Related Experiment Video
Updated: Oct 25, 2025
Osmotic Minipump Implantation for Increasing Glucose Concentration in Mouse Cerebrospinal Fluid
Published on: April 7, 2023
Increasing plasma glucose before the development of type 1 diabetes-the TRIGR study
Johnny Ludvigsson1, David Cuthbertson2, Dorothy J Becker3
1Crown Princess Victoria Children's Hospital and Div of Pediatrics, Dept of Biomedical and Clinical Sciences, Linköping university, Linköping, Sweden.
Insights
Increased plasma glucose and HbA1c levels precede type 1 diabetes development. While glucose changes predict clinical diabetes, HbA1c changes are linked to autoantibodies and disease onset, supporting the β-cell stress hypothesis.
Area of Science:
- Endocrinology
- Immunology
- Pediatrics
Background:
- The β-cell stress hypothesis posits that increased insulin demand contributes to type 1 diabetes development.
- Assessing metabolic profiles before clinical diagnosis is crucial for understanding disease pathogenesis.
Purpose of the Study:
- To investigate the relationship between plasma glucose and HbA1c levels and the development of autoantibodies or clinical type 1 diabetes in at-risk children.
- To evaluate the predictive value of changes in glucose and HbA1c for disease progression.
Main Methods:
- A prospective cohort study of 2159 children with a family history of diabetes and increased HLA risk was conducted.
- Kaplan-Meier curves and mixed-effects models were used to analyze plasma glucose and HbA1c data over time.
- Data were collected between 2002-2007 and followed until 2017.
Main Results:
- A family history of type 2 diabetes was associated with increased plasma glucose (p < 0.001).
- Increases in plasma glucose predicted clinical diabetes (p < 0.001), while increases in HbA1c predicted both autoantibody development and clinical diabetes (p < 0.003 and p < 0.001, respectively).
- Children progressing to clinical disease had higher HbA1c than those developing autoantibodies.
Conclusions:
- Significant increases in plasma glucose and HbA1c precede the clinical onset of type 1 diabetes.
- The association between metabolic markers and autoantibody development is complex.
- Findings support the hypothesis that increased insulin demand contributes to type 1 diabetes pathogenesis.
Objective:
The β-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children.
Research Design And Methods:
A cohort of children (N = 2159) with an affected first-degree relative and increased HLA risk were recruited 2002-2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan-Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately.
Results:
A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp <0.001) and the development of diabetes (p < 0.002 resp <0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003).
Conclusions:
A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes.
More Related Videos
08:13Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
08:03Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
Published on: June 25, 2017
Related Concept Videos
01:22Diabetes Mellitus: Type 2 and Gestational
01:22Diabetes Mellitus: Overview and Type I Subtype
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
01:15Diabetes: Symptoms, Diagnosis, and Complications
01:16Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
01:20Pathophysiology of Diabetes
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
01:36Carbohydrate Metabolism
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...