diabetes in the offspring-- when genetic background was taken into account (Mattsson et al. 2015). The more cigarettes, the higher the risk. The other studies did not take into account genetic risk, which could explain the differing findings.
Kristina Mattsson found that if a mother smokes during pregnancy, her daughters were at increased risk of gestational diabetes and obesity (Mattsson et al. 2013).
As part of her PhD research, she found that when genetic background is taken into account, maternal smoking during pregnancy is associated with an increased risk of type 1 diabetes in her children (Mattson et al. 2015).
Mothers who smoke during pregnancy also have a higher risk of developing gestational diabetes (Bar-Zeev et al. 2019).
Animal studies find that maternal -- and paternal-- smoking during pregnancy increases the risk of diabetes in the offspring, as well as causes changes to gut microbiota (Wu et al. 2019).
What about marijuana? An animal study found that female (but not male) offspring exposed to THC (which is present in marijuana) in utero were glucose intolerant, had a lower density of islets, and reduced beta cell mass at 5 months of age. These findings raise concern about the female offspring of mothers who smoke marijuana while pregnant (Gillies et al. 2020).
Alcohol, Caffeine, and More
Exposure to maternal substance abuse (alcohol, cocaine, and nicotine) may increase the offspring's later risk of type 2 diabetes as well as related conditions (Vaiserman 2015). In animals, even drinking alcohol only around the time of conception can increases the offspring's later risk of glucose intolerance and insulin resistance (Gårdebjer et al. 2015). Also in animals, maternal intake of caffeine impairs insulin secretion and increases the risk of diabetes in offspring (Sun et al. 2014).
Maternal Body Weight, Diabetes, and Weight Gain During Pregnancy
Maternal Diabetes/Obesity and Later Risks for the Mother
Gestational diabetes and high maternal weight both (individually and combined) increase the mother's later risk of developing diabetes, high blood pressure, and cardiovascular disease (Kaul et al. 2015).
Maternal Diabetes/Obesity and Risk of Type 1 in Offspring
What about her children? It is becoming more and more clear that the mother's body weight during pregnancy (as well as blood glucose levels, type 1 and 2 diabetes, and insulin resistance), can affect the risk of metabolic diseases in the offspring later in life (Barbour 2014). They can also affect the risk of type 1 diabetes in the offspring. A meta-analysis of 21 studies found that offspring of women with overweight or obesity were at an increased risk of developing childhood-onset type 1 diabetes. Maternal diabetes was associated with an increased risk, especially maternal type 1 diabetes, followed by maternal gestational diabetes, and lastly by maternal type 2 diabetes (Hidayat et al. 2019).
Maternal Weight Before and During Pregnancy and Type 1 in Offspring
I was happy to learn that weight gain during pregnancy is not associated with the development of beta cell autoimmunity in the offspring (I gained a lot of weight while pregnant). The mother's BMI (body mass index) before pregnancy was not associated with beta cell autoimmunity in the offspring either (Arkkola et al. 2011). On the other hand, other studies found that a high BMI before pregnancy was associated with beta cell autoimmunity in the offspring (Rasmussen et al. 2009). And in a very large study from Sweden, high maternal BMI in the first trimester was associated with an increased risk of type 1 diabetes in the offspring (the risk was increased if either parent had diabetes as well) (Hussen et al. 2015). Further studies from Sweden found that maternal obesity is associated with an increased risk of type 1 diabetes in the offspring as well (Lindell et al. 2018; Waernbaum et al. 2019). Maternal obesity is associated with altered immune cells in the umbilical cord, implying that obesity affects the infant's immune system (Wilson et al. 2015).
Yet a study from Denmark and Norway found that both maternal and paternal obesity were associated with type 1 diabetes, implying that family-level mechanisms may explain the association between maternal obesity and type 1. (Maternal weight gain during pregnancy was not associated) (Magnus et al. 2018). Other studies have found that maternal BMI, however, is not associated with type 1 diabetes in offspring (although maternal type 2 diabetes was linked to a higher risk of type 1 in offspring (Azeredo et al. 2021).
Maternal Gestational Diabetes and Type 1 in Offspring
A large, long-term, population-wide study from Denmark found that gestational diabetes was not reported in any of the mothers of children who ended up developing type 1 diabetes, although the difference was statistically insignificant (Haupt-Jorgensen et al. 2018). On the other hand, a large Canadian study found that the offspring of mothers with gestational diabetes had a higher risk of developing diabetes in youth (from birth up to age 22). The researchers were not able to distinguish the type of diabetes, but most Canadian youth with diabetes have type 1 (Blotsky et al. 2019).
Maternal Diabetes/Obesity and Risk of Type 2/Obesity in Offspring
For a free full text review on the role of maternal diabetes/obesity ("developmental overnutrition") and the risk of type 2 diabetes and obesity in the offspring, see Perng et al. 2019. ("Developmental undernutrition," e.g., famine, is also linked to metabolic diseases in offspring, reviewed by Stein et al. 2019). A Californian study found maternal type 2 diabetes, gestational diabetes requiring medication, and obesity/overweight increased the offspring's risk of a high BMI (Wang et al. 2019).
A high BMI does have the potential to affect the offspring in a variety of ways, involving various mechanisms, from epigenetics to inflammation, that can influence the growth and development of the child, and even lead to later disease in adulthood (Tarantal and Berglund 2014). A long-term study from Finland found that maternal obesity increased the offspring's risk of death, cancer, coronary heart disease, stroke, and diabetes. The associations were strongest for cardiovascular disease and type 2 diabetes, and the association with type 2 diabetes was stronger in women (Eriksson et al. 2014).
There is not only an increased risk of obesity in children if the mother gains too much weight while pregnant, but there is also an increased risk if the mother gains too little weight as well (Sridhar et al. 2014). A large U.S. study found that maternal diabetes and obesity were strongly associated with type 2 diabetes in their children (Dabelea et al. 2008). Another U.S. study found that if the mother had gestational diabetes or high blood glucose during pregnancy, her children had a higher risk of obesity, especially if the mother was overweight or obese (Kubo et al. 2014).
Interestingly, adequate weight gain during pregnancy may help protect the fetus from exposure to environmental chemicals. If a pregnant woman does not gain enough weight while pregnant, her body loses fat as the baby grows, releasing persistent organic pollutants (POPs) into her blood, which can then enter the fetus. The newborn babies of women who have gained adequate weight while pregnant have lower levels of POPs than babies of women who do not gain enough weight (Vizcaino et al. 2014).
Maternal Type 1 Diabetes and Offspring Obesity
A systematic review and meta-analysis found that if a mother has diabetes (type 1, type 2, or gestational), her children are at higher risk of obesity and glucose intolerance-- especially if the mother has type 1 (Kawasaki et al. 2018). A long-term study from Germany, for example, found that the offspring of mothers with type 1 diabetes have a higher BMI in childhood, along with an increased risk of being overweight, plus higher insulin, glucose, insulin resistance, and waist circumference (as compared to children of mothers without diabetes (Pitchika et al. 2018a). The TEDDY study found that children of mothers with gestational or type 1 diabetes have a higher risk of being overweight (Pitchika et al. 2018b). A Californian study found maternal type 1 diabetes increased the offspring's risk of a high BMI (Wang et al. 2019).
Maternal Gestational/Type 2 Diabetes and Offspring Obesity
A review finds that maternal gestational diabetes is linked to offspring overweight/obesity and glucose intolerance, especially in female offspring, and even after adjusting for maternal body weight (Nijs and Benhalima 2020).
Other studies found that if the mother has diabetes, her children have an increased rate of BMI growth in late childhood (ages 10-13), thus increasing their long term risk for obesity (Crume et al. 2011a). Another study by the same authors found that gestational diabetes in the mother was associated with later weight gain in the offspring at ages 6-13 (Crume et al. 2011b). Higher maternal body size before pregnancy (at least up to the "obese" level) as well as gestational diabetes were associated with higher insulin resistance in the offspring (Maftei et al. 2015).
Other studies have also found that higher glucose levels in pregnancy (from gestational diabetes) are associated with higher BMI in the children (at age 7) (Zhu et al. 2016). Gestational diabetes, in fact, is linked to a variety of metabolic effects in the offspring, including higher weight/BMI, higher glucose and insulin levels, more insulin resistance, higher triglycerides, lower HDL (the "good" cholesterol), and even earlier puberty (Grunnet et al. 2017). The good news is that higher maternal blood glucose during pregnancy (but not to the level of diabetes) is not associated with obesity in the offspring during childhood (Thaware et al. 2015). And, in the long term, the association between maternal impaired glucose tolerance or gestational diabetes and offspring weight or insulin resistance may not last into adolescence (Gingras et al. 2018).
Breastfeeding in infancy reduced the subsequent risk of later weight gain in the offspring, and reduces the excess weight gain associated with exposure to diabetes in utero (Crume et al. 2011c). Moreover, a healthy diet and physical activity by the offspring can also counteract the association between maternal gestational diabetes and excess weight in her offspring (Sauder et al. 2019).
Epigenetic mechanisms probably have something to do with the associations between maternal diabetes/obesity and offspring metabolism (Agarwal et al. 2018). Maternal gestational diabetes, for example, is associated with epigenetic changes in the umbilical cord blood and placenta (Finer et al. 2015). Maternal BMI is also associated with epigenetic changes in newborns (Sharp et al. 2017).
So which is worse for the child, maternal diabetes or maternal obesity? Diabetes. If a mother has diabetes, the offspring have higher risks than if the mother is obese. Both together are worse than either alone, at least for pregnancy outcomes (Langer 2016).
Laboratory studies confirm that maternal obesity, with or without diabetes, or high birth weight increases the likelihood of later life obesity. The potential mechanisms include altered organ development, cellular signalling, and epigenetic changes (Desai et al. 2013). The offspring of mice who have high blood sugar (and high insulin levels) during pregnancy (as in type 2 diabetes) have an impaired pancreas with fewer beta cells and lower beta cell mass, higher blood sugar and insulin levels, low birth weight and rapid weight gain, in addition to other hormonal changes (Kahraman et al. 2014). In mice, the effects of maternal obesity on the offspring was greater than that of malnutrition. The pancreas and liver were the tissues most affected, and the mechanism appeared to involve oxidative stress (Saad et al. 2016).
In animals, exposure to high blood glucose in the womb had effects on glucose tolerance and weight of the offspring later in life (Blue et al. 2015), and maternal diabetes affects the fatty tissue of offspring (Oliveira et al. 2015). In laboratory animals, flax oil during pregnancy protects the offspring from the negative effects of maternal diabetes and high blood sugar in the womb (Correia-Santos et al. 2014).
Pre-Eclampsia or High Blood Pressure
An analysis of pooled data on maternal pre-eclampsia (high blood pressure and protein in urine during pregnancy) found little evidence of increased risk of type 1 diabetes in the offspring (Henry et al. 2011). A large study from Sweden also found no increased risk (Waernbaum et al. 2019).
However a long-term study from Finland found that exposure to a mother's hypertension (high blood pressure) in the womb was associated with an increased risk of type 2 diabetes as an adult (Kajantie et al. 2017).
For More Information
Factsheets from the National Institute of Environmental Health Sciences (NIEHS):
Child Spacing and Birth Order
Children born less than 3 years apart have a lower risk of type 1 diabetes than those born more than 3 years apart (Cardwell et al. 2012).
Birth order has not been consistently associated with type 1 diabetes (Stene et al. 2004). That is, first born vs. later born children do not appear to have a higher or lower risk of disease. However, a newer meta-analysis of 31 separate studies found there was some evidence for a slightly lower risk of type 1 diabetes in later born children as compared to first born children, especially in children under 5 years of age. The association varied a lot between studies (Cardwell et al. 2011). A more recent study from Poland found that first born children did not have a higher risk of type 1 diabetes (unless they were diagnosed after age 18) (Żurawska-Kliś et al. 2015), while a Finnish study found that first born children did have a higher risk than subsequent children (Metsälä et al. 2020).
A systematic review and meta-analysis of 23 studies found that preterm birth was associated with an increased risk of both type 1 and type 2 diabetes later in life (Li et al. 2014). A population-wide study from Israel found that children born early had an increased risk of endocrine and metabolic disorders during childhood, including type 1 diabetes and overweight/obesity (Paz Levy et al. 2017). A large study from Sweden found that birth at between 33-38 weeks was associated with a slightly higher risk of type 1 diabetes, as was being small for gestational age (Khashan et al. 2015). Another large Swedish study found that birth before 32 weeks was associated with a lower risk of type 1, but 32-36 weeks with a higher risk (Waernbaum et al. 2019). An additional large Swedish study found that pre-term birth was associated with an increased risk of both type 1 and type 2 diabetes in offspring from childhood to mid-adulthood (Crump et al. 2019). In England, a large study found that children born pre-term or early-term had a higher risk of type 1 diabetes (Goldacre 2018). In Finland, premature birth was linked to a higher risk of type 1 diabetes (Metsälä et al. 2020). In China, preterm birth was linked to an increased risk of type 1 diabetes during childhood (Huang et al. 2021). A study from the Middle East, however, found no association between premature birth and type 1 diabetes during childhood (Adar et al. 2018).
A U.S. study found that pregnant women with type 1 diabetes may be at greater risk for adverse childbirth outcomes including preterm birth when exposed to air pollution than women without autoimmune disease (Williams et al. 2021).
Preterm birth has also been linked to insulin resistance in childhood and adulthood, perhaps leading to the increased risk of type 2 diabetes. Babies born premature have been found to have higher insulin levels, and these levels persisted into childhood. The earlier the birth, the higher the insulin levels (Wang et al. 2014). Mothers who give birth to babies prematurely also have an increased risk of metabolic syndrome up to 25 years later (Catov et al. 2016).
Type 1 Diabetes
An analysis of the data from 29 studies found that babies weighing over 7.7 lbs (3.5 kg) at birth have a 6% higher risk of type 1 diabetes, and those that weigh over 8.8 lbs (4 kg) at birth have a 10% higher risk of developing the disease. This study controlled for factors such as maternal diabetes, gestational age, and some other factors that might affect birth weight (Cardwell et al. 2010b). A German study found that children who later developed diabetes were more likely to have a higher birth weight than those who did not (Kuchlbauer et al. 2014). And, another analysis of data from multiple studies found that high birth weight was associated with an increased risk of type 1 diabetes (Harder et al. 2009). A large study from England also found that high birth weight was associated with an increased risk of type 1 diabetes. Yet this study also found that low birth weight was associated with a reduced risk (Goldacre 2018). Large Swedish studies also found high birth weight associated with an increased risk of type 1 diabetes (Waernbaum et al. 2019) as did large size for gestational age (Lindell et al. 2021). Interestingly, low birth weight is also associated with LADA (latent autoimmune diabetes in adults) (a form of adult-onset type 1 diabetes) just as strongly as it is with type 2 diabetes, in a population-based study from Sweden (Hjort et al. 2015). Not all studies have found links between birthweight and type 1 diabetes (e.g., Pacaud et al. 2020).
High birth length was associated with a higher risk of type 1 diabetes in Finland (Metsälä et al. 2020).
Type 2 Diabetes and Obesity
A lower birth weight (and fast growth in infancy or childhood) appears to be associated with later obesity, insulin resistance, and type 2 diabetes (Inadera 2013; Labayen et al. 2012; Labayen et al. 2008). In black U.S. women, those with very low birth weight had a 40% higher risk of type 2 diabetes than women with normal birth weight, and those with low birth weight had a 13% higher risk -- no matter the BMI of the women (Ruiz-Narváez et al. 2014). In China, both high and low birth weights were associated with an increased risk of later diabetes (Hu et al. 2019).
However, a Danish study of identical twins with different birth weights found that low birth weight was not associated with glucose metabolism in adulthood, once genetics and the environment were controlled for (Frost et al. 2012). And a systematic review and meta-analysis of 20 studies actually found that high birth weight was associated with later obesity, but not low birth weight (Yu et al. 2011).
"Two Old Grandpas"
Dr. Jerry Heindel (formerly of NIEHS) and Dr. Philippe Grandjean (Harvard School of Public Health) have organized numerous scientific meetings on "Prenatal Programming and Toxicity." They are interested in how environmental chemical exposures during early life affect the later risk of diabetes, obesity, immune system changes, and other diseases (and they told me to call them "two old grandpas").
Weight Gain During Infancy
A study based on two large population-based datasets from Scandinavia found that babies who gained the most weight during their first year of life had an increased risk of type 1 diabetes during childhood. The effect was highest in the first 6 months of life. The average change in weight was over 13 lbs during the first 12 months of life. This study also found that birth weight was not associated with type 1 diabetes development, nor was height or height gain in infancy (Magnus et al. 2015). Other studies have also found this association, see the height and weight page for more info.
C-Sections and Birth Complications
An analysis of data from 20 studies found that Caesarean sections were associated with a 20% increased risk of type 1 diabetes in offspring (Cardwell et al. 2008). More recent studies have also found that birth by C-section may increase the later risk of type 1 diabetes (Phillips et al. 2012), as have other meta-analyses, although the increased risk might be small (Tanoey et al. 2020).
Why? Some authors suggest that perhaps this association is due to the gut microbiota. The gut microbiota differ in children born by C-section compared with those born vaginally (Cardwell et al. 2008). Another hypothesis is that immune function differs in babies born by C-section vs. vaginally (Puff et al. 2015). Others have found that gene expression is a possible mechanism (Laimighofer et al. 2019).
However, findings from a Swedish study show that the situation may be more complex. The Swedish study there was an increased risk of type 1 diabetes in children born by C-section (as well as "instrumental vaginal delivery"), but only by elective, and not emergency C-section. On the other hand, the association disappeared when siblings were compared, implying that the association between C-sections and type 1 diabetes may be due to family and/or environmental factors instead (Khashan et al. 2014). Another (population-wide) Swedish study also found no association between C-sections and type 1 diabetes; it was maternal diabetes that most strongly influenced the risk of type 1 diabetes in the offspring (Samuelsson et al. 2015). And another (population-wide, Swedish) study found that while C-sections were associated with type 1 development, the association disappeared after accounting for maternal obesity (Waernbaum et al. 2019). A Danish study also found no association between pre-labor C-sections and type 1 diabetes in the offspring; the results were explained by maternal type 1 diabetes (and paternal type 1 diabetes had an even stronger effect) (Clausen et al. 2016). In southern Australia, a population-wide study found that while C-sections might be linked to a slightly increased risk of type 1 diabetes in offspring, the difference was not statistically significant. It also found that the risk was lower for pre-labor C-sections compared to C-sections during labor, implying that exposure to vaginal microbiota is not involved as a mechanism (Begum et al. 2019). A different (small) study, however, found that the vaginal microbiome might in fact be a factor in type 1 diabetes development (Tejesvi et al. 2019), so we shall see.
One study has also found differences in the levels of immune system cells called cytokines in babies born vaginally as compared to those born by C-section. Vaginal birth may instigate a form of inflammation that activates the baby's (and mother's) immune systems in a beneficial manner (Malamitsi-Puchner et al. 2005). And, in a Denmark-wide study, birth by C-section was associated with several immune system disorders in children, although not type 1 diabetes (Sevelsted et al. 2015). In Quebec, Canada, however, birth by C-section was not associated with hospitalization for an autoimmune disorder by age 14, including type 1 diabetes or celiac disease (Soullane et al. 2021).
A prospective U.S. study found that complicated deliveries (e.g., breech, forceps, vacuum extraction) was associated with increased risk of type 1 diabetes-related autoantibodies in children genetically at risk for type 1 diabetes. How complicated deliveries would influence the development of autoantibodies is not known. Unlike most of the above studies (which measured the development of type 1 diabetes), this study did not find that C-sections increased the risk of type 1-associated autoantibodies. The results of this study remained the same when women with gestational or type 1 diabetes were excluded from the analysis (Stene et al. 2004). Premature rupture of membranes have also been associated with type 1 development in the offspring (Waernbaum et al. 2019).
On a related note, a long-term nationwide study from Denmark found that broad-spectrum antibiotics during the first two years of life was associated with an increased risk of type 1 diabetes in the next 13 years of life, but only in children delivered by C-section (not in children delivered vaginally) (Clausen et al. 2016). (Additional studies on antibiotics during pregnancy and in early life are discussed on the Diet and the Gut page.)
Also related, C-sections are not associated with an increased risk of celiac disease in the offspring (common in people with type 1 diabetes) (Koletzko et al. 2018).
And, exclusive breastfeeding partly restores the gut microbiota in infants delivered by C-section (Liu et al. 2019). (In addition, the mother's gut microbiota during pregnancy can influence her offspring's development of autoimmunity (Nyangahu and Jaspan 2019) and their growth (Sato et al. 2019).)
Obesity and Metabolic Syndrome
In UK children, C-sections are associated with an increased body mass in childhood and adolescence in the offspring from 6 weeks until 15 years of age, according to a long-term study. Again, the mechanism may involve the microbiome, but that remains to be seen (Blustein et al. 2013). Meanwhile a long-term German study shows different results. It found that children born by C-section were more likely to be obese at age 2, but not at ages 6 or 10 (Pei et al. 2014). A U.S. study found children who had been delivered by C-section were more likely to be obese at age 3 (Huh et al. 2012), and another U.S. study found that C-sections increased the risk of obesity by 46% by age 7 (Mueller et al. 2015). A third U.S. study found that C-sections were associated with an increased risk of overweight or obesity in childhood (Mueller et al. 2017). A study from Singapore found C-sections increased the risk of the offspring being overweight at 12 months (Cai et al. 2018). And a South African study found C-sections were associated with obesity in early adulthood (Sogunle et al. 2019). However, a Swedish study found no link between C-section delivery and male offspring obesity in young adulthood (Ahlqvist et al. 2019).
A meta-analysis of 15 studies found that people born by C-section had a higher BMI and were more likely to be overweight or obese in adulthood, as compared to those born vaginally (Darmasseelane et al. 2014).
A U.K. study found that babies born by non-elective C-section were more likely to have metabolic syndrome as adults. Since the risk of metabolic syndrome in vaginal and elective C-section were similar to each other, the authors suggest that a different mechanism may be involved, e.g., fetal stress (Bouhanick et al. 2014).
Neonatal jaundice has been associated with a small increased risk of type 1 diabetes in some studies (McNamee et al. 2012) but not in others (Waernbaum et al. 2019). Neonatal hyperbilirubinemia, which is basically the cause of jaundice, is also associated with an increased risk of type 1 diabetes (Liao et al. 2019).
Assisted Reproductive Technologies
Women who undergo assisted reproductive technologies have a high risk of developing gestational diabetes during pregnancy, according to a large systematic review and meta-analysis (Maroufizadeh et al. 2019), as well as other studies (Lei et al. 2019).
Children conceived by assisted reproductive technologies may be at increased predisposition for insulin resistance, obesity, metabolic syndrome, and other metabolic issues, according to some studies (Cui et al. 2020; Gkourogianni et al. 2014).
A Danish study using nation-wide data from 1987-2010 found no increased risk of type 1 diabetes in children born to women with fertility problems (Hargreave et al. 2016). A different Danish study using nation-wide data from 1995-2003 found no overall association between fertility treatments and type 1 diabetes in the offspring. However, the researchers did find an association between type 1 in the offspring and the use of ovulation induction or intrauterine insemination with follicle-stimulating hormone (Kettner et al. 2016). Hopefully we will see further studies on this topic to determine whether this is a chance finding or not.
A nation-wide study of Swedish singletons born between 1985 and 2015 found that children born after assisted reproductive technology had an increased risk of type 1 diabetes, but this association was only significant in children born after frozen embryo transfer (Norman et al. 2020).
In mice, impaired glucose tolerance and decreased insulin tolerance occurred in male offspring conceived using frozen and thawed embryo transfer (FET) (Qin et al. 2021).
Maybe irrelevant, but I thought it was interesting: a boy fetus (vs a girl) is associated with a higher risk of gestational diabetes in the mother, as well as worse beta cell function and higher blood sugar levels (Retnakaran et al. 2015). Huh. I'd like to see if this holds true in larger studies.
Blood Type and Maternal Microchimerism
There is some evidence of an increased risk of type 1 diabetes if mothers and offspring have different blood types (Dahlquist et al. 1999).
Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common, and has been detected in the circulation and pancreas of people with type 1 diabetes. MMc levels in umbilical cord blood, however, were not related to future type 1 diabetes development (Tapia et al. 2019).
Maternal Diabetes and Other Health Risks in Offspring
ADHD and Autism
A meta-analysis of data from 13 studies (of over 5 million people) finds that if a mother has diabetes before pregnancy ("maternal pregestational diabetes"), or if a mother or father has type 1 diabetes, their offspring have an increased risk of ADHD (Zeng et al. 2019). Another large meta-analysis also finds that maternal pregestational diabetes increased the risk of ADHD in offspring (Guo et al. 2020). And another one finds an increased risk of autism spectrum disorders but not ADHD in offspring of women who had gestational diabetes (Rowland and Wilson, 2021).
In Southern California, a large study examined whether a pregnant woman's diabetes was associated with the risk of attention deficit hyperactivity disorder (ADHD) in her children. Compared with children unexposed to maternal diabetes, in utero exposure to maternal type 1 diabetes was associated with the highest risk of ADHD in children, followed by maternal type 2 diabetes, followed by gestational diabetes requiring medications. Children whose mothers had gestational diabetes that did not require medications did not have a higher risk of ADHD (Xiang et al. 2018). Thus the more severe the diabetes, the higher the risk of offspring ADHD. A study from China also found the risk of ADHD was higher in the children (especially boys) of mothers who had diabetes as compared to mothers without diabetes (Lin et al. 2019).
A population-based study of over 2 million people in Sweden found that all types of maternal diabetes were associated with an increased risk of neurodevelopmental disorders in offspring, with type 2 diabetes most strongly associated with autism. Paternal type 1 and type 2 diabetes were also associated with offspring neurodevelopmental disorders, but these associations were weaker than those with maternal diabetes (Chen et al. 2020).
Children of mothers with type 1, type 2, or gestational diabetes (diagnosed early in pregnancy) are at a higher risk of autism spectrum disorders. A large study from southern California found that children whose mothers had HbA1c levels greater than 6.5% during early pregnancy were almost two times as likely to be diagnosed with autism in the first 4 years of life as those whose mothers had HbA1c levels below 5.7% (Xiang et al. 2019).
A large population-based study from Australia found that any autoimmune disease in mothers is also linked to an increased risk of ADHD in offspring, including specifically type 1 diabetes. This article also included a review and meta-analysis of multiple studies, and found the same increased risks (Nielsen et al. 2021).
In laboratory animals, maternal diabetes causes autism-like behavior in offspring via oxidative stress, and prenatal and postnatal treatment using antioxidants partly reduced this effect (Wang et al. 2019).
A U.S. study found that if a woman has diabetes while pregnant, her offspring have earlier puberty and faster speed of puberty (Hockett et al. 2019).
In Denmark, children of mothers with any type of diabetes, especially those mothers with a history of cardiovascular disease or diabetic complications, have increased rates of early onset cardiovascular disease from childhood to early adulthood (Yu et al. 2019).
Infants born to mothers with type 1 diabetes have more viruses in their guts than infants of mothers without diabetes. We don't know if there are any health consequences of this finding (Kim et al. 2019).
The babies of women with gestational diabetes also have more inflammatory gut microbiota than babies of women without diabetes (Ponzo et al. 2019).
According to a systematic review and meta-analysis, maternal diabetes is associated with an increased risk of childhood cancer in the offspring, particularly for acute lymphoblastic leukemia. There was not an association for offspring of women with gestational diabetes, just pre-existing diabetes (Yan et al. 2020).
To download or see the references cited on this page, as well as other references related to environmental exposures (e.g., nutrition, chemical exposures, etc.) from fetal development through childhood, see the collection Gestation, birth and early-life exposures and diabetes/obesity in PubMed.