Gestational Diabetes Mellitus, N 560 Advanced Concepts in Physiology and Pathophysiology annotated Bibliography

Gestational Diabetes Mellitus, N 560 Advanced Concepts in Physiology and Pathophysiology annotated Bibliography

28 October 2010

Box 363

Gestational Diabetes Mellitus

There are approximately 200,000 cases of gestational diabetes mellitus diagnosed per year, and it continues to increase (American Diabetes Association, 2010). Gestational Diabetes Mellitus (GDM) is a subgroup of diabetes mellitus and is defined as “any degree of glucose intolerance with onset or first recognition during pregnancy” (American Diabetes Association, 2010, p. S65). Gestational diabetes manifests as hyperglycemia and insulin resistance caused by dysfunctional beta cells and decreased beta cell adaptation (Pridjian & Benjamin, 2010). There are several risk factors including age, obesity, current glycosuria, history of glucose intolerance, and family history of diabetes (Serlin & Lash, 2009). The symptoms of GDM normally include polydipsia, polyuria, and sometimes polyphagia (American Diabetes Association, 2010). Gestational diabetes has been known to cause complications in both the mother and the fetus. Some complications to the fetus include birth trauma, macrosomia, hyperinsulinism, hypoglycemia, hyperbilirubinemia (The HAPO Cooperative Study Research Group, 2008). This paper will discuss the normal physiology of the placenta, pathophysiology and clinical manifestations of gestational diabetes, treatments, and implications for advanced practice nurses.

Annotated Bibliography

Ross, M. G., Ervin, M. G., Novak, D. (2007). Chapter 2 fetal physiology. In S. Gabbe, J. Niebyl, & J. Simpson (Eds.), Obstetrics: Normal and problem pregnancies (pp. 26-33). Philadelphia, PA: Churchill Livingstone Elsevier.

The placenta is an organ with high metabolic demands, providing nutrients, oxygen, water, immunologic protection, and hormones to the fetus; glucose is the primary solute essential for fetal growth. It is estimated the placenta metabolically uses 70% of the maternal glucose, and the remainder is for fetal growth. The microvillus plasma membrane on the maternal side is the transport mechanism through the placental plasma membrane to the basal membrane on the fetal side. GLUT 1 transports glucose to the fetus. In normal pregnancy, the transfer rate of glucose to the fetus decreases as maternal glucose concentration increases. Maternal diabetes may alter the GLUT 1 transporter, causing the fetus to receive higher concentrations of maternal glucose. The fetus produces insulin to transport glucose for growth, thus it increases in response to elevated levels of blood glucose. This phenomenon explains why the neonates of diabetic mothers are macrosomic, or large bodied.

Barta, E., & Drugan, A. (2010). Glucose transport from mother to fetus— A theoretical study. Journal of Theoretical Biology, 263, 295-302. doi: 10.1016/j.jtbi.2009.12.010

The authors used mathematical equations to form a model explaining the transport process of glucose via GLUT 1 through the placenta to the fetus. Glucose is essential for metabolic consumption of the placenta and the development of the fetus. The researchers found that GLUT 1 is the glucose transporter that transfers maternal glucose to the fetus. The glucose supply to the fetus depends on the concentration gradient between mother to the fetus in a process that includes diffusion. Through the model, it becomes clearer why the GLUT 1 transporter doubles in the late part of the second trimester; therefore, allowing the fetus to grow 20-fold between 16 weeks gestation and term. The placenta aids in buffering the glucose supply to the fetus in order to keep the glucose levels normal when hyperglycemia occurs. Barta and Drugan recommend improving their model by forming a three-dimensional model that reveals a more geometrical or morphologic situation. They also recommend a study of the effects of hormones and insulin on glucose transport, leading to implications for clinical settings.

The HAPO Study Cooperative Research Group. (2008). Hyperglycemia and adverse pregnancy outcomes. The New England Journal of Medicine, 358(19), 1991-2002.

The HAPO Study Cooperative Research Group performed a study on 25,505 pregnant women to clarify the risks of adverse outcomes associated with various degrees of maternal glucose intolerance. The frequency of each adverse outcome increased with increasing maternal glucose levels. The odds ratios for an increase in the glucose level by one standard deviation (SD) were highest for birth weight greater than ninetieth percentile and cord-blood serum C-peptide level above the ninetieth percentile. Shoulder dystocia or birth injury occurred more often in relation to increasing maternal blood glucose with an SD of 1.20. The 1 hr and 2 hr plasma glucose tests were significantly related to premature delivery with an SD level of 1.18 and 1.16, intensive neonatal care admissions with an SD level of 1.07 and 1.09, and hyperbilirubinemia with an SD level of 1.11 and 1.08. The significant quadratic associations were the fasting plasma glucose level in relation to primary cesarean delivery (P < 0.001), and the neonate’s age with the fasting, 1 hour, and 2 hour plasma glucose levels were associated with clinical neonatal hypoglycemia (P = 0.05, P = 0.03, P = 0.001). The authors suggest the current criteria for diagnosing and treating hyperglycemia in pregnancy needs to be reevaluated.

Lawlor, D. A., Fraser, A., Lindsay, R.S., Ness, A., Dabelea, D., Catalano, P., . . . Nelson, S. M. (2010). Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: Findings from a prospective pregnancy cohort. Diabetologia, 53, 89-97. doi: 10.1007/s00125-009-1560-z

Lawlor et al. examined 10,591 mother-offspring pairs for the association of existing diabetes, gestational diabetes, and glycosuria in pregnancy with birthweight, macrosomia, and future offspring BMI, waist circumference and fat mass at ages 9-11 years. Of the infants born of these pairs, 1,426 (10-16%) were born macrosomic, 1,570 (23%) were overweight at 9-11 years, 2,614 (38%) were centrally obese at 9-11 years, and 13 were on insulin treatment for diabetes. Overweight or obesity was more common in females than males (25% vs. 21%) with a P < 0.0001. Infants of diabetic mothers had a 4.3-8.5 fold increased risk of macrosomia. The authors also found that offspring of gestational diabetic mothers were more likely to be overweight, have higher BMI (SD 0.302) and waist circumference (SD 0.038).

The researchers recommend that the study be replicated with a larger sample size with more detailed measurements of gestational glycaemia. This study reflects the importance of monitoring and controlling blood glucose levels in those with gestational diabetes and existing diabetes in order to prevent the long-term effects in the offspring.

Hedderson, M. M., Gunderson, E. P., & Ferrara, A. (2010). Gestational weight gain and risk of gestational diabetes mellitus. Obstetrics and Gynecology, 115(3), 597-604.

The goal was to assess the frequency of which gestational diabetes occurs in relation to the rate of weight gain during pregnancy prior to the 50 g 1 hour oral glucose tolerance test. Hedderson et al. found that the women who were in the highest class for weight gain in the first trimester had an 80% significant increased risk of GDM, with an odds ratio of 2.3. They also found that women who exceeded the Institute of Medicine’s (IOM) guidelines for weight gain during pregnancy had a 50% increase in the risk for GDM. The woman’s pregravid BMI and the rate of gestational weight gain up to the time of GDM screening was statistically significant with a P < 0.5. Overweight women in the greater class for weight gain and women of non-white ethnicity were twice as likely to develop gestational diabetes with odd ratios of 2.1 and 2.66.

Hedderson et al. recommend more studies to assess if the findings of this study can be replicated. Clinicians must be aware that greater weight gain during pregnancy may lead to the diagnosis of gestational diabetes and education should be given to higher risk individuals.

Retnakaran, R., Qi, Y., Sermer, M., Connelly, P. W., Hanley, A. J. G., & Zinman, B. (2010). Beta-cell function declines within the first year postpartum in women with recent glucose intolerance in pregnancy. Diabetes Care, 33(8), 1798-1804. doi: 10.2337/dc10-0351

The aim of this study was to evaluate the metabolic changes that occur in the first year postpartum to assess for future diabetic risk. Both insulin sensitivity and beta-cell function decreased from the normal glucose tolerance group to the gestational diabetes group at 3 months postpartum (P < 0.0005), and there was an increase in the occurrence of dysglycemic states after 12 months postpartum. The findings showed that beta-cell dysfunction occurs very early without insulin sensitivity and varies according to the severity of gestational dysglycemia. In the study, gestational diabetes emerged as a negative independent predictor of the change in beta cell function with a P of 0.0006 within 3-12 months postpartum, which may contribute to the development of type 2 diabetes.

The researchers propose that health care providers identify women at risk for gestational diabetes. Women at risk should be educated on lifestyle modification during pregnancy and postpartum to prevent the development of type 2 diabetes.

Landon, M. B., Spong, C. Y., Thom, E., Carpenter, M. W., Ramin, S. M., Casey, B., . . . Anderson, G. B. (2009). A multicenter, randomized trial of treatment for mild gestational diabetes. The New England Journal of Medicine, 361(14), 1339-1348.

This study was performed on 1,889 women who were in their twenty-fourth to thirty-first week of gestation and diagnosed with gestational diabetes, to assess if treatment for GDM would reduce perinatal and obstetrical complications. The treatment group received formal nutritional counseling and diet therapy, along with insulin, if required. The study found that birth weight (3302 g vs. 3408 g, P < 0.001), neonatal fat mass (427g vs. 464 g, P = 0.003), as well as the occurrence of large-for-gestational-age infants (7.1% vs. 14.5%, P < 0.001) were considerably reduced in those being treated for gestational diabetes. The rate of cesarean section delivery (29% vs. 33.8%), shoulder dystocia (1.5% vs. 4%, P = 0.02), preeclampsia (8.6% vs. 13.6%, P = 0.01), maternal weight gain (P < 0.001), and body-mass index levels (P < 0.001) were greatly reduced in the treatment group than the control group. The authors encourage health care providers to treat and educate their patients in order to reduce complications.

Rowan, J. A., Hague, W. M., Gao, W., Battin, M. R., & Moore, M. P. (2008). Metformin versus insulin for the treatment of gestational diabetes. The New England Journal of Medicine, 358(19), 2003-2015.

This study was conducted to determine whether an increase in a number of perinatal complications in infants of women treated with metformin as compared with insulin treatment. The three participant groups were treated with only metformin, only insulin, or both. They did not find a substantial increase of neonatal complications between those treated with metformin versus insulin. Neonatal hypoglycemia occurred less often (P = 0.008) in the metformin group. The overall mean maternal 2 hour postprandial glucose levels were slightly lower in the metformin group (P = 0.003, P = 0.006, P = 0.19), meaning the goal glucose levels were reached sooner in women treated with metformin than those treated with insulin. The adverse effect more common in the metformin group was the increased incidence of preterm birth (P = 0.04), but the authors stated it could be due to chance or an unrecognized effect of metformin on the labor process.

Metformin is a beneficial and safe treatment for gestational diabetes, but further studies are needed to assess the long-term effects and safety of metformin.

Chertok, I. R. A., Raz, I., Shoham, I., Haddad, H., & Wiznitzer, A. (2009). Effects of early breastfeeding on neonatal glucose levels of term infants born to women with gestational diabetes. Journal of Human Nutrition and Dietetics, 22, 166-169. doi: 10.1111/j.1365-277X.2008.00921.x

This study was performed to compare the blood glucose levels of infants of diabetic mothers, who received early breastfeeding to those who did not, or those who were given formula for the first feeding. Among the 84 infants in this study, those who received breast milk within 30 minutes to 1.5 hours after birth had less occurrence of hypoglycemia than those who were not fed early (P = 0.05). The breastfed infants also had much higher plasma glucose levels (3.2 mmol L) than those who were formula fed (2.68 mmol L) within 3 hours postpartum (P = 0.002).

The results indicate that breast-feeding is the preferred method of feeding and treatment for hypoglycemia in infants of diabetic mothers. They suggest more studies be conducted with more control over the timing of when the infants are fed, and to continue exploring the physiological outcomes associated with feeding infants of diabetic women.

Ozcimen, E. E., Uckuyu, A., Ciftci, F. C., Yanik, F. F., & Bakar, C. (2008). Diagnosis of gestational diabetes mellitus by use of the homeostasis model assessment-insulin resistance index in the first trimester. Gynecological Endocrinology, 24(4), 224-229. doi: 10.1080/09513590801948416

The study was performed to predict gestational diabetes prior to the twenty-fourth week of gestation by using the homeostasis model assessment insulin resistance index (HOMA-IR) to measure insulin sensitivity in the first trimester. Participants with a HOMA-IR score above 2.38 were more likely to have higher fasting glucose levels, insulin levels, and BMI (P < 0.05). Women with gestational diabetes were found to have higher HOMA-IR levels than those without GDM (P = 0.0001).

The limitations include that the lack of a cut-off value for the HOMA-IR, so the researchers determined their own value for insulin resistance. They suggest performing larger randomized control studies, and others that look at BMI as it relates to GDM in the first trimester. The researchers conclude that using the HOMA-IR test during the first trimester is a reliable way of diagnosing GDM. They recommend screening patients at risk in the first trimester to prevent adverse maternal and perinatal outcomes.

International Association of Diabetes and Pregnancy Study Groups Consensus Panel. (2010). International association of diabetes and pregnancy study groups recommendations of the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care, 33(3), 676-682. doi: 10.2337/dc09-1848

The International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel met in 2008 to develop criteria for the diagnosis and classification of diabetes in pregnancy to be used internationally. This group used the results from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study to develop new diagnostic criteria for GDM. The IADPSG panel decided that at least one of these thresholds must be met to be classifed as GDM: Fasting plasma glucose level about 92 mg/dl, 1 hour plasma glucose above 180 mg/dl, and 2 hour plasma glucose level above 153 mg/dl. The following results would be considered overt diabetes in pregnancy: Fasting plasma glucose greater than 126 mg/dl, hemoglobin A1C greater than 6.5%, and random plasma glucose level greater than 200 mg/dl and confirmations. It was also decided that all clinics would use a 75 g glucose oral glucose tolerance test to diagnose diabetes. The group suggests that these new approaches will increase the number of hyperglycemic disorders in pregnancy.

Summary

Glucose is necessary for fetal development during pregnancy. During normal pregnancy, there is a decrease insulin sensitivity to allow for increased transport of glucose to the fetus. According to Pridijian and Benjamin (2010, p. 255), “pregnancy is characterized by increased and adaptive pancreatic beta-cell function to compensate for decreased insulin sensitivity and increased requirements”. However, women with gestational diabetes have beta cell dysfunction that results in insulin resistance (Pridijian & Benjamin, 2010).

Gestational diabetes mellitus (GDM) is a damaging disease that has many adverse effects on the mother and fetus. The maternal adverse effects include increased cesarean sections, preeclampsia, and impaired beta cell function leading to development type 2 diabetes mellitus after birth, along with many others (The HAPO Study Cooperatie Researc Group, 2008; Hedderson et al., 2010; Retnakaran et al., 2010). GDM has many perinatal complications including macrosomnia, birth weight above ninetieth percentile, fetal hyperinsulinemia, neonatal hypoglycemia, hyperbilirubinemia, premature delivery, shoulder dystocia or birth injury, and increased occurrences of intensive care unit admissions (The HAPO Study Cooperative Research Group, 2008; Lawlor et al., 2010). Lawlor et al. (2010) found that children born to diabetic women were more likely to be overweight or centrally obese, and some were classified as diabetic and on insulin treatment by 9 years old. These results reveal that the effect of gestational diabetes has a long-term effect on the health of the mother and infant.

Advanced practice nurses must be aware of the increased occurrence of gestational diabetes and screen women early in pregnancy. Ozcimen et al. (2008) and IADPSG Consensus Panel (2010) recommend identifying and screening women early during pregnancy, preferably at the first prenatal visit, to reduce perinatal adverse outcomes. A 75 g oral glucose tolerance test (OGTT) should be performed on all patients, who are not already diagnosed with overt diabetes or GDM, at 24-28 weeks gestation. A diagnosis of GDM includes one or more of the following values: fasting plasma glucose greater than 92 mg/dl, plasma glucose greater than 180 mg/dl at the 1 hour mark, and a level greater than 153 at the 2 hour mark (International Association of Diabetes and Pregnancy Study Groups Consensus Panel, 2010).

A woman diagnosed with gestational diabetes be informed on the management of the disease to prevent adverse effects. Follow up appointments are made every 1-2 weeks to monitor the effects of treatment and for complications. The health care provider should provide the patient with information on nutritional therapy, exercise and weight management, and medication treatment. Nutritional therapy and monitoring blood glucose 3-4 times daily is started first (Pridijian & Benjamin, 2010). A dietitian should be consulted for dietary management, and the woman may be placed on a 1,900-2,400 k calorie diet with a 30-40% carbohydrate restriction (Pridijian & Benjamin, 2010). Because exercise aids with glycemic control, women with GDM should be encouraged to do light exercise at least three times per week. If nutritional therapy and exercise do not reduce blood glucose levels, health care professionals should prescribe either oral glycemic medications, such as metformin or subcutaneous insulin, or both. The patient should be informed of the side effects, drug and food interactions associated with the medication. She should also be informed that metformin and insulin are safe to the fetus (Landon et al., 2009; Rowan et al., 2008).

Most health care providers will induce labor for women with GDM in order to prevent birth complications due to macrosomia of the infant. During labor, women who were treated with glycemic medications might require an intravenous (IV) insulin drip and their blood glucose monitored closely (Pridijian & Benjamin, 2010). It is necessary that both the mother and fetus be monitored closely for birthing complications and perform a cesarean section if needed.

Because GDM women are more likely to develop type 2 diabetes postpartum, they should have their blood glucose monitored. Therefore, a 75 g OGTT should be done at their 6 week postpartum visit, and they should continue to have it monitored three times per year (Pridijian & Benjamin, 2010). They should also be informed of lifestyle modifications that may be needed to prevent the development of type 2 diabetes.

The infant of a GDM mother should be monitored very closely after birth for complications. Healthcare providers should monitor the infant for hypoglycemia and initiate breast or bottle feeding within the first 30 minutes after birth, and check their blood glucose levels closely (Barnes-Powell, 2007; Chertok et al., 2009). If the infant is symptomatic and the blood glucose level is below 47 mg/dl, then IV dextrose must be initiated immediately. The infant may also present with hyperbilirubinemia due to the increased breakdown of red blood cells, and may need to be placed under phototherapy and have exchange transfusions (Barnes-Powell, 2007).

Gestational diabetes has many hazardous effects on the mother and fetus. Therefore, it is necessary to keep her blood glucose under control through nutritional management, exercise, and medical management. The frequency of gestational diabetes mellitus will continue to increase if it is not diagnosed early in pregnancy.

References

Agarwal, M. M., Dhatt, G. S., & Shah, S. M. (2010). Gestational diabetes mellitus simplifying the international association of diabetes and pregnancy diagnostic algorithm using fasting plasma glucose. Diabetes Care, 33(9), 2018-2020.

American Diabetes Association. (2010). Diagnosis and classification of diabetes mellitus. Diabetes Care, 33(1), S62-S69. Doi: 10.2337/dc10-S062

Barnes-Powell, L. L. (2007). Infants of diabetic mothers: The effects of hyperglycemia on the fetus and neonate. Neonatal Network, 26(5), 283-290.

Barta, E., Drugan, A. (2010). Glucose transport from mother to fetus a theoretical study. Journal of Theoretical Biology, 263, 295-302. doi: 10.1016/j.jtbi.2009.12.010

Chertok, I. R. A., Raz, I., Shoham, I., Haddad, H., & Wiznitzer, A. (2009). Effects of early breastfeeding on neonatal glucose levels of term infants born to women with gestational diabetes. Jounral of Human Nutrition and Dietetics. 22, 166-169. Doi: 10.1111/j.1365-277X.2008.00921.x

The HAPO Study Cooperative Research Group. (2008). Hyperglycemia and adverse pregnancy outcomes. The New England Journal of Medicine, 358(19), 1991-2002.

Hedderson, M. M., Gunderson, E. P., & Ferrara, A. (2010). Gestational weight gain and risk of gestational diabetes mellitus. Obstetrics and Gynecology, 115(3), 597-604.

Landon, M. B., Spong, C. Y., Thom, E., Carpenter, M. W., Ramin, S. M., Casey, B., . . . & Anderson, G. B. (2009). A multicenter, randomized trial of treatment for mild gestational diabetes. The New England Journal of Medicine, 361(14), 1339-1348.

Lawlor, D. A., Fraser, A., Lindsay, R. S., Ness, A., Dabelea, D., Catalano, P., . . . & Nelson, S. M. (2010). Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: Findings from a prospective pregnancy cohort. Diabetologia, 53, 89-97. doi: 10.1007/s00125-009-1560-z

Ozcimen, E. E., Uckuyu, A., Ciftci, F. C., Yanik, F. F., & Bakar, C. (2008). Diagnosis of gestational diabetes mellitus by use of the homeostasis model assessment-insulin resistance index in the first trimester. Gynecological Endocrinology, 24(4), 224-229. Doi: 10.1080/09513590801948416

Pridjian, G., & Benjamin, T. D. (2010). Upadate on Gestational Diabetes. Obstetric and Gynecology Clinics North America, 37(2), 255-267. doi: 10.1016/j.ogc.2010.02.017

Retnakaran, R., Qi, Y., Sermer, M., Connelly, P. W., Hanley, A. J. G., & Zinman, B. (2010). Beta-cell function declines within the first year postpartum in women with recent glucose intolerance in pregnancy. Diabetes Care, 33(8), 1798-1804. doi: 10.2337/dc10-0351

Ross, M. G., Ervin, M. G., & Novak, D. (2007). Chapter 2 fetal physiology. In S. Gabbe, J. Niebyl, & J. Simpson (Eds.), Obstetrics: Normal and problem pregnancies (pp. 26-33). Philadelphia, PA: Churchill Livingtone Elsevier.

Rowan, J. A., Hague, W. M., Gao, W., Battin, M. R., Moore, M. P. (2008). Metformin versus insulin for the treatment of gestational diabetes. The New England Journal of Medicine, 358(19), 2003-2015.

Serlin, D. C., & Lash, R. W. (2009). Diagnosis and management of gestational diabetes mellitus. American Family Physician, 80(1), 57-62.