Gestational diabetes | |
---|---|
Other names | Gestational diabetes mellitus (GDM) |
Universal blue circle symbol for diabetes [1] | |
Specialty | Obstetrics and endocrinology |
Symptoms | Typically few symptoms [2] |
Complications | Pre-eclampsia, stillbirth, depression, increased risk of requiring a Caesarean section [2] |
Usual onset | Most common last three months of pregnancy [2] |
Causes | Not enough insulin in the setting of insulin resistance [2] |
Risk factors | Overweight, previously having gestational diabetes, family history of type 2 diabetes, polycystic ovarian syndrome [2] |
Diagnostic method | Screening blood tests [2] |
Prevention | Maintaining a healthy weight and exercising before pregnancy [2] |
Treatment | Diabetic diet, exercise, insulin injections [2] |
Frequency | ~6% of pregnancies [3] |
Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. [2] Gestational diabetes generally results in few symptoms; [2] however, it increases the risk of pre-eclampsia, depression, and of needing a Caesarean section. [2] Babies born to mothers with poorly treated gestational diabetes are at increased risk of macrosomia, of having hypoglycemia after birth, and of jaundice. [2] If untreated, diabetes can also result in stillbirth. [2] Long term, children are at higher risk of being overweight and of developing type 2 diabetes. [2]
Gestational diabetes can occur during pregnancy because of insulin resistance or reduced production of insulin. [2] Risk factors include being overweight, previously having gestational diabetes, a family history of type 2 diabetes, and having polycystic ovarian syndrome. [2] Diagnosis is by blood tests. [2] For those at normal risk, screening is recommended between 24 and 28 weeks' gestation. [2] [3] For those at high risk, testing may occur at the first prenatal visit. [2]
Maintenance of healthy weight and exercising before pregnancy assist in prevention. [2] Gestational diabetes is treated with a diabetic diet, exercise, medication (such as metformin), and sometimes insulin injections. [2] Most women manage blood sugar with diet and exercise. [3] Blood sugar testing among those who are affected is often recommended four times a day. [3] Breastfeeding is recommended as soon as possible after birth. [2]
Gestational diabetes affects 3–9% of pregnancies, depending on the population studied. [3] It is especially common during the third trimester. [2] It affects 1% of those under the age of 20 and 13% of those over the age of 44. [3] A number of ethnic groups including Asians, American Indians, Indigenous Australians, and Pacific Islanders are at higher risk. [3] [2] However, the variations in prevalence are also due to different screening strategies and diagnostic criteria being used. In 90% of cases, gestational diabetes resolves after the baby is born. [2] Women, however, are at an increased risk of developing type 2 diabetes. [3]
Gestational diabetes is formally defined as "any degree of glucose intolerance with onset or first recognition during pregnancy". [4] This definition acknowledges the possibility that a woman may have previously undiagnosed diabetes mellitus, or may have developed diabetes coincidentally with pregnancy. Whether symptoms subside after pregnancy is also irrelevant to the diagnosis. [5] A woman is diagnosed with gestational diabetes when glucose intolerance continues beyond 24 to 28 weeks of gestation.
The White classification, named after Priscilla White, [6] who pioneered research on the effect of diabetes types on perinatal outcome, is widely used to assess maternal and fetal risk. [7] It distinguishes between gestational diabetes (type A) and pregestational diabetes (diabetes that existed prior to pregnancy). These two groups are further subdivided according to their associated risks and management. [8]
The two subtypes of gestational diabetes under this classification system are:
Diabetes which existed prior to pregnancy is also split up into several subtypes under this system:[ medical citation needed ]
An early age of onset or long-standing disease comes with greater risks, hence the first three subtypes.[ medical citation needed ]
Two other sets of criteria are available for diagnosis of gestational diabetes, both based on blood-sugar levels. [9]
Criteria for diagnosis of gestational diabetes, using the 100 gram Glucose Tolerance Test, according to Carpenter and Coustan: [10]
Criteria for diagnosis of gestational diabetes according to National Diabetes Data Group: [9] [11]
Classical risk factors for developing gestational diabetes are: [12]
In addition to this, statistics show a double risk of GDM in smokers. [18] Some studies have looked at more controversial potential risk factors, such as short stature. [19]
About 40–60% of women with GDM have no demonstrable risk factor; for this reason many advocate to screen all women. [20] Typically, women with GDM exhibit no symptoms (another reason for universal screening), but some women may demonstrate increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection, yeast infections and blurred vision. [21]
The precise mechanisms underlying gestational diabetes remain unknown. The hallmark of GDM is increased insulin resistance. Pregnancy hormones and other factors are thought to interfere with the action of insulin as it binds to the insulin receptor. The interference probably occurs at the level of the cell signaling pathway beyond the insulin receptor. [22] Since insulin promotes the entry of glucose into most cells, insulin resistance prevents glucose from entering the cells properly. As a result, glucose remains in the bloodstream, where glucose levels rise. More insulin is needed to overcome this resistance; about 1.5–2.5 times more insulin is produced than in a normal pregnancy. [22]
Insulin resistance is a normal phenomenon emerging in the second trimester of pregnancy, which in cases of GDM progresses thereafter to levels seen in a non-pregnant woman with type 2 diabetes. It is thought to secure glucose supply to the growing fetus. Women with GDM have an insulin resistance that they cannot compensate for with increased production in the β-cells of the pancreas. Placental hormones, and, to a lesser extent, increased fat deposits during pregnancy, seem to mediate insulin resistance during pregnancy. Cortisol and progesterone are the main culprits, but human placental lactogen, prolactin and estradiol contribute, too. Multivariate stepwise regression analysis reveals that, in combination with other placental hormones, leptin, tumor necrosis factor alpha, and resistin are involved in the decrease in insulin sensitivity occurring during pregnancy, with tumor necrosis factor alpha named as the strongest independent predictor of insulin sensitivity in pregnancy. [23] An inverse correlation with the changes in insulin sensitivity from the time before conception through late gestation accounts for about half of the variance in the decrease in insulin sensitivity during gestation: in other words, low levels or alteration of TNF alpha factors corresponds with a greater chance of, or predisposition to, insulin resistance or sensitivity. [24]
It is unclear why some women are unable to balance insulin needs and develop GDM; however, a number of explanations have been given, similar to those in type 2 diabetes: autoimmunity, single gene mutations, obesity, along with other mechanisms. [25]
Though the clinical presentation of gestational diabetes is well characterized, the biochemical mechanism behind the disease is not well known. One proposed biochemical mechanism involves insulin-producing β-cell adaptation controlled by the HGF/c-MET signaling pathway. β-cell adaption refers to the change that pancreatic islet cells undergo during pregnancy in response to maternal hormones in order to compensate for the increased physiological needs of mother and baby. These changes in the β-cells cause increased insulin secretion as a result of increased β-cell proliferation. [26] HGF/c-MET has also been implicated in β-cell regeneration, which suggests that HGF/c-MET may help increase β-cell mass in order to compensate for insulin needs during pregnancy. Recent studies support that loss of HGF/c-MET signaling results in aberrant β-cell adaptation. [27] [28]
c-MET is a receptor tyrosine kinase (RTK) that is activated by its ligand, hepatocyte growth factor (HGF), and is involved in the activation of several cellular processes. When HGF binds c-MET, the receptor homodimerizes and self-phosphorylates to form an SH2 recognition domain. The downstream pathways activated include common signaling molecules such as RAS and MAPK, which affect cell motility, and cell cycle progression. [29]
Studies have shown that HGF is an important signaling molecule in stress related situations where more insulin is needed. Pregnancy causes increased insulin resistance and so a higher insulin demand. The β-cells must compensate for this by either increasing insulin production or proliferating. If neither of the processes occur, then markers for gestational diabetes are observed. It has been observed that pregnancy increases HGF levels, showing a correlation that suggests a connection between the signaling pathway and increased insulin needs. In fact, when no signaling is present, gestational diabetes is more likely to occur. [27]
The exact mechanism of HGF/c-MET regulated β-cell adaptation is not yet known but there are several hypotheses about how the signaling molecules contribute to insulin levels during pregnancy. c-MET may interact with FoxM1, a molecule important in the cell cycle, as FOXM1 levels decrease when c-MET is not present. Additionally, c-MET may interact with p27 as the protein levels increase with c-MET is not present. Another hypothesis says that c-MET may control β-cell apoptosis because a lack of c-MET causes increases cell death but the signaling mechanisms have not been elucidated. [28]
Although the mechanism of HGF/c-MET control of gestational diabetes is not yet well understood, there is a strong correlation between the signaling pathway and the inability to produce an adequate amount of insulin during pregnancy and thus it may be the target for future diabetic therapies. [27] [28]
Because glucose travels across the placenta (through diffusion facilitated by GLUT1 carrier), which is located in the syncytiotrophoblast on both the microvillus and basal membranes, these membranes may be the rate-limiting step in placental glucose transport. There is a two- to three-fold increase in the expression of syncytiotrophoblast glucose transporters with advancing gestation. Finally, the role of GLUT3/GLUT4 transport remains speculative. If the untreated gestational diabetes fetus is exposed to consistently higher glucose levels, this leads to increased fetal levels of insulin (insulin itself cannot cross the placenta). The growth-stimulating effects of insulin can lead to excessive growth and a large body (macrosomia). After birth, the high glucose environment disappears, leaving these newborns with ongoing high insulin production and susceptibility to low blood glucose levels (hypoglycemia). [30]
Non-challenge blood glucose test
|
Screening glucose challenge test |
Oral glucose tolerance test (OGTT) |
A number of screening and diagnostic tests have been used to look for high levels of glucose in plasma or serum in defined circumstances. One method is a stepwise approach where a suspicious result on a screening test is followed by diagnostic test. Alternatively, a more involved diagnostic test can be used directly at the first prenatal visit for a woman with a high-risk pregnancy. (for example in those with polycystic ovarian syndrome or acanthosis nigricans). [30]
Non-challenge blood glucose tests involve measuring glucose levels in blood samples without challenging the subject with glucose solutions. A blood glucose level is determined when fasting, two hours after a meal, or simply at any random time. In contrast, challenge tests involve drinking a glucose solution and measuring glucose concentration thereafter in the blood; in diabetes, they tend to remain high. The glucose solution has a very sweet taste which some women find unpleasant; sometimes, therefore, artificial flavours are added. Some women may experience nausea during the test, and more so with higher glucose levels. [31] [32]
There is currently not enough research to show which way is best at diagnosing gestational diabetes. [33] Routine screening of women with a glucose challenge test may find more women with gestational diabetes than only screening women with risk factors. [34] Hemoglobin A1c (HbA1c) is not recommended for diagnosing gestational diabetes, as it's a less reliable marker of glycemia during pregnancy than oral glucose tolerance testing (OGTT). [35]
Opinions differ about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs. [36] The most elaborate regimen entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks' gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, a woman may be tested earlier. [5]
In the United States, most obstetricians prefer universal screening with a screening glucose challenge test. [37] In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. [30] [38] The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the woman is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors) [5] [36] The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening. [39] [40] The U.S. Preventive Services Task Force found there is insufficient evidence to recommend for or against routine screening, [41] and a 2017 a Cochrane review found that there is not evidence to determine which screening method is best for women and their babies. [34]
Some pregnant women and careproviders choose to forgo routine screening due to the absence of risk factors, however this is not advised due to the large proportion of women who develop gestational diabetes despite having no risk factors present and the dangers to the mother and baby if gestational diabetes remains untreated. [20]
When a plasma glucose level is found to be higher than 126 mg/dL (7.0 mmol/L) after fasting, or over 200 mg/dL (11.1 mmol/L) on any occasion, and if this is confirmed on a subsequent day, the diagnosis of GDM is made, and no further testing is required. [5] These tests are typically performed at the first antenatal visit. They are simple to administer and inexpensive, but have a lower test performance compared to the other tests, with moderate sensitivity, low specificity and high false positive rates. [42] [43] [44]
The screening glucose challenge test (sometimes called the O'Sullivan test) is performed between 24 and 28 weeks, and can be seen as a simplified version of the oral glucose tolerance test (OGTT). No previous fasting is required for this screening test, [45] in contrast to the OGTT. The O'Sullivan test involves drinking a solution containing 50 grams of glucose, and measuring blood levels one hour later. [46]
If the cut-off point is set at 140 mg/dL (7.8 mmol/L), 80% of women with GDM will be detected. [5] If this threshold for further testing is lowered to 130 mg/dL, 90% of GDM cases will be detected, but there will also be more women who will be subjected to a consequent OGTT unnecessarily.
A standardized oral glucose tolerance test (OGTT) [47] should be done in the morning after an overnight fast of between 8 and 14 hours. During the three previous days the subject must have an unrestricted diet (containing at least 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated during the test and should not smoke throughout the test.
IADPSG (International Association of Diabetes and Pregnancy Study Groups) has developed diagnostic criteria for GDM, based on the results of adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. [48] These were recommended by WHO 2013. [49]
According to these gestational diabetes mellitus should be diagnosed at any time in pregnancy if one of the following criteria are met, using a 75 g glucose OGTT:
Women with GDM may have high glucose levels in their urine (glucosuria). Although dipstick testing is widely practiced, it performs poorly, and discontinuing routine dipstick testing has not been shown to cause underdiagnosis where universal screening is performed. [50] Increased glomerular filtration rates during pregnancy contribute to some 50% of women having glucose in their urine on dipstick tests at some point during their pregnancy. The sensitivity of glucosuria for GDM in the first two trimesters is only around 10% and the positive predictive value is around 20%. [51] [52]
Vitamin D supplementation during pregnancy may help to prevent gestational diabetes. [53] A 2015 review found that when done during pregnancy moderate physical exercise is effective for the prevention of gestational diabetes. [54] A 2014 review however did not find a significant effect. [55] It is uncertain if additional dietary advice interventions help to reduce the risk of gestational diabetes. [56] However, data from the Nurses' Health Study shows that adherence to a healthy plant-based diet is associated with lower risk for GDM. [57] Diet and physical activity interventions designed to prevent excessive gestational weight gain reduce the rates of gestational diabetes. However, the impact of these interventions varies with the body-mass index of the person as well as with the region in which the studies were performed. [58]
Moderate-quality evidence suggest that there is a reduced risk of gestational diabetes mellitus and caesarean section with combined diet and exercise interventions during pregnancy as well as reductions in gestational weight gain, compared with standard care. [59]
A 2023 review found that a plant-based diet (including fruits, vegetables, whole grains, nuts and seeds, and tea) rich in phytochemicals lowers the risk of GDM. [60] A Cochrane review, updated 2023, stated that myo‐inositol has a potential beneficial effect of improving insulin sensitivity, which suggested that it may be useful for women in preventing gestational diabetes″. [61]
It has been suggested that for women who have had gestational diabetes, diet, exercise, education, and lifestyle changes between pregnancies may lower their chances of having gestational diabetes again in future pregnancies. [62] However, there is no research to show whether interventions between pregnancies lower the number of women who develop gestational diabetes again. [62]
Treatment of GDM with diet and insulin reduces health problems mother and child. [63] Treatment of GDM is also accompanied by more inductions of labour. [63]
A repeat OGTT should be carried out 6 weeks after delivery, to confirm the diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is advised. [12]
Lifestyle interventions include exercise, diet advice, behavioural interventions, relaxation, self-monitoring glucose, and combined interventions. [64] Women with gestational diabetes who receive lifestyle interventions seem to have less postpartum depression, and were more likely to reach their weight loss targets after giving birth, than women who had no intervention. [64] Their babies are also less likely to be large for their gestational age, and have less percentage of fat when they are born. [64] More research is needed to find out which lifestyle interventions are best. [64] Some women with GDM use probiotics but it is very uncertain if there are any benefits in terms of blood glucose levels, high blood pressure disorders or induction of labour. [65]
If a diabetic diet or G.I. Diet, exercise, and oral medication are inadequate to control glucose levels, insulin therapy may become necessary.[ citation needed ]
The development of macrosomia can be evaluated during pregnancy by using sonography. Women who use insulin, with a history of stillbirth, or with hypertension are managed like women with overt diabetes. [20]
Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes. [66] Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy.[ citation needed ]
Any diet needs to provide sufficient calories for pregnancy, typically 2,000–2,500 kcal with the exclusion of simple carbohydrates. [20] The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources—known as the G.I. Diet. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more. [12]
The Mediterranean diet may be associated with reduced incidence of gestational diabetes. [67] However, there is not enough evidence to indicate if one type of dietary advice is better than another. [68]
Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM. [12] [69] Pregnant women who exercise have lower blood sugar levels when fasting and after meals compared to those who do not exercise. [70] It is not clear which form of exercise is best when pregnant. [70]
Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low. [71] There is not a lot of research into what target blood sugar levels should be for women with gestational diabetes and targets recommended to women vary around the world. [72] Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows: [12]
Regular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period. [12]
Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child. [73]
If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might be necessary. This is most commonly fast-acting insulin given just before eating to blunt glucose rises after meals. [12] Care needs to be taken to avoid low blood sugar levels due to excessive insulin. Insulin therapy can be normal or very tight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits. [30] [74] A 2016 Cochrane review (updated in 2023) concluded that quality evidence is not yet available to determine the best blood sugar range for improving health for pregnant women with GDM and their babies. [72]
There is some evidence that certain medications by mouth might be safe in pregnancy, or at least, are less dangerous to the developing fetus than poorly controlled diabetes. When comparing which diabetes tablets (medication by mouth) work best and are safest, there is not enough quality research to support one medication over another. [75] The medication metformin is better than glyburide. [76] If blood glucose cannot be adequately controlled with a single agent, the combination of metformin and insulin may be better than insulin alone. [76] Another review found good short term safety for both the mother and baby with metformin but unclear long term safety. [77]
People may prefer metformin by mouth to insulin injections. [3] Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels. [78]
Almost half of the women did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight. [79] With no long-term studies into children of women treated with the drug, there remains a possibility of long-term complications from metformin therapy. [3] Babies born to women treated with metformin have been found to develop less visceral fat, making them less prone to insulin resistance in later life. [79]
Gestational diabetes generally resolves once the baby is born. Based on different studies, the chances of developing GDM in a second pregnancy, if a woman had GDM in her first pregnancy, are between 30 and 84%, depending on ethnic background. A second pregnancy within one year of the previous pregnancy has a large likelihood of GDM recurrence. [80]
Women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future. The risk is highest in women who needed insulin treatment, had antibodies associated with diabetes (such as antibodies against glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2), women with more than two previous pregnancies, and women who were obese (in order of importance). [81] [82] Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years. [83] Depending on the population studied, the diagnostic criteria and the length of follow-up, the risk can vary enormously. [84] The risk appears to be highest in the first 5 years, reaching a plateau thereafter. [84] One of the longest studies followed a group of women from Boston, Massachusetts; half of them developed diabetes after 6 years, and more than 70% had diabetes after 28 years. [84] In a retrospective study in Navajo women, the risk of diabetes after GDM was estimated to be 50 to 70% after 11 years. [85] Another study found a risk of diabetes after GDM of more than 25% after 15 years. [86] In populations with a low risk for type 2 diabetes, in lean subjects and in women with auto-antibodies, there is a higher rate of women developing type 1 diabetes (LADA). [82]
Children of women with GDM have an increased risk for childhood and adult obesity and an increased risk of glucose intolerance and type 2 diabetes later in life. [87] This risk relates to increased maternal glucose values. [88] It is currently unclear how much genetic susceptibility and environmental factors contribute to this risk, and whether treatment of GDM can influence this outcome. [89]
Relative benefits and harms of different oral anti-diabetic medications are not yet well understood as of 2017. [75]
There are scarce statistical data on the risk of other conditions in women with GDM; in the Jerusalem Perinatal study, 410 out of 37,962 women were reported to have GDM, and there was a tendency towards more breast and pancreatic cancer, but more research is needed to confirm this finding. [90] [91]
Research is being conducted to develop a web-based clinical decision support system for GDM prediction using machine learning techniques. Results so far demonstrated great potential in clinical practicality for automatic GDM prognosis. [92]
GDM poses a risk to mother and child. This risk is largely related to uncontrolled blood glucose levels and its consequences. The risk increases with higher blood glucose levels. [93] Treatment resulting in better control of these levels can reduce some of the risks of GDM considerably. [71]
The two main risks GDM imposes on the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit. Infants born to mothers with GDM are at risk of being both large for gestational age (macrosomic) [93] in unmanaged GDM, and small for gestational age and Intrauterine growth retardation [94] in managed GDM. Macrosomia in turn increases the risk of instrumental deliveries (e.g. forceps, ventouse and caesarean section) or problems during vaginal delivery (such as shoulder dystocia). Macrosomia may affect 12% of normal women compared to 20% of women with GDM. [30] However, the evidence for each of these complications is not equally strong; in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study for example, there was an increased risk for babies to be large but not small for gestational age in women with uncontrolled GDM. [93] In a recent birth cohot study of 5150 deliveries, a research group active at the University of Helsinki and Helsinki University Hospital, Finland demonstrated that the mother's GDM is an independent factor that increases the risk of fetal hypoxia, during labour. The study was published in the Acta Diabetologica in June 2021. [95] Another finding was that GDM increased the susceptibility of the fetus to intrapartum hypoxia, regardless of the size of the fetus. [95] The risk of hypoxia and the resulting risk of poor condition in newborn infants was nearly 7-fold in the fetuses of mothers with GDM compared to the fetuses of non-diabetic mothers. [95] Furthermore, according to the findings, the risk of needing to perform resuscitation on the newborn after birth was 10-fold. [95]
Another finding was that gestational diabetes increased the susceptibility of the fetus to intrapartal hypoxia, regardless of the size of the fetus.[ citation needed ]
"The risk of hypoxia and the resulting risk of poor condition in newborn infants was nearly seven-fold in the fetuses of mothers with gestational diabetes compared to the fetuses of non-diabetic mothers," says researcher Mikko Tarvonen. According to the findings, the risk of needing to perform resuscitation on the newborn was ten-fold.Research into complications for GDM is difficult because of the many confounding factors (such as obesity). Labelling a woman as having GDM may in itself increase the risk of having an unnecessary caesarean section. [96] [97]
Neonates born from women with consistently high blood sugar levels are also at an increased risk of low blood glucose (hypoglycemia), jaundice, high red blood cell mass (polycythemia) and low blood calcium (hypocalcemia) and magnesium (hypomagnesemia). [98] Untreated GDM also interferes with maturation, causing dysmature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis. [98]
Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first and early second trimester. Studies have shown that the offspring of women with GDM are at a higher risk for congenital malformations. [99] [100] [101] A large case-control study found that gestational diabetes was linked with a limited group of birth defects, and that this association was generally limited to women with a higher body mass index (≥ 25 kg/m2). [102] It is difficult to make sure that this is not partially due to the inclusion of women with pre-existent type 2 diabetes who were not diagnosed before pregnancy.
Because of conflicting studies, it is unclear at the moment whether women with GDM have a higher risk of preeclampsia. [103] In the HAPO study, the risk of preeclampsia was between 13% and 37% higher, although not all possible confounding factors were corrected. [93]
Gestational diabetes affects 3–10% of pregnancies, depending on the population studied. [3] [104]
Insulin resistance (IR) is a pathological condition in which cells either fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.
The glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, impaired beta cell function, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of carbohydrate metabolism. In the most commonly performed version of the test, an oral glucose tolerance test (OGTT), a standard dose of glucose is ingested by mouth and blood levels are checked two hours later. Many variations of the GTT have been devised over the years for various purposes, with different standard doses of glucose, different routes of administration, different intervals and durations of sampling, and various substances measured in addition to blood glucose.
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent fasting blood glucose range between ~5.6 and ~7 mmol/L is considered slightly hyperglycemic, and above 7 mmol/L is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.
Type 2 diabetes (T2D), 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 urination, fatigue and unexplained weight loss. Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics. Metformin is not associated with weight gain and is taken by mouth.
Drugs used in diabetes treat diabetes mellitus by decreasing the glucose level in the blood. With the exception of insulin, most GLP receptor agonists, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and their selection depends on the nature of diabetes, age, and situation of the person, as well as other factors.
Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea, a dehydrogenated derivative of urea). The side chains R1 and R2 distinguish various sulfonylureas. Sulfonylureas are the most widely used herbicide.
Hyperinsulinemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and conditions, as well as non-nutritive sugars in the diet. While hyperinsulinemia is often seen in people with early stage type 2 diabetes mellitus, it is not the cause of the condition and is only one symptom of the disease. Type 1 diabetes only occurs when pancreatic beta-cell function is impaired. Hyperinsulinemia can be seen in a variety of conditions including diabetes mellitus type 2, in neonates and in drug-induced hyperinsulinemia. It can also occur in congenital hyperinsulinism, including nesidioblastosis.
Large for gestational age (LGA) is a term used to describe infants that are born with an abnormally high weight, specifically in the 90th percentile or above, compared to other babies of the same developmental age. Macrosomia is a similar term that describes excessive birth weight, but refers to an absolute measurement, regardless of gestational age. Typically the threshold for diagnosing macrosomia is a body weight between 4,000 and 4,500 grams, or more, measured at birth, but there are difficulties reaching a universal agreement of this definition.
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate glucose levels in the bloodstream. Before treatment this results in high blood sugar levels in the body. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks if not months.
The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentrations of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces significant amounts of the hormone insulin, usually owing to the autoimmune destruction of the insulin-producing beta cells of the pancreas. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance. The pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the various forms of maturity-onset diabetes of the young, may represent some combination of insufficient insulin production and insulin resistance. Some degree of insulin resistance may also be present in a person with type 1 diabetes.
For pregnant women with diabetes, some particular challenges exist for both mother and fetus. If the pregnant woman has diabetes as a pre-existing disorder, it can cause early labor, birth defects, and larger than average infants. Therefore, experts advise diabetics to maintain blood sugar level close to normal range about 3 months before planning for pregnancy.
Exenatide, sold under the brand name Byetta and Bydureon among others, is a medication used to treat diabetes mellitus type 2. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after metformin and sulfonylureas. It is given by injection under the skin twice daily or once weekly.
Slowly evolving immune-mediated diabetes, or latent autoimmune diabetes in adults (LADA), is a form of diabetes that exhibits clinical features similar to both type 1 diabetes (T1D) and type 2 diabetes (T2D), and is sometimes referred to as type 1.5 diabetes. It is an autoimmune form of diabetes, similar to T1D, but patients with LADA often show insulin resistance, similar to T2D, and share some risk factors for the disease with T2D. Studies have shown that LADA patients have certain types of antibodies against the insulin-producing cells, and that these cells stop producing insulin more slowly than in T1D patients. Since many people develop the disease later in life, it is often misdiagnosed as type 2 diabetes.
Metabolic imprinting refers to the long-term physiological and metabolic effects that an offspring's prenatal and postnatal environments have on them. Perinatal nutrition has been identified as a significant factor in determining an offspring's likelihood of it being predisposed to developing cardiovascular disease, obesity, and type 2 diabetes amongst other conditions.
Prediabetes is a component of metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesity, dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. It is also associated with increased risk for cardiovascular disease (CVD). Prediabetes is more accurately considered an early stage of diabetes as health complications associated with type 2 diabetes often occur before the diagnosis of diabetes.
A high-risk pregnancy is a pregnancy where the mother or the fetus has an increased risk of adverse outcomes compared to uncomplicated pregnancies. No concrete guidelines currently exist for distinguishing “high-risk” pregnancies from “low-risk” pregnancies; however, there are certain studied conditions that have been shown to put the mother or fetus at a higher risk of poor outcomes. These conditions can be classified into three main categories: health problems in the mother that occur before she becomes pregnant, health problems in the mother that occur during pregnancy, and certain health conditions with the fetus.
Diabetes mellitus, often known simply as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body becoming unresponsive to the hormone's effects. Classic symptoms include thirst, polyuria, weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Untreated or poorly treated diabetes accounts for approximately 1.5 million deaths every year.
The Disposition index (DI) is a measure for the loop gain of the insulin-glucose feedback control system. It is defined as the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. "Metabolically healthy" Insulin resistant individuals can maintain normal responses to blood glucose due to the fact that higher levels of insulin are secreted as long as the beta cells of the pancreas are able to increase their output of insulin to compensate for the insulin resistance. But the ratio of the incremental increase in plasma insulin associated with an incremental increase in plasma glucose provides a better measure of beta cell function than the plasma insulin response to a glucose challenge. Loss of function of the beta cells, reducing their capacity to compensate for insulin resistance, results in a lower disposition index.
Dr. Maria Ruth B. Pineda-Cortel is an associate professor and laboratory coordinator at the University of Santo Tomas (UST) where she teaches at the Department of Medical Technology of the Faculty of Pharmacy. She also does research at the university's Research Center for the Natural Sciences and Applied Sciences (RCNAS). Pineda-Cortel has done extensive research focusing on gestational diabetes mellitus and polycystic ovarian syndrome (PCOS) as a way to shed light on diseases that only affect women. As a woman of science, she advocates and works towards improving healthcare for women. Pineda-Cortel has also done research covering many health-related issues that include the effects of climate change on infectious diseases that are prevalent in the Philippines, such as dengue and malaria.
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