Pregestational Diabetes Case File

Pregestational Diabetes Case File

Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 19

A 30-year-old G2P0020 presents to the office for preconception counseling secondary to an 8-year history of diabetes mellitus. She regularly sees an internist who manages her diabetes and general medical care. She has been treated with multiple oral hypoglycemic medications in order to achieve appropriate glycemic control. Her current regimen includes glyburide which she has taken for the past year and metformin which was added 6 months prior to improve her level of glycemic control. She denies hypertension, retinopathy, and renal disease. Her obstetric history is significant for two first trimester pregnancy losses occurring 1 and 3 years prior. The patient and her husband are contemplating a pregnancy; however she is concerned about her risk of pregnancy loss and other potential effects of diabetes on her pregnancy.

➤ What is the next step in evaluating this patient?

➤ What are potential maternal complications of diabetes mellitus in pregnancy?

➤ What are potential fetal complications?

➤ How would you counsel this patient in terms of pregnancy planning?

➤ How would you manage her if she became pregnant?

ANSWERS TO CASE 19:

Pregestational Diabetes

Summary: An essential nulliparous with a personal history of diabetes and multiple pregnancy losses presents for preconception counseling.

➤ First step in evaluating this patient: A detailed history and physical examination including baseline laboratory testing should be completed to assess the severity of her disease. A conversation should be had stressing the importance of effective contraception to ensure that conception does not occur until diabetic control is optimized.

➤ Potential maternal complications of diabetes mellitus in pregnancy: Women with diabetes who become pregnant often experience less stable glycemic control. They are also at increased risk of chronic hypertension, preeclampsia, diabetic retinopathy, and cesarean delivery.

➤ Potential fetal complications: Diabetics with suboptimal glycemic control have higher rates of pregnancy loss birth defects, preterm delivery, disturbances in fetal growth, and stillbirth.

➤ Counselling this patient in terms of pregnancy planning: The patient should be counseled that she should optimize her diabetic control prior to conception. A glycosylated hemoglobin level (HbA1c) less than 7% is recommended in order to obtain neonatal morbidity and mortality rates similar to the general population.

➤ Management plan in case of pregnancy: She should receive frequent physician visits in order to monitor glycemic control. She should receive ophthalmologic evaluations every trimester and during the postpartum period. She should receive a detailed anatomy ultrasound and potentially a fetal echocardiogram during the second trimester. Fetal surveillance should be achieved with antenatal testing and serial growth ultrasounds. If glycemic control is optimal, delivery should occur between 39 and 40 weeks’ gestation. Women with suboptimal control should be delivered prior to 39 weeks after fetal lung maturity is confirmed.

ANALYSIS

Objectives

1. Describe the effect of pregestational diabetes on the pregnancy.
2. Describe the management of pregestational diabetes.
3. List the complications that may occur to a pregestational diabetic during pregnancy.

Considerations

Diabetes affects approximately 8 million women annually and complicates approximately 1% of all pregnancies. Pregestational diabetes accounts for approximately 10% of insulin resistance encountered in pregnant women with the larger share being owed to gestational diabetes1 (Level III).

The most important aspects of managing women with diabetes who become pregnant should occur prior to conception. These women should be thoroughly educated on the impact of pregnancy on their disease and disease management in addition to the effect that diabetes may have on their baby. Women with suboptimal diabetic control should be counseled in terms of appropriate contraception in order to ensure that conception occurs only after appropriate control has been established.

Preconception counseling should include a detailed history and physical examination in order to assess the severity of their disease as well as their level of glycemic control. Initial laboratory tests should include measurements of glycosylated hemoglobin (HbA1c), thyroid-stimulating hormone (TSH), screening for creatinine clearance and urinary protein excretion, complete blood count, and a blood chemistry screen2,3 (Level III). The purpose of these laboratory tests are twofold, first of all it is important to assess the baseline health status and severity of disease prior to pregnancy in order to make plans regarding timing of pregnancy and appropriate surveillance. Second, women with chronic health condition such as diabetes are at risk of other comorbid conditions which may affect maternal and neonatal outcome. All pregestational diabetics should have ophthalmologic examinations prior to and during pregnancy. The frequency of surveillance can be based on the degree of retinopathy. Those with chronic conditions such as hypertension and hypercholesterolemia should receive appropriate evaluations such as ECG and echocardiograms with cardiology consultations as appropriate. Medications which are contraindicated during pregnancy such as angiotensin converting enzyme inhibitors (ACE-I) should be discontinued prior to conception. Oral hypoglycemic agents can be discontinued during the first trimester if glycemic control is optimal based on HbA1C. Insulin treatment can be started based on glucose monitoring. Alternatively, if the patient’s glycemic control is suboptimal on oral hypoglycemic agents, she can be switched to insulin immediately.

APPROACH TO

Pregestational Diabetes

The previously used White classification was devised to classify diabetes based on the duration of disease and the presence or absence of end-stage organ disease. One of the main utilities of this system was that it assisted physicians in predicting risk of perinatal loss and serious morbidity. As neonatal and maternal prognosis has greatly improved, this system has proven to be less useful. The classification system that most physicians currently use classifies insulin resistance based on whether the physiology is due to β-cell dysfunction resulting in an absolute insulin deficiency as is seen in type 1 diabetes or due to insulin resistance and relative insulin deficiency as is seen in type 2 diabetesn2,4 (Level III). Additional information should be provided concerning diabetic complications. This classification scheme relates outcomes to the degree of metabolic control and thus better directs treatment modalities.

Maternal Effects

Physiologic changes of pregnancy affect the degree of insulin resistance resulting in a need to adjust insulin dosing as pregnancy progresses. The primary fuel source for the fetus is glucose, therefore there are mechanisms in place to ensure that this source is readily available. The placenta produces diabetogenic hormones such as growth hormone, corticotrophin-releasing hormone, human placental lactogen, and progesterone which create an insulin resistant state3 (Level III). As a result there is postprandial hyperglycemia providing a ready supply for the fetus. In a nondiabetic woman, there is a responsive up-regulation of insulin production by β-cells which restores maternal glycemic levels2,3,5 (Level II-2, III). In a woman with diabetes, this does not occur, either due to β-cell dysfunction or lack of β-cell reserve resulting in persistent hyperglycemia.

End-organ damage is a major concern in all patients with diabetes; however, there are considerations which are specific to pregnancy. Diabetic retinopathy is the leading cause of blindness in reproductive age women6 (Level II-2). Retinal vasculopathy should be considered in all pregnant women with longstanding diabetes as the progression of diabetic retinopathy is accelerated during pregnancy. The severity of retinopathy and duration of diabetes influence progression of retinopathy during pregnancy. Rapid changes in glucose control are associated with worsening retinopathy; for this reason, it is preferred that control be achieved prior to pregnancy in a gradual manner1-3,7,8 (Level III, II-2). Women with diabetes should receive baseline screens prior to pregnancy with follow-up evaluations approximately every trimester and again during the postpartum period. Laser photocoagulation during pregnancy may be performed as needed in order to improve maternal symptoms and to decrease the progression of vasculopathy and subsequent vision loss.

While pregnancy does not appear to accelerate renal damage in women with minimal preexisting disease, it is not uncommon to document a transient worsening in creatinine clearance and protein excretion. Diabetic nephropathy accounts for 40% of all end-stage renal disease. Although pregnancy is not believed to alter the overall course of this complication, women with preexisting renal damage defined by creatinine levels greater than 1.4 mg/dL, microalbuminuria or proteinuria may experience a worsening of renal pathology and also experience hypertensive disorders at higher rates2 (Level III).

Hypertensive disorders are a major complication of women with diabetes who become pregnant. Often times it is hypertension and not diabetes which leads to morbidity and subsequent iatrogenic preterm delivery. This includes chronic hypertension as well as preeclampsia. Approximately 10% to 20% of women with diabetes will experience hypertensive disease related to pregnancy9 (Level II-2). This percentage is increased in women with preexisting renal dysfunction; as 40% of women with mild preexisting nephropathy and nearly 50% with significant disease will experience pregnancy-related hypertensive disease9 (Level II-2), women with diabetic retinopathy and chronic hypertension experience rates of preeclampsia as high as 60%2,3 (Level III).

Neonatal Effects

Women with diabetes who become pregnant experience higher rates of fetal wastage which appears to be related to the degree of glycemic control. This includes higher rates of first-trimester losses as well as increased rates of stillbirth in later trimesters2,3 (Level III).

Fetal overgrowth or macrosomia is commonly associated with poor maternal glycemic control. This is due to increased adiposity manifested by an increase in both size and number of fat cells which has been documented in babies born to mothers with diabetes1,10 (Level II-2, III). Fetal macrosomia is associated with increased rates of maternal and neonatal birth trauma and higher rates of neonatal ICU admissions.

Care should also be taken to monitor for fetal growth restriction in women with long-standing diabetes. Women with underlying vascular and/or renal disease experience increased rates of fetal growth restriction. It is important to monitor fetal growth and to tailor antenatal surveillance based on findings. In our center, we obtain fetal growth ultrasounds at 32 weeks and again before delivery (36-38 wk gestational) in order to make decisions regarding route of delivery.

Babies born to mothers with suboptimal glycemic control experience increased rates of congenital anomalies8 (Level III). These include cardiac malformations, skeletal dysplasias, and CNS complications. The rate of anomalies appears to be related to the degree of glycemic control. Women with HbA1c less than 7% prior to conception experience rates similar to nondiabetic women. However, increasingly poorer glycemic control leads to an increase in congenital anomalies. Women with a HbA1c greater than 10% experience rates of congenital anomalies as high as 20% to 25%. Therefore, a detailed anatomy ultrasound is recommended for all diabetics. It is our practice to obtain fetal echocardiograms in all patients with a HbA1c greater than 8%.

Medical Management

Antibody-free human insulin is the gold standard for glycemic control during pregnancy; however, the use of insulin analogs may present a better option for the overall health of the patient. Benefits on insulin analogs include elimination of antibody formation seen with the use of natural insulin as well as better efficacy profiles which result in higher peak insulin concentrations in less time with a shorter duration of action1,5,7,8(Level II-2, III).

The goal of insulin therapy is to provide coverage for meal-derived glucose loads, to control between-meal glucose levels, and to maintain overnight blood glucose levels during fasting. There are a number of viable options for insulin formulations which are useful, however, certain physiologic changes of pregnancy such as fasting hypoglycemia and postprandial hyperglycemia make intermediate and ultrafast-acting formulations more practical5 (Level II-2).

Neutral protamine hagedorn (NPH) is intermediate-acting and is the basal insulin of choice as it has more predictability. Use of rapid-acting insulin such as aspart (Novolog) or lispro (Humalog) allows for tighter control and individualized meal titrations on insulin11 (Level I). Further, by using insulin with a shorter half-life such as Humalog and Novolog we decrease the frequency of hypoglycemic episodes which occur during times of fasting. Preprandial regular insulin also has good coverage of meals; however, postprandial hypoglycemia can develop 2 to 4 hours after meals requiring snacks to oppose this side effect. Glargine (Lantus) has not been studied adequately for use in pregnancy. Single dosing and prolonged action profile increase the risk of nocturnal hypoglycemia as well as undertreatment during the day (Table 19–1).

Open-loop continuous subcutaneous insulin infusion pump therapy is another option for a select group of motivated patients. Use of an insulin pump necessitates 6 to 8 capillary glucose measurements daily for insulin titration. Basal rates are usually 1 U/h, representing 50% to 60% of daily insulin dose. Prior to initiating pump therapy, patients must be thoroughly screened and made aware of the commitment which is necessary to achieve adequate management of their disease12 (Level I).

Weisz et al looked at the benefits of measuring 1-hour versus 2-hour postprandial glucose levels and found no difference in efficacy. Due to a factor of

convenience most practitioners opt for 1-hour measurements to guide therapy13 (Level II-2). De Veciana et al looked at preprandial versus postprandial glucose measurements. They found that in the group where postprandial measurements were used there was a better control evident by lower HbA1c levels at delivery, as well as less neonatal hypoglycemia, less neonatal macrosomia, and fewer large for gestational age (LGA) infants14 (Level II-2). The fourth International Workshop on Gestational Diabetes recommended that fasting as well as postprandial measurements be used to guide therapy1 (Level III).

It is important to individualize the insulin regimen for each patient taking into account daily activities and meal schedules to provide adequate coverage. Fasting targets should be less than 105 mg/dL and 1-hour postprandial targets should be less than 140 mg/dL. As pregnancy progresses insulin requirements change. In general, during the first trimester insulin requirements are calculated at 0.7 to 0.8 U/kg/d, during the second trimester 0.8 to 1.0 U/kg/d, and during the third trimester 0.9 to 1.2 U/kg/d1.15 (level II-2, III). In order to initiate insulin therapy it is necessary to calculate the estimated total daily insulin requirements using the above guidelines. Approximately two-thirds of the total insulin should be allotted for daytime coverage, of which approximately two-thirds of this coverage should be achieved with an intermediateacting formulation such as NPH insulin and one-third of coverage should be achieved using a rapid-acting formulation such as lispro insulin. Approximately one-third of the total daily insulin requirements should be allocated for evening and nighttime coverage; this should be divided equally between intermediate and rapid-acting formulations. Patients should be monitored with fasting and postprandial levels in order to titrate insulin dosing1.13.15 (Level II-2, III).

Glycemic control is also important during labor and delivery. Infants born with neonatal hypoglycemia are 2 to 3.5 times more likely to have neurodevelopmental delay at 18 months to 7 years of age. Insulin therapy should be titrated to achieve and maintain glucose levels between 80 and 110 mg/dL16 (Level III). This can be accomplished with insulin infusions or with subcutaneous injections.

Although insulin is the gold standard for glycemic control during pregnancy, oral hypoglycemic medications may present an additional option in some patients. In many cases they are more easily accepted by patients as they eliminate or at least limit the need for injections. Both glyburide as well as metformin have shown promising results in women with gestational diabetes and polycystic ovarian syndrome (PCOS), respectively17,18 (Level I). However, it is unclear if this data can be applied to women with pregestational diabetes. The American College of Obstetrics and Gynecology recommendations states that “the use of all oral agents for control of type 2 diabetes mellitus during pregnancy should be limited and individualized until data regarding the safety and efficacy of these drugs becomes available”1 (Level III).

Fetal Surveillance and Delivery

Women requiring insulin therapy for diabetes and those with additional comorbid conditions who do not require insulin should undergo increased surveillance to improve neonatal outcome19,20 (Level II-2). Early ultrasound evaluations are useful to provide accurate dating, while anatomy surveys performed between 18 to 20 weeks’ gestation are important to evaluate for congenital anomalies. In addition, ultrasound evaluations should be performed during the third trimester to assess for signs of fetal hyperglycemia including fetal overgrowth and polyhydramnios1 (Level III).

Antenatal testing should begin no later than 32 weeks’ gestation and may be accomplished at least weekly with fetal non-stress tests or biophysical profile evaluations. Decisions regarding timing of delivery should be based on level of control and maternal and neonatal morbidity. However, generally delivery should occur between 39 to 40 weeks in women with good control. Deliveries occurring prior to 39 weeks should consider documentation of fetal lung maturity via amniocentesis1.20 (Level II-2, III). Route of delivery should be based on the estimated fetal weight (EFW) by ultrasound and most would agree that elective cesarean delivery should be discussed and offered to diabetics with EFW of greater than 4500 g due to the potential for shoulder dystocia.

Diabetic Emergencies

Diabetic ketoacidosis (DKA) presents a medical emergency which may be more difficult to diagnose during pregnancy. This is due to the fact that during pregnancy it occurs at lower blood glucose levels and its onset may be more rapid than in the nonpregnant state2,3 (Level III). Precipitating factors include emesis, infection, noncompliance or unrecognized new onset of diabetes, pump failure, and maternal steroid use. Signs and symptoms are similar to those in the nonpregnancy state, however, they also may mimic normal symptoms of pregnancy. These include polyuria, polyphagia, polydipsia, weight loss, weakness and signs of dehydration, nausea/vomiting, abdominal pain, and intercurrent illnesses.

DKA occurs more commonly during the second and third trimesters. Although its prevalence is higher in patients with type 1 diabetes, it may also occur in patients with type 2 diabetes or gestational diabetes. Laboratory findings include hyperglycemia greater than 200 to 250 mg/dL, acidosis defined as an arterial pH less than 7.35, anion gap greater than 12 mEq/L, bicarbonate less than 15 mEq/L, and positive serum ketones2,3 (Level III). of regular insulin is 0.2 to 0.4 U/kg regular insulin followed by continuous insulin infusion of 6 to 10 U/h. When glucose levels approach 200 to 250 mg/dL, the insulin infusion rate may be decreased to 1 to 2 U/h1-3 (Level III).

Electrolyte replacement should be provided as needed. If serum potassium is elevated, potassium replacement should be provided at 20 mEq/h after urine output is established. If serum potassium is below normal, replacement should be initiated immediately at the above rate. Serum magnesium and phosphorus levels should be evaluated and provided as needed. Careful monitoring should be continued at least 12 to 24 hours after resolution of laboratory derangements1-3 (Level III).

Comprehension Questions

19.1 A 36-year-old G2P1001 presents for her initial prenatal visit at 6 weeks’ gestation. She has a long-standing history of type 2 diabetes mellitus which is managed with oral hypoglycemic medications. Initial laboratory test reveals a HbA1c of 10%. The patient is very motivated to have a successful outcome and asks for information concerning management of her pregnancy. Which of the following surveillance tools is not indicated for this patient?

A. Serial umbilical Doppler measurements starting at 32 weeks’ gestation.

B. Fetal echocardiogram at approximately 20 weeks’ gestation.

C. Antenatal testing with either non-stress test or biophysical profile starting at 32 weeks.

D. Initiation of insulin therapy with titration guided by fasting and postprandial glucose measurements.

E. Detail anatomy survey at 18 to 20 weeks’ gestation.

19.2 A 21-year-old G1P0 woman at 11 weeks’ gestation is seen in the emergency center complaining of nausea, vomiting, abdominal pain, and fatigue. The patient is a known diabetic since age 12 years, and has been in good control. On examination, her BP is 90/60 mm Hg, HR 120 beats per minute, and RR 28 per minute. The arterial blood gas reveals a pH of 7.28, pO2 of 100 mm Hg, pCO2 of 22 mm Hg, and bicarbonate level of 12 mEq/L. Which of the following is the best management of this patient?

A. Administer 2 L of normal saline intravenously.

B. Infuse two ampules of bicarbonate IV.

C. Obtain a spiral CT scan.

D. Obtain a gallbladder ultrasound examination.

ANSWERS

19.1 A. Serial Doppler measurements are not indicated in this patient as Doppler studies have only been shown to be informative in cases of growth restriction. Doppler studies are not routinely used for surveillance of other high-risk pregnancies. This patient should undergo a detailed anatomy survey including a fetal echocardiogram due to her elevated HbA1c measurement which increases her risk of structural anomalies including but not limited to cardiac defects. As her glycemic control is suboptimal on oral medications, insulin therapy should be initiated and titrated based on fasting and postprandial values. Finally, women managed with insulin should receive antenatal testing beginning at least by 32 weeks’ gestation.

19.2 A. This patient likely has diabetic ketoacidosis. Pregnancy will often cause diabetes to become more difficult to control. The pH is acidotic, whereas the normal pH in pregnancy is slightly alkalotic. Together with the low bicarbonate level, this is consistent with an anion gap metabolic acidosis. The patient’s oxygenation is good, and thus, a pulmonary embolus is not suspected. The pCO2 is lower than the normal 28 mm Hg seen in pregnancy, which is indicative of partial respiratory compensation. The blood sugar is likely to be elevated. The cornerstones of management of DKA include IV fluid hydration, insulin intravenous drip to control the blood sugars and correct the acidosis, correction of metabolic abnormalities such as hypokalemia, hypophosphatemia, or hypomagnesemia, and addressing the etiological factor. A gallbladder ultrasound may be indicated; however, the first priority is volume repletion.

Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1

➤ Diabetic retinopathy may accelerate during pregnancy and thus women should be followed with ophthalmology evaluations prior to conception, every trimester, and at 3 to 6 months postpartum (Level II-3).

➤ Although diabetic nephropathy generally does not generally worsen with pregnancy,women with preexisting moderate to severe nephropathy may experience a worsening of their renal disease (Level III).

➤ Preeclampsia rates may be as high as 50% in some women with diabetes (Level II-2).

➤ HbA1c levels less than 7% prior to conception is associated with neonatal morbidity rates comparable to the general population (Level II-3).

➤ HbA1c levels greater than 11.2% prior to conception are associated with neonatal morbidity rates as high as 25% (Level II-3).

➤ Postprandial glucose measurements are better than preprandial measurement in order to improve neonatal outcomes (Level II-1).

➤ DKA occurs more rapidly and at lower serum glucose levels during pregnancy compared to outside of pregnancy (Level III).

➤ Pregestational diabetics should be recommended delivery at 39 weeks with earlier delivery (after mature amniocentesis) if suboptimal control (Level III).

CONTROVERSIES

• Management of women with pregestational diabetes with oral hypoglycemic medications. ACOG position is that their use in patients with type 2 diabetes mellitus should be limited and individualized until more data are available.
• Patients in whom the estimated fetal weight exceeds 4500 g should be offered cesarean delivery in order to decrease risk of traumatic delivery.

REFERENCES

1. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician- Gynecologists. Number 60, March 2005. Pregestational diabetes mellitus. Obstet Gynecol. 2005;105:675-685 (Level III). 

2. Metzger BE, Phelps RL, Dooley SL. The mother in pregnancies complicated by diabetes mellitus. In: Porte D SR, Baron A, eds. Ellenberg and Rifkin’s Diabetes Mellitus. New York, NY: The McGraw-Hill Companies Inc.; 2003 (Level III). 

3. Moore TR CP. Diabetes in pregnancy. In: Creasy RK RR, Iams JD, Lockwood CJ, Moore TR, eds. Creasy and Resnik’s Maternal-Fetal Medicine, Principles and Practice. Philadelphia, PA: Saunder Elsevier; 2009 (Level III). 

4. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2006;29 (Suppl 1): 43S-48S (Level III). 

5. Mello G, Parretti E, Mecacci F, Pratesi M, Lucchetti R, Scarselli G. Excursion of daily glucose profiles in pregnant women with IDDM: relationship with perinatal outcome. J Perinat Med. 1997;25:488-497 (Level II-2). 

6. Rosenn B, Miodovnik M, Kranias G, et al. Progression of diabetic retinopathy in pregnancy: association with hypertension in pregnancy. Am J Obstet Gynecol. 1992;166:1214-1218 (Level II-2). 154 women with insulin dependent diabetes were followed prospectively with serial ophthalmologic evaluations during pregnancy and postpartum to evaluate for progression of retinopathic complications. The investigators found that progression of disease was associated with rapid glycemic changes in early pregnancy and with the presence of hypertensive disorders. 

7. Boinpally T, Jovanovic L. Management of type 2 diabetes and gestational diabetes in pregnancy. Mt Sinai J Med. 2009;76:269-280 (Level III). 

8. Kinsley B. Achieving better outcomes in pregnancies complicated by type 1 and type 2 diabetes mellitus. Clin Ther. 2007;29 Suppl D:153S-160S (Level III). 

9. Combs CA, Rosenn B, Kitzmiller JL, Khoury JC, Wheeler BC, Miodovnik M. Early-pregnancy proteinuria in diabetes related to preeclampsia. Obstet Gynecol. 1993;82:802-807 (Level II-2). 

10. Wong SF, Lee-Tannock A, Amaraddio D, Chan FY, McIntyre HD. Fetal growth patterns in fetuses of women with pregestational diabetes mellitus. Ultrasound Obstet Gynecol. 2006;28:934-938 (Level II-2). 

11. Perriello G, Pampanelli S, Porcellati F, et al. Insulin aspart improves meal time glycemic control in patients with type 2 diabetes: a randomized, stratified, doubleblind and cross-over trial. Diabet Med. 2005;22:606-611 (Level I). A multicenter randomized control trial was conducted to compare efficacy of regular human insulin and insulin aspart in pregnant women with type 2 diabetes. The investigators found that women treated with insulin aspart had better glycemic control and more favorable insulin profiles. 

12. Doyle EA, Weinzimer SA, Steffen AT, Ahern JA, Vincent M, Tamborlane WV. A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Diabetes Care. 2004;27:1554-1558 (Level I). 

13. Weisz B, Shrim A, Homko CJ, Schiff E, Epstein GS, Sivan E. One hour versus two hours postprandial glucose measurement in gestational diabetes: a prospective study. J Perinatol. 2005;25:241-244 (Level II-2). 

14. de Veciana M, Major CA, Morgan MA, et al. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. N Engl J Med. 1995;333:1237-1241 (Level II-2). 

15. Langer O, Anyaegbunam A, Brustman L, Guidetti D, Levy J, Mazze R. Pregestational diabetes: insulin requirements throughout pregnancy. Am J Obstet Gynecol. 1988;159:616-621 (Level II-2). To evaluate insulin requirements during pregnancy 103 women with pregestational diabetes were monitored. The investigators found that insulin requirements were triphasic and that overall requirements were higher in all gestations for women with type 2 diabetes compared to type 1 diabetes. 

16. Garber AJ, Moghissi ES, Bransome ED, Jr., et al. American College of Endocrinology position statement on inpatient diabetes and metabolic control. Endocr Pract. 2004;10 (Suppl 2):4-9 (Level III). 

17. 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;343:1134-1138 (Level I). 

18. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358:2003-2015 (Level I). 

19. Barrett JM, Salyer SL, Boehm FH. The nonstress test: an evaluation of 1000 patients. Am J Obstet Gynecol. 1981;141:153-157 (Level II-2). 

20. Graves CR. Antepartum fetal surveillance and timing of delivery in the pregnancy complicated by diabetes mellitus. Clin Obstet Gynecol. 2007;50:1007-1013 (Level II-2). 

21. Kjos SL, Leung A, Henry OA, Victor MR, Paul RH, Medearis AL. Antepartum surveillance in diabetic pregnancies: predictors of fetal distress in labor. Am J Obstet Gynecol. 1995;173:1532-1539 (Level II-2).

HomeHigh-Risk Obstetrics Case FilePregestational Diabetes Case File