Understanding Type 1 Diabetes: Stages, Screening, and Management
Understanding Type 1 Diabetes: Stages, Screening, and Management
Dr. Jon Caine Sumarizes the TPL Podcast #141 with Dr. Luigi Menenghini, MD, MBA
# Understanding Type 1 Diabetes: Stages, Screening, and Management
Type 1 diabetes (T1D) is an autoimmune disease that progresses into a metabolic disorder requiring lifelong insulin therapy. In susceptible individuals, the immune system mistakenly recognizes proteins on the surface of pancreatic beta cells as "foreign," leading to the production of antibodies and, ultimately, the destruction of these insulin-producing cells by T-cells.
## The Antibody Process and Stages of T1D
The antibody process starts early in life, often as early as 9 months, and peaks around age 2. Four antibodies can be screened for:
- GAD (Glutamic Acid Decarboxylase Autoantibody)
- IA-2A (Insulinoma-Associated-2 Autoantibody)
- IAA (Insulin Autoantibody)
- ZnT8A (Zinc Transporter 8 Autoantibody)
In 2015, the stages of T1D were classified as follows:
**Stage 1**: 2 or more positive autoantibodies and normoglycemia (fasting plasma glucose <100 mg/dL, HbA1c <5.7%, 2-hour oral glucose tolerance test <140 mg/dL)
**Stage 2**: 2 or more positive autoantibodies and dysglycemia (fasting plasma glucose 100-125 mg/dL, HbA1c 5.7-6.4%, 2-hour oral glucose tolerance test 140-199 mg/dL)
**Stage 3**: 2 or more positive autoantibodies and insulin dependence (fasting plasma glucose >125 mg/dL, HbA1c >6.4%, 2-hour oral glucose tolerance test >199 mg/dL)
Notably, 75% of those in Stage 2 will progress to Stage 3 (clinical disease) within 4 years.
## Importance of Early Screening and Intervention1
Early identification of individuals in Stage 1 or 2 can be beneficial in several ways:
1. Reduces the likelihood of presenting with diabetic ketoacidosis (DKA) at diagnosis from 40-60% to 5-10%.
2. Avoids cognitive impairment, difficulty in maintaining therapeutic HbA1c levels, and increased risk of complications associated with DKA.
3. Allows greater awareness of metabolic complications and preparedness, particularly in underserved and rural areas.
4. Decreases the costs of hospital care, improves quality of life, and reduces the risk of cardiovascular disease, renal disease, and the estimated loss of years of life.
5. 10% Reduction in Hemoglobin A1C decreases the burden of Diabetic Retinopathy by 40%2
## Who Should Be Screened?3
While family members (first-degree relatives) of individuals with T1D should be screened, it's important to note that 90% of those who present with T1D do not have a family history. The lifetime risk for autoimmune detection in a first-degree relative is 3-5%, while the risk without a family history is 0.3-0.5%.
Focused screening should also be considered for individuals with a first-degree relative with another autoimmune condition, such as autoimmune thyroid disease, celiac disease, or type A gastritis.
To make screening more cost-effective and less burdensome, it can be done at three time points during childhood: ages 1-2, 4-6, and 9-11. Tests can be performed using whole blood from a venipuncture or a micro-specimen from a fingerstick and can be sent to private labs or research trials like ASK and TrialNet at no cost to the patient.
## Interventions for Stages 2
If a patient is in Stage 2, interventions such as the monoclonal antibody Teplizumab (Tzield) can delay the onset of metabolic complications. Teplizumab binds to the CD3 receptor on the T-cell surface, delaying the need for insulin on average by two years.4
## Differentiating T1D from T2D and Insulin Resistance
Thirty percent of adolescents with T1D are obese, and some may have type 2 diabetes (T2D) or a combination of both conditions. Insulin resistance, a condition where the body has enough or excessive insulin but is less effective in getting glucose from the bloodstream into cells, is more common with excess body fat, especially around the waist area. Hyperglycemia can cause glucotoxicity (and hyperlipidemia can cause lipotoxicity), leading to "stunning" of the beta-cells, which can be reversible within 3-4 weeks with correction of the hyperglycemia.
Insulin resistance can also be seen in other disorders like polycystic ovary syndrome (PCOS).
By understanding the stages of T1D, the importance of early screening and intervention, and the differences between T1D, T2D, and insulin resistance, we can better manage this lifelong condition and improve outcomes for those affected.
Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021 Diabetes Care 2021;44(Supplement_1): S15–S33https://doi.org/10.2337/dc21-S002
Ghalwash M, Dunne JL, Lundgren M, Rewers M, Ziegler AG, Anand V, Toppari J, Veijola R, Hagopian W; Type 1 Diabetes Intelligence Study Group. Two-age islet-autoantibody screening for childhood type 1 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. 2022 Aug;10(8):589-596. doi: 10.1016/S2213-8587(22)00141-3. Epub 2022 Jul 5. PMID: 35803296; PMCID: PMC10040253.
Simmons KMW, Frohnert BI, O'Donnell HK, Bautista K, Geno Rasmussen C, Gerard Gonzalez A, Steck AK, Rewers MJ. Historical Insights and Current Perspectives on the Diagnosis and Management of Presymptomatic Type 1 Diabetes. Diabetes Technol Ther. 2023 Nov;25(11):790-799. doi: 10.1089/dia.2023.0276. PMID: 37695674.
An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes Published June 9, 2019N Engl J Med 2019;381:603-613DOI: 10.1056/NEJMoa1902226VOL. 381 NO. 7