Distribution of C-Peptide and Its Determinants in North American Children at Risk for Type 1 Diabetes

Xu, Ping; Qian, Xiaoning; Schatz, Desmond; Cuthbertson, David; Krischer, Jeffrey P.

doi:10.2337/dc13-2603

Cited by 7 publications

(7 citation statements)

References 32 publications

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“…Both glucose and C‐peptide measures have proved useful in predicting T1D onset in autoantibody positive individuals, 9–11 highlighting the importance of associations between mod + vig PA and fasting glucose, 120‐min glucose, glucose AUC, and fasting C‐peptide, 120‐min C‐peptide, and C‐peptide AUC as reported herein. We also confirmed the association of both child age and BMIz score to C‐peptide results, supporting prior work suggesting that any effort to identify C‐peptide cut‐points to classify individuals as having loss of beta‐cell function must take these factors into account 35 …”

Section: Discussionsupporting

confidence: 86%

The association of physical activity to oral glucose tolerance test outcomes in multiple autoantibody positive children: The TEDDY Study

et al. 2022

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Objective To examine the association of physical activity (PA), measured by accelerometry, to hemoglobin AIC (HbA1c) and oral glucose tolerance test (OGTT) outcomes in children who were multiple persistent confirmed autoantibody positive for type 1 diabetes (T1D). Methods The Environmental Determinants of Diabetes in the Young (TEDDY) multinational study followed children from birth. Children ≥3 years of age who were multiple persistent confirmed autoantibody positive were monitored by OGTTs every 6 months. TEDDY children's PA was measured by accelerometry beginning at 5 years of age. We examined the relationship between moderate plus vigorous (mod + vig) PA, HbA1c, and OGTT in 209 multiple autoantibody children who had both OGTT and PA measurements. Results Mod + vig PA was associated with both glucose and C‐peptide measures (fasting, 120‐min, and AUC); higher mod + vig PA was associated with a better OGTT response primarily in children with longer duration of multiple autoantibody positivity. Mod + vig PA also interacted with child age; lower mod + vig PA was associated with a greater increase in C‐peptide response across age. Mod + vig PA was not related to fasting insulin, HOMA‐IR or HbA1c. Conclusions The OGTT is the gold standard for diabetes diagnosis and is used to monitor those at high risk for T1D. We found higher levels of mod + vig PA were associated with better OGTT outcomes in children ≥5 years of age who have been multiple autoantibody positive for longer periods of time. Physical activity should be the focus of future efforts to better understand the determinants of disease progression in high‐risk children.

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Section: Discussionsupporting

confidence: 86%

The association of physical activity to oral glucose tolerance test outcomes in multiple autoantibody positive children: The TEDDY Study

et al. 2022

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“…However, the coefficient estimates derived from the Cox proportional hazards model may be biased as a result of violating assumptions of independence. In the previous studies (20,21) that examined the relationship between metabolic and immunologic risk factors among at-risk subjects, the results showed the significant correlations among some of the risk factors. As well, in previous studies (22–25) some autoantibodies have been shown to be age related.…”

Section: Discussionmentioning

confidence: 87%

Prognostic Classification Factors Associated With Development of Multiple Autoantibodies, Dysglycemia, and Type 1 Diabetes—A Recursive Partitioning Analysis

Krischer

2016

Diabetes Care

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OBJECTIVETo define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes.RESEARCH DESIGN AND METHODSThree distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes. Clinical characteristics, including genotype, antibody titers, and metabolic markers were analyzed.RESULTSAge and GAD65 autoantibody (GAD65Ab) titers defined three risk classes for progression from single to multiple autoantibodies. The 5-year risk was 11% for those subjects >16 years of age with low GAD65Ab titers, 29% for those ≤16 years of age with low GAD65Ab titers, and 45% for those subjects with high GAD65Ab titers regardless of age. Progression to dysglycemia was associated with islet antigen 2 Ab titers, and 2-h glucose and fasting C-peptide levels. The 5-year risk is 28%, 39%, and 51% for respective risk classes defined by the three predictors. Progression to type 1 diabetes was associated with the number of positive autoantibodies, peak C-peptide level, HbA1c level, and age. Four risk classes defined by RPA had a 5-year risk of 9%, 33%, 62%, and 80%, respectively.CONCLUSIONSThe use of RPA offered a new classification approach that could predict the timing of transitions from one preclinical stage to the next in the development of type 1 diabetes. Using these RPA classes, new prevention techniques can be tailored based on the individual prognostic risk characteristics at different preclinical stages.

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“…Also, age continues to affect C-peptide levels up to 4 years from diagnosis [35]. It has also been shown that sex is significantly associated only with stimulated C-peptide [27]. Inclusion of age and sex did not improve the model (M6 vs M8) [36].…”

Section: Modelling Residual Beta Cell Functionmentioning

confidence: 95%

“…Thus, apparently the other clinical measures accounted for the effect of age and sex on beta cell function. It is still to be tested how well the model works in the range of very low C-peptide levels that still respond to hyperglycaemia with increased C-peptide production [40] and if it performs equally well over the full spectrum of Cpeptide values [27].…”

Section: Modelling Residual Beta Cell Functionmentioning

confidence: 99%

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Capturing residual beta cell function in type 1 diabetes

Pociot

2018

Diabetologia

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Since the 1970s, C-peptide has been used as a surrogate marker for monitoring the progression of type 1 and type 2 diabetes and to determine the effects of interventions designed to preserve or improve residual beta cell function. C-peptide measurement is a well-established surrogate of residual beta cell activity and of clinical significance as it is associated with HbA 1c , risk for microvascular complications and the incidence of hyperglycaemia in longitudinal studies. Measurement of C-peptide after a mixed meal tolerance test is considered the gold standard of measuring beta cell function in type 1 diabetes, but the method is laborious and inconvenient. In this issue of Diabetologia, Wentworth et al (https://doi.org/10.1007/s00125-018-4722-z) report an algorithm for estimating C-peptide (CP EST ) based on six routine clinical measures. These do not include stimulated C-peptide measurement and outperform other prevailing algorithms for estimating residual beta cell function. Going forward it is very likely that this new algorithm will serve as a simple measure of beta cell function in routine practice and as a more acceptable primary outcome measure in future trials of disease-modifying therapies.

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Distribution of C-Peptide and Its Determinants in North American Children at Risk for Type 1 Diabetes

Cited by 7 publications

References 32 publications

The association of physical activity to oral glucose tolerance test outcomes in multiple autoantibody positive children: The TEDDY Study

The association of physical activity to oral glucose tolerance test outcomes in multiple autoantibody positive children: The TEDDY Study

Prognostic Classification Factors Associated With Development of Multiple Autoantibodies, Dysglycemia, and Type 1 Diabetes—A Recursive Partitioning Analysis

Capturing residual beta cell function in type 1 diabetes

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