Case Presentation
A 2.5-year-old girl presents to her primary care physician with increased thirst, lethargy, irritability, excessive urination, vision difficulties, and fruity breath. One week prior, the patient—who is recently toilet trained—began experiencing nocturnal enuresis despite evening fluid restriction. Her parents noted significant polydipsia and new-onset squinting while watching television. The patient had 1 episode of emesis the previous week and a noticeable change in breath odor, particularly in the morning. Although she appears thinner, the weight loss is initially attributed to a growth spurt.
In-office evaluation reveals a random blood glucose level of 425 mg/dL, ketonuria, and a 2.5-lb weight loss over the preceding month. The medical history is notable for an upper respiratory infection 1 month prior. The patient is referred to the emergency department, where she is diagnosed with diabetic ketoacidosis (DKA).
Following stabilization with fluid resuscitation and intravenous insulin, she is admitted to the pediatric intensive care unit (PICU). Laboratory results confirm a hemoglobin A1c (HbA1c) of 11.3% and positive insulinoma-associated antigen 2 (IA2) antibodies. After 24 hours in the PICU and 2 days in the pediatric progressive care unit, she is discharged on a regimen of insulin lispro and glargine, along with a Dexcom G6 continuous glucose monitor. Insulin pump therapy will be considered in 6 months. The initial follow-up visit is scheduled for 6 weeks post-diagnosis.
Follow-up Notes
The patient had no family history of T1D, and autoantibody (AAB) screening had not been discussed. After 6 months of multiple daily injections, the patient transitioned to the Omnipod Dash system; the family selected this tubeless device to accommodate her young age and high activity level.
Earlier recognition of isolated symptoms during primary care visits may have prevented the development of DKA and subsequent hospitalization. Given that the patient has a younger sibling, this case highlights the critical shift from reactive to proactive primary care for at-risk patients through the implementation of evidence-based screening and education.
Discussion
As Type 1 diabetes (T1D) global prevalence continues to rise—affecting approximately 9.5 million people and projected to reach 14,7 million by 2040—early identification remains a critical clinical challenge.1 While more than 513,000 new cases were diagnosed in 2025 alone, significant mortality persists because of missed diagnoses and diabetic ketoacidosis (DKA).1
Screening programs for at-risk patients significantly reduce DKA rates and facilitate early intervention or clinical trial enrollment.2,3 Despite high healthcare utilization rates—with 95.1% of children seeing a provider in 2024—opportunities for preventative management are often missed because of gaps in screening utilization.4
By increasing understanding of screening options, nurses, nurse practitioners (NPs), and physician associates (PAs) can better support families in decision-making and education.
More than 70 genetic variants have been identified in T1D development. Having a first-degree relative with T1D is associated with an approximately 15-fold increased lifetime risk.2 However, 90% of individuals diagnosed do not have a family history of T1D.2 Because of this, there tends to be a delay in diagnosis.6 The risk of autoimmunity declines with age. Viral illnesses and environmental exposures are potential triggers for seroconversion.2,7
This manuscript reviews current T1D diagnostic, treatment, and screening protocols, emphasizing the primary care practitioner’s essential role in education and multidisciplinary coordination to improve patient outcomes.
Clinical Presentation of T1D
T1D typically presents in 1 of 3 ways. The classical presentation is characterized by weight loss, polyuria, and polydipsia, often accompanied by hyperglycemia and either ketonuria or ketonemia.8 Young patients may present with bedwetting, incontinence, or nocturia. Additional findings may include cataracts, perineal candidiasis, or acute visual disturbances.8 A second presentation is DKA, in which patients present with significantly elevated blood glucose and metabolic acidosis due to ketone accumulation. Finally, it can be an incidental or silent finding, often identified through asymptomatic screening for diabetes-associated autoantibodies due to risk factor identification.5,8
Differential Diagnoses
Because of the constellation of symptoms that patients often present with and the utilization of blood glucose and urine ketones, it is challenging to miss a diagnosis of elevated glucose in a patient. However, if the patient presents with individual symptoms, there are a variety of differentials that need to be considered (Table 1).8
Table 1. Differential Diagnoses Associated with Symptoms of Pediatric Type 1 Diabetes
– Cushing syndrome
– Pheochromocytoma
– Growth hormone excess
– Glucagon-secreting tumors
– Sepsis
– Medication effects (eg, corticosteroids)Polyuria– Diabetes mellitus
– Diabetes insipidus
– Urinary tract infectionVisual Disturbances– Refractive changes from hyperglycemiaWeight Loss– Viral illness
– Hyperthyroidism
– Malignancy
– Eating disorders, depression, anxiety
Treatment of T1D
Diabetes management is initiated and driven by an interprofessional pediatric diabetes team starting at diagnosis.9 This includes a physician, an advanced practitioner, a certified diabetes educator (CDE), and a nutritionist.10 Standards of care include safely minimizing hyperglycemia with the use of insulin therapy via an automated insulin delivery (AID) or insulin pump therapy alone if unable to use the AID system. Additionally, glucose should be monitored at least 10 times per day via glucose meter or continuous glucose monitor (CGM).
The goal for children and adolescents is an HbA1c less than 7%.9 This is set for patients with hypoglycemic unawareness, who cannot verbalize symptoms, are without CGM and/or insulin pump, or cannot check regularly. Evaluating time in range, above range, and below range over a 14-day period is also recommended in conjunction with A1C monitoring. Regular screening is recommended for autoimmune conditions, thyroid disease, celiac disease, management of cardiovascular risk factors, and microvascular complications.9
Stages of Type 1 Diabetes
Traditionally, T1D was diagnosed only upon the presentation of overt hyperglycemia. Advancements in disease pathogenesis have since identified a progressive staging model5:
Stage 1 is defined by the presence of at least 2 diabetes-associated AABs in an asymptomatic, normoglycemic individual, confirmed by 2 separate samples.
Stage 2 involves persistent AABs alongside dysglycemia—evidenced by an HbA1c of 5.7% to 6.4%, a 10% or greater rise in HbA1c, impaired oral glucose tolerance test (OGTT) results, or elevated fasting glucose. Children in Stage 2 face a high risk of progression: 44% develop clinical disease within 5 years, and 80% to 90% progress within 15 years.2
Stage 2 may be further categorized into Stage 2a (mild dysglycemia) and Stage 2b (advanced dysglycemia).
Stage 3 represents the clinical diagnosis of insulin-dependent T1D based on established glycemic thresholds.2,5,7,11 Approximately 350,000 individuals in the US are at high risk for Stage 3, with 62% of this population aged 20 years or older.5
DKA occurs at the time of Stage 3 diagnosis in 15% to 80% of patients. However, the incidence drops to less than 5% to 10% when a diagnosis is made during Stage 1 or 2 through screening.2,3 DKA is associated with severe complications, including cerebral edema, cognitive and memory deficits, poorer long-term glycemic control, increased psychological distress, and higher morbidity and mortality.2,3,5 Barriers to early recognition include symptom ambiguity, knowledge gaps, and socioeconomic or cultural hurdles. Increasing awareness of risk factors and improving access to blood glucose monitoring can prevent greater than 80% of DKA-related hospitalizations.6
Screening Considerations and Implications
Current guidelines recommend screening presymptomatic individuals who are at risk of developing T1D, such as a first-degree relative. Individuals with a first-degree relative who has diabetes have a markedly higher likelihood of developing Stage 3 T1D by age 20, about 5%, compared to the general population, which is about 0.3%.11 Blood samples being monitored include antibodies, HbA1C, and random glycemia or CGM if in a more advanced stage. When the AAB is positive, it requires 2 consecutive lab draws.2 (Table 2)
Those who are diagnosed in the silent phase or early-stage through T1D screening have decreased rates of DKA, are eligible for possible intervention, and clinical research studies.5 Screening is available through different research studies, consumer, and clinical laboratories. A study by Hummel et al found that children diagnosed with presymptomatic T1D through public health screening programs had lower A1c, less insulin needs at time of diagnosis, lower prevalence of ketonuria, and decreased incidence of DKA.3
Table 2. Monitoring After Positive Type 1 Diabetes Autoantibody (AAB) Screening
– Every 12 months for 3 years
– Stop if no progression
1≥3 years old– Every 12 months for 3 years
– Stop if no progression
≥2≤3 years old1– Every 3 months≥23–9 years old1– Every 6 months≥2≥3 years old1– Every 12 months≥2<18 years old2– Every 3 months≥2≥18 years old2– Every 6 months
Role of Advanced Practice Nurses and Physician Associates
The approach to caring for newly diagnosed T1D patients remains interdisciplinary. Although the Endocrinology team is managing their treatment plan, the primary care team sees the patients in the clinic for other interim concerns and is likely managing the care for siblings who have an increased risk for developing T1D.
By increasing understanding of screening options, nurses, nurse practitioners (NPs), and physician associates (PAs) can better support families in decision-making and education. Utilizing standardized screening tools at clinical visits may help evaluate psychological burden and parental anxiety. This data allows providers to deliver targeted education on insulin therapy, DKA manifestations, and disease management to facilitate the transition to Stage 3.2
The psychological impact of a positive screening is multifaceted, involving cognitive, emotional, and behavioral implications.5 Providers must continuously assess a family’s risk perception, accounting for diverse educational and psychosocial backgrounds. While risk awareness enables preparation for Stage 3, it simultaneously increases anxiety. Post-screening anxiety and depression remain significant concerns, exacerbated by a lack of dedicated support resources for those with positive AAB results.2,12
Clinical infrastructure is a critical factor for primary care screening.5 Because patients with early-stage T1D are managed in primary care rather than specialty settings, successful programs require robust risk assessment protocols, adequate staffing, and clear follow-up pathways. However, the financial and operational implications of these requirements may limit the feasibility of high-quality screening programs in certain primary care environments.
Although the idea of general population screening has not been widely accepted, advocating for those patients who are at risk to be screened through the available options is an important component that NPs and PAs are capable of doing. Remaining informed and connected with the endocrinology team can help support these patients and hopefully improve patient outcomes.