Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts

Objective: To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody positive (Ab+) relatives of people with type 1 diabetes. Methods: We examined 2-hour OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (Mean±SD age: 13.84±9.53 years; BMI-Z-Score: 0.33±1.07; 56.1% male) and 3,720 PTP participants (age: 16.01±12.33 Years, BMI-Z-Score 0.66±1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-Score, HOMA-IR and peak Glucose/C-peptide levels, respectively) were performed. Results: In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose >30 min and time to peak C-peptide >60 min (p<0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: X2 = 25.76 vs. X2 = 8.62 and PTP: X2 = 149.19 vs. X2 = 79.98; all p<0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time. Conclusions: In two independent at risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression.

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Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts

Diabetes Care ◽

10.2337/dc21-0226 ◽

2021 ◽

pp. dc210226

Author(s):

Michael G. Voss ◽

David D. Cuthbertson ◽

Mario M. Cleves ◽

Ping Xu ◽

Carmella Evans-Molina ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetes Prevention ◽

Prevention Trial ◽

C Peptide ◽

Time To Peak

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Trends of Earlier and Later Responses of C-peptide to Oral Glucose Challenges With Progression to Type 1 Diabetes in Diabetes Prevention Trial-Type 1 Participants

Diabetes Care ◽

10.2337/dc09-1770 ◽

2009 ◽

Vol 33 (3) ◽

pp. 620-625 ◽

Cited By ~ 37

Author(s):

J. M. Sosenko ◽

J. P. Palmer ◽

L. E. Rafkin ◽

J. P. Krischer ◽

D. Cuthbertson ◽

...

Keyword(s):

Type 1 Diabetes ◽

Trial Type ◽

Diabetes Prevention ◽

Prevention Trial ◽

Oral Glucose ◽

C Peptide

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One-Hour Oral Glucose Tolerance Tests for the Prediction and Diagnostic Surveillance of Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa592 ◽

2020 ◽

Vol 105 (11) ◽

Author(s):

Kimber M Simmons ◽

Jay M Sosenko ◽

Megan Warnock ◽

Susan Geyer ◽

Heba M Ismail ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glucose Tolerance ◽

Risk Score ◽

Trial Type ◽

Diabetes Prevention ◽

Prevention Trial ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

C Peptide

Abstract Context Once islet autoantibody–positive individuals are identified, predicting which individuals are at highest risk for type 1 diabetes (T1D) is important. A metabolic risk score derived from 2-hour oral glucose tolerance test (OGTT) data, the Diabetes Prevention Trial-Type 1 risk score (DPTRS), can accurately predict T1D. However, 2-hour OGTTs are time-consuming and costly. Objective We aimed to determine whether a risk score derived from 1-hour OGTT data can predict T1D as accurately as the DPTRS. Secondarily, we evaluated whether a 1-hour glucose value can be used for diagnostic surveillance. Methods The DPTRS was modified to derive a 1-hour OGTT risk score (DPTRS60) using fasting C-peptide, 1-hour glucose and C-peptide, age, and body mass index. Areas under receiver operating curves (ROCAUCs) were used to compare prediction accuracies of DPTRS60 with DPTRS in Diabetes Prevention Trial–Type 1 (DPT-1) (n = 654) and TrialNet Pathway to Prevention (TNPTP) (n = 4610) participants. Negative predictive values (NPV) for T1D diagnosis were derived for 1-hour glucose thresholds. Results ROCAUCs for T1D prediction 5 years from baseline were similar between DPTRS60 and DPTRS (DPT-1: 0.805 and 0.794; TNPTP: 0.832 and 0.847, respectively). DPTRS60 predicted T1D significantly better than 2-hour glucose (P < .001 in both cohorts). A 1-hour glucose of less than 180 mg/dL had a similar NPV, positive predictive value, and specificity for T1D development before the next 6-month visit as the standard 2-hour threshold of less than 140 mg/dL (both ≥ 98.5%). Conclusion A 1-hour OGTT can predict T1D as accurately as a 2-hour OGTT with minimal risk of missing a T1D diagnosis before the next visit.

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Time-to-Peak C-Peptide and Peak Glucose during an Oral Glucose Tolerance Test (OGTT) Are Independent Risk Factors for Type 1 Diabetes (T1D) in Antibody-Positive (Ab+) Individuals

Diabetes ◽

10.2337/db18-1688-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1688-P

Author(s):

HEBA M. ISMAIL ◽

PING XU ◽

CARMELLA EVANS-MOLINA ◽

JERRY P. PALMER ◽

JAY SOSENKO

Keyword(s):

Risk Factors ◽

Type 1 Diabetes ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

C Peptide ◽

Time To Peak ◽

Independent Risk Factors

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Glucose and C-Peptide Changes in the Perionset Period of Type 1 Diabetes in the Diabetes Prevention Trial-Type 1

Diabetes Care ◽

10.2337/dc08-0935 ◽

2008 ◽

Vol 31 (11) ◽

pp. 2188-2192 ◽

Cited By ~ 52

Author(s):

J. M. Sosenko ◽

J. P. Palmer ◽

L. Rafkin-Mervis ◽

J. P. Krischer ◽

D. Cuthbertson ◽

...

Keyword(s):

Type 1 Diabetes ◽

Trial Type ◽

Diabetes Prevention ◽

Prevention Trial ◽

C Peptide

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Faculty Opinions recommendation of Glucose and C-peptide changes in the perionset period of type 1 diabetes in the Diabetes Prevention Trial-Type 1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725154394.793513547 ◽

2016 ◽

Author(s):

Matthias von Herrath ◽

Gustaf Christoffersson ◽

Teresa Rodriguez Calvo

Keyword(s):

Type 1 Diabetes ◽

Trial Type ◽

Diabetes Prevention ◽

Prevention Trial ◽

C Peptide

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The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1

Pediatric Diabetes ◽

10.1111/pedi.12609 ◽

2017 ◽

Vol 19 (3) ◽

pp. 403-409 ◽

Cited By ~ 7

Author(s):

Jay M Sosenko ◽

Susan Geyer ◽

Jay S Skyler ◽

Lisa E Rafkin ◽

Heba M Ismail ◽

...

Keyword(s):

Body Mass Index ◽

Type 1 Diabetes ◽

Body Mass ◽

Trial Type ◽

Diabetes Prevention ◽

Prevention Trial ◽

C Peptide

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TCF7L2 Genetic Variants do not Influence Insulin Sensitivity or Secretion Indices in Autoantibody-positive Individuals at Risk for Type 1 Diabetes

10.2337/figshare.14770083 ◽

2021 ◽

Author(s):

Maria J. Redondo ◽

Megan V. Warnock ◽

Ingrid M. Libman ◽

Laura E. Bocchino ◽

David Cuthbertson ◽

...

Keyword(s):

At Risk ◽

Type 1 Diabetes ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Genetic Variants ◽

Disposition Index ◽

Oral Glucose ◽

Z Score ◽

C Peptide

Objective: We aimed to test whether type 2 diabetes (T2D)-associated TCF7L2 genetic variants affect insulin sensitivity or secretion in autoantibody-positive relatives at risk for type 1 diabetes (T1D). Research Design and Methods: We studied autoantibody-positive TrialNet Pathway to Prevention study participants (n=1,061; mean age=16.3 years) with TCF7L2 SNP information and baseline oral glucose tolerance test (OGTT) to calculate indices of insulin sensitivity and secretion. With Bonferroni correction for multiple comparisons, p-values <0.0086 were considered statistically significant. Results: None, one and two T2D-linked TCF7L2 alleles were present, respectively, in 48.1%, 43.9% and 8.0% of the participants. Insulin sensitivity (as reflected by 1/IF) decreased with increasing BMI-Z-score and was lower in Hispanics. Insulin secretion (as measured by 30-min C-peptide index) positively correlated with age and BMI-Z-score. Oral disposition index was negatively correlated with age, BMI-Z-score and Hispanic ethnicity. None of the indices were associated with TCF7L2 SNPs. In multivariate analysis models with age, BMI Z-score, ethnicity, sex and TCF7L2 alleles as independent variables, C-peptide index increased with age, while BMI Z-score was associated with higher insulin secretion (C-peptide index), lower insulin sensitivity (1/IF) and lower disposition index; there was no significant effect of the TCF7L2 SNPs on any of these indices. When restricting the analyses to participants with normal OGTT (n=743, 70%), the results were similar. Conclusions: In non-diabetic autoantibody-positive individuals, TCF7L2 SNPs were not related to insulin sensitivity or secretion indices after accounting for BMI-Z-score, age, sex and ethnicity.

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TCF7L2 Genetic Variants do not Influence Insulin Sensitivity or Secretion Indices in Autoantibody-positive Individuals at Risk for Type 1 Diabetes

10.2337/figshare.14770083.v2 ◽

2021 ◽

Author(s):

Maria J. Redondo ◽

Megan V. Warnock ◽

Ingrid M. Libman ◽

Laura E. Bocchino ◽

David Cuthbertson ◽

...

Keyword(s):

At Risk ◽

Type 1 Diabetes ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Genetic Variants ◽

Disposition Index ◽

Oral Glucose ◽

Z Score ◽

C Peptide

Objective: We aimed to test whether type 2 diabetes (T2D)-associated TCF7L2 genetic variants affect insulin sensitivity or secretion in autoantibody-positive relatives at risk for type 1 diabetes (T1D). Research Design and Methods: We studied autoantibody-positive TrialNet Pathway to Prevention study participants (n=1,061; mean age=16.3 years) with TCF7L2 SNP information and baseline oral glucose tolerance test (OGTT) to calculate indices of insulin sensitivity and secretion. With Bonferroni correction for multiple comparisons, p-values <0.0086 were considered statistically significant. Results: None, one and two T2D-linked TCF7L2 alleles were present, respectively, in 48.1%, 43.9% and 8.0% of the participants. Insulin sensitivity (as reflected by 1/IF) decreased with increasing BMI-Z-score and was lower in Hispanics. Insulin secretion (as measured by 30-min C-peptide index) positively correlated with age and BMI-Z-score. Oral disposition index was negatively correlated with age, BMI-Z-score and Hispanic ethnicity. None of the indices were associated with TCF7L2 SNPs. In multivariate analysis models with age, BMI Z-score, ethnicity, sex and TCF7L2 alleles as independent variables, C-peptide index increased with age, while BMI Z-score was associated with higher insulin secretion (C-peptide index), lower insulin sensitivity (1/IF) and lower disposition index; there was no significant effect of the TCF7L2 SNPs on any of these indices. When restricting the analyses to participants with normal OGTT (n=743, 70%), the results were similar. Conclusions: In non-diabetic autoantibody-positive individuals, TCF7L2 SNPs were not related to insulin sensitivity or secretion indices after accounting for BMI-Z-score, age, sex and ethnicity.

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