Distinct Growth Phases in Early Life Associated With the Risk of Type 1 Diabetes: The TEDDY Study

Overview

Journal Diabetes Care

Specialty Endocrinology

Date 2020 Jan 4

PMID 31896601

Citations 24

Authors

Xiang Liu

Kendra Vehik

Yangxin Huang

Helena Elding Larsson

Jorma Toppari

Anette G Ziegler

Jin-Xiong She

Marian Rewers

William A Hagopian

Beena Akolkar

Jeffrey P Krischer

Affiliations

Soon will be listed here.

Abstract

Objective: This study investigates two-phase growth patterns in early life and their association with development of islet autoimmunity (IA) and type 1 diabetes (T1D).

Research Design And Methods: The Environmental Determinants of Diabetes in the Young (TEDDY) study followed 7,522 genetically high-risk children in Sweden, Finland, Germany, and the U.S. from birth for a median of 9.0 years (interquartile range 5.7-10.6) with available growth data. Of these, 761 (10.1%) children developed IA and 290 (3.9%) children were diagnosed with T1D. Bayesian two-phase piecewise linear mixed models with a random change point were used to estimate children's individual growth trajectories. Cox proportional hazards models were used to assess the effects of associated growth parameters on the risks of IA and progression to T1D.

Results: A higher rate of weight gain in infancy was associated with increased IA risk (hazard ratio [HR] 1.09 [95% CI 1.02, 1.17] per 1 kg/year). A height growth pattern with a lower rate in infancy (HR 0.79 [95% CI 0.70, 0.90] per 1 cm/year), higher rate in early childhood (HR 1.48 [95% CI 1.22, 1.79] per 1 cm/year), and younger age at the phase transition (HR 0.76 [95% CI 0.58, 0.99] per 1 month) was associated with increased risk of progression from IA to T1D. A higher rate of weight gain in early childhood was associated with increased risk of progression from IA to T1D (HR 2.57 [95% CI 1.34, 4.91] per 1 kg/year) in children with first-appearing GAD autoantibody only.

Conclusions: Growth patterns in early life better clarify how specific growth phases are associated with the development of T1D.

Citing Articles

Type 1 Diabetes Risk Variants Reduce Beta Cell Function.

Ratajczak W, Jones A, Atkinson S, Kelly C Genes (Basel). 2025; 16(2).

PMID: 40004501 PMC: 11855905. DOI: 10.3390/genes16020172.

Looking back at the TEDDY study: lessons and future directions.

Lernmark A, Agardh D, Akolkar B, Gesualdo P, Hagopian W, Haller M Nat Rev Endocrinol. 2024; 21(3):154-165.

PMID: 39496810 PMC: 11825287. DOI: 10.1038/s41574-024-01045-0.

Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden.

Metsala J, Risnes K, Persson M, Veijola R, Pulakka A, Heikkila K Diabetologia. 2024; 67(7):1315-1327.

PMID: 38613666 PMC: 11153267. DOI: 10.1007/s00125-024-06139-y.

Low-Protein Infant Formula Enriched with Alpha-Lactalbumin during Early Infancy May Reduce Insulin Resistance at 12 Months: A Follow-Up of a Randomized Controlled Trial.

Tinghall Nilsson U, Lonnerdal B, Hernell O, Kvistgaard A, Jacobsen L, Karlsland Akeson P Nutrients. 2024; 16(7).

PMID: 38613059 PMC: 11013926. DOI: 10.3390/nu16071026.

Decrease in multiple complement proteins associated with development of islet autoimmunity and type 1 diabetes.

Webb-Robertson B, Nakayasu E, Dong F, Waugh K, Flores J, Bramer L iScience. 2024; 27(2):108769.

PMID: 38303689 PMC: 10831269. DOI: 10.1016/j.isci.2023.108769.

References

Elding Larsson H, Vehik K, Haller M, Liu X, Akolkar B, Hagopian W . Growth and Risk for Islet Autoimmunity and Progression to Type 1 Diabetes in Early Childhood: The Environmental Determinants of Diabetes in the Young Study. Diabetes. 2016; 65(7):1988-95. PMC: 4915577. DOI: 10.2337/db15-1180. View

Fabricius-Bjerre S, Jensen R, Faerch K, Larsen T, Molgaard C, Michaelsen K . Impact of birth weight and early infant weight gain on insulin resistance and associated cardiovascular risk factors in adolescence. PLoS One. 2011; 6(6):e20595. PMC: 3107215. DOI: 10.1371/journal.pone.0020595. View

. Rapid early growth is associated with increased risk of childhood type 1 diabetes in various European populations. Diabetes Care. 2002; 25(10):1755-60. DOI: 10.2337/diacare.25.10.1755. View

Wilkin T . The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes. Diabetologia. 2001; 44(7):914-22. DOI: 10.1007/s001250100548. View

. Standards of medical care in diabetes--2014. Diabetes Care. 2013; 37 Suppl 1:S14-80. DOI: 10.2337/dc14-S014. View

Krischer J, Lynch K, Schatz D, Ilonen J, Lernmark A, Hagopian W . The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia. 2015; 58(5):980-7. PMC: 4393776. DOI: 10.1007/s00125-015-3514-y. View

Brilleman S, Howe L, Wolfe R, Tilling K . Bayesian Piecewise Linear Mixed Models With a Random Change Point: An Application to BMI Rebound in Childhood. Epidemiology. 2017; 28(6):827-833. PMC: 5625953. DOI: 10.1097/EDE.0000000000000723. View

Kelley K, Oh Y, Gargosky S, Gucev Z, Matsumoto T, Hwa V . Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol. 1996; 28(6):619-37. DOI: 10.1016/1357-2725(96)00005-2. View

Beyerlein A, Liu X, Uusitalo U, Harsunen M, Norris J, Foterek K . Dietary intake of soluble fiber and risk of islet autoimmunity by 5 y of age: results from the TEDDY study. Am J Clin Nutr. 2015; 102(2):345-52. PMC: 4515865. DOI: 10.3945/ajcn.115.108159. View

10.

Lifshitz F . Nutrition and growth. J Clin Res Pediatr Endocrinol. 2011; 1(4):157-63. PMC: 3005655. DOI: 10.4274/jcrpe.v1i4.39. View

11.

Lamb M, Yin X, Zerbe G, Klingensmith G, Dabelea D, Fingerlin T . Height growth velocity, islet autoimmunity and type 1 diabetes development: the Diabetes Autoimmunity Study in the Young. Diabetologia. 2009; 52(10):2064-71. PMC: 2813468. DOI: 10.1007/s00125-009-1428-2. View

12.

Mendivil C, Toloza F, Ricardo-Silgado M, Morales-Alvarez M, Mantilla-Rivas J, Pinzon-Cortes J . Antibodies against glutamic acid decarboxylase and indices of insulin resistance and insulin secretion in nondiabetic adults: a cross-sectional study. Diabetes Metab Syndr Obes. 2017; 10:179-185. PMC: 5428762. DOI: 10.2147/DMSO.S137216. View

13.

Krischer J, Liu X, Lernmark A, Hagopian W, Rewers M, She J . The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History on the Progression From Multiple Autoantibodies to Type 1 Diabetes: A TEDDY Study Report. Diabetes. 2017; 66(12):3122-3129. PMC: 5697938. DOI: 10.2337/db17-0261. View

14.

Hagopian W, Erlich H, Lernmark A, Rewers M, Ziegler A, Simell O . The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes. 2011; 12(8):733-43. PMC: 3315186. DOI: 10.1111/j.1399-5448.2011.00774.x. View

15.

Dahlquist G . Can we slow the rising incidence of childhood-onset autoimmune diabetes? The overload hypothesis. Diabetologia. 2005; 49(1):20-4. DOI: 10.1007/s00125-005-0076-4. View

16.

Vehik K, Dabelea D . The changing epidemiology of type 1 diabetes: why is it going through the roof?. Diabetes Metab Res Rev. 2011; 27(1):3-13. DOI: 10.1002/dmrr.1141. View

17.

. The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Ann N Y Acad Sci. 2009; 1150:1-13. PMC: 2886800. DOI: 10.1196/annals.1447.062. View

18.

. The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes. 2007; 8(5):286-98. DOI: 10.1111/j.1399-5448.2007.00269.x. View

19.

Knip M, Veijola R, Virtanen S, Hyoty H, Vaarala O, Akerblom H . Environmental triggers and determinants of type 1 diabetes. Diabetes. 2005; 54 Suppl 2:S125-36. DOI: 10.2337/diabetes.54.suppl_2.s125. View

20.

Bruining G . Association between infant growth before onset of juvenile type-1 diabetes and autoantibodies to IA-2. Netherlands Kolibrie study group of childhood diabetes. Lancet. 2000; 356(9230):655-6. DOI: 10.1016/s0140-6736(00)02612-x. View