Screening and care for preclinical stage 1-2 type 1 diabetes in first-degree relatives: French expert position statement

Abstract

The natural history of type 1 diabetes (T1D) evolves from stage 1 (islet autoimmunity with normoglycemia; ICD-10 diagnostic code E10.A1) to stage 2 (autoimmunity with dysglycemia; E10.A2) and subsequent clinical stage 3 (overt hyperglycemia), which is commonly the first time of referral. Autoantibody testing can diagnose T1D at its preclinical stages 1-2 and lead to earlier initiation of care, particularly for first-degree relatives of people living with T1D, who are at higher genetic risk. Preclinical T1D screening and monitoring aims to avoid inaugural ketoacidosis and prolong preservation of endogenous insulin secretion, thereby improving glycemic control and reducing long-term morbidity. Moreover, early management can help coping with T1D and correct modifiable risk factors (obesity, sedentary lifestyle). New treatments currently under clinical deployment or trials also offer the possibility of delaying clinical progression. All these arguments lead to the proposition of a national screening and care pathway open to interested first-degree relatives. This pathway represents a new expertise to acquire for healthcare professionals. By adapting international consensus guidance to the French specificities, the proposed screening strategy involves testing for ≥ 2 autoantibodies (among IAA, anti-GAD, anti-IA-2) in relatives aged 2-45 years. Negative screening (∼95 % of cases) should be repeated every 4 years until the age of 12. A management workflow is proposed for relatives screening positive (∼5 % of cases), with immuno-metabolic monitoring by autoantibody testing, OGTT, glycemia and/or HbA1c of variable frequency, depending on T1D stage, age, patient preference and available resources, as well as the definition of expert centers for preclinical T1D.

Keywords: Autoantibodies; Insulin secretion; Ketoacidosis; OGTT; Screening; Stages.