Cardiac Dysfunction: Pregnancy in Diabetes as Risk Factor in Babies

Negative long-term effect on cardiac function in babies born from diabetic mothers.

Having a disease such as diabetes has many risks and long-term possible cardiovascular effects if not managed well. Furthermore, being a diabetic pregnant patient has even more risks and can lead to complications maternally and congenital complications and malformations in the offspring. One of the significant tasks for a patient with pre-conceptional diabetes and becoming pregnant is controlling hyperglycemia and preventing hypoglycemia. The prevalence of diabetes is on the rise, and gestational diabetes is one of the most widespread complications of pregnancy. The prevalence of gestational diabetes is currently about 10% of all pregnancies in the USA. Many studies have investigated the impact that maternal hyperglycemia has on the health of the offspring; furthermore, the concept of fetal programming has suggested that the intrauterine environment can affect offspring health due to postnatal environmental factors such as growth and nutrition. Most data on the influence of diabetes during pregnancy focuses on the offspring’s metabolic status, such as obesity issues and diabetes development in the offspring. In contrast, the impact on cardiac function Is much less studied. Studies that have been done show diabetic pregnancy disturbing metabolic status and altering fetal programming and studies that show high energy diets leading to hyperglycemia, insulin resistance, and late-onset cardiac dysfunction.

The hypothesis of this study suggested that in the transgenic rat model, a diabetic pregnancy impairs cardiac function in the adult offspring when fed with a high-fat diet. The objective is to investigate potential cardiac maladaptation independent of metabolic risk factors such as glucose intolerance and body weight. The study was done in rat models to show maternal type 2 diabetes characterized by maternal insulin resistance with hyperglycemia and hyperinsulinemia. Diabetes was preconceptionally induced in the rat models by a doxycycline-induced knockdown of the insulin receptor in transgenic rats. The male wild-type offspring of diabetic and normoglycemic pregnancies were raised by foster mothers and followed into adulthood. Subgroups were further divided by high-fat diet ad control. The rat models accessed the cardiac phenotype by speckle tracking echocardiography, circulating factors, immunohistochemistry, and gene expression in the heart.

During pregnancy, diabetic dams (pregnant female rats) showed a significantly higher blood glucose level in comparison to normoglycemic dams in the 1st, 2nd, and 3rd trimesters. 24.34 vs. 5.75 mmol/l in the first, 23.60 vs. 5.44 mmol/l in the second, and 17.48 vs. 5.26 mmol/l in the third trimester. Cardiovascular end-organ damage was also analyzed in the offspring, done at the end of the dietary challenge. The control fed group showed no noteworthy differences between the diabetic offspring and the non-diabetic offspring. However, after the high-fat diet challenge was complete and analyzed, data demonstrated global longitudinal strain and global circumferential strain were significantly reduced in the diabetic offspring compared to the non-diabetic offspring. In the diabetic offspring being fed a high-fat diet, there was also an increase in relative wall thickness, altered cardiac gene expression, enlarged cardiomyocytes, accumulation of immune cells in the heart, and increased BNP levels compared with normoglycemic offspring on a high-fat diet.

It is concluded that in rat models’ diabetic pregnancy induces cardiac dysfunction, left ventricular hypertrophy, and altered pro-inflammatory status in adult male offspring only after consuming a high-fat diet. The diabetic pregnancy was not enough to cause any sufficient myocardial dysfunction and gene expression later in life. Limitations to this study include the models being only male species; more studies should be done comparing male offspring to female offspring with other factors remaining the same. With the heart being such an essential major organ that is susceptible to damage during diabetic pregnancy in the presence of other major lifestyle modifications, it’s essential to continue to study the effect that diabetes and diet have on developmental defects in maternal diabetic offspring. The findings from these studies can lead to suggestions and guidelines on feeding for offspring of patients with preconceptual diabetes.

Practice Pearls:

• The prevalence of gestational diabetes is currently about 10% of all pregnancies in the USA.
• Diabetic pregnancy induces cardiac disfunction as well as left ventricular hypertrophy and altered proinflammatory status in adult male offspring only after consumption of a high fat diet in rat models.
• The heart is an important major organ, more studies should be conducted to conclude the predisposition diabetes and other lifestyle modifications have on cardiovascular health in offspring born from periconceptually diabetic mothers.

1. Schütte, T., Kedziora, S.M., Haase, N.et al. Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring—the heart as a target for fetal programming in rats. Diabetologia (2021). https://doi.org/10.1007/s00125-021-05566-5
2. https://www.express.co.uk/life-style/health/1490003/diabetes-gestational-high-blood-sugar-pregnancy-risks-astigmatism-eyesight

Erica Hicks, PharmD Candidate 2022, South College School of Pharmacy