Gestational diabetes
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224359889
2008-07-08T14:40:08Z
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/* Prognosis */
{{DiseaseDisorder infobox |
Name = Gestational diabetes |
ICD10 = {{ICD10|O|24||o|20}} |
ICD9 = {{ICD9|648.8}} |
MedlinePlus = 000896 |
}}
'''Gestational diabetes''' (or '''gestational diabetes mellitus''', '''GDM''') is a condition in which women without previously diagnosed [[Diabetes mellitus|diabetes]] exhibit [[hyperglycemia|high blood glucose]] levels during pregnancy. Gestational diabetes affects 3-10% of pregnancies, depending on the population studied.<ref name="emedicine">Thomas R Moore, MD et al. Diabetes Mellitus and Pregnancy. {{eMedicine|med|2349}}. Version: Jan 27, 2005 update.</ref> No specific cause has been identified, but it is believed that the hormones produced during pregnancy reduce a woman's sensitivity to [[insulin]], resulting in high blood sugar levels.
Gestational diabetes generally has few [[symptoms]] and it is most commonly diagnosed by [[screening]] during pregnancy. Diagnostic tests detect high levels of [[glucose]] in blood samples.
Babies born to mothers with gestational diabetes are at increased risk of complications, primarily growth abnormalities and chemical imbalances such as [[hypoglycemia|low blood sugar]]. Gestational diabetes is a reversible condition and women who have adequate [[glycemic control|control of glucose levels]] can effectively decrease the associated risks and give birth to healthy babies.
Women with gestational diabetes are at increased risk of developing [[type 2 diabetes mellitus]] after pregnancy, while their offspring are prone to developing [[childhood obesity]], with [[type 2 diabetes]] later in life. Most patients are treated only with diet modification and moderate exercise but some take [[anti-diabetic drugs]], including [[insulin]].
<br clear="right">{{Diabetes}}
==Definition==
Gestational diabetes is formally defined as "any degree of [[glucose intolerance]] with onset or first recognition during pregnancy".<ref name="definition">Metzger BE, Coustan DR (Eds.). Proceedings of the Fourth International Work-shop-Conference on Gestational Diabetes Mellitus. ''Diabetes Care'' 1998; '''21 (Suppl. 2)''': B1–B167.</ref> This definition acknowledges the possibility that patients 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 .<ref name="ADA2004">[[American Diabetes Association]]. Gestational Diabetes Mellitus. ''Diabetes Care'' 2004; '''27''': S88-90. PMID 14693936</ref>
==Epidemiology==
The frequency of gestational diabetes varies widely by study depending on the population studied and the [[study design]]. It occurs in between 5 and 10% of all pregnancies (between 1-14% in various studies).<ref name="ADA2004"/>
==Pathophysiology==
[[Image:insulin glucose metabolism.jpg|left|thumbnail|400px|'''Effect of insulin on glucose uptake and metabolism.''' Insulin binds to its receptor (1) on the cell membrane which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the [[plasma membrane]] and influx of glucose (3), [[glycogen]] synthesis (4), [[glycolysis]] (5) and [[fatty acid]] synthesis (6).]]
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 behind the insulin receptor.<ref name="clinicaldiabetes">Carr DB, Gabbe S. [http://journal.diabetes.org/clinicaldiabetes/v16n1J-F98/pg4.htm Gestational Diabetes: Detection, Management, and Implications]. Clin Diabetes 1998; 16(1): 4.</ref>. 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 in a normal pregnancy.<ref name="clinicaldiabetes">Carr DB, Gabbe S. [http://journal.diabetes.org/clinicaldiabetes/v16n1J-F98/pg4.htm Gestational Diabetes: Detection, Management, and Implications]. Clin Diabetes 1998; 16(1): 4.</ref>
Insulin resistance is a normal phenomenon emerging in the second trimester of pregnancy, which progresses thereafter to levels seen in non-pregnant patients with type 2 diabetes. It is thought to secure glucose supply to the growing fetus. Women with GDM have an insulin resistance they cannot compensate with increased production in the β-cells of the pancreas. [[Placenta]]l [[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 chorionic somatomammotropin]], [[prolactin]] and [[estradiol]] contribute too.<ref name="clinicaldiabetes">Carr DB, Gabbe S. [http://journal.diabetes.org/clinicaldiabetes/v16n1J-F98/pg4.htm Gestational Diabetes: Detection, Management, and Implications]. Clin Diabetes 1998; 16(1): 4.</ref>
How this imbalance between insulin needs and production develops in GDM, remains unclear. Suggested mechanisms are similar to those in type 2 diabetes: [[autoimmunity]], single gene [[mutations]], and other mechanisms.<ref name="pathophysiology">Buchanan TA, Xiang AH. Gestational diabetes mellitus. ''J Clin Invest'' 2005; '''115(3)''': 485–491. PMID 15765129</ref>
Because glucose travels across the placenta (through [[Facilitated diffusion|diffusion facilitated]] by [[GLUT3]] carriers), the fetus is exposed to 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]]).<ref name="controversies">Kelly L, Evans L, Messenger D. Controversies around gestational diabetes. Practical information for family doctors. ''Can Fam Physician'' 2005; '''51''': 688-95. PMID 15934273 {{PMC|15934273}}</ref>
==Risk factors and symptoms==
Classical risk factors for developing gestational diabetes are the following:<ref name="ACHOISreview">Ross G. Gestational diabetes. ''Aust Fam Physician'' 2006; 35(6): '''392-6'''. PMID 16751853</ref>
* a previous diagnosis of gestational diabetes or prediabetes, [[impaired glucose tolerance]], or [[impaired fasting glycaemia]]
* a [[Family history (medicine)|family history]] revealing a first degree relative with [[Diabetes mellitus type 2|type 2 diabetes]]
* maternal age - a woman's risk factor increases as she gets older (especially for women over 35 years of age)
* ethnic background (those with higher risk factors include [[African-Americans]], [[Afro-Caribbeans]], [[Indigenous peoples of the Americas|Native Americans]], [[Hispanics]] and people originating from the [[Indian subcontinent]])
* being [[overweight]], [[obesity|obese]] or severely obese increases the risk by a factor 2.1, 3.6 and 8.6, respectively.<ref name="obesity">Chu SY, Callaghan WM, Kim SY, Schmid CH, Lau J, England LJ, Dietz PM. Maternal obesity and risk of gestational diabetes mellitus. ''Diabetes Care'' 2007; '''30(8)''': 2070-6. PMID 17416786</ref>
* a previous pregnancy which resulted in a child with a high birth weight (>90th centile, or >4000 g)
* previous poor obstetric history
In addition to this, statistics show a double risk of GDM in [[smoking|smokers]].<ref name="smoking">England LJ, Levine RJ, Qian C, ''et. al''. Glucose tolerance and risk of gestational diabetes mellitus in nulliparous women who smoke during pregnancy. Am J Epidemiol 2004; 160(12): 1205-13. PMID 15583373</ref> [[Polycystic ovarian syndrome]] is also a risk factor.<ref name="ACHOISreview"/> Some studies have looked at more controversial potential risk factors, such as [[short stature]].<ref name="short">Ma RM, Lao TT, Ma CL, ''et. al''. Relationship between leg length and gestational diabetes mellitus in Chinese pregnant women. ''Diabetes Care'' 2007; '''30(11)''': 2960-1. PMID 17666468</ref>
Frequently women with gestational diabetes exhibit no symptoms (which is an argument in favour of screening during pregnancy). However, possible symptoms include increased [[thirst]], increased [[urination]], [[Fatigue (medical)|fatigue]], [[nausea]] and [[vomiting]], [[cystitis|bladder infection]], [[yeast infection]]s and [[blurred vision]].
==Diagnosis and screening==
Because GDM is asymptomatic in most cases, the diagnosis of gestational diabetes is a process that takes into account a clinical assessment of risk factors, [[screening test]]s and diagnostic tests. These tests look for high levels of [[glucose]] in [[plasma]] or [[serum]]. This can be done in a stepwise approach where a suspicious result on a screening test is followed by diagnosic test. Alternatively, a more complicated diagnostic test can be used directly at the first antenatal visit in high-risk patients (for example in those with [[polycystic ovarian syndrome]] or [[acanthosis nigricans]]).<ref name="controversies"/>
{| class="wikitable" style="text-align:left; margin: 1em auto 1em auto"
|+Tests for gestational diabetes
|-
|Non-challenge blood glucose tests
*Fasting glucose test
*2-hour [[postprandial]] (after a meal) glucose test
*Random glucose test
|-
|Screening glucose challenge test
|-
|[[Oral glucose tolerance test]] (OGTT)
|-
|}
Non-challenge blood glucose tests involve measuring glucose levels in blood samples without challenging the subject with glucose solutions. A blood glucose levels can be determined when fasting, 2 hours after a meal, or simply at any random time. Both screening glucose challenge tests and oral glucose tolerance tests involve drinking a glucose solution, to check how the body handles this glucose challenge.
The screening glucose challenge test and oral glucose tolerance test involve drinking a standard solution with a high concentration of glucose, which has a very sweet taste some women find unpleasant. Sometimes, artificial flavours are added for this reason. Some women may experience nausea during the test, and more so with higher glucose levels.<ref name="taste">Sievenpiper JL, Jenkins DJ, Josse RG, Vuksan V. Dilution of the 75-g oral glucose tolerance test improves overall tolerability but not reproducibility in subjects with different body compositions. ''Diabetes Res Clin Pract'' 2001; '''51(2)''': 87-95. PMID 11165688</ref><ref name="notaste">Reece EA, Holford T, Tuck S, Bargar M, O'Connor T, Hobbins JC. Screening for gestational diabetes: one-hour carbohydrate tolerance test performed by a virtually tasteless polymer of glucose. ''Am J Obstet Gynecol'' 1987; '''156(1)''': 132-4. PMID 3799747</ref>
===Screening pathways===
Screening and diagnostic measures are controversial and differ between countries, in part due to differences in population risks, cost-effectiveness considerations, and lack of an [[evidence based medicine|evidence base]] to support large national screening programs.<ref name="SOGCguidelines">Berger H, Crane J, Farine D, ''et. al''. Screening for gestational diabetes mellitus. ''J Obstet Gynaecol Can'' 2002; '''24''': 894–912. PMID 12417905</ref> The most elaborate regime 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, women may be tested earlier.<ref name="ADA2004"/>
In the [[United States]], most obstetricians prefer universal screening of all women with a screening glucose tolerance test.<ref name="USquestionnaire">Gabbe SG, Gregory RP, Power ML, Williams SB, Schulkin J. Management of diabetes mellitus by obstetrician-gynecologists. ''Obstet Gynecol'' 2004; '''103(6)''': 1229-34. PMID 15172857</ref> In the [[United Kingdom]], obstetric units often rely on risk factors and a random blood glucose test.<ref name="UKquestionnaire">Mires GJ, Williams FL, Harper V. Screening practices for gestational diabetes mellitus in UK obstetric units. ''Diabet Med'' 1999; '''16(2)''': 138-41. PMID 10229307</ref><ref name="controversies"/> The [[American Diabetes Association]] and the [[Society of Obstetricians and Gynecologists of Canada]] recommend routine screening unless the patient 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)<ref name="ADA2004"/><ref name="SOGCguidelines">Berger H, Crane J, Farine D, ''et. al''. Screening for gestational diabetes mellitus. ''J Obstet Gynaecol Can'' 2002; '''24''': 894–912. PMID 12417905</ref> The [[Canadian Diabetes Association]] and the [[American College of Obstetricians and Gynecologists]] recommend universal screening.<ref name="CDA2003">Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. ''Can J Diabetes'' 2003; '''27 (Suppl 2)''': 1–140.</ref><ref name="ACOG">Gabbe SG, Graves CR. Management of diabetes mellitus complicating pregnancy. ''Obstet Gynecol'' 2003; '''102(4)''': 857-68. PMID 14551019</ref>
===Urinary glucose testing===
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.<ref name="routine">Rhode MA, Shapiro H, Jones OW 3rd. Indicated vs. routine prenatal urine chemical reagent strip testing. ''J Reprod Med'' 2007; '''52(3)''': 214-9. PMID 17465289</ref> Increased [[glomerular filtration rate]]s 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 2 trimesters is only around 10% and the [[positive predictive value]] is around 20%.<ref name="glucosuria">Alto WA. No need for glycosuria/proteinuria screen in pregnant women. ''J Fam Pract'' 2005; '''54(11)''': 978-83. PMID 16266604</ref><ref name="ascorbicacid">Ritterath C, Siegmund T, Rad NT, Stein U, Buhling KJ. Accuracy and influence of ascorbic acid on glucose-test with urine dip sticks in prenatal care. ''J Perinat Med'' 2006; 34(4): 285-8. PMID 16856816</ref>
===Non-challenge blood glucose tests===
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.<ref name="ADA2004"/> These tests are typically performed at the first antenatal visit. They are patient-friendly and inexpensive, but have a lower test performance compared to the other tests, with moderate sensitivity, low [[specificity]] and high [[false positive]] rates.<ref name="FGTreview">Agarwal MM, Dhatt GS. Fasting plasma glucose as a screening test for gestational diabetes mellitus. ''Arch Gynecol Obstet'' 2007; '''275(2)''': 81-7. PMID 16967273</ref><ref name="FGT">Sacks DA, Chen W, Wolde-Tsadik G, Buchanan TA. Fasting plasma glucose test at the first prenatal visit as a screen for gestational diabetes. ''Obstet Gynecol'' 2003; '''101(6)''': 1197-203. PMID 12798525</ref><ref name="fasting">Agarwal MM, Dhatt GS, Punnose J, Zayed R. Gestational diabetes: fasting and postprandial glucose as first prenatal screening tests in a high-risk population. ''J Reprod Med'' 2007; '''52(4)''': 299-305. PMID 17506370</ref>
===Screening glucose challenge test===
The screening glucose challenge test is performed between 24-28 weeks, and can be seen as a simplified version of the oral glucose tolerance test (OGTT). It involves drinking a solution containing 50 grams of glucose, and measuring blood levels 1 hour later.<ref name=niddk>{{cite web | Boyd E. Metzger, M.D., Susan A. Biastre, R.D., L.D.N., C.D.E., Beverly Gardner, R.D., L.D.N., C.D.E. | title =What I need to know about Gestational Diabetes | publisher=National Diabetes Information Clearinghouse | work =National Diabetes Information Clearinghouse | url=http://diabetes.niddk.nih.gov/dm/pubs/gestational/ | year = 2006 | accessdate=2006-11-27}}</ref>
If the cut-off point is set at 140 mg/dl (7.8 mmol/l), 80% of women with GDM will be detected.<ref name="ADA2004"/> 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.
===Oral glucose tolerance test===
The [[Glucose tolerance test|oral glucose tolerance test]] (OGTT)<ref name="MedlineOGTT">[http://www.nlm.nih.gov/medlineplus/ency/article/003466.htm Glucose tolerance test]. [[MedlinePlus]], November 8, 2006.</ref> 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.
The test involves drinking a solution containing a certain amount of glucose, and drawing blood to measure glucose levels at the start and on set time intervals thereafter.
The diagnostic criteria from the National Diabetes Data Group (NDDG) have been used most often, but some centers rely on the Carpenter and Coustan criteria, which set the cutoff for normal at lower values. Compared with the NDDG criteria, the Carpenter and Coustan criteria lead to a diagnosis of gestational diabetes in 54 percent more pregnant women, with an increased cost and no compelling evidence of improved perinatal outcomes.<ref name=NCBI2>Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. ''Am J Obstet Gynecol'' 1982; '''144(7)''': 768-73. PMID 83071919</ref>
The following are the values which the [[American Diabetes Association]] considers to be abnormal during the 100 g of glucose OGTT:
* Fasting blood glucose level ≥95 mg/dl (5.33 mmol/L)
* 1 hour blood glucose level ≥180 mg/dl (10 mmol/L)
* 2 hour blood glucose level ≥155 mg/dl (8.6 mmol/L)
* 3 hour blood glucose level ≥140 mg/dl (7.8 mmol/L)
An alternative test uses a 75 g glucose load and measures the blood glucose levels before and after 1 and 2 hours, using the same reference values. This test will identify less women who are at risk, and there is only a weak concordance (agreement rate) between this test and a 3 hour 100 g test.<ref name="comparison">Mello G, Elena P, Ognibene A, Cioni R, Tondi F, Pezzati P, Pratesi M, Scarselli G, Messeri G. Lack of concordance between the 75-g and 100-g glucose load tests for the diagnosis of gestational diabetes mellitus. ''Clin Chem'' 2006; '''52(9)''': 1679-84. PMID 16873295</ref>
The glucose values used to detect gestational diabetes were first determined by O'Sullivan and Mahan (1964) in a [[retrospective study]] (using a 100 grams of glucose OGTT) designed to detect risk of developing type 2 diabetes in the future. The values were set using whole blood and required two values reaching or exceeding the value to be positive. <ref name=AMN>{{cite web | Carla Janzen, MD, Jeffrey S. Greenspoon, MD | title =Gestational Diabetes | publisher=Armenian Medical Network | work =Diabetes Mellitus & Pregnancy - Gestational Diabetes | url=http://www.health.am/pregnancy/gestational-diabetes/ | year = 2006 | accessdate=2006-11-27}}</ref> Subsequent information led to alterations in O'Sullivan's criteria. When methods for blood glucose determination changed from the use of whole blood to venous plasma samples, the criteria for GDM were also changed.
==Complications==
GDM poses a risk to mother and child. This risk is largely related to high blood glucose levels and its consequences. The risk increases with higher blood glucose levels.<ref name="HAPO2008">HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991-2002. PMID 18463375</ref> Treatment resulting in better control of these levels can reduce some of the risks of GDM considerably.<ref name="Langer1994">Langer O, Rodriguez DA, Xenakis EM, McFarland MB, Berkus MD, Arrendondo F. Intensified versus conventional management of gestational diabetes. ''Am J Obstet Gynecol'' 1994; '''170(4)''': 1036-46. PMID 8166187</ref>
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)<ref name="HAPO2008"/> and [[small for gestational age]]. 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 patients with GDM.<ref name="controversies"/> 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.<ref name="HAPO2008"/> 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 a caesarean section.<ref name="Toronto">Naylor CD, Sermer M, Chen E, Farine D. Selective screening for gestational diabetes mellitus. Toronto Trihospital Gestational Diabetes Project Investigators. ''N Engl J Med'' 1997; '''337(22)''': 1591–1596. PMID 9371855</ref><ref name="SantaBarbara">Jovanovic-Peterson L, Bevier W, Peterson CM. The Santa Barbara County Health Care Services program: birth weight change concomitant with screening for and treatment of glucose-intolerance of pregnancy: a potential cost-effective intervention? Am ''J Perinatol'' 1997; '''14(4)''': 221-8. PMID 9259932</ref>
Neonates 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]]).<ref name="impactneonate">Jones CW. Gestational diabetes and its impact on the neonate. Neonatal Netw. 2001;'''20(6)''':17-23. PMID 12144115</ref> GDM also interferes with maturation, causing dysmature babies prone to [[respiratory distress syndrome]] due to incomplete lung maturation and impaired [[surfactant]] synthesis.<ref name="impactneonate"/>
Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for [[birth defect]]s. Birth defects usually originate sometime during the [[Pregnancy#First trimester|first trimester]] (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first trimester. Studies have shown that the offspring of women with GDM are at a higher risk for congenital malformations; this is thought to be due to the inclusion of women with pre-existent type 2 diabetes who were not diagnosed before pregnancy.<ref name="teratogenicity">Allen VM, Armson BA, Wilson RD, et al. Teratogenicity associated with pre-existing and gestational diabetes. ''J Obstet Gynaecol Can'' 2007; '''29(11)''': 927-34. PMID 17977497</ref><ref name="predict-malformations">Martínez-Frías ML, Frías JP, Bermejo E, Rodríguez-Pinilla E, Prieto L, Frías JL. Pre-gestational maternal body mass index predicts an increased risk of congenital malformations in infants of mothers with gestational diabetes. ''Diabet Med'' 2005; '''22(6)''': 775-81. PMID 15910631</ref><ref name="embryonal">Savona-Ventura C, Gatt M. Embryonal risks in gestational diabetes mellitus. ''Early Hum Dev'' 2004; '''79(1)''': 59-63. PMID 15449398</ref>
Because of conflicting studies, it is unclear at the moment whether women with GDM have a higher risk of [[preeclampsia]].<ref name="hypertension">Leguizamón GF, Zeff NP, Fernández A. Hypertension and the pregnancy complicated by diabetes. ''Curr Diab Rep'' 2006; '''6(4)''': 297-304. PMID 16879782</ref> In the HAPO study, the risk of preeclampsia was between 13% and 37% higher, although not all possible confounding factors were corrected.<ref name="HAPO2008"/>
==Prognosis==
Gestational diabetes generally resolves once the baby is born. Based on different studies, the chances of developing GDM in a second pregnancy are between 30 and 84%, depending on ethnic background. A second pregnancy within 1 year of the previous pregnancy has a high rate of recurrence.<ref name="recurrence">Kim C, Berger DK, Chamany S. Recurrence of gestational diabetes mellitus: a systematic review. ''Diabetes Care'' 2007; '''30(5)''': 1314-9. PMID 17290037</ref>
If a woman develops gestational diabetes, it implies her body processes glucose differently. 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 [[antibody|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).<ref name="rsikfactors">Löbner K, Knopff A, Baumgarten A, ''et. al''. Predictors of postpartum diabetes in women with gestational diabetes mellitus. ''Diabetes'' 2006; '''55(3)''': 792-7. PMID 16505245</ref><ref name="antibodies">Järvelä IY, Juutinen J, Koskela P ''et. al''. Gestational diabetes identifies women at risk for permanent type 1 and type 2 diabetes in fertile age: predictive role of autoantibodies. ''Diabetes Care'' 2006; '''29(3)''': 607-12. PMID 16505514</ref> Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years.<ref name=AMN>{{cite web | Carla Janzen, MD, Jeffrey S. Greenspoon, MD | title =Gestational Diabetes | publisher=Armenian Medical Network | work =Diabetes Mellitus & Pregnancy - Gestational Diabetes | url=http://www.health.am/pregnancymore/diabetes-intrapartum-postpartum-management/ | year = 2006 | accessdate=2007-02-28}}</ref> Depending on the population studied, the diagnostic criteria and the length of follow-up, the risk can vary enormously.<ref name="DM2">Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care. 2002;'''25(10)''':1862-8. PMID 12351492</ref> The risk appears to be highest in the first 5 years, reaching a plateau thereafter.<ref name="DM2"/> 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.<ref name="DM2"/> In a retrospective study in [[Navajo people|Navajo]] women, the risk of diabetes after GDM was estimated to be 50 to 70% after 11 years.<ref name="Navajo">Steinhart JR, Sugarman JR, Connell FA. Gestational diabetes is a herald of NIDDM in Navajo women. High rate of abnormal glucose tolerance after GDM. Diabetes Care. 1997;'''20(6)''':943-7. PMID 9167104</ref> Another study found a risk of diabetes after GDM of more than 25% after 15 years.<ref name="Lee2007">Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M. Gestational diabetes mellitus: clinical predictors and long-term risk of developing type 2 diabetes: a retrospective cohort study using survival analysis. Diabetes Care. 2007;'''30(4)''':878-83. PMID 17392549</ref> In populations with a low risk for [[type 2 diabetes]], in lean subjects and in patients with [[autoimmunity|auto-antibodies]], there is a higher rate of women developing [[type 1 diabetes]].<ref name="antibodies"/>
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.<ref name="Metabolicsyndrome">Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. ''Pediatrics'' 2005; '''115(3)''': e290-6. PMID 15741354</ref> This risk relates to increased maternal glucose values.<ref name="imprinting">Hillier TA, Pedula KL, Schmidt MM, Mullen JA, Charles MA, Pettitt DJ. Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia. ''Diabetes Care'' 2007; '''30(9)''': 2287-92. PMID 17519427</ref> It is currently unclear how much genetic susceptibility and environmental factors each contribute to this risk, and if treatment of GDM can influence this outcome.<ref name="long-term">Metzger BE. Long-term Outcomes in Mothers Diagnosed With Gestational Diabetes Mellitus and Their Offspring. Clin Obstet Gynecol 2007; 50(4): 972-9. PMID 17982340</ref>
There are scarce statistical data on the risk of other conditions in women with GDM; in the Jerusalem Perinatal study, 410 out of 37962 patients 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.<ref name="breast">Perrin MC, Terry MB, Kleinhaus K, ''et. al''. Gestational diabetes and the risk of breast cancer among women in the Jerusalem Perinatal Study. ''Breast Cancer Res Treat'' 2007 [Epub]. PMID 17476589</ref><ref name="pancreas">Perrin MC, Terry MB, Kleinhaus K, ''et. al''. Gestational diabetes as a risk factor for pancreatic cancer: a prospective cohort study. ''BMC Med'' 2007; '''5''': 25. {{PMC|17705823}}</ref>
==Classification==
The White classification, named after [[Priscilla White (physician)|Priscilla White]]<ref name="PWhite">White P. Pregnancy complicating diabetes. ''Am J Med'' 1949; 7: 609. PMID 15396063</ref> who pioneered in research on the effect of diabetes types on perinatal outcome, is widely used to assess maternal and fetal risk. It distinguishes between gestational diabetes (type A) and diabetes that existed prior to pregnancy (pregestational diabetes). These two groups are further subdivided according to their associated risks and management.<ref name="OBSTETRICS">Gabbe S.G., Niebyl J.R., Simpson J.L. OBSTETRICS: Normal and Problem Pregnancies. Fourth edition. Churchill Livingstone, New York, 2002. ISBN 0-443-06572-1</ref>
There are 2 subtypes of gestational diabetes (diabetes which began during pregnancy):
* Type A1: abnormal oral glucose tolerance test (OGTT) but normal blood glucose levels during fasting and 2 hours after meals; diet modification is sufficient to control glucose levels
* Type A2: abnormal OGTT compounded by abnormal glucose levels during fasting and/or after meals; additional therapy with insulin or other medications is required
The second group of [[Diabetes mellitus and pregnancy|diabetes which existed prior to pregnancy]] is also split up into several subtypes.
==Treatment==
The goal of treatment is to reduce the risks of GDM for mother and child. Scientific evidence is beginning to show that controlling glucose levels can result in less serious fetal complications (such as [[macrosomia]]) and increased maternal [[quality of life]]. Unfortunately, treatment of GDM is also accompanied by more infants admitted to neonatal wards and more [[induction of labour|inductions of labour]], with no proven decrease in [[cesarean section]] rates or [[perinatal mortality]].<ref name="ACHOIS">Crowther CA, Hiller JE, Moss JR et. al, Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. ''N Engl J Med'' 2005; '''352(24)''': 2477-86. PMID 15951574</ref><ref name="Tri-Hospital">Sermer M, Naylor CD, Gare DJ et al. Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project. Am J Obstet Gynecol 1995; 173(1): 146-56. PMID 7631672</ref> These findings are still recent and controversial.<ref name="Cochrane2003">Tuffnell DJ, West J, Walkinshaw SA. Treatments for gestational diabetes and impaired glucose tolerance in pregnancy. ''Cochrane Database of Systematic Reviews'' 2003, Issue 3. Art. No.: CD003395. PMID 12917965</ref>
Counselling before pregnancy (for example, about preventive [[folic acid]] supplements) and multidisciplinary management are important for good pregnancy outcomes.<ref name="diabetespregnancy">Kapoor N, Sankaran S, Hyer S, Shehata H. Diabetes in pregnancy: a review of current evidence. ''Curr Opin Obstet Gynecol'' 2007; '''19(6)''': 586-590. PMID 18007138</ref> Most women can be managed with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need [[antidiabetic drugs]], most commonly [[insulin]] therapy.
Any diet needs to provide sufficient calories for pregnancy. 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. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more.<ref name="ACHOISreview"/>
Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM.<ref name="ACHOISreview"/><ref name="exercise">Mottola MF. The role of exercise in the prevention and treatment of gestational diabetes mellitus. ''Curr Sports Med Rep'' 2007; '''6(6)''': 381-6. PMID 18001611</ref>
[[Image:Gestational diabetes kit.jpg|thumb|A kit with a glucose meter and diary used by a woman with gestational diabetes.]]
Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low.<ref name="Langer1994"> Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows:<ref name="ACHOISreview"/>
* fasting capillary blood glucose levels <5.5 mmol/L
* 1 hour postprandial capillary blood glucose levels <8.0 mmol/L
* 2 hour postprandial blood glucose levels <6.7 mmol/L
Regular blood samples can be used to determine [[HbA1c]] levels, which give an idea of glucose control over a longer time period.<ref name="ACHOISreview"/>
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 become necessary. The most common therapeutic regime involves premeal fast-acting insulin to blunt sharp glucose rises after meals.<ref name="ACHOISreview"/> Care needs to be taken to avoid low blood sugar levels ([[hypoglycemia]]) due to excessive insulin injections. Insulin therapy can be normal or very thight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits.<ref name="controversies"/><ref name="fourinjections">Nachum Z, Ben-Shlomo I, Weiner E, Shalev E. Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial. ''BMJ'' 1999; '''319(7219)''': 1223-7.</ref><ref name="verytight">Walkinshaw SA. Very tight versus tight control for diabetes in pregnancy (WITHDRAWN). ''Cochrane Database Syst Rev'' 2007; '''(2)''': CD000226. PMID 17636623</ref>
There is some evidence that certain oral glycemic agents might be safe in pregnancy, or at least, are significantly less dangerous to the developing fetus than poorly controlled diabetes. However, few studies have been performed as of this time and this is not a generally accepted treatment. These agents may be used in research settings, or if the patient needs intervention but refuses insulin therapy, and is aware of the risks.<ref name="ACHOISreview"/> [[Glyburide]], a second generation [[sulfonylurea]], has been shown to be an effective alternative to insulin therapy.<ref name="glyburide-review">Kremer CJ, Duff P. Glyburide for the treatment of gestational diabetes. ''Am J Obstet Gynecol'' 2004; 190(5): 1438-9. PMID 15167862</ref><ref name="glyburide-NEJM">Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus.
''N Engl J Med''. 2000;'''343(16)''':1134-8. PMID 11036118</ref> In one study, 4% of women needed supplemental insulin to reach blood sugar targets.<ref name="glyburide-NEJM"/>
[[Metformin]] has shown promising results. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels.<ref name="metformin">Simmons D, Walters BN, Rowan JA, McIntyre HD. Metformin therapy and diabetes in pregnancy. ''Med J Aust'' 2004; 180(9): 462-4. PMID 15115425</ref> A recent [[randomized controlled trial]] of metformin versus insulin showed that women preferred metformin tablets to insulin injections, and that metformin is safe and equally effective as insulin.<ref name="MiG">Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. ''N Engl J Med''. 2008;'''358(19)''':2003-15. PMID 18463376</ref> Severe neonatal hypoglycemia was less common in insulin-treated women, but preterm delivery was more common. Almost half of patients 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.<ref name="MiG"/> There remains a possibility of long-term complications from metformin therapy, although follow-up at the age of 18 months of children born to women with [[polycystic ovarian syndrome]] and treated with metformin revealed no developmental abnormalities.<ref name="metformin-followup">Glueck CJ, Goldenberg N, Pranikoff J, Loftspring M, Sieve L, Wang P. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. ''Hum Reprod''. 2004;'''19(6)''':1323-30. PMID 15117896</ref>
Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child.<ref name="breastfeeding">Taylor JS, Kacmar JE, Nothnagle M, Lawrence RA. A systematic review of the literature associating breastfeeding with type 2 diabetes and gestational diabetes. ''J Am Coll Nutr'' 2005; '''24(5)''': 320-6. PMID 16192255</ref>
A repeat OGTT should be carried out 2-4 months after delivery, to confirm the diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is advised.<ref name="ACHOISreview"/>
==Controversy==
Gestational diabetes is a controversial subject. Some critics question whether GDM is a disease in its own right. Labelling women as 'suffering from GDM' seems to predispose them to more interventions (like cesarean sections) for perceived increased risks,<ref name="Toronto"/><ref name="SantaBarbara"/> while treatment of GDM has not been proven to affect perinatal mortality or caesarean section rates.<ref name="ACHOIS"/> Lack of reproduceability of glucose tolerance testing is another problematic area.<ref name=childbirthconnection>Murray Enkin, Marc J.N.C. Keirse, James Neilson, et al. A Guide to Effective Care in Pregnancy and Childbirth: [http://www.childbirthconnection.org/article.asp?ck=10025 Chapter 11: Gestational Diabetes] (requires login). Oxford University Press, 2000.</ref>
==See also==
* [[Diabetes mellitus and pregnancy]]
==Footnotes==
{{reflist|2}}
== External links ==
* National Institute of Child Health and Human Development - [http://www.nichd.nih.gov/publications/pubs/upload/gest_diabetes_risk_2005.pdf Am I at Risk for Gestational Diabetes?]
* National Institute of Child Health and Human Development - [http://www.nichd.nih.gov/publications/pubs/gest_diabetes/ Managing Gestational Diabetes: A Patient's Guide to a Healthy Pregnancy]
* Gestational Diabetes Resource Guide - [http://www.diabetes.org/gestational-diabetes.jsp American Diabetes Association]
* MSN Health: [http://health.msn.com/encyclopedia/healthtopics/articlepage.aspx?cp-documentid=100066070 Gestational Diabetes]
{{Pathology of pregnancy, childbirth and the puerperium}}
[[Category:Obstetrics]]
[[Category:Diabetes]]
[[de:Schwangerschaftsdiabetes]]
[[es:Diabetes mellitus gestacional]]
[[fr:Diabète gestationnel]]
[[nl:Zwangerschapsdiabetes]]
[[pl:Cukrzyca ciężarnych]]
[[pt:Diabetes gestacional]]
[[ru:Диабет беременных]]
[[sr:Гестациони дијабетес]]
[[zh:妊娠期糖尿病]]