Diabetes in pregnancy.

Why is there insulin resistance in pregnancy? The placenta secretes  diabetogenic hormones which include growth hormone, corticotropin-releasing hormone, placental lactogen (chorionic somatomammotropin), prolactin, and progesterone. These and other metabolic changes ensure that the fetus has an ample supply of nutrients.

Why does gestational diabetes develop?

Gestational diabetes mellitus develops during pregnancy in women whose pancreatic function is insufficient to overcome the insulin resistance associated with the pregnant state. Among the main consequences are increased risks of preeclampsia, macrosomia, and cesarean delivery, and their associated morbidities.

What is the likelihood if a pregnant woman has an abnormally high blood sugar?

  • A woman may have type 1 or type 2 pre-existing diabetes at the time of conception.
  • Develop transient hyperglycemia caused by placental hormones and transient pancreatic insufficiency: gestational diabetes.
  • Undiagnosed type 2 diabetes in reproductive-age women related to the ongoing epidemic of obesity. There has been an attempt to distinguish women with probable preexisting diabetes that is first recognized during early pregnancy. These women will need to be followed up and treated for Type 2 diabetes after the pregnancy is over. This is different from those whose disease is a transient manifestation of pregnancy-related insulin resistance and diagnosed in the late second or the third trimester.
  • The oral glucose tolerance test is no longer recommended for the diagnosis of diabetes except in gestational diabetes.
  • One-step and two-step approaches to OGTT for gestational diabetes.

    • Two-step approach – The two-step approach is the most widely used approach for identifying pregnant women with gestational diabetes mellitus in the United States. The first step is a 50 gram one-hour glucose challenge test (GCT) without regard to time of day/previous meals. Screen-positive patients go on to the second step, a 100 gram, three-hour oral glucose tolerance test (GTT), which is the diagnostic test for gestational diabetes mellitus.

    • One-step approach – The one-step approach omits the screening test and simplifies diagnostic testing by performing only a 75 gram, two-hour oral GTT but requires an overnight fast. The following thresholds have been proposed to define a positive screen: ≥130 mg/dL, ≥135 mg/dL, or ≥140 mg/dL (7.2 mmol/L, 7.5 mmol/L, or 7.8 mmol/L).

    • The positive predictive value (PPV) of this test varies depending on the prevalence of gestational diabetes mellitus in the population tested and the GTT criteria used for diagnosis of gestational diabetes mellitus. A 50 gram one-hour plasma glucose >182 mg/dL (10.1 mmol/L) had >95 percent probability of gestational diabetes mellitus. At glucose levels ≥200 mg/dL (11.1 mmol/L), others have reported PPVs of 47 to 80 percent for an abnormal GTT.
Range of diagnostic criteria for gestational diabetes mellitus
Approach Criteria Fasting mg/dL One-hour mg/dL Two-hour mg/dL Three-hour mg/dL
Two step (100-gram load) Carpenter and Coustan 95 (5.3 mmol/L) 180 (10.0 mmol/L) 155 (8.6 mmol/L) 140 (7.8 mmol/L)
Two step (75-gram load) CDA 95 (5.3 mmol/L) 191 (10.6 mmol/L) 160 (8.9 mmol/L)
One step (75-gram load) WHO 92 to 125 (5.1 to 6.9 mmol/L) 180 (10.0 mmol/L) 153 to 199 (8.5 to 11 mmol/L)
IADPSG 92 to 125 (5.1 to 6.9 mmol/L) 180 (10.0 mmol/L) 153 (8.5 mmol/L)

Why worry about gestational diabetes or hyperglycemia in a pregnant woman? Here is a list of complications likely to arise.

  • Preeclampsia, gestational hypertension
  • Polyhydramnios
  • Macrosomia and large for gestational age infant
  • Maternal and infant birth trauma
  • Operative delivery (cesarean, instrumental)
  • Perinatal mortality
  • Fetal/neonatal hypertrophic cardiomyopathy
  • Neonatal respiratory problems and metabolic complications (hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia)

Diagnosis of Diabetes in non-pregnant patients.

  • Early screening and diagnosis allow for the identification of at-risk persons (so that preventive measures, primarily lifestyle changes, may be undertaken) and those with early disease (so that treatment can be initiated).
  • The diagnostic cutoff point for diabetes is a fasting plasma glucose level of 126 mg per deciliter (7.0 mmol per liter) or more or a glycated hemoglobin level of 6.5% or more; the diagnosis requires confirmation by the same or the other test.
  • A fasting glucose level of 100 to 125 mg per deciliter (5.6 to 6.9 mmol per liter) is consistent with prediabetes; the range of glycated hemoglobin levels that are diagnostic of prediabetes is controversial, but the American Diabetes Association recommends a range of 5.7 to 6.4%.
  • Hemoglobinopathies and conditions of altered red-cell turnover can give spurious results for glycated hemoglobin; racial and ethnic differences in glycated hemoglobin levels have been reported for given ambient glucose levels.
  • Testing of glycated hemoglobin or fasting plasma glucose appears to identify different groups of patients with diabetes and prediabetes, yet both tests identify patients at similar risk for adverse sequelae.
  • Approximately one-quarter of women with A1C 5.7 to 6.4 percent ([39 to 46 mmol/mol] suggestive of impaired glucose intolerance) in early pregnancy develop gestational diabetes mellitus when screened and tested later in pregnancy compared with <10 percent of those with A1C <5.7 percent (39 mmol/mol).
  • A two-step testing approach at 24 to 28 weeks of gestation, is recommended by the American College of Obstetrician and Gynecologists (ACOG) guidelines (50 gram oral glucose challenge test followed by the 100 gram three-hour oral glucose tolerance test [GTT] in screen-positive women)

When is glycated Hb unreliable?

Depending on the assay, spuriously low values may occur in patients with certain hemoglobinopathies (e.g., sickle cell disease and thalassemia) or who have increased red-cell turnover (e.g., hemolytic anemia and spherocytosis) or stage 4 or 5 chronic kidney disease, especially if the patient is receiving erythropoietin. In contrast, falsely high glycated hemoglobin levels have been reported in association with iron deficiency and other states of decreased red-cell turnover.

Obesity is associated with an increased risk of adverse pregnancy outcomes. Lifestyle-intervention studies have not shown improved outcomes. Metformin improves insulin sensitivity and in pregnant patients with gestational diabetes it leads to less weight gain than occurs in those who do not take metformin.



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I am a Professor of Medicine and a Nephrologist. Having served in the Army Medical College, Pakistan Army for 27 years I eventually became the Dean and Principal of the Bahria University Medical and Dental College Karachi from where I retired in 2016. My passion is teaching and mentoring young doctors. I am associated with the College of Physicians and Surgeons Pakistan as a Fellow and an examiner. I find that many young doctors make mistakes because they do not understand how they should answer questions; basically they do not understand why a question is being asked. My aim is to help them process the information they acquire as part of their education to answer questions, pass examinations and to best take care of patients without supervision of a consultant. Read my blog, interact and ask questions so that I can help you more.

One thought on “Diabetes in pregnancy.”

  1. In a metaanalysis of four randomized controlled trials (conducted on 2582 participants) it was concluded that the one step approach had a significantly lower risk of adverse perinatal outcomes including large for gestational age fetuses,admission to NICU and neonatal hypoglycemia compared to those randomized to the screening with the two step approach. The one step approach was also associated with lower mean birth weight. No significant difference in the incidence of GDM was found comparing the one step versus the two step approach .


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