LEARNING OBJECTIVES
After completing Module 4, the learner should be able to:
1. Identify key clinical signs, symptoms, and risk factors that should prompt screening for T1D in the emergency department.
2. Recognize features of early-stage T1D and factors (e.g., illness, medications) that can worsen dysglycemia in acute care settings.
3. Describe screening methods for early-stage T1D, including glucose testing, HbA1c, and islet autoantibody assessment.
4. Summarize common and severe adverse effects of teplizumab and outline appropriate acute care evaluation
and follow-up planning.
Recognizing and Managing Early-Stage T1D in the Emergency Department
04 |
Module Authors: Brigitte Frohnert, Rick Bacher, Marian Rewers, Arleta Rewers
Diabetes mellitus is a major global public health problem associated with significant morbidity, mortality, and healthcare costs. Many individuals with diabetes remain undiagnosed until complications develop. Emergency departments (EDs) and acute care settings serve as critical points of contact for patients who may have limited access to primary care, making them valuable settings for opportunistic diabetes screening as well as evaluation of current T1D stage in those with known islet autoimmunity.
EDs frequently treat patients presenting with conditions linked to hyperglycemia, including infections, cardiovascular disease, dehydration, and altered mental status. Studies suggest that a substantial proportion of ED patients have abnormal glucose levels without a prior diagnosis of diabetes. Opportunistic screening in the ED can support earlier diagnosis, timely intervention, and appropriate follow-up care, helping reduce the risk of complications such as diabetic ketoacidosis (DKA), nephropathy, retinopathy, neuropathy, and cardiovascular disease.
Finally, the emerging population of individuals receiving immunotherapy for T1D necessitates basic familiarity with associated symptoms and side effects in patients who may present for acute care evaluation.
This Module will cover:
1. Diabetes Screening in the Emergency Department
2. ED/Acute Care protocol (flowchart)
3. Known Early-Stage T1D in the Acute Care Setting
4. Management of complications of teplizumab in the Acute Care setting
1. Diabetes Screening in the Emergency Department
Emergency departments are not traditionally designed for population screening programs; however, they remain important sites for opportunistic identification of undiagnosed T1D and T2D.
Children and adults presenting with the following symptoms should prompt immediate diabetes evaluation:
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Polyuria
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Polydipsia
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Weight loss
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Vomiting
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Abdominal pain
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Fatigue
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Dehydration
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Altered mental status
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Kussmaul respirations, which can sometimes be mistaken for asthma exacerbation.
Point-of-care glucose testing should be considered routine in symptomatic pediatric patients because delayed diagnosis remains common and frequently contributes to DKA development.(1) Missed recognition of pediatric DKA is associated with adverse outcomes.(2) Further, delayed referral may occur even when healthcare providers suspect diabetes, highlighting the need for streamlined ED diagnostic pathways.(3)
Methods of Screening
Diagnostic glycemic values for both Stage 3 (symptomatic) type 1 diabetes (T1D) and type 2 diabetes (T2D) are the same; however, the entities have distinct pathophysiology and genetic predisposition.(4) Historical features and laboratory findings (including the presence of islet autoantibodies) are helpful in differentiating the two conditions. While both T1D and T2D can present with DKA, it is significantly more prevalent in T1D. Glycemic thresholds for prediabetes (a risk state for development of T2D) and Stage 2 T1D (a risk state for development of Stage 3 T1D) are similar; however, Stage 2 T1D has additional criteria albeit with minimal application in the acute care setting.(4)
Several methods are used to screen for diabetes in the ED/Acute Care setting:
Random Blood Glucose Testing
Random plasma glucose testing is commonly performed in EDs because it is rapid and readily available. A blood glucose level ≥200 mg/dL in the presence of classic symptoms of hyperglycemia strongly suggests diabetes.(4)
Fasting Plasma Glucose
Although fasting plasma glucose is a standard diagnostic tool, it is less practical in emergency settings because patients are rarely fasting upon presentation. In children who develop T1D, elevated fasting plasma glucose is a later finding. Post-prandial glucose elevations are often the first abnormality noted due to the loss of first-phase insulin response.
Hemoglobin A1c (HbA1c)
HbA1c testing reflects average blood glucose levels over the previous two to three months and is useful for identifying chronic hyperglycemia, both prediabetes and diabetes, and monitoring progression.(4)
Reference values are:
• Normal: ≤ 5.6%
• Prediabetes/Stage 2 T1D: 5.7–6.4%
• Diabetes: ≥ 6.5%
In addition, HbA1c does not require fasting which makes it particularly valuable in the ED/Acute Care setting; however, it has been shown to be less sensitive in the youngest children in whom progression to Stage 3 T1D can be particularly rapid. For this reason, an HbA1c of 5.7% or higher requires prompt follow-up, particularly prompt in the youngest children.
Oral Glucose Tolerance Test (OGTT)
OGTT may detect early dysglycemia in autoantibody-positive patients before overt hyperglycemia develops.(5) Although less practical in emergency settings, it remains important in specialized endocrine follow-up programs for individuals with early-stage T1D.
Risk Assessment Tools
Questionnaires assessing risk factors such as family history of T1D or T2D, personal or family history of autoimmunity, obesity, hypertension, and age may help identify high-risk individuals who would benefit from laboratory testing.
Islet Autoantibody Screening
The cornerstone of T1D screening is detection of pancreatic islet autoantibodies. Commonly tested antibodies include:
• Glutamic acid decarboxylase antibodies (GADA)
• Insulinoma-associated antigen-2 antibodies (IA-2A)
• Zinc transporter 8 antibodies (ZnT8A)
• Insulin autoantibodies (IAA)
Presence of multiple autoantibodies significantly increases the likelihood of progression to clinical diabetes. Casalini et al. demonstrated that children with persistent islet autoantibody positivity showed progressive evolution toward overt diabetes, supporting longitudinal monitoring strategies in pediatric populations.(6)
Risk of progression approaches 75% within 10 years and nearly 100% over a lifetime in children with multiple positive autoantibodies.(7-9)
Rationale for Specific T1D Screening
T1D is an autoimmune disease characterized by progressive destruction of pancreatic β-cells, ultimately resulting in insulin deficiency and hyperglycemia. Unlike type 2 diabetes, T1D frequently develops rapidly and commonly presents during childhood or adolescence. Because many children remain asymptomatic until substantial β-cell destruction has occurred, opportunities for early diagnosis are often missed, increasing the risk of DKA at presentation.(10)
Recent advances in immunological and genetic testing have shifted the focus of T1D screening toward identification of presymptomatic disease stages. The ISPAD Clinical Practice Consensus Guidelines emphasize that T1D progresses through identifiable stages before symptomatic disease develops.(7) Stage 1 disease is characterized by normoglycemia with multiple islet autoantibodies, Stage 2 involves dysglycemia, and Stage 3 corresponds to symptomatic clinical diabetes.
Early identification of children at risk for T1D has several potential benefits:
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Reduction in DKA at diagnosis
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Earlier diabetes education and metabolic monitoring
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Improved family preparedness
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Potential preservation of residual β-cell function
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Eligibility for disease-modifying therapies and clinical trials
Importance of Prevention of Diabetic Ketoacidosis (DKA)
One of the principal goals of T1D screening is prevention of DKA at disease onset.
Delayed diagnosis is one of the strongest predictors of DKA in pediatric T1D,(10) and high rates of DKA at diagnosis persist despite advances in pediatric healthcare systems.(11) Children identified through surveillance programs or autoantibody screening are significantly less likely to present in severe DKA because families and clinicians are aware of evolving disease risk.(12)
Populations Recommended for T1D Screening
Current evidence supports targeted rather than universal screening in most healthcare systems.
High-Risk Groups
Children considered at increased risk include:
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First-degree relatives of individuals with T1D
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Children with other autoimmune disorders (thyroid disease, celiac disease)
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Individuals with genetic susceptibility markers
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Children with unexplained hyperglycemia or intermittent glycosuria
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Children with stress hyperglycemia
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Patients presenting repeatedly with symptoms suggestive of diabetes
Structured early screening programs have been advocated for pediatric high-risk populations to facilitate earlier diagnosis and reduce DKA incidence.(13)
Benefits of Emergency Department Screening
Early Diagnosis
Screening can identify previously undiagnosed diabetes, prediabetes or early-stage T1D, allowing earlier treatment and optimized approach:
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Early-stage T1D: engagement in ongoing monitoring to prevent development of DKA and to provide opportunities for interventions, including immunotherapies to delay progression.
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Prediabetes: Engagement in care to address lifestyle modifications or pharmacotherapeutic options to delay/prevent T2D.
Improved Public Health Outcomes
Early intervention reduces long-term complications and healthcare expenditures associated with uncontrolled diabetes.
Access to Vulnerable Populations
The ED often serves uninsured, underserved, and minority populations who may not receive routine preventive care.
Opportunity for Patient Education
Patients diagnosed or suspected of having diabetes can receive counseling regarding diet, exercise, medication adherence, and follow-up care.
Challenges and Limitations
Despite its benefits, diabetes screening in the ED presents several challenges:
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Time Constraints: EDs prioritize acute care, and staff may have limited time for preventive screening and counseling.
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Resource Limitations: Routine HbA1c testing and follow-up coordination may increase healthcare costs and workload.
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Follow-Up Challenges: Many patients identified with abnormal glucose levels fail to attend outpatient follow-up appointments, limiting the effectiveness of screening programs.
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False Positives and Stress Hyperglycemia: Acute illness and physiological stress may temporarily elevate blood glucose levels, potentially leading to false-positive results. It should be noted however, that children with stress hyperglycemia have a 15-fold higher risk of developing T1D over the following 10 years. Thus, the presence of stress hyperglycemia may represent an important opportunity for islet autoantibody assessment to identify this at-risk population.
Recommendations for Effective Screening
To improve the effectiveness of diabetes screening in emergency settings, healthcare systems should:
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Develop standardized screening protocols
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Use HbA1c testing when feasible
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Target high-risk populations
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Establish referral systems for outpatient follow-up
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Incorporate diabetes education into discharge planning
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Utilize electronic medical records to track abnormal results and ensure continuity of care
Emerging Strategies and Future Directions
Population-Based Screening
Several countries are evaluating broader population-based T1D screening initiatives using autoantibody panels. Such programs aim to identify children during asymptomatic disease stages.(14)
Disease-Modifying Therapy
Early identification is increasingly important because immune-modulating therapies may delay progression to clinical diabetes. Screening therefore has implications beyond diagnosis alone.
Electronic Screening Protocols
Integration of electronic alerts and standardized diabetes pathways within emergency departments may improve recognition of high-risk children and reduce missed diagnoses.
CONCLUSION
Screening for diabetes in the ED is an important strategy for identifying undiagnosed diabetes and prediabetes, especially in high-risk and underserved populations. For T1D, screening has evolved from simple glucose testing toward identification of presymptomatic autoimmune disease using islet autoantibodies and metabolic testing.
The ED can also play a critical role in early recognition of symptomatic T1D, particularly in children with nonspecific symptoms. Timely screening can reduce delayed diagnosis, prevent diabetic ketoacidosis, and improve long-term outcomes.
Despite challenges such as limited resources and follow-up barriers, efficient tools like HbA1c testing can improve early detection. As screening programs expand and disease-modifying therapies emerge, early identification of T1D will become increasingly important in pediatric and adult emergency and preventive care.
3. Known Early-Stage T1D in the Acute Care Setting
Early-stage T1D (Stage 1 or Stage 2) may be reported by a patient or family member, or may be noted in the chart. By definition, people with early-stage T1D do not yet require daily insulin treatment; however, this may change acutely during times of physiologic stress (fever, infection, surgery, trauma) or with use of medications which impact insulin sensitivity (corticosteroids).
Recognition of chart elements that may indicate early-stage T1D
Historical elements:
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Multiple islet autoantibodies
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Islet autoimmunity
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Early-stage T1D
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History of intermittent glucometer or CGM glucose monitoring
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History of teplizumab infusion
Problem list entries:
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Prediabetes (R73.03):
This is the historical term for people with dysglycemia meeting prediabetes thresholds. While it is distinct from early-stage T1D and is more appropriately considered a pre-T2D state, there may be some ambiguity in classification in the absence of islet autoantibody testing. -
Stage 1 T1D (E10.A1)
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Stage 2 T1D (E10.A2)
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Unspecified presymptomatic T1D (E10.A0)
Lab results:
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Positive results for GADA, IA-2A, ZnT8A, IAA
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Previous elevated OGTT or HbA1c results that do not meet the threshold for clinical diabetes
Evaluation for Individuals with history of early-stage T1D
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Assess for hyperglycemia and ketoacidosis
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Assess for progression to Stage 3 T1D
Triage urgency of follow-up: Progression is known to be more rapid in the youngest individuals. Young children may also be less able to express symptoms. A plan should be in place for prompt follow-up in individuals at Stage 3 T1D who are not in DKA. Consider admission for education and start of insulin therapy based on age and availability of outpatient education, according to local practice.
Discharge instructions for early T1D
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Counsel regarding risk for blood glucose changes, especially during illness
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Plan for monitoring, if patient has access to glucometer/CGM
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Plan for follow up with PCP/endocrinology
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Prompt return for development/escalation in symptoms:
vomiting, rapid breathing, nausea, abdominal pain, or signs of dehydration.
4. Management of complications of teplizumab in the Acute Care setting
Teplizumab (Tzield®) is a 14-day infusion which can be used in selected patients with Stage 2 T1D to delay progression to clinical (Stage 3) T1D.(15) Patients may experience a variety of adverse events during or shortly following infusion therapy and may be at risk for infections due to transient lymphopenia caused by the treatment. Pre-infusion evaluation includes CBC, CMP and evaluation for active or chronic infections.
Most common side effects: (15-19)
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Transient lymphopenia (73-100%)
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Rash (36-77%)
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Leukopenia (21-83%)
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Headache (11-47%)
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Nausea (5-83%)
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Transient elevated transaminase (5-40%)
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Transient neutropenia (5-40%)
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Diarrhea (5%)
Hyperglycemia during infusion is not reported in the FDA package insert, but was observed in 13% (n=4) of patients being monitored with CGM during infusions by Karakus et al.(17) All but one patient was weaned off subcutaneous insulin within one week of completing infusion.
Most severe side effects:
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Cytokine release syndrome:
Fever, nausea, headache, myalgia, arthralgia, transaminase elevations (2%-6%) -
Severe lymphopenia
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Hypersensitivity reactions
Acute care evaluation should include CBC, LFTs and assessment for fever, rash, altered breathing, hypotension or other signs of infection. Severe side effects should be treated according to ED protocol and prompt communication to the endocrinology/infusion team as infusions may need to be paused or discontinued.(19)
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