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Factors predicting course of beta-cell function in IDDM
A Schiffrin1, S Suissa, G Weitzner
1Division of Endocrinology and Metabolism, Montreal Children's Hospital, Quebec, Canada.
Insights
Younger age, male sex, and presence of islet cell antibodies (ICA) predict faster loss of insulin secretion in children with type 1 diabetes. These factors accelerate C-peptide decline, impacting disease progression.
Area of Science:
- Endocrinology
- Immunology
- Pediatrics
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing beta cells.
- Residual insulin secretion, measured by C-peptide levels, is a key indicator of beta cell function and disease progression in T1D.
- Predictors of the rate of C-peptide decline are crucial for understanding T1D heterogeneity and developing targeted interventions.
Purpose of the Study:
- To investigate whether clinical presentation severity, sex, age, HLA type, and the presence of islet-associated antibodies (IAs) and islet cell antibodies (ICAs) predict residual insulin secretion.
- To analyze the variation in serum C-peptide response to a Sustacal meal as a measure of insulin secretion.
Main Methods:
- Prospective follow-up of 151 newly diagnosed T1D children for 3 years.
- Measurement of serum C-peptide response to a Sustacal meal.
- Analysis of clinical data including age, sex, symptom duration, clinical presentation severity, HLA type, and ICA titers.
Main Results:
- Age, sex, ICA presence, clinical presentation severity, and symptom duration significantly predicted the rate of C-peptide secretion loss.
- Accelerated C-peptide decline was associated with younger age, male sex, and the presence of ICA.
- Older age groups showed a decreased risk of accelerated C-peptide disappearance.
- A significant negative correlation was observed between ICA titers and C-peptide levels at 18 and 24 months post-diagnosis.
Conclusions:
- Younger age of onset, male sex, high ICA titers, severe clinical presentation, and shorter symptom duration are significant predictors of accelerated C-peptide secretion loss.
- These factors contribute to the heterogeneity in T1D progression and beta cell destruction rates.
Objective:
The purpose of this study was to determine whether the severity o clinical presentation, sex, age, HLA type, and the presence of IAs and ICAs could predict the variation of residual insulin secretion as measured by the serum C-peptide response to a Sustacal meal.
Research Design And Methods:
A cohort of 151 newly diagnosed IDDM children (mean age 10.2 +/- 4.6 yr) was followed prospectively for 3 yr. Thirty-five patients (12 males, 23 females) were still secreting C-peptide after 36 mo.
Results:
We found that age (P = 0.0001), sex (P = 0.003), presence of ICA (P = 0.006), severity of clinical presentation (P = 0.001), and symptom duration (P = 0.002) significantly predicted the rate of loss of C-peptide secretion. The risks of accelerated C-peptide disappearance decreased with increasing age, the risk ratios being 0.25 for the older group (greater than 12 yr) compared with the younger group (less than 6 yr) and 0.50 for the intermediate group (6-12 yr) compared with the younger group. The risk for the presence of ICA was 1.7, and the risk for males was 1.7 also. There was a significant negative correlation between ICA titers and C-peptide at 18 and 24 mo after diagnosis (P = 0.04). There were no significant differences in HbA1 values between patients who secreted C-peptide and those who did not.
Conclusions:
We conclude that younger age of onset, male sex, high titers of ICA, severe clinical presentation, and shorter symptom duration significantly predict accelerated rates of loss of C-peptide secretion.