Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study

TEDDY Study Group; Laura M Jacobsen; Kendra Vehik; Riitta Veijola; Katharina Warncke; Jorma Toppari; Andrea K Steck; Patricia Gesualdo; Beena Akolkar; Markus Lundgren; William A Hagopian; Jin-Xiong She; Marian Rewers; Anette G Ziegler; Jeffrey P Krischer; Helena Elding Larsson; Michael J Haller; Marian Rewers; Aaron Barbour; Kimberly Bautista; Judith Baxter; Daniel Felipe-Morales; Brigitte I Frohnert; Marisa Stahl; Patricia Gesualdo; Rachel Haley; Michelle Hoffman; Rachel Karban; Edwin Liu; Alondra Munoz; Jill Norris; Stesha Peacock; Hanan Shorrosh; Suvi Ahonen; Mari Åkerlund; Leena Hakola; Heikki Hyöty; Mikael Knip; Mirva Koreasalo; Kalle Kurppa; Salla Kuusela; Jutta Laiho; Katri Lindfors; Maria Lönnrot; Markus Mattila; Tiina Niininen; Mia Nyblom; Sami Oikarinen; Anne Riikonen; Päivi Tossavainen; Suvi M Virtanen

doi:10.2337/dc21-0422

Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study

TEDDY Study Group, Laura M Jacobsen, Kendra Vehik, Riitta Veijola, Katharina Warncke, Jorma Toppari, Andrea K Steck, Patricia Gesualdo, Beena Akolkar, Markus Lundgren, William A Hagopian, Jin-Xiong She, Marian Rewers, Anette G Ziegler, Jeffrey P Krischer, Helena Elding Larsson, Michael J Haller, Marian Rewers, Aaron Barbour, Kimberly BautistaJudith Baxter, Daniel Felipe-Morales, Brigitte I Frohnert, Marisa Stahl, Patricia Gesualdo, Rachel Haley, Michelle Hoffman, Rachel Karban, Edwin Liu, Alondra Munoz, Jill Norris, Stesha Peacock, Hanan Shorrosh, Suvi Ahonen, Mari Åkerlund, Leena Hakola, Heikki Hyöty, Mikael Knip, Mirva Koreasalo, Kalle Kurppa, Salla Kuusela, Jutta Laiho, Katri Lindfors, Maria Lönnrot, Markus Mattila, Tiina Niininen, Mia Nyblom, Sami Oikarinen, Anne Riikonen, Päivi Tossavainen, Suvi M Virtanen

Tutkimustuotos: Article › Scientific › vertaisarvioitu

Abstrakti

OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA).

RESEARCH DESIGN AND METHODS: The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0-4, 5-9, and 10-14 years; n = 142, 151, and 86, respectively) with comparisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes.

RESULTS: Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04-1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42-1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83-0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16-1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Of 23 (6.1%) of 379 children with DKA at onset, only 1 (4.3%) of 23 had a first-degree relative (FDR) with type 1 diabetes compared with 102 (28.7%) of 356 FDR children without DKA (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001).

CONCLUSIONS: DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.

Alkuperäiskieli	Englanti
Julkaisu	Diabetes care
DOI - pysyväislinkit	https://doi.org/10.2337/dc21-0422
Tila	Julkaistu - 2022
Julkaistu ulkoisesti	Kyllä
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli

Pääsy asiakirjaan

10.2337/dc21-0422

Siteeraa tätä

TEDDY Study Group, Jacobsen, L. M., Vehik, K., Veijola, R., Warncke, K., Toppari, J., Steck, A. K., Gesualdo, P., Akolkar, B., Lundgren, M., Hagopian, W. A., She, J-X., Rewers, M., Ziegler, A. G., Krischer, J. P., Larsson, H. E., Haller, M. J., Rewers, M., Barbour, A., ... Virtanen, S. M. (2022). Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study. Diabetes care. https://doi.org/10.2337/dc21-0422

TEDDY Study Group ; Jacobsen, Laura M ; Vehik, Kendra ; Veijola, Riitta ; Warncke, Katharina ; Toppari, Jorma ; Steck, Andrea K ; Gesualdo, Patricia ; Akolkar, Beena ; Lundgren, Markus ; Hagopian, William A ; She, Jin-Xiong ; Rewers, Marian ; Ziegler, Anette G ; Krischer, Jeffrey P ; Larsson, Helena Elding ; Haller, Michael J ; Rewers, Marian ; Barbour, Aaron ; Bautista, Kimberly ; Baxter, Judith ; Felipe-Morales, Daniel ; Frohnert, Brigitte I ; Stahl, Marisa ; Gesualdo, Patricia ; Haley, Rachel ; Hoffman, Michelle ; Karban, Rachel ; Liu, Edwin ; Munoz, Alondra ; Norris, Jill ; Peacock, Stesha ; Shorrosh, Hanan ; Ahonen, Suvi ; Åkerlund, Mari ; Hakola, Leena ; Hyöty, Heikki ; Knip, Mikael ; Koreasalo, Mirva ; Kurppa, Kalle ; Kuusela, Salla ; Laiho, Jutta ; Lindfors, Katri ; Lönnrot, Maria ; Mattila, Markus ; Niininen, Tiina ; Nyblom, Mia ; Oikarinen, Sami ; Riikonen, Anne ; Tossavainen, Päivi ; Virtanen, Suvi M. / Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study. Julkaisussa: Diabetes care. 2022.

@article{913a1cbc5da247e9a0138cc4b30e5e79,

title = "Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study",

abstract = "OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA).RESEARCH DESIGN AND METHODS: The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0-4, 5-9, and 10-14 years; n = 142, 151, and 86, respectively) with comparisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes.RESULTS: Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04-1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42-1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83-0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16-1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Of 23 (6.1%) of 379 children with DKA at onset, only 1 (4.3%) of 23 had a first-degree relative (FDR) with type 1 diabetes compared with 102 (28.7%) of 356 FDR children without DKA (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001).CONCLUSIONS: DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.",

author = "{TEDDY Study Group} and Jacobsen, {Laura M} and Kendra Vehik and Riitta Veijola and Katharina Warncke and Jorma Toppari and Steck, {Andrea K} and Patricia Gesualdo and Beena Akolkar and Markus Lundgren and Hagopian, {William A} and Jin-Xiong She and Marian Rewers and Ziegler, {Anette G} and Krischer, {Jeffrey P} and Larsson, {Helena Elding} and Haller, {Michael J} and Marian Rewers and Aaron Barbour and Kimberly Bautista and Judith Baxter and Daniel Felipe-Morales and Frohnert, {Brigitte I} and Marisa Stahl and Patricia Gesualdo and Rachel Haley and Michelle Hoffman and Rachel Karban and Edwin Liu and Alondra Munoz and Jill Norris and Stesha Peacock and Hanan Shorrosh and Suvi Ahonen and Mari {\AA}kerlund and Leena Hakola and Heikki Hy{\"o}ty and Mikael Knip and Mirva Koreasalo and Kalle Kurppa and Salla Kuusela and Jutta Laiho and Katri Lindfors and Maria L{\"o}nnrot and Markus Mattila and Tiina Niininen and Mia Nyblom and Sami Oikarinen and Anne Riikonen and P{\"a}ivi Tossavainen and Virtanen, {Suvi M}",

note = "{\textcopyright} 2022 by the American Diabetes Association.",

year = "2022",

doi = "10.2337/dc21-0422",

language = "English",

}

TEDDY Study Group, Jacobsen, LM, Vehik, K, Veijola, R, Warncke, K, Toppari, J, Steck, AK, Gesualdo, P, Akolkar, B, Lundgren, M, Hagopian, WA, She, J-X, Rewers, M, Ziegler, AG, Krischer, JP, Larsson, HE, Haller, MJ, Rewers, M, Barbour, A, Bautista, K, Baxter, J, Felipe-Morales, D, Frohnert, BI, Stahl, M, Gesualdo, P, Haley, R, Hoffman, M, Karban, R, Liu, E, Munoz, A, Norris, J, Peacock, S, Shorrosh, H, Ahonen, S , Åkerlund, M , Hakola, L , Hyöty, H, Knip, M, Koreasalo, M , Kurppa, K , Kuusela, S , Laiho, J , Lindfors, K , Lönnrot, M , Mattila, M , Niininen, T , Nyblom, M , Oikarinen, S, Riikonen, A, Tossavainen, P & Virtanen, SM 2022, 'Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study', Diabetes care. https://doi.org/10.2337/dc21-0422

Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study. / TEDDY Study Group; Jacobsen, Laura M; Vehik, Kendra; Veijola, Riitta; Warncke, Katharina; Toppari, Jorma; Steck, Andrea K; Gesualdo, Patricia; Akolkar, Beena; Lundgren, Markus; Hagopian, William A; She, Jin-Xiong; Rewers, Marian; Ziegler, Anette G; Krischer, Jeffrey P; Larsson, Helena Elding; Haller, Michael J; Rewers, Marian; Barbour, Aaron; Bautista, Kimberly; Baxter, Judith; Felipe-Morales, Daniel; Frohnert, Brigitte I; Stahl, Marisa; Gesualdo, Patricia; Haley, Rachel; Hoffman, Michelle; Karban, Rachel; Liu, Edwin; Munoz, Alondra; Norris, Jill; Peacock, Stesha; Shorrosh, Hanan; Ahonen, Suvi ; Åkerlund, Mari ; Hakola, Leena ; Hyöty, Heikki; Knip, Mikael; Koreasalo, Mirva ; Kurppa, Kalle ; Kuusela, Salla ; Laiho, Jutta ; Lindfors, Katri ; Lönnrot, Maria ; Mattila, Markus ; Niininen, Tiina ; Nyblom, Mia ; Oikarinen, Sami; Riikonen, Anne; Tossavainen, Päivi; Virtanen, Suvi M.

julkaisussa: Diabetes care, 2022.

Tutkimustuotos: Article › Scientific › vertaisarvioitu

TY - JOUR

T1 - Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study

AU - TEDDY Study Group

AU - Jacobsen, Laura M

AU - Vehik, Kendra

AU - Veijola, Riitta

AU - Warncke, Katharina

AU - Toppari, Jorma

AU - Steck, Andrea K

AU - Gesualdo, Patricia

AU - Akolkar, Beena

AU - Lundgren, Markus

AU - Hagopian, William A

AU - She, Jin-Xiong

AU - Rewers, Marian

AU - Ziegler, Anette G

AU - Krischer, Jeffrey P

AU - Larsson, Helena Elding

AU - Haller, Michael J

AU - Rewers, Marian

AU - Barbour, Aaron

AU - Bautista, Kimberly

AU - Baxter, Judith

AU - Felipe-Morales, Daniel

AU - Frohnert, Brigitte I

AU - Stahl, Marisa

AU - Gesualdo, Patricia

AU - Haley, Rachel

AU - Hoffman, Michelle

AU - Karban, Rachel

AU - Liu, Edwin

AU - Munoz, Alondra

AU - Norris, Jill

AU - Peacock, Stesha

AU - Shorrosh, Hanan

AU - Ahonen, Suvi

AU - Åkerlund, Mari

AU - Hakola, Leena

AU - Hyöty, Heikki

AU - Knip, Mikael

AU - Koreasalo, Mirva

AU - Kurppa, Kalle

AU - Kuusela, Salla

AU - Laiho, Jutta

AU - Lindfors, Katri

AU - Lönnrot, Maria

AU - Mattila, Markus

AU - Niininen, Tiina

AU - Nyblom, Mia

AU - Oikarinen, Sami

AU - Riikonen, Anne

AU - Tossavainen, Päivi

AU - Virtanen, Suvi M

PY - 2022

Y1 - 2022

N2 - OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA).RESEARCH DESIGN AND METHODS: The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0-4, 5-9, and 10-14 years; n = 142, 151, and 86, respectively) with comparisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes.RESULTS: Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04-1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42-1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83-0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16-1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Of 23 (6.1%) of 379 children with DKA at onset, only 1 (4.3%) of 23 had a first-degree relative (FDR) with type 1 diabetes compared with 102 (28.7%) of 356 FDR children without DKA (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001).CONCLUSIONS: DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.

AB - OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA).RESEARCH DESIGN AND METHODS: The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0-4, 5-9, and 10-14 years; n = 142, 151, and 86, respectively) with comparisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes.RESULTS: Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04-1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42-1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83-0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16-1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Of 23 (6.1%) of 379 children with DKA at onset, only 1 (4.3%) of 23 had a first-degree relative (FDR) with type 1 diabetes compared with 102 (28.7%) of 356 FDR children without DKA (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001).CONCLUSIONS: DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.

U2 - 10.2337/dc21-0422

DO - 10.2337/dc21-0422

M3 - Article

C2 - 35043162

ER -

Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study

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