Arriving at a type 1 diagnosis
Patients with type 1 diabetes often present with modest hyperglycemia, but may rapidly progress to severe hyperglycemia and diabetic ketoacidosis (DKA) when infection or other physical stressors occur.
While screening for autoantibodies in asymptomatic individuals is not recommended,5 patients with blood glucose levels ≥200 mg/dL and symptoms of polydipsia, polyuria, and polyphagia who do not meet the profile for type 2 diabetes may be candidates for additional laboratory work. Approximately 85% to 90% of patients with type 1 diabetes will have antibodies to islet cells or glutamic acid decarboxylase (GAD).5,23
Even without antibody testing, there are distinguishing characteristics that help support a type 1 diagnosis. As a general rule, individuals who develop type 1 diabetes—especially children—are not obese, although patients usually gain weight over time. In addition, many patients with type 1 diabetes have an auto-immune disease, such as celiac or Graves’ disease, hypothyroidism, adrenal anemia, or pernicious anemia; and a first-degree relative with type 1 diabetes. DKA, with acute symptoms of polydipsia and/or polyuria and recent, unintentional weight loss, is suggestive of—but not definitive for—type 1 diabetes.
A recently validated type 1 risk calculator may be particularly useful for screening patients who have a sibling, parent, or child with type 1 diabetes. Using age, BMI, C-peptide concentration, and OGTT results, the algorithm was highly predictive of type 1 diabetes in family members of patients who tested positive for islet cell antibodies.24
Patient doesn’t “fit” type 1 or 2? Consider LADA
LADA, a gradual, progressive form of type 1 diabetes, can be difficult to identify. Circulating GAD or islet cell antibodies are present, but patients don’t have an absolute need for insulin at the time of diagnosis. Thus, they’re often thought to have type 2 diabetes.25 Individuals with LADA show no signs of insulin resistance, however, and over time, β cells decline and insulin usually becomes necessary.
There are no universal recommendations for testing for LADA. Rather, the diagnosis should be considered in those who don’t fit the classic profile for type 1 or type 2 diabetes,26 but have some of the following features:
- age <50 years
- acute symptoms of polydipsia, polyuria, and/or unintentional weight loss
- BMI <25
- a personal history of autoimmune disease
- a family history of autoimmune disease.27
A prospective analysis found that the majority of LADA patients had at least 2 of these distinguishing characteristics.28 Other recent research found heterogeneity among patients with LADA. Noting that not all patients with LADA become insulin-dependent, researchers concluded that the need for insulin is linked to the degree of autoimmunity and β-cell failure.29
When GDM complicates prenatal care
Any degree of carbohydrate intolerance that is first recognized during pregnancy is classified as GDM, whether or not the condition resolves after delivery. A GDM diagnosis does not preclude the possibility of undiagnosed type 2 diabetes or prediabetes, or (rarely) type 1 diabetes.
Approximately 7% of all pregnancies in the United States are complicated by GDM, totaling more than 200,000 cases annually.5 The rate of GDM is in direct proportion to the prevalence of type 2 diabetes in the population in question, and ranges from 1% to 14%. GDM is the diagnosis in nearly 90% of pregnancies complicated by diabetes.5
The GDM screening controversy
Screening for GDM—whether it should be done universally or selectively on the basis of risk factors—is highly controversial. The USPSTF maintains that there is insufficient evidence to recommend for or against screening women with no history of GDM. The American College of Obstetricians and Gynecologists (ACOG)30 and ADA5 recommend selective screening based on patient history, clinical presentation, and, possibly, prior impaired glucose test results or other abnormal laboratory values. AACE calls for universal screening of pregnant women, starting at 20 weeks for high-risk individuals and between 24 and 28 weeks for those at low risk.12
Identifying patients at risk. Maternal age (>25 years), obesity (BMI ≥30), prior GDM or delivery of a large-forgestational-age infant, belonging to a high-risk ethnic group, glycosuria, history of glucose resistance or glucose tolerance, and a first-degree relative with diabetes (TABLE) are risk factors for GDM. Women at high risk—those who meet all or most of these criteria—should undergo early screening: at the first prenatal visit, according to ACOG;30 upon confirmation of pregnancy (ADA);5 at 20 weeks’ gestation (AACE);12 or between 24 and 28 weeks’ gestation (USPSTF).7 ADA and ACOG recommend a 2-stage approach, starting with a 50-g 1-hour OGTT and following up with a 100-g 3-hour OGTT if the first test results are not definitive.5,30 Testing for patients at average risk—which includes any pregnant woman with even a single risk factor, such as being older than 25 years—should be done between 24 and 28 weeks’ gestation, according to ACOG and ADA; testing is not required for women who are <25 years, have a normal body weight, and no other risk factors.
GDM screening in primary care. Because most women fit the criteria for average or high risk,31 family physicians may find universal screening to be more practical than individual risk assessment. Universal screening is associated with favorable outcomes,32 but screening limited to those at high and average risk also has evidence to support it. In a study of 25,118 deliveries, only 4% of women with GDM were missed by the exclusion of low-risk patients.33
In the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, researchers tracked 25,505 women from 9 countries and found a continuous relationship between the risk of macrosomia and the rise in maternal glucose levels.34 The impact on the developing fetus of varying degrees of glucose was studied after a 75-g 2-hour OGTT. The risk of macrosomia increased with fasting blood glucose >75 mg/dL, 1-hour glucose levels >105 mg/dL, and 2-hour glucose concentration >90 mg/dL.35 The most compelling results for adverse effects were associated with fasting glucose levels, rather than glucose tolerance tests.