Gestational diabetes overview
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Gestational diabetes (GDM) is a form of diabetes that is first detected during pregnancy. It usually occurs in the second or third trimester, in women who were not known to be diabetic before pregnancy. There is no known specific cause, but it is believed that the hormones produced during pregnancy reduces receptivity to insulin, resulting in high blood sugar. Gestational diabetes mellitus (GDM) is similar to type 2 diabetes, a combination of relatively inadequate insulin secretion and reduced responsiveness to insulin occurs. Gestational diabetes occurs in approximately 7.5% of all pregnancies in the United States, and there is often improvements/complete resolution after delivery. Untreated gestational diabetes can damage the health of the fetus and the mother. The risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction.
- Diabetes mellitus is an ancient term first found in the Egyptian Eberes papyrus around 1500 BC. Hyperglycemia in pregnancy was first described by Bennewitz, a German physician in 1824. In 1950, the terminology 'GDM' was accepted.
- John B. O’Sullivan, Wilkerson and Remein in 1957 proposed offering a 3-hour oral glucose tolerance test (OGTT) for patients presenting with risk factors for diabetes such as a family history of diabetes, gestational glycosuria and overdeveloped infants at birth.
Gestational diabetes refers to hyperglycemia during the second or third trimester of pregnancy.
Insulin sensitivity reduces slightly during the first and second trimesters but it decreases by 40-60% during the third trimester. Other changes at the molecular level that may lead to insulin resistance include a reduced ability of insulin to phosphorylate the insulin receptor, decreased expression of insulin receptor substrate 1 (IRS-1), and increased levels of a specific kinase. Factors affecting insulin sensitivity include estrogens and progesterone, human chorionic somatomammotropin (hCS) or placental lactogen (HPL), prolactin, placental growth hormone variant (hGH-V), corticotropin-releasing factor (CRF) and corticotropin, leptin, tumor necrosis factor α (TNF-α), adiponectin, resistin, ghrelin, and interleukin-6.
Maternal metabolic changes
Basal and postprandial levels of glucose, FFAs, triglycerides, and amino acids are higher in GDM than in normal pregnancy. Maternal hyperglycemia leads to fetal hyperinsulinism, which is responsible for the macrosomia and neonatal morbidity. The development of macrosomia (defined as birth weight >4000g or above the 90th percentile for gestational age), is a frequent occurrence in pregnancies complicated by DM and GDM. Increased adiposity is the primary component of the macrosomia. Infants of diabetic mothers may have up to twice the body fat content of infants of normal mothers.
Differentiating Gestational diabetes other Diseases
GDM must be differentiated from other causes of hyperglycemia during pregnancy such as diabetes type 1 or type 2.
Epidemiology and Demographics
The prevalence of gestational diabetes mellitus varies widely. It may range from 1% to 14% of all pregnancies. The prevalence of GDM showed a 12% increase per year from 1994 to 2002 in one study. The increasing rate over time is possibly due to increases in mean maternal age and weight. According to another study, the age and race/ethnicity adjusted prevalence of GDM was from 7.5 per 100 in 1999 compared to 7.4 per 100 in 2005. The ethnical prevalence of GDM was noticed to be higher in Asian/Pacific Islanders (relative risk=1.97), Hispanic (RR=1.69) and African-American(RR=1.26) than for caucasian women after adjustment for the year and maternal age.
- A family history of diabetes especially in first degree relatives
- Maternal age >25 yrs
- Certain ethnic groups (such as Native American, Hispanic-American, African-American, South or East Asian, Pacific Islander)
- Body mass index greater than 25 kg/m2
- Gestational diabetes or impaired glucose tolerance test in previous pregnancies
- Previous delivery of a baby >9 pounds
- Personal history of impaired glucose tolerance or impared fasting glucose (pre-diabetes)
- Glycosuria at the first prenatal visit
- Certain medical conditions (such as metabolic syndrome, polycystic ovary syndrome (PCOS), current use of glucocorticoids, hypertension)
- Previous history of unexplained miscarriage or stillbirth
- Smoking (doubles the risk for gestational diabetes)
- Multiple gestation
- Genetic predisposition (.e.g. glucokinase mutation)
Screening can be performed during the first prenatal visit, especially in mothers with risk factors for GDM. If the result is negative, or the test was not carried out during the first prenatal visit, screening at 24-28 weeks gestational age is ideal.
50 gram Glucose Test
- Regardless of the fasting status of mother ,a one hour plasma glucose level is measured following a 50 gram glucose load. Measurements greater than 130 mg/dl are considered positive for GDM. 130 mg/dl threshold has 88% to 99% sensitivity, and 66% to 77% specificity.
- The next step is to confirm the diagnosis by performing a 100 gram 3 hour Glucose Test.
Natural History and Prognosis
- Most women with GDM return to their pre pregnancy glycemic status after delivery.
- Women diagnosed with gestational diabetes have an increased risk of developing overt diabetes mellitus in the future. Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years. 
- One-third to two-thirds of women will re-experience GDM in subsequent pregnancies.
- Risk factors for recurrence include older age, multiparity, higher maternal weight in the index pregnancy, and weight gain between pregnancies.
- Maternal complications of GDM can be categorized into obstetrical and long term glycemic status related complications. Pre-eclampsia, polyhydramnios, and difficult labor due to fetal macrosomia, are obstetrical complications. Risk of developing prediabetes or even overt diabetes is noticeable in GDM patients.
- Poor glycemic control and increased insulin level may result in increased metabolic demands in the fetus, resulting in fetal and neonatal complications. Large for gestational age, prematurity, respiratory distress syndrome, hyperbilirubinemia, polycythemia, and congenital anomalies, are the most common complications in neonates.
There are two method for diagnosing GDM.
- One-step approach: 75-g Oral glucose tolerance test; and
- Two-step approach with a 50-g (non fasting) screen followed by a 100-g OGTT for those who screen positive.
Both methods have good diagnostic yields.
History and Symptoms
- Usually there are no symptoms, or the symptoms are mild and not life threatening to the pregnant woman.
- Symptoms may include:
There is no specific physical examination finding for gestational diabetes. Signs of insulin resistance (i.e. acanthosis nigricans) may be seen on physical examination.
Generally a test for gestational diabetes is carried out between the 24th and 28th week of pregnancy.
If the patient is at risk for gestational diabetes (see risk factors), a screening test should be done earlier in the pregnancy.
After the diagnosis of GDM, treatment should be commenced with medical nutrition therapy, physical activity, and weight management, depending on the pregestational weight. The aim of treatment is to achieve the following target for the plasma glucose level:
- Fasting <95 mg/dL (5.3 mmol/L)
- One-hour postprandial <140 mg/dL (7.8 mmol/L)
- Two-hour postprandial <120 mg/dL (6.7 mmol/L)
- Many randomized controlled trials suggest that the risk of GDM may be reduced by diet, exercise, and lifestyle counseling.
- All women diagnosed with GDM require nutritional counseling for the appropriate amount of weight gain during pregnancy as well as dietary control. Women with a normal BMI [20-25], can consume about 30kcal/kg/d while those who are obese [BMI >25-34] should restrict their diet to 25 kcal/kg/d, and those with a BMI >34 should consume 20kcal/kg/d or less.
- These patients should restrict fat intake and substitute simple or refined sugars in their diet for more complex carbohydrates.
- In the first trimester, the insulin requirement is approximately 0.7 units per kilogram body weight.
- By the second trimester, the insulin requirement is 0.8 units per kilogram body weight.
- By term, the insulin requirement is 0.9 -1.0 unit per kilogram body weight per day.
It is associated with a lower risk of hypoglycemia and potential lower weight gain, may be preferable to insulin if it adequately controls hyperglycemia, however, metformin may slightly increase the risk of prematurity.
Weight control, dietary control, and life style modification, are the mainstay modalities for preventing GDM.
After delivery, mothers diagnosed with GDM should have close follow up to prevent overt diabetes in future. Testing with 75 g OGTT 6 to 12 weeks after delivery and then every 1-3 years is recommended for early diagnosis.
Cost-Effectiveness of Therapy
Future or Investigational Therapies
- Negrato CA, Gomes MB (2013). "Historical facts of screening and diagnosing diabetes in pregnancy". Diabetol Metab Syndr. 5 (1): 22. doi:10.1186/1758-5996-5-22. PMC 3644500. PMID 23634949.
- WILKERSON HL, REMEIN QR (1957). "Studies of abnormal carbohydrate metabolism in pregnancy; the significance of impaired glucose tolerance". Diabetes. 6 (4): 324–9. PMID 13447761.
- "Standards of Medical Care in Diabetes-2016: Summary of Revisions". Diabetes Care. 39 Suppl 1: S4–5. 2016. doi:10.2337/dc16-S003. PMID 26696680.
- Catalano PM, Tyzbir ED, Wolfe RR, Calles J, Roman NM, Amini SB, Sims EA (1993). "Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes". Am. J. Physiol. 264 (1 Pt 1): E60–7. PMID 8430789.
- Buchanan TA, Metzger BE, Freinkel N, Bergman RN (1990). "Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes". Am. J. Obstet. Gynecol. 162 (4): 1008–14. PMID 2183610.
- Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EA (1991). "Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women". Am. J. Obstet. Gynecol. 165 (6 Pt 1): 1667–72. PMID 1750458.
- Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP, Catalano PM, Friedman JE (2007). "Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes". Diabetes Care. 30 Suppl 2: S112–9. doi:10.2337/dc07-s202. PMID 17596458.
- Freinkel N (1980). "Banting Lecture 1980. Of pregnancy and progeny". Diabetes. 29 (12): 1023–35. PMID 7002669.
- Lepercq J, Cauzac M, Lahlou N, Timsit J, Girard J, Auwerx J, Hauguel-de Mouzon S (1998). "Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin". Diabetes. 47 (5): 847–50. PMID 9588462.
- Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM (2002). "TNF-alpha is a predictor of insulin resistance in human pregnancy". Diabetes. 51 (7): 2207–13. PMID 12086951.
- Retnakaran R, Hanley AJ, Raif N, Hirning CR, Connelly PW, Sermer M, Kahn SE, Zinman B (2005). "Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications". Diabetologia. 48 (5): 993–1001. doi:10.1007/s00125-005-1710-x. PMID 15778860.
- Metzger BE, Phelps RL, Freinkel N, Navickas IA (1980). "Effects of gestational diabetes on diurnal profiles of plasma glucose, lipids, and individual amino acids". Diabetes Care. 3 (3): 402–9. PMID 7190092.
- Catalano PM, Thomas A, Huston-Presley L, Amini SB (2003). "Increased fetal adiposity: a very sensitive marker of abnormal in utero development". Am. J. Obstet. Gynecol. 189 (6): 1698–704. PMID 14710101.
- Dabelea D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ, Hamman RF, McDuffie RS (2005). "Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program". Diabetes Care. 28 (3): 579–84. PMID 15735191.
- Lawrence JM, Contreras R, Chen W, Sacks DA (2008). "Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999-2005". Diabetes Care. 31 (5): 899–904. doi:10.2337/dc07-2345. PMID 18223030.
- Solomon CG, Willett WC, Carey VJ, Rich-Edwards J, Hunter DJ, Colditz GA, Stampfer MJ, Speizer FE, Spiegelman D, Manson JE (1997). "A prospective study of pregravid determinants of gestational diabetes mellitus". JAMA. 278 (13): 1078–83. PMID 9315766.
- Kim C, Liu T, Valdez R, Beckles GL (2009). "Does frank diabetes in first-degree relatives of a pregnant woman affect the likelihood of her developing gestational diabetes mellitus or nongestational diabetes?". Am. J. Obstet. Gynecol. 201 (6): 576.e1–6. doi:10.1016/j.ajog.2009.06.069. PMC 2789883. PMID 19691951.
- Gibson KS, Waters TP, Catalano PM (2012). "Maternal weight gain in women who develop gestational diabetes mellitus". Obstet Gynecol. 119 (3): 560–5. doi:10.1097/AOG.0b013e31824758e0. PMID 22353954.
- Retnakaran R, Shah BR (2016). "Impact of Twin Gestation and Fetal Sex on Maternal Risk of Diabetes During and After Pregnancy". Diabetes Care. 39 (8): e110–1. doi:10.2337/dc16-0825. PMID 27222507.
- Lucinda J. England , Richard J. Levine, Cong Qian, Lisa M. Soule, Enrique F. Schisterman, Kai F. Yu and Patrick M. Catalano (2004). "Glucose Tolerance and Risk of Gestational Diabetes Mellitus in Nulliparous Women Who Smoke during Pregnancy,". American Journal of Epidemiology. External link in
- "2. Classification and Diagnosis of Diabetes". Diabetes Care. 39 Suppl 1: S13–22. 2016. doi:10.2337/dc16-S005. PMID 26696675.
- Moyer VA (2014). "Screening for gestational diabetes mellitus: U.S. Preventive Services Task Force recommendation statement". Ann. Intern. Med. 160 (6): 414–20. doi:10.7326/M13-2905. PMID 24424622.
- Donovan L, Hartling L, Muise M, Guthrie A, Vandermeer B, Dryden DM (2013). "Screening tests for gestational diabetes: a systematic review for the U.S. Preventive Services Task Force". Ann. Intern. Med. 159 (2): 115–22. doi:10.7326/0003-4819-159-2-201307160-00657. PMID 23712349.
- "Gestational Diabetes". Diabetes Mellitus & Pregnancy - Gestational Diabetes. Armenian Medical Network. 2006. Retrieved 2007-02-28. Text " Carla Janzen, MD, Jeffrey S. Greenspoon, MD " ignored (help)
- Getahun D, Fassett MJ, Jacobsen SJ (2010). "Gestational diabetes: risk of recurrence in subsequent pregnancies". Am. J. Obstet. Gynecol. 203 (5): 467.e1–6. doi:10.1016/j.ajog.2010.05.032. PMID 20630491.
- MacNeill S, Dodds L, Hamilton DC, Armson BA, VandenHof M (2001). "Rates and risk factors for recurrence of gestational diabetes". Diabetes Care. 24 (4): 659–62. PMID 11315827.
- Moses RG (1996). "The recurrence rate of gestational diabetes in subsequent pregnancies". Diabetes Care. 19 (12): 1348–50. PMID 8941462.
- Yogev Y, Xenakis EM, Langer O (2004). "The association between preeclampsia and the severity of gestational diabetes: the impact of glycemic control". Am. J. Obstet. Gynecol. 191 (5): 1655–60. doi:10.1016/j.ajog.2004.03.074. PMID 15547538.
- Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev, Yogev (2010). "Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: preeclampsia". Am. J. Obstet. Gynecol. 202 (3): 255.e1–7. doi:10.1016/j.ajog.2010.01.024. PMC 2836485. PMID 20207245.
- Casey BM, Lucas MJ, Mcintire DD, Leveno KJ (1997). "Pregnancy outcomes in women with gestational diabetes compared with the general obstetric population". Obstet Gynecol. 90 (6): 869–73. PMID 9397092.
- Mitanchez D, Burguet A, Simeoni U (2014). "Infants born to mothers with gestational diabetes mellitus: mild neonatal effects, a long-term threat to global health". J. Pediatr. 164 (3): 445–50. doi:10.1016/j.jpeds.2013.10.076. PMID 24331686.
- Widness JA, Teramo KA, Clemons GK, Voutilainen P, Stenman UH, McKinlay SM, Schwartz R (1990). "Direct relationship of antepartum glucose control and fetal erythropoietin in human type 1 (insulin-dependent) diabetic pregnancy". Diabetologia. 33 (6): 378–83. PMID 2199280.
- "Professional Practice Committee for the Standards of Medical Care in Diabetes-2016". Diabetes Care. 39 Suppl 1: S107–8. 2016. doi:10.2337/dc16-S018. PMID 26696673.
- Melmed, Shlomo (2015). Williams textbook of endocrinology. Philadelphia, PA: Elsevier. ISBN 978-0323297387.
- Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger DB, Hadden DR, Hod M, Kitzmiller JL, Kjos SL, Oats JN, Pettitt DJ, Sacks DA, Zoupas C (2007). "Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus". Diabetes Care. 30 Suppl 2: S251–60. doi:10.2337/dc07-s225. PMID 17596481.
- Bain E, Crane M, Tieu J, Han S, Crowther CA, Middleton P (2015). "Diet and exercise interventions for preventing gestational diabetes mellitus". Cochrane Database Syst Rev (4): CD010443. doi:10.1002/14651858.CD010443.pub2. PMID 25864059.
- Koivusalo SB, Rönö K, Stach-Lempinen B, Eriksson JG (2016). "Response to Comment on Koivusalo et al. Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled Trial. Diabetes Care 2016;39:24-30". Diabetes Care. 39 (8): e126–7. doi:10.2337/dci16-0014. PMID 27457642.
- Jovanovic L, Druzin M, Peterson CM (1981). "Effect of euglycemia on the outcome of pregnancy in insulin-dependent diabetic women as compared with normal control subjects". Am. J. Med. 71 (6): 921–7. PMID 7032287.
- Balsells M, García-Patterson A, Solà I, Roqué M, Gich I, Corcoy R (2015). "Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis". BMJ. 350: h102. PMC 4301599. PMID 25609400.
- Jiang YF, Chen XY, Ding T, Wang XF, Zhu ZN, Su SW (2015). "Comparative efficacy and safety of OADs in management of GDM: network meta-analysis of randomized controlled trials". J. Clin. Endocrinol. Metab. 100 (5): 2071–80. doi:10.1210/jc.2014-4403. PMID 25803270.
- Camelo Castillo W, Boggess K, Stürmer T, Brookhart MA, Benjamin DK, Jonsson Funk M (2015). "Association of Adverse Pregnancy Outcomes With Glyburide vs Insulin in Women With Gestational Diabetes". JAMA Pediatr. 169 (5): 452–8. doi:10.1001/jamapediatrics.2015.74. PMID 25822253.