Environmental Determinants of Type 1 Diabetes Risk

Type 1 diabetes (T1D) is a hyperglycemic disease caused by absolute insulin deficiency. It has an acute and early onset, and patients require lifelong insulin therapy. Global T1D incidence is rising yearly. China has the fourth-largest number of T1D patients and the second-fastest increase in incidence, with a marked rise in adults. T1D results from genetic and environmental factors that cause immune destruction of pancreatic β cells. Genetic risk is relatively clear: HLA DR4-DQ8 and DR3-DQ2 carry the highest risk, and over 70 related loci have been identified. However, environmental factors remain insufficiently characterized. Studies of migrants, socioeconomic differences, and mobile populations suggest that environment and lifestyle have significant effects. Since China's genetic background has not changed substantially while incidence continues to rise, environment-induced immune dysregulation combined with genetic susceptibility may be key. International cohorts such as TEDDY and DAISY confirm that diet, viral infections, and gut microbiota can trigger islet autoimmunity. Among specific factors, high maternal early-pregnancy BMI, rapid childhood growth, and obesity increase risk; vitamin D is protective, and China's north-high/south-low incidence gradient may relate to sunlight and vitamin D. Gluten may trigger islet autoimmune inflammation via gut microbiota and immune activation. Viral infection, pollution, chemical exposure, and socioeconomic status may also contribute. Most evidence comes from European and American populations, while Chinese studies are limited. Therefore, systematically identifying China-specific environmental risk factors has important scientific and public-health value. In summary, genetics determines susceptibility, while modifiable environmental factors are critical in triggering and progression and are key to early prevention and precision management of T1D.

Inclusion criteria

• Individuals with type 1 diabetes (no age restriction):

• Clinically diagnosed with T1D by a specialist.
• Meeting any one of the following conditions:(1) Age of onset < 15 years;(2) No overweight or obesity at onset;(3) History of ketoacidosis.
• Insulin-dependent since disease onset;
• Positive for at least one islet autoantibody (GADA, IA-2A, ZnT8A, IAA, ICA);
• Disease duration ≤ 3 years.
• First-degree relatives:

• Parents, siblings, or children of an individual with T1D.
• Age ≤ 45 years.

Exclusion criteria

• Individuals with type 1 diabetes

• Gestational diabetes.
• Confirmed monogenic diabetes.
• Secondary diabetes.
• Type 2 diabetes.
• Other specific types of diabetes.
• First-degree relatives:

• Diagnosed with diabetes before screening;
• Previous or current use of glucose-lowering drugs.

Common exclusion criteria:

• Severe active disease or a condition likely to substantially affect life expectancy, including malignancy or severe cardiac, pulmonary, hepatic, or renal disease.
• A condition that may require immunosuppressive therapy during the study period.
• Current systemic immunosuppressive therapy.
• Current systemic glucocorticoid therapy.
• Participation in another drug or medical device trial during recruitment or the study period.
• History of major surgery or severe trauma.