Diabetic embryopathy refers to congenital maldevelopments that are linked to maternal

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

. Prenatal exposure to hyperglycemia can result in

spontaneous abortions Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is fetal viability, able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE a ...

perinatal mortality Perinatal mortality (PNM) refers to the death of a fetus or neonate and is the basis to calculate the perinatal mortality rate. Variations in the precise definition of the perinatal mortality exist, specifically concerning the issue of inclusion o ...

, and

malformations A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

. Type 1 and Type 2 diabetic pregnancies both increase the risk of diabetes induced

teratogenicity Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related ...

. The rate of

congenital malformation A birth defect, also known as a congenital disorder, is an abnormal condition that is present at childbirth, birth regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellect ...

s is similar in Type 1 and 2 mothers because of increased

adiposity Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...

and the age of women with type 2 diabetes. Genetic predisposition and different environmental factors both play a significant role in the development of diabetic embryopathy.

Metabolic dysfunction Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndrom ...

in pregnant mothers also increases the risk of fetal malformations.

Risk factors

Women with pregestational

are at the highest risk for fetal malformations. The risk of

s in pregestational

type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar ...

is directly correlated with

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

and glycohemoglobin levels in the blood. It is also inversely related to the gestational age at first exposure. The

comorbidities In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...

associated with pregestational

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...

include advanced maternal age, lipid preroxidation and

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

. Overweight women ( BMI ≥ 25) who develop gestational diabetes have an intermediate risk for malformations. Pregnant women who have gestational diabetes but don't have prediabetic markers experience perinatal outcomes that are similar to women without diabetes.

Gestational consequences

Malformations

Type 1 diabetes in pregnant women can result in malformations that affect the

musculoskeletal The human musculoskeletal system (also known as the human locomotor system, and previously the activity system) is an organ system that gives humans the ability to move using their muscular and skeletal systems. The musculoskeletal system prov ...

urogenital The genitourinary system, or urogenital system, are the organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathwa ...

, and

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

s. Most of these malformations occur within the first 4 weeks of gestation. Caudal dysgenesis is one of the most strongly associated diseases to diabetes. This malformation has the highest risk for diabetic embryopathy. Infants from diabetic mothers usually have several blastogenic malformations. Diabetic embryopathy is therefore an etiological subgroup of defects of blastogenesis that present different monotopic and polytopic developmental defects.

Abortion and perinatal deaths

Diabetic embryopathy may result in early or late spontaneous abortion and stillbirth. In maternal diabetes, 90% of pregnancy losses happen in the

first trimester Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

due to

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

. Diabetic embryopathy abortions in the second-trimester are most likely due to severe

birth defect A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities ca ...

, maternal metabolic derangement,

placental insufficiency Placental insufficiency or utero-placental insufficiency is the failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy, and is often a result of insufficient blood flow to the placenta. The term is also sometimes use ...

and fetal hypoxia due to membrane rupture.

Pathogenesis

The development of birth defects associated with maternal hyperglycemia is multi-factorial. Environmental factors and genetic predisposition (paternal, maternal and offspring

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...

) are important in diabetic embryopathy. The diets of diabetic mothers impacts the rate at which malformations form in their offspring. Furthermore, there is evidence that resistance to certain malformations caused by diabetes is genetic. Epigenetics and its relationship with various environmental factors such as metabolism and diet play a significant role in

teratogenesis Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related ...

. Hyperglycemia and associated teratogenic mediators influence DNA methylation,

non-coding RNA A non-coding RNA (ncRNA) is a functional RNA molecule that is not Translation (genetics), translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally im ...

expression,

histone modification In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are w ...

s and other epigenetic regulation mechanisms. Research is focused on exploring the impact of diabetic embryopathy on methylation signatures, which could potentially serve as a diagnostic

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...

for the condition.

Prevention

Preconception

The probability of major birth defects in offspring of mothers with diabetes is 0.7-4.4% for glycohemoglobin levels <7%. For glycohemoglobin levels >10% the probability of major birth defects is 16.1-100% with an average of 26.6%. The National Institute of Health and Clinical Excellence in the UK indicated that glycohemoglobin levels <6.1% are correlated with the lowest risk of malformations while the reproductive risks are higher in women above this threshold and prohibitive for glycohemoglobin levels >10%. Consumption of

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

and antioxidant substances before fertilization result in a reduced rate of malformations in the offspring of mothers with diabetes. Antioxidants such as lipoic acid,

vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) ...

, and

vitamin E Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vi ...

, increase the probability of favorable prenatal outcomes in offspring of diabetic mothers because oxidative stress is a teratogenic mediator of hyperglycemia in mothers with diabetes.

After fertilization

Optimal weight and

glycemic The glycemic response to a food or meal is the effect that food or meal has on blood sugar (glucose) levels after consumption.Sadler M. Food, Glycaemic Response and Health. ILSI Europe Concise Monograph Series 2011:1-30Available from ILSI Europe ...

management encourage good outcomes because diabetes has the potential to influence the mother and fetus during the entire pregnancy. The integrity of embryofetal development and placental function can be monitored by

fetal echocardiography Fetal echocardiography, or Fetal echocardiogram, is the name of the test used to diagnose cardiac conditions in the fetal stage. Cardiac defects are amongst the most common birth defects. Their diagnosis is important in the fetal stage as it might ...

and

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...

scanning.

References

{{DEFAULTSORT:Diabetic Embryopathy Diabetes

Risk factors

Gestational consequences

Malformations

Abortion and perinatal deaths

Pathogenesis

Prevention

Preconception

After fertilization

See also

References