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  • 1
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    85-OR: Modifiers of C-Peptide Change during the Progression to Type 1 Diabetes (T1D) in the TrialNet Pathway to Prevention Study
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: It is not known to what extent characteristics of individuals modify C-peptide changes prior to T1D diagnosis. Thus, we assessed whether 4 characteristics [age, BMIZ, autoantibodies (abs), and HLA genotype] modified changes in 2-hr OGTT indices [AUC C-peptide and 30-0 minutes (early) C-peptide in ng/ml] during the progression to T1D. We studied 519 progressors to T1D (mean±SD age at first OGTT: 14.2±11.0 yo; BMIZ: 0.8±1.2; 50.0% male). Slopes were derived for changes in C-peptide indices from 36 to 6 months before diagnosis using mixed effects regression models. Slopes differed significantly by DR3/DR4 both (more inverse) vs. not both (30-0 minutes: p=0.005; AUC: p=0.034) and by ≥12.0 (more inverse) vs. & lt;12.0 yo (30-0 minutes: p=0.002; AUC: p=0.001) with narrowed differences in C-peptide at 6 months. In contrast, the slopes were similar in 1 vs. ≥2 abs and BMIZ ≤1.0 vs. & gt;1.0 comparisons. The Figures show curves for the changes in the C-peptide indices according to age and BMIZ categories from 36 to 6 months (* indicates significant differences at the 36 and 6 months time points). These novel findings indicate that slopes of C-peptide change vary according to DR3/DR4 and age during the progression to T1D, resulting in smaller differences at 6 months. BMIZ and ab slopes have little variation. Attributes of individuals should be considered when studying β-cell function decline during the progression to T1D. Disclosure H.M. Ismail: None. M.A. Cleves: None. S.E. Gitelman: Advisory Panel; Self; Avortes, Intermountain Therapeutics, Lilly Diabetes, Tolerion, Inc. Research Support; Self; Caladrius Biosciences, Inc., Janssen Research & Development. Other Relationship; Self; Novo Nordisk Inc. J.S. Skyler: Advisory Panel; Self; ADOCIA, Applied Therapeutics, Dance Biopharm Holdings Inc., Orgenesis Ltd., Tolerion, Inc., Viacyte, Inc. Board Member; Self; Dexcom, Inc., Intarcia Therapeutics, Inc., Moerae Matrix, Inc. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dalcor, Dialogics, Elcelyx Therapeutics, Inc., Esperion, GeNeuro Innovation, Ideal Life, Immunomolecular Therapeutics, Intrexon, Kamada, Nestlé, Sanofi, Valeritas, Inc., Zafgen, Inc. Stock/Shareholder; Self; Dexcom, Inc., Ideal Life, Intarcia Therapeutics, Inc., Intrexon, Moerae Matrix, Inc. A. Steck: None. H. Rodriguez: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Daiichi Pharm Corp, MannKind Corporation, Medtronic MiniMed, Inc. Research Support; Spouse/Partner; Medtronic MiniMed, Inc. Research Support; Self; Takeda Pharmaceutical Company Limited. Other Relationship; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc. M.A. Atkinson: None. B.M. Nathan: None. M.J. Redondo: None. K.C. Herold: Consultant; Self; Provention Bio, Roche Pharma. J.P. Palmer: None. C. Evans-Molina: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J.M. Sosenko: None. Funding National Institutes of Health
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-85-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 2
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    1441-P: Index60 Stratification Enhances Current Staging for Type 1 Diabetes by Identifying At-Risk Single Islet Autoantibody Positive (Ab+) Individuals
    American Diabetes Association ; 2023
    In:  Diabetes Vol. 72, No. Supplement_1 ( 2023-06-20)
    Details
    In: Diabetes, American Diabetes Association, Vol. 72, No. Supplement_1 ( 2023-06-20)
    Abstract: The current staging system for T1D development is used for participant selection in prevention trials. This system is based on multiple Ab+ and the presence or absence of dysglycemia, but does not address C-peptide measures or single Ab+ individuals. Since a limited number of Ab+ individuals are available for trials, we used TrialNet Pathway to Prevention (TNPTP) study data to assess whether a composite glucose and C-peptide measure, Index60, could identify single Ab+ individuals (designated as Stage 0) with comparable risk to those in Stages 1 or 2 for progression to Stage 3. Table 1A compares normoglycemic Stage 0 individuals with Index60 values above the median ( & gt;-0.045) of the full TNPTP cohort (n=6107) vs. those at Stage 1 with Index60 below the median ( & lt; -0.045). Table 1B compares those at Stage 0 with dysglycemia and higher Index60 vs. those at Stage 2 with lower Index60. In both comparisons, Index60 stratification identified Stage 0 individuals with metabolic features characteristic of T1D (e.g., lower C-peptide with higher glucose) and comparable 5-year risk to Stage 1 or Stage 2 individuals. Thus, by considering individuals with 1 Ab and C-peptide measures, the current staging system could be improved for risk discernment and to identify appropriate eligibility for prevention trials. Disclosure E.K.Sims: Speaker's Bureau; Medscape, American Diabetes Association. D.D.Cuthbertson: None. E.Bosi: None. C.Evans-molina: Advisory Panel; Provention Bio, Inc., DiogenX, Avotres Inc., Neurodon, MaiCell Therapeutics, Other Relationship; Isla Technology, Bristol-Myers Squibb Company, Nimbus Therapeutics, Research Support; Lilly, Astellas Pharma Inc. M.J.Redondo: None. B.M.Nathan: None. H.M.Ismail: Consultant; Rise Therapeutics. L.M.Jacobsen: None. J.Sosenko: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db23-1441-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
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  • 3
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    1343-P: A Comparison of C-Peptide and Glucose Responses between Children and Adolescents Who Progress to Type 1 Diabetes (T1D)
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Type 1 diabetes is a heterogeneous disease with differences in β-cell dysfunction and rates of progression. We thus assessed whether there are differences in C-peptide and glucose responses during 2-hour oral (OGTTs) and intravenous (IVGTTs) glucose tolerance tests between children and adolescents at high risk for T1D. Data from the Diabetes Prevention Trial-type 1 (DPT-1) study participants who progressed to T1D was used for the analysis. We compared C-peptide and glucose responses between children ( & lt;10.0 years old; 7.1±1.9 years; n=125) and adolescents (10.0 years to & lt;18.0 years old; 12.8±2.2 years; n=94). The risks for T1D were similar between the children and adolescents (mean 3-year T1D estimates from DPT-1 Risk Score: 63% and 56% respectively), as was the time to diagnosis (2.4±2.1 years vs. 2.5±2.2 years, respectively). Adolescents had higher OGTT derived AUC C-peptide levels (3.8±1.5 ng/ml vs. 1.9±1.4 ng/ml; p & lt;0.001 with BMIZ adjustment), whereas their AUC glucose levels were similar to children (138.6±25.1 mg/dl vs. 139.6±22.8 mg/dl). The 0 to 30 minute C-peptide response from baseline OGTTs was significantly higher among adolescents compared to children (2.6±1.6 vs. 2.1±1.2, p=0.004 with BMIZ adjustment). However, C-peptide and glucose changes for each subsequent 30-minute OGTT interval were nearly identical between the children and adolescents. Similar to the 0 to 30 minute C-peptide response, the first-phase insulin response from baseline IVGTTs was higher in adolescents (114.1±74.0 µU/ml vs. 88.6±59.9 µU/ml; p & lt;0.001 with BMIZ adjustment). In conclusion, the findings showed that despite a lower early insulin response in children, OGTT glucose levels were not higher. This suggests increased insulin sensitivity. The findings also showed that despite the lower early insulin response, the time to diagnosis did not differ. Other aspects of insulin responsiveness, and perhaps sensitivity, appear to also determine the progression rate to T1D. Disclosure H.M. Ismail: None. B.M. Nathan: None. J.P. Palmer: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J.M. Sosenko: None. Funding National Institutes of Health
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1343-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 4
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    1684-P: Using Index60 to Detect Heterogeneity and Identify Subpopulations with Characteristic Type 1 Diabetes (T1D) Profiles among Individuals with Normal Two-Hour Glucose Levels
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: We assessed whether Index60 could identify subpopulations with heterogeneous T1D features among autoantibody positive (Ab+) individuals with a normal 2-hour glucose. Index60 is a composite measure of fasting C-peptide, 60-minute C-peptide, and 60-minute glucose that has potential utility as a prediabetes endpoint when values are ≥1.00. Baseline 2-hour OGTTs of Ab+ TrialNet Pathway to Prevention participants in the normal 2-hour glucose ( & lt;140 mg/dl) range and low Index60 range ( & lt;1.00) were studied. The top 2-hour glucose & lt;140 mg/dl quartile was compared with the top Index60 & lt;1.00 quartile for characteristic T1D features (groups mutually exclusive). Those in the top Index60 quartile (Group B) or in both top quartiles (Group C) had profiles more typical of T1D than those in the top 2-hour glucose quartile (Group A), who had higher C-peptide levels, lower Ab+ frequencies, and were older (Table). Also, as indicated by within group odds ratios, Group A had less association of DR3-DQ2/DR4-DQ8 with the top quartile (Group A: 1.19, ns; Group B: 1.49, p & lt;0.01; Group C: 1.63, p & lt;0.01). In summary, Index60 can detect heterogeneity among those with normal 2-hour glucose levels, and identify subpopulations with appreciably more characteristic T1D features. The atypia of Group A demonstrates the importance of this Index60 utility. Disclosure B.M. Nathan: None. S. Geyer: None. L.E. Bocchino: None. J.P. Palmer: None. L.M. Jacobsen: None. M.J. Redondo: None. E.K. Sims: None. J.S. Skyler: Advisory Panel; Self; ADOCIA, Applied Therapeutics, Dance Biopharm Holdings Inc., Orgenesis Ltd., Tolerion, Inc., Viacyte, Inc. Board Member; Self; Dexcom, Inc., Intarcia Therapeutics, Inc., Moerae Matrix, Inc. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dalcor, Dialogics, Elcelyx Therapeutics, Inc., Esperion, GeNeuro Innovation, Ideal Life, Immunomolecular Therapeutics, Intrexon, Kamada, Nestlé, Sanofi, Valeritas, Inc., Zafgen, Inc. Stock/Shareholder; Self; Dexcom, Inc., Ideal Life, Intarcia Therapeutics, Inc., Intrexon, Moerae Matrix, Inc. J.M. Sosenko: None. Funding National Institutes of Health; JDRF
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1684-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 5
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    1447-P: Metabolic Heterogeneity of Antibody-Positive Individuals (Ab+I) with Impaired Glucose Tolerance (IGT) according to Glucose Fractions
    American Diabetes Association ; 2024
    In:  Diabetes Vol. 73, No. Supplement_1 ( 2024-06-14)
    Details
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Abstract: Introduction and Objective: Among Ab+I, we examined the metabolic heterogeneity of IGT, a marker of progression toward stage 3 type 1 diabetes (T1D), using glucose fractions dependent or independent of insulin secretion. Methods: Data from Ab+I with baseline OGTTs meeting IGT criteria (2-hr glucose ≥140 to & lt;200 mg/dl, n=1103) enrolled in TrialNet Pathway to Prevention were analyzed. AUC glucose was divided into fractions dependent (dAUCGLU) or independent (iAUCGLU) of insulin secretion, defined by the linear regression of AUC glucose vs. Index60 (as an insulin secretion proxy). dAUCGLU was the AUC glucose value predicted by Index60, while iAUCGLU was the AUC glucose residual value above or below the regression slope. Results: AUC C-peptide decreased as dAUCGLU quartiles increased, whereas AUC C-peptide increased as iAUCGLU quartiles increased (Figure). AUC C-peptide was inversely correlated with dAUCGLU (r=-0.84) and positively correlated with iAUCGLU (r=0.62) (p & lt;0.0001 for both). AUC C-peptide trended little with unfractionated AUC glucose quartiles. Conclusion: Opposite associations of AUC C-peptide with dAUCGLU and iAUCGLU indicate that AUC C-peptide was not only attributable to insulin secretion, but also to other factors (e.g. insulin resistance). It appears that among Ab+I, IGT is a heterogeneous metabolic state that may not be an optimal marker for T1D. Disclosure B.M. Nathan: None. D.D. Cuthbertson: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. L.M. Jacobsen: Advisory Panel; Insulet Corporation. E.K. Sims: Consultant; Sanofi. Board Member; American Diabetes Association. Other Relationship; American Diabetes Association, Medscape. Consultant; DRI. J. Sosenko: None. Funding National Institutes of Health (U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085461, U01 DK085465, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, UC4 DK117009)JDRF
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db24-1447-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
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  • 6
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    1448-P: The Role of a Glucose Fraction Independent of Insulin Secretion in Predicting Hyperglycemia Endpoints in Autoantibody-Positive Individuals (Ab+I)
    American Diabetes Association ; 2024
    In:  Diabetes Vol. 73, No. Supplement_1 ( 2024-06-14)
    Details
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Abstract: Objective and Introduction: It has been shown that AUC glucose from oral glucose tolerance tests (OGTTs) can be divided into fractions dependent or independent of insulin secretion. We assessed whether the independent fraction is predictive of incident IGT, a pre-diagnostic marker (2-hr glucose ≥140 to & lt;200 mg/dl), and T1D among Ab+I. Methods: AUC glucose, calculated from baseline OGTTs of 5182 normoglycemic TrialNet Pathway to Prevention participants with ≥1 Ab+, was divided into fractions dependent (dAUCGLU) or independent (iAUCGLU) of insulin secretion. Fractions were derived from linear regression of AUC glucose vs. Index60 (insulin secretion proxy). dAUCGLU was the expected AUC glucose value, while iAUCGLU was the residual value of AUC glucose above or below the regression slope. Fractions were assessed for predicting IGT and T1D. Results: dAUCGLU and iAUCGLU were each predictive of both IGT and T1D (p & lt;0.0001 for both, Figure). iAUCGLU was a stronger predictor of IGT, while dAUCGLU was a stronger predictor of T1D. When added to dAUCGLU in regression models, iAUCGLU contributed to the prediction (p & lt;0.0001) of both IGT and T1D. Conclusion: A glucose fraction independent of insulin secretion predicts both IGT and T1D in Ab+I. This merits investigation into other factors (e.g., insulin resistance) contributing to these hyperglycemic endpoints. Disclosure B.M. Nathan: None. D.D. Cuthbertson: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. L.M. Jacobsen: Advisory Panel; Insulet Corporation. E.K. Sims: Consultant; Sanofi. Board Member; American Diabetes Association. Other Relationship; American Diabetes Association, Medscape. Consultant; DRI. J. Sosenko: None. Funding National Institutes of Health (U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085461, U01 DK085465, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, UC4 DK117009)JDRF
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db24-1448-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
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  • 7
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    1344-P: Persistent ß-Cell Responsiveness in Children at High Risk for Type 1 Diabetes (T1D) Is Associated with Decreased Progression to T1D in the Diabetes Prevention Trial-Type 1 (DPT-1)
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: High-risk individuals with islet autoantibody positivity (Ab+) vary in their rates of progression to T1D. We hypothesized that changes in C-peptide over time account for some of this variation. Among Ab+ children ( & lt;18.0 years) followed with 2-hour OGTTs for development of T1D in DPT-1, we compared Progressors to T1D with Non-Progressors for the change in AUC C-peptide from the baseline OGTT to the last available OGTT (last before diagnosis in Progressors). Results were stratified by low or high baseline DPT-1 Risk Score (DPTRS: fasting C-peptide, sum C-peptide and sum glucose values from 30-120 minutes, age and BMI; DPTRS & lt;7.00= lower risk and ≥7.00= higher risk). As shown in the Table, Non-Progressors from each group exhibited increases in AUC C-peptide over time, while Progressors showed no significant changes in AUC C-peptide. A logistic regression model with adjustment for age indicated an inverse association of T1D development with increasing AUC-C-peptide/year [Odds ratio: 0.587 (0.430, 0.802), p & lt;0.001]. In conclusion, even in individuals with high baseline risk assessments, increasing AUC C-peptide over time is associated with decreased progression to T1D. This persistent C-peptide responsiveness could result from increased β-cell reserve (either functional or mass) or β-cell regeneration. Disclosure E.K. Sims: None. H.M. Ismail: None. B.M. Nathan: None. J.M. Sosenko: None. Funding National Institutes of Health
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1344-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 8
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    1618-P: Insulin Secretion Variability According to the Specific Type 1 Diabetes (T1D) Risk Predictor
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. Supplement_1 ( 2020-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. Supplement_1 ( 2020-06-01)
    Abstract: The risk for T1D, a major criterion for entry into disease prevention trials, can be assessed in various ways, but usually includes autoantibody (Ab) and/or metabolic measures. Given inherent variations in these biomarkers, it is possible that informative characteristics differ between populations selected by different risk measures. Thus, we assessed whether indices of insulin secretion [C-pep; first phase insulin response (FPIR)] vary between groups defined by distinctive risk measures. We used data from Diabetes Prevention Trial-Type 1 (DPT-1) participants, all being ICA positive subjects with or without biochemical Ab (bAb) positivity (GADA, IA-2A, mIAA). C-pep and FPIR values from baseline oral and intravenous glucose tolerance tests were compared between those who had 2-3 bAbs (≥2bAb) and those who had 0-1 bAb plus Index60≥0.40 (≤1bAb+Ind60). Index60 is a composite C-pep and glucose measure. These groups were chosen so that T1D risk would be similar (50% 5-year risk for both, log rank p=0.95). Ages (mean±SD) for ≥2bAb (n=289) and ≤1bAb+Ind60 (n=175) were 12.8±8.2 and 13.3±9.6 yrs, respectively (p=0.53). BMI Z-score was greater for ≥2bAb (0.42±1.12 vs. 0.15±1.09, p=0.01). C-pep levels were consistently higher for ≥2bAb than ≤1bAb+Ind60 [30-0 minute C-pep: 2.73±1.58 vs. 2.04±1.12 ng/mL, p & lt;0.0001; area under the curve (AUC) C-pep: 3.70±1.55 vs. 3.27±1.12 ng/ml, p=0.013; AUC C-pep/AUC glucose: 0.030±0.013 vs. 0.025±0.007 (ng/ml)/(mg/dl), p & lt;0.001]. FPIR was also higher for ≥2bAb (122.0±87.3 vs. 96.2±47.1 µU/ml, p & lt;0.01). All comparisons remained significant with adjustments for age and BMI Z-score. Of those with ≤1bAb+Ind60, 0 bAb did not differ from 1 bAb for C-pep indices or FPIR. In conclusion, C-pep and FPIR values can differ appreciably according to the measure that defines risk. This should be considered in choosing risk measures for prevention trials. Disclosure L.M. Jacobsen: None. B.M. Nathan: None. H.M. Ismail: None. M.J. Redondo: None. D. Schatz: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc. E.K. Sims: None. J.S. Skyler: Advisory Panel; Self; Abvance Therapeutics, ADOCIA, Avotres, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings, Inc., Immunomolecular Therapeutics, Intrexon, Oramed Pharmaceuticals, Orgenesis Inc., Sanofi, Tolerion, Inc., Viacyte, Inc. Board Member; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Tolerion, Inc. Stock/Shareholder; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. J.P. Palmer: None. K.C. Herold: Consultant; Self; Provention Bio, Inc. J. Sosenko: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-1618-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 9
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    330-OR: Narrow Variation of Glucose Inflection Points (IPs) during Progression to Type 1 Diabetes (T1D) Stratified by Demographic and Genetic Differences in Autoantibody-Positive (Ab+) Individuals
    American Diabetes Association ; 2024
    In:  Diabetes Vol. 73, No. Supplement_1 ( 2024-06-14)
    Details
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Abstract: Introduction and Objective: Evidence suggests an IP occurs 1 to 2 years before the diagnosis of T1D, after which accelerated metabolic decline occurs. We assessed whether IPs vary when stratified by age, obesity, sex, and presence of both HLA DR3 and DR4 vs. neither. Methods: TrialNet Pathway to Prevention Ab+ participants (n=596) who had OGTTs between 0.5 years and 3 years before diagnosis were studied. Mixed-effects modeling was used to estimate AUC glucose and AUC C-peptide IPs with 95% confidence intervals (CIs), and to compare IP times before diagnosis. Since AUC C-peptide IPs had wide CIs, only AUC glucose IPs are shown. Results: The overall AUC glucose IP was 1.39 years before diagnosis. Those older or obese had IPs significantly earlier; however, the difference by age groups was only ~0.2 years and that by obesity 0.1 year (table). The difference between those positive for both DR3 and DR4 was small while males and females did not differ. IPs were consistently within 1.3 and 1.5 years before diagnosis. Conclusion: Older and more obese individuals have earlier AUC glucose IPs prior to diagnosis. However, the timing of the IPs differs only by a few months between populations that have demographic or genetic differences. This suggests common pathologic progression patterns to T1D despite variations in characteristics. Disclosure H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. D.D. Cuthbertson: None. L.M. Jacobsen: Advisory Panel; Insulet Corporation. B.M. Nathan: None. E.K. Sims: Consultant; Sanofi. Board Member; American Diabetes Association. Other Relationship; American Diabetes Association, Medscape. Consultant; DRI. M.J. Redondo: None. J. Sosenko: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db24-330-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
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  • 10
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    1460-P: Antibody+ (Ab+) Individuals with Marked Metabolic Heterogeneity at Screening Have Similar Evolution in the Progression to Type 1 Diabetes (T1D) with Converging Metabolic Status
    American Diabetes Association ; 2024
    In:  Diabetes Vol. 73, No. Supplement_1 ( 2024-06-14)
    Details
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Abstract: Introduction: We asked if marked OGTT metabolic heterogeneity at screening persists at T1D diagnosis. Methods: Multiple Ab+ TrialNet Pathway to Prevention participants (n=364) who had diagnostic OGTTs ≥1 yr after screening OGTTs were stratified by median fasting glucose x fasting C-peptide (fgxfp; basic metabolic component of C-peptide HOMA-IR). Glucose and C-peptide response curves (shapes from mean OGTT glucose and C-peptide at 30, 60, 90 and 120 min; GCRCs) were derived from OGTTs at baseline and diagnosis. Results: The fgxfp group & gt;median (Figure: blue) had much higher baseline AUC C-peptide (p & lt;0.001), indicated by the wider shape and rightward location of their GCRC. They subsequently had upward and leftward GCRC movement from baseline to diagnosis vs. mostly upward movement for the group Disclosure E.K. Sims: Consultant; Sanofi. Board Member; American Diabetes Association. Other Relationship; American Diabetes Association, Medscape. Consultant; DRI. L.M. Jacobsen: Advisory Panel; Insulet Corporation. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. M.J. Redondo: None. B.M. Nathan: None. J. Sosenko: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db24-1460-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
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