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Jay S. Skyler - One of the best experts on this subject based on the ideXlab platform.

  • Dysglycemia Is as Common in Autoantibody-Negative Relatives as in Single-Autoantibody-Positive Relatives of Type 1 Diabetes (T1D) Patients
    Diabetes, 2018
    Co-Authors: Emily K. Sims, Jay S. Skyler, Alberto Pugliese, Jeffrey P. Krischer, Carla J. Greenbaum, Jeffrey L. Mahon, Kevan C. Herold, Jerry P. Palmer, Jay M. Sosenko
    Abstract:

    Autoantibody positive (Ab+) relatives of T1D patients have an increased risk for Dysglycemia and progression to T1D. However, the occurrence of Dysglycemia in Ab- relatives is not known. Thus, we compared the frequency and pattern of Dysglycemia from oral glucose tolerance tests (OGTTs) between Ab- (n=101; mean age: 11.7± 3.6 years) and single Ab+ (n=977; mean age 10.4± 3.9 years) relatives in the TrialNet Pathway to Prevention study. Single Abs were ICA, GADA, IA-2A, mIAA, or ZnT8A. The glucose criteria for Dysglycemia were: fasting 110-125 mg/dl; 30, 60, and/or 90-minutes glucose ≥ 200 mg/dl; and/or 120-minutes glucose 140-199 mg/dl. Of the Ab-’s, 29/101 (28.7%) had at least one dysglycemic OGTT at baseline or during follow-up, whereas 192/977 (19.7%) Ab+’s had a dysglycemic OGTT. At baseline, there were no significant differences in the proportions of Dysglycemia [Ab-’s: 13/101 (12.9%) vs. Ab+’s: 114/977 (11.7%)]. Of those with normal OGTTs at baseline, the proportion progressing to Dysglycemia was actually higher (p=0.007) in the Ab-’s (Dysglycemia/total: [16/87 (18.4%) vs. 78/846 (9.2%)], but the hazard ratio for Dysglycemia risk from a Cox regression analysis was not significant after adjustments for age, BMI%tile, relation to proband, and number of OGTTs performed. OGTT glucose and C-peptide at the first dysglycemic OGTT did not differ significantly between Ab-’s and Ab+’s after adjustments, except for a higher 90-minutes glucose in the Ab-’s (p=0.004). The early C-peptide response values (30-0 minutes C-peptide) did not differ significantly between the groups and were not indicative of overt insulin deficiency (Ab-’s: 5.6± 3.2 ng/ml vs. Ab+’s: 5.2± 3.3 ng/ml). In summary, Dysglycemia was as common in Ab- relatives as in single Ab+ relatives with similar dysglycemic OGTT patterns. These findings suggest that Dysglycemia can precede Ab’s during the progression to T1D and/or an appreciable proportion of single Ab+ dysglycemic individuals do not develop T1D. Disclosure E.K. Sims: None. P. Xu: None. J.S. Skyler: Advisory Panel; Self; ADOCIA, Abvance. Consultant; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Dance Biopharm. Consultant; Self; Diavacs, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Ideal Life Inc., ImmunoMolecular Therapeutics, Intrexon, Merck & Co., Inc.. Advisory Panel; Self; Orgenesis Inc.. Consultant; Self; Sanofi, Servier, VTV Therapeutics, Valeritas, Inc., Viacyte, Inc.. Board Member; Self; Dexcom, Inc.. Stock/Shareholder; Self; Dexcom, Inc.. Board Member; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; Intarcia Therapeutics, Inc.. Board Member; Self; Moerae Matrix. Stock/Shareholder; Self; Moerae Matrix, Dance Biopharm, Ideal Life Inc., Intrexon, VasoPrep Surgical. A. Pugliese: None. J. Krischer: None. C. Greenbaum: Research Support; Self; Janssen Research & Development. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. J. Mahon: None. K.C. Herold: None. J.P. Palmer: None. J. Sosenko: None.

  • incident Dysglycemia and progression to type 1 diabetes among participants in the diabetes prevention trial type 1
    Diabetes Care, 2009
    Co-Authors: Jay M. Sosenko, Jeffrey P. Krischer, Carla J. Greenbaum, Jerry P. Palmer, David Cuthbertson, Jeffery Mahon, Catherine C. Cowie, Lisa Rafkinmervis, Jay S. Skyler
    Abstract:

    Abstract Objective: We studied the incidence of Dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether Dysglycemia was sustained. Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident Dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident Dysglycemia at the 6-month visit was assessed for T1D prediction. Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of Dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of Dysglycemia. Incident Dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident Dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.

  • Incident Dysglycemia and Progression to Type 1 Diabetes Among Participants in the Diabetes Prevention Trial–Type 1
    Diabetes Care, 2009
    Co-Authors: Jay M. Sosenko, Jeffrey P. Krischer, Carla J. Greenbaum, Jerry P. Palmer, Lisa Rafkin-mervis, David Cuthbertson, Jeffery Mahon, Catherine C. Cowie, Jay S. Skyler
    Abstract:

    Abstract Objective: We studied the incidence of Dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether Dysglycemia was sustained. Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident Dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident Dysglycemia at the 6-month visit was assessed for T1D prediction. Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of Dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of Dysglycemia. Incident Dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident Dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.

Jay M. Sosenko - One of the best experts on this subject based on the ideXlab platform.

  • Dysglycemia Is as Common in Autoantibody-Negative Relatives as in Single-Autoantibody-Positive Relatives of Type 1 Diabetes (T1D) Patients
    Diabetes, 2018
    Co-Authors: Emily K. Sims, Jay S. Skyler, Alberto Pugliese, Jeffrey P. Krischer, Carla J. Greenbaum, Jeffrey L. Mahon, Kevan C. Herold, Jerry P. Palmer, Jay M. Sosenko
    Abstract:

    Autoantibody positive (Ab+) relatives of T1D patients have an increased risk for Dysglycemia and progression to T1D. However, the occurrence of Dysglycemia in Ab- relatives is not known. Thus, we compared the frequency and pattern of Dysglycemia from oral glucose tolerance tests (OGTTs) between Ab- (n=101; mean age: 11.7± 3.6 years) and single Ab+ (n=977; mean age 10.4± 3.9 years) relatives in the TrialNet Pathway to Prevention study. Single Abs were ICA, GADA, IA-2A, mIAA, or ZnT8A. The glucose criteria for Dysglycemia were: fasting 110-125 mg/dl; 30, 60, and/or 90-minutes glucose ≥ 200 mg/dl; and/or 120-minutes glucose 140-199 mg/dl. Of the Ab-’s, 29/101 (28.7%) had at least one dysglycemic OGTT at baseline or during follow-up, whereas 192/977 (19.7%) Ab+’s had a dysglycemic OGTT. At baseline, there were no significant differences in the proportions of Dysglycemia [Ab-’s: 13/101 (12.9%) vs. Ab+’s: 114/977 (11.7%)]. Of those with normal OGTTs at baseline, the proportion progressing to Dysglycemia was actually higher (p=0.007) in the Ab-’s (Dysglycemia/total: [16/87 (18.4%) vs. 78/846 (9.2%)], but the hazard ratio for Dysglycemia risk from a Cox regression analysis was not significant after adjustments for age, BMI%tile, relation to proband, and number of OGTTs performed. OGTT glucose and C-peptide at the first dysglycemic OGTT did not differ significantly between Ab-’s and Ab+’s after adjustments, except for a higher 90-minutes glucose in the Ab-’s (p=0.004). The early C-peptide response values (30-0 minutes C-peptide) did not differ significantly between the groups and were not indicative of overt insulin deficiency (Ab-’s: 5.6± 3.2 ng/ml vs. Ab+’s: 5.2± 3.3 ng/ml). In summary, Dysglycemia was as common in Ab- relatives as in single Ab+ relatives with similar dysglycemic OGTT patterns. These findings suggest that Dysglycemia can precede Ab’s during the progression to T1D and/or an appreciable proportion of single Ab+ dysglycemic individuals do not develop T1D. Disclosure E.K. Sims: None. P. Xu: None. J.S. Skyler: Advisory Panel; Self; ADOCIA, Abvance. Consultant; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Dance Biopharm. Consultant; Self; Diavacs, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Ideal Life Inc., ImmunoMolecular Therapeutics, Intrexon, Merck & Co., Inc.. Advisory Panel; Self; Orgenesis Inc.. Consultant; Self; Sanofi, Servier, VTV Therapeutics, Valeritas, Inc., Viacyte, Inc.. Board Member; Self; Dexcom, Inc.. Stock/Shareholder; Self; Dexcom, Inc.. Board Member; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; Intarcia Therapeutics, Inc.. Board Member; Self; Moerae Matrix. Stock/Shareholder; Self; Moerae Matrix, Dance Biopharm, Ideal Life Inc., Intrexon, VasoPrep Surgical. A. Pugliese: None. J. Krischer: None. C. Greenbaum: Research Support; Self; Janssen Research & Development. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. J. Mahon: None. K.C. Herold: None. J.P. Palmer: None. J. Sosenko: None.

  • incident Dysglycemia and progression to type 1 diabetes among participants in the diabetes prevention trial type 1
    Diabetes Care, 2009
    Co-Authors: Jay M. Sosenko, Jeffrey P. Krischer, Carla J. Greenbaum, Jerry P. Palmer, David Cuthbertson, Jeffery Mahon, Catherine C. Cowie, Lisa Rafkinmervis, Jay S. Skyler
    Abstract:

    Abstract Objective: We studied the incidence of Dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether Dysglycemia was sustained. Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident Dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident Dysglycemia at the 6-month visit was assessed for T1D prediction. Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of Dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of Dysglycemia. Incident Dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident Dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.

  • Incident Dysglycemia and Progression to Type 1 Diabetes Among Participants in the Diabetes Prevention Trial–Type 1
    Diabetes Care, 2009
    Co-Authors: Jay M. Sosenko, Jeffrey P. Krischer, Carla J. Greenbaum, Jerry P. Palmer, Lisa Rafkin-mervis, David Cuthbertson, Jeffery Mahon, Catherine C. Cowie, Jay S. Skyler
    Abstract:

    Abstract Objective: We studied the incidence of Dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether Dysglycemia was sustained. Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident Dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident Dysglycemia at the 6-month visit was assessed for T1D prediction. Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of Dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of Dysglycemia. Incident Dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident Dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.

Trine M. Reine - One of the best experts on this subject based on the ideXlab platform.

  • Acute exercise increases syndecan-1 and -4 serum concentrations
    Glycoconjugate Journal, 2019
    Co-Authors: Svein O. Kolset, Kåre I. Birkeland, Christian A. Drevon, Trine M. Reine
    Abstract:

    The effects of acute and long-term exercise on syndecans and the relationship to insulin sensitivity are not fully explored. We aimed to examine the effects of acute and 12 weeks of exercise on (1) serum levels of syndecan-1 and -4, (2) gene expression related to syndecan synthesis and modification in skeletal muscle and adipose tissue, and (3) the relationship to insulin sensitivity. Sedentary men with ( n  = 13) or without (n = 13) Dysglycemia underwent two 45 min acute bicycle tests interspersed by 12 weeks of exercise intervention. Euglycemic hyperinsulinemic clamp and mRNA-sequencing of skeletal muscle and adipose tissue biopsies were performed before and after intervention. Serum syndecan-1 and -4 levels were quantified before, immediately after and 2 h after bicycling. Syndecan-1 and -4 serum concentrations increased in response to acute physical exercise. Baseline syndecan-4 but not syndecan-1 concentrations were higher in dysglycemic compared to normoglycemic men, and correlated to change in insulin sensitivity, but did not change during the 12 weeks exercise intervention. Only syndecan-4 was expressed in skeletal muscle and adipose tissue. Adipose tissue mRNA levels of transcripts affecting syndecan structure and shedding were upregulated in Dysglycemia, and muscle mRNA responded to long-term physical activity. The increase in serum syndecan-1 and -4 due to acute exercise suggest increased syndecan shedding and disruption of glycocalyx in response to increased blood flow. The higher syndecan-4 baseline serum levels in Dysglycemia, association to insulin sensitivity, and changes in mRNA transcripts may suggest syndecan-4 involvement in muscle and adipose tissue response to exercise.

Jeffrey P. Krischer - One of the best experts on this subject based on the ideXlab platform.

  • Dysglycemia Is as Common in Autoantibody-Negative Relatives as in Single-Autoantibody-Positive Relatives of Type 1 Diabetes (T1D) Patients
    Diabetes, 2018
    Co-Authors: Emily K. Sims, Jay S. Skyler, Alberto Pugliese, Jeffrey P. Krischer, Carla J. Greenbaum, Jeffrey L. Mahon, Kevan C. Herold, Jerry P. Palmer, Jay M. Sosenko
    Abstract:

    Autoantibody positive (Ab+) relatives of T1D patients have an increased risk for Dysglycemia and progression to T1D. However, the occurrence of Dysglycemia in Ab- relatives is not known. Thus, we compared the frequency and pattern of Dysglycemia from oral glucose tolerance tests (OGTTs) between Ab- (n=101; mean age: 11.7± 3.6 years) and single Ab+ (n=977; mean age 10.4± 3.9 years) relatives in the TrialNet Pathway to Prevention study. Single Abs were ICA, GADA, IA-2A, mIAA, or ZnT8A. The glucose criteria for Dysglycemia were: fasting 110-125 mg/dl; 30, 60, and/or 90-minutes glucose ≥ 200 mg/dl; and/or 120-minutes glucose 140-199 mg/dl. Of the Ab-’s, 29/101 (28.7%) had at least one dysglycemic OGTT at baseline or during follow-up, whereas 192/977 (19.7%) Ab+’s had a dysglycemic OGTT. At baseline, there were no significant differences in the proportions of Dysglycemia [Ab-’s: 13/101 (12.9%) vs. Ab+’s: 114/977 (11.7%)]. Of those with normal OGTTs at baseline, the proportion progressing to Dysglycemia was actually higher (p=0.007) in the Ab-’s (Dysglycemia/total: [16/87 (18.4%) vs. 78/846 (9.2%)], but the hazard ratio for Dysglycemia risk from a Cox regression analysis was not significant after adjustments for age, BMI%tile, relation to proband, and number of OGTTs performed. OGTT glucose and C-peptide at the first dysglycemic OGTT did not differ significantly between Ab-’s and Ab+’s after adjustments, except for a higher 90-minutes glucose in the Ab-’s (p=0.004). The early C-peptide response values (30-0 minutes C-peptide) did not differ significantly between the groups and were not indicative of overt insulin deficiency (Ab-’s: 5.6± 3.2 ng/ml vs. Ab+’s: 5.2± 3.3 ng/ml). In summary, Dysglycemia was as common in Ab- relatives as in single Ab+ relatives with similar dysglycemic OGTT patterns. These findings suggest that Dysglycemia can precede Ab’s during the progression to T1D and/or an appreciable proportion of single Ab+ dysglycemic individuals do not develop T1D. Disclosure E.K. Sims: None. P. Xu: None. J.S. Skyler: Advisory Panel; Self; ADOCIA, Abvance. Consultant; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Dance Biopharm. Consultant; Self; Diavacs, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Ideal Life Inc., ImmunoMolecular Therapeutics, Intrexon, Merck & Co., Inc.. Advisory Panel; Self; Orgenesis Inc.. Consultant; Self; Sanofi, Servier, VTV Therapeutics, Valeritas, Inc., Viacyte, Inc.. Board Member; Self; Dexcom, Inc.. Stock/Shareholder; Self; Dexcom, Inc.. Board Member; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; Intarcia Therapeutics, Inc.. Board Member; Self; Moerae Matrix. Stock/Shareholder; Self; Moerae Matrix, Dance Biopharm, Ideal Life Inc., Intrexon, VasoPrep Surgical. A. Pugliese: None. J. Krischer: None. C. Greenbaum: Research Support; Self; Janssen Research & Development. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. J. Mahon: None. K.C. Herold: None. J.P. Palmer: None. J. Sosenko: None.

  • incident Dysglycemia and progression to type 1 diabetes among participants in the diabetes prevention trial type 1
    Diabetes Care, 2009
    Co-Authors: Jay M. Sosenko, Jeffrey P. Krischer, Carla J. Greenbaum, Jerry P. Palmer, David Cuthbertson, Jeffery Mahon, Catherine C. Cowie, Lisa Rafkinmervis, Jay S. Skyler
    Abstract:

    Abstract Objective: We studied the incidence of Dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether Dysglycemia was sustained. Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident Dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident Dysglycemia at the 6-month visit was assessed for T1D prediction. Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of Dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of Dysglycemia. Incident Dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident Dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.

  • Incident Dysglycemia and Progression to Type 1 Diabetes Among Participants in the Diabetes Prevention Trial–Type 1
    Diabetes Care, 2009
    Co-Authors: Jay M. Sosenko, Jeffrey P. Krischer, Carla J. Greenbaum, Jerry P. Palmer, Lisa Rafkin-mervis, David Cuthbertson, Jeffery Mahon, Catherine C. Cowie, Jay S. Skyler
    Abstract:

    Abstract Objective: We studied the incidence of Dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether Dysglycemia was sustained. Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident Dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident Dysglycemia at the 6-month visit was assessed for T1D prediction. Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of Dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of Dysglycemia. Incident Dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident Dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.

Carla J. Greenbaum - One of the best experts on this subject based on the ideXlab platform.

  • Dysglycemia Is as Common in Autoantibody-Negative Relatives as in Single-Autoantibody-Positive Relatives of Type 1 Diabetes (T1D) Patients
    Diabetes, 2018
    Co-Authors: Emily K. Sims, Jay S. Skyler, Alberto Pugliese, Jeffrey P. Krischer, Carla J. Greenbaum, Jeffrey L. Mahon, Kevan C. Herold, Jerry P. Palmer, Jay M. Sosenko
    Abstract:

    Autoantibody positive (Ab+) relatives of T1D patients have an increased risk for Dysglycemia and progression to T1D. However, the occurrence of Dysglycemia in Ab- relatives is not known. Thus, we compared the frequency and pattern of Dysglycemia from oral glucose tolerance tests (OGTTs) between Ab- (n=101; mean age: 11.7± 3.6 years) and single Ab+ (n=977; mean age 10.4± 3.9 years) relatives in the TrialNet Pathway to Prevention study. Single Abs were ICA, GADA, IA-2A, mIAA, or ZnT8A. The glucose criteria for Dysglycemia were: fasting 110-125 mg/dl; 30, 60, and/or 90-minutes glucose ≥ 200 mg/dl; and/or 120-minutes glucose 140-199 mg/dl. Of the Ab-’s, 29/101 (28.7%) had at least one dysglycemic OGTT at baseline or during follow-up, whereas 192/977 (19.7%) Ab+’s had a dysglycemic OGTT. At baseline, there were no significant differences in the proportions of Dysglycemia [Ab-’s: 13/101 (12.9%) vs. Ab+’s: 114/977 (11.7%)]. Of those with normal OGTTs at baseline, the proportion progressing to Dysglycemia was actually higher (p=0.007) in the Ab-’s (Dysglycemia/total: [16/87 (18.4%) vs. 78/846 (9.2%)], but the hazard ratio for Dysglycemia risk from a Cox regression analysis was not significant after adjustments for age, BMI%tile, relation to proband, and number of OGTTs performed. OGTT glucose and C-peptide at the first dysglycemic OGTT did not differ significantly between Ab-’s and Ab+’s after adjustments, except for a higher 90-minutes glucose in the Ab-’s (p=0.004). The early C-peptide response values (30-0 minutes C-peptide) did not differ significantly between the groups and were not indicative of overt insulin deficiency (Ab-’s: 5.6± 3.2 ng/ml vs. Ab+’s: 5.2± 3.3 ng/ml). In summary, Dysglycemia was as common in Ab- relatives as in single Ab+ relatives with similar dysglycemic OGTT patterns. These findings suggest that Dysglycemia can precede Ab’s during the progression to T1D and/or an appreciable proportion of single Ab+ dysglycemic individuals do not develop T1D. Disclosure E.K. Sims: None. P. Xu: None. J.S. Skyler: Advisory Panel; Self; ADOCIA, Abvance. Consultant; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Dance Biopharm. Consultant; Self; Diavacs, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Ideal Life Inc., ImmunoMolecular Therapeutics, Intrexon, Merck & Co., Inc.. Advisory Panel; Self; Orgenesis Inc.. Consultant; Self; Sanofi, Servier, VTV Therapeutics, Valeritas, Inc., Viacyte, Inc.. Board Member; Self; Dexcom, Inc.. Stock/Shareholder; Self; Dexcom, Inc.. Board Member; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; Intarcia Therapeutics, Inc.. Board Member; Self; Moerae Matrix. Stock/Shareholder; Self; Moerae Matrix, Dance Biopharm, Ideal Life Inc., Intrexon, VasoPrep Surgical. A. Pugliese: None. J. Krischer: None. C. Greenbaum: Research Support; Self; Janssen Research & Development. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. J. Mahon: None. K.C. Herold: None. J.P. Palmer: None. J. Sosenko: None.

  • incident Dysglycemia and progression to type 1 diabetes among participants in the diabetes prevention trial type 1
    Diabetes Care, 2009
    Co-Authors: Jay M. Sosenko, Jeffrey P. Krischer, Carla J. Greenbaum, Jerry P. Palmer, David Cuthbertson, Jeffery Mahon, Catherine C. Cowie, Lisa Rafkinmervis, Jay S. Skyler
    Abstract:

    Abstract Objective: We studied the incidence of Dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether Dysglycemia was sustained. Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident Dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident Dysglycemia at the 6-month visit was assessed for T1D prediction. Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of Dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of Dysglycemia. Incident Dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident Dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.

  • Incident Dysglycemia and Progression to Type 1 Diabetes Among Participants in the Diabetes Prevention Trial–Type 1
    Diabetes Care, 2009
    Co-Authors: Jay M. Sosenko, Jeffrey P. Krischer, Carla J. Greenbaum, Jerry P. Palmer, Lisa Rafkin-mervis, David Cuthbertson, Jeffery Mahon, Catherine C. Cowie, Jay S. Skyler
    Abstract:

    Abstract Objective: We studied the incidence of Dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether Dysglycemia was sustained. Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident Dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident Dysglycemia at the 6-month visit was assessed for T1D prediction. Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of Dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of Dysglycemia. Incident Dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident Dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.