Hostname: page-component-8448b6f56d-sxzjt Total loading time: 0 Render date: 2024-04-24T02:02:07.462Z Has data issue: false hasContentIssue false
  • English
  • Français

The next generation cohort: a description of a cohort at high risk for childhood onset type 2 diabetes

Part of: DOHaD in Indigenous Populations

Published online by Cambridge University Press:  06 August 2018

F. Jabar ,
S. Colatruglio ,
E. Sellers ,
K. Kroeker  and
B. Wicklow
F. Jabar
Affiliation:
The Children’s Hospital Research Institute of Manitoba
S. Colatruglio
Affiliation:
The Children’s Hospital Research Institute of Manitoba
E. Sellers
Affiliation:
The Children’s Hospital Research Institute of Manitoba Department of Pediatrics and Child Health, Rady Faculty of Health Sciences, University of Manitoba
K. Kroeker
Affiliation:
Biostatistical Consulting Unit, George and Fay Yee Centre for Healthcare Innovation
B. Wicklow
Affiliation:
The Children’s Hospital Research Institute of Manitoba Department of Pediatrics and Child Health, Rady Faculty of Health Sciences, University of Manitoba
Get access Rights & Permissions [Opens in a new window]

Abstract

Children of mothers with youth-onset (<18 years) type 2 diabetes (T2D) are at increased risk of youth-onset T2D. In Canada, the highest reported prevalence of youth-onset T2D is in First Nation youth, some of whom harbor a unique genetic predisposition HNF1α polymorphism which has been associated with age of onset and clinical presentation. To describe the characteristics of the Next Generation birth cohort (n=260) at 7–9 years (n=88) and 14–16 years of age (n=27). This is a cross-sectional study of offspring exposed in utero to T2D (Next Generation Birth Cohort). Annual assessments from age 7 include height and weight, and biochemical testing (glucose, insulin, lipids, HbA1c). Descriptive statistics were employed. χ2 tests and repeated-measures ANOVA were used to compare categorical and continuous characteristics, respectively. In total, 11.9% of the total cohort have developed T2D. Of those 14–16.9 years of age, 16.0% have developed T2D. 92% of the offspring ages 7–9 and 70.3% of offspring ages 14–16 are overweight or obese. Children had a significantly higher body mass index z-score than adolescents (2.9 v. 1.5, P=0.001). Comparing the different HNF1α genotypes (G/G wildtype, G/S heterozygote, S/S homozygote); HbA1c (GG: 5.5% v. G/S: 5.7% v. S/S: 8.8%; P=0.0052), insulin (GG: 103 v. G/S: 202; P=0.05) and T2D status (G/G: 5.7% v. G/S: 28.1% v. S/S: 72.7%; P<0.0001) were significantly different between groups. T2D is very common among adolescents of mothers with youth-onset T2D. Early childhood obesity and the HNF1α G319S allele are associated with the incidence of T2D in the Next Gen offspring.

Keywords

maternal diabetes, offspring, outcomes, type 2 diabetes
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Special Issue 1: Themed Issue: Canada / Indigenous Populations , February 2019 , pp. 24 - 30
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Pinhas-Hamiel, O, Zeitler, P. The global spread of type 2 diabetes mellitus in children and adolescents. J Pediatr. 2005; 146, 693–700.Google Scholar
2. Amed, S, Dean, H, Panagiotopoulos, S, et al. Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study. Diabetes Care. 2010; 33, 786–791.Google Scholar
3. Sellers, EAC, Wicklow, BA, Dean, HJ. Clinical and demographic characteristics of type 2 diabetes in youth at diagnosis in Manitoba and Northwestern Ontario (2006–2011). Can J Diab. 2012; 36, 114–118.Google Scholar
4. Dart, AB, Martens, PJ, Rigatto, C, et al. Earlier onset of complications in youth with type 2 diabetes. Diabetes Care. 2014; 37, 436–443.Google Scholar
5. Dabelea, D, Hanson, RL, Lindsay, RS, et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. 2000; 49, 2208–2211.Google Scholar
6. Young, TK, Martens, PJ, Taback, SP, et al. Type 2 diabetes mellitus in children: prenatal and early infancy risk factors among native Canadians. Arch Pediatr Adolesc Med. 2002; 156, 651–655.Google Scholar
7. Dabelea, D, Mayer-Davis, EJ, Lamichhane, AP, et al. Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: the SEARCH Case-Control Study. Diabetes Care. 2008; 31, 1422–1426.Google Scholar
8. Dean, H. Type 2 diabetes in youth: a new epidemic. Adv Exp Med Biol. 2001; 498, 1–5.Google Scholar
9. Dean, HJ, Mundy, RL, Moffatt, M. Non-insulin-dependent diabetes mellitus in Indian children in Manitoba. CMAJ. 1992; 147, 52–57.Google Scholar
10. Hegele, RA, Cao, H, Harris, SB, Hanley, AJ, Zinman, B. The hepatic nuclear factor-1alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree. J Clin Endocrinol Metab. 1999; 84, 1077–1082.Google Scholar
11. Pontoglio, M, Sreenan, S, Roe, M, et al. Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice. J Clin Invest. 1998; 101, 2215–2222.Google Scholar
12. Okita, K, Yang, Q, Yamagata, K, et al. Human insulin gene is a target gene of hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-1beta. Biochem Biophys Res Commun. 1999; 263, 566–569.Google Scholar
13. Yang, Q, Yamagata, K, Yamamoto, K, et al. Structure/function studies of hepatocyte nuclear factor-1alpha, a diabetes-associated transcription factor. Biochem Biophys Res Commun. 1999; 266, 196–202.Google Scholar
14. Harries, LW, Sloman, MJ, Sellers, EA, Hattersley, AT, Ellard, S. Diabetes susceptibility in the Canadian Oji-Cree population is moderated by abnormal mRNA processing of HNF1A G319S transcripts. Diabetes. 2008; 57, 1978–1982.Google Scholar
15. Triggs-Raine, BL, Kirkpatrick, RD, Kelly, SL, et al. HNF-1alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community. Proc Natl Acad Sci U S A. 2002; 99, 4614–4619.Google Scholar
16. Sellers, EA, Triggs-Raine, BL, Rockman-Greenberg, C, Dean, HJ. The prevalence of the HNF-1alpha G319S mutation in Canadian aboriginal youth with type 2 diabetes. Diabetes Care. 2002; 25, 2202–2206.Google Scholar
17. Jonasson, ME, Wicklow, BA, Sellers, EA, Dolinsky, VW, Doucette, CA. Exploring the role of the HNF-1alpha G319S polymorphism in beta cell failure and youth-onset type 2 diabetes: lessons from MODY and Hnf-1alpha-deficient animal models. Biochem Cell Biol. 2015; 93, 487–494.Google Scholar
18. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes, 2008: 37: S1–S201.Google Scholar
19. Kuczmarski, RJ, Ogden, CL, Grummar-Strawn, LM, et al. CDC growth charts: United States. Adv Data. 2000; 314, 1–27.Google Scholar
20. Amed, S, Islam, N, Sutherland, J, Reimer, K. Incidence and prevalence trends of youth-onset type 2 diabetes in a cohort of Canadian youth: 2002-2013. Pediatr Diabetes. 2018; 19: 630–636.Google Scholar
21. Matyka, KA. Type 2 diabetes in childhood: epidemiological and clinical aspects. Br Med Bull. 2008; 86, 59–75.Google Scholar
22. Linares Segovia, B, Gutierrez Tinoco, M, Izquierdo Arrizon, A, Guizar Mendoza, JM, Amador Licona, N. Long-term consequences for offspring of paternal diabetes and metabolic syndrome. Exp Diabetes Res. 2012; 2012, 684562.Google Scholar
23. Ruchat, SM, Hivert, MF, Bouchard, L. Epigenetic programming of obesity and diabetes by in utero exposure to gestational diabetes mellitus. Nutr Rev. 2013; 71(Suppl. 1), S88–S94.Google Scholar
24. Houde, AA, Ruchat, SM, Allard, C, et al. LRP1B, BRD2 and CACNA1D: new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia. Epigenomics. 2015; 7, 1111–1122.Google Scholar
25. del Rosario, MC, Ossowski, V, Knowler, WC, et al. Potential epigenetic dysregulation of genes associated with MODY and type 2 diabetes in humans exposed to a diabetic intrauterine environment: an analysis of genome-wide DNA methylation. Metabolism. 2014; 63, 654–660.Google Scholar
26. Quilter, CR, Cooper, WN, Cliffe, KM, et al. Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk. FASEB J. 2014; 28, 4868–4879.Google Scholar
27. O’Connor, EA, Evans, CV, Burda, BU, et al. Screening for obesity and intervention for weight management in children and adolescents: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2017; 317, 2427–2444.Google Scholar
28. Dabelea, D, Harrod, CS. Role of developmental overnutrition in pediatric obesity and type 2 diabetes. Nutr Rev. 2013; 71(Suppl 1), S62–S67.Google Scholar
29. Bjerregaard, LG, Jensen, BW, Angquist, L, et al. Change in overweight from childhood to early adulthood and risk of type 2 diabetes. N Engl J Med. 2018; 378, 1302–1312.Google Scholar
30. Charison, J, Wicklow, BA, Dean, HJ, Sellers, EA. The metabolic phenotype of youth onset type 2 diabetes: the role of pregestational diabetes exposure and the hepatic nuclear factor 1Alpha G319S Polymorphism. Can J Diabetes. 2016; 40, 210–215.Google Scholar
31. Wicklow, BA, Wittmeier, KD, MacIntosh, AC, et al. Metabolic consequences of hepatic steatosis in overweight and obese adolescents. Diabetes Care. 2012; 35, 905–910.Google Scholar
32. Saad, V, Wicklow, B, Wittmeier, K, et al. A clinically relevant method to screen for hepatic steatosis in overweight adolescents: a cross sectional study. BMC Pediatr. 2015; 15, 151.Google Scholar
33. Volkmar, M, Dedeurwaerder, S, Cunha, DA, et al. DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J. 2012; 31, 1405–1426.Google Scholar
34. Strawbridge, RJ, Dupuis, J, Prokopenko, I, et al. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes. 2011; 60, 2624–2634.Google Scholar
35. Chen, P, Piaggi, P, Trautig, M, et al. Differential methylation of genes in individuals exposed to maternal diabetes in utero. Diabetologia. 2017; 60, 645–655.Google Scholar