Skip to main content

Neonatal Diabetes

  • Chapter
  • 173 Accesses

Abstract

Neonatal Diabetes Mellitus (NDM) is defined as persistent hyperglycemia occurring in the first months of life, lasting for more than two weeks and requiring insulin for management1. It is considered distinct from autoimmune type 1 DM which manifests after the first three to six months of life2. Whereas type 1 DM in the first year of life is characterized by markers of autoimmunity such as ICA, GAD65, or IA2 antibodies, neonatal DM does not share these characteristics. Rather, NDM is increasingly recognized as a genetic disorder with disturbances in the genes regulating islet organogenesis and function, including insulin secretion3,4. The tools of molecular biology have permitted remarkable progress in delineating the defects responsible for transient and permanent NDM, providing a rational basis for classification, prognosis and management3,4. Moreover, the identified defects in genes during islet organogenesis or insulin secretion are being investigated as potential contributors to diabetes mellitus in later life3-5. Thus, although NDM is rare, with an incidence of approximately 1:500,000 births1 , it has been quite instructive for providing insight on the regulation of insulin secretion and action3,4.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. von Muhlendahl KE, Herkenhoff H. Long-term course of neonatal diabetes. NEJM 1995; 333:704–708.

    Article  Google Scholar 

  2. Hathout EH, Sharkey J, Racine M, et al. Diabetic autoimmunity in infants and pre-schoolers with type 1 diabetes. Pediatric Diabetes 2000; 1:131–134.

    Article  PubMed  CAS  Google Scholar 

  3. Shield JPH, Temple IK. Neonatal diabetes mellitus. Pediatric Diabetes 2002; 3:109–112.

    Article  PubMed  CAS  Google Scholar 

  4. Temple IK, Gardner RJ, MacKay DJG, et al. Transient neonatal diabetes mellitus: widening our understanding of the aetiopathogenesis of diabetes. Diabetes 2000; 49:1359–1366.

    Article  PubMed  CAS  Google Scholar 

  5. Stoffers DA, Stanojevic V, Haberer JF. Insulin promoter factor-1 gene mutation gene linked to early-onset type 2 diabetes mellitus directions expression a dominant negative isoprotein. J Clin Invest 1998; 102:232–241.

    Article  PubMed  CAS  Google Scholar 

  6. Cowett RM, Farrag HM. Neonatal glucose metabolism. In: Cowett RM, ed. Principles of perinatal-neonatal metabolism. New York Springer—Verlag 1998:663.

    Chapter  Google Scholar 

  7. Humphrey RK, Smith MS, Tuch BE, et al. Regulation of the pancreatic cell differentiation and morphogenesis. Pediatric Diabetes 2002; 3:46–63.

    Article  PubMed  Google Scholar 

  8. Sander M, German MS. The beta cell transcription factors and development of the pancreas. J Mol Med 1997; 75:327–340.

    Article  PubMed  CAS  Google Scholar 

  9. Kemp DM, Thomas MK, Habener JF. Developmental aspects of the endocrine pancreas. Reviews in Endocrine and Metabolic Disorders, in press.

    Google Scholar 

  10. Stoffers DA, Zinkin NT, Stanojevic V, et al. Pancreatic agenesis attributable to a single nucleotide deletion in the human EPFI gene coding sequence. Nat Genet 1997; 1997:15–106.

    Google Scholar 

  11. Habener JF, Stoffers DA. A newly discovered role of transcription factors involved in pancreas development and the pathogenesis of diabetes mellitus. Proc Assoc Am Physicians 1998; 110:12–21.

    PubMed  CAS  Google Scholar 

  12. Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysioloyg of maturity-onset diabetes of the young. NEJM 2001; 345:971–980.

    Article  PubMed  CAS  Google Scholar 

  13. Njolstad PR, Sovik O, Cuesta-Munoz A, et al. Neonatal diabetes mellitus due to complete glucokinase deficiency. NEJM 2001; 344:1588–1592.

    Article  PubMed  CAS  Google Scholar 

  14. Arava Y, Adamsky K, Ezerzer C, et al. Specific gene expression in pancreatic beta cells cloning and characterization of differentially expressed genes. Diabetes 1999; 48:552 – 556.

    Article  PubMed  Google Scholar 

  15. Jiang FX, Cram DS, DeAizpurua HJ, et al. Laminin-1 promotes differentiation of fetal mouse pancreatic beta-cells. Diabetes 1999; 48:772 –730.

    Google Scholar 

  16. Yamaoka T, Itakura M. Development of pancreatic islets. In J Mol Med 1999; 3:247–261.

    CAS  Google Scholar 

  17. Menon RK, Sperling MA. Carbohydrate metabolism is neonatal adaptation: the transition to post-natal life. Semin Perinatol 1988; 12:157–162.

    PubMed  CAS  Google Scholar 

  18. Pagliara AS, Karl IE, Kipnis DB. Transient neonatal diabetes: delayed maturation of the pancreatic beta-cell. J Pediatr 1973; 82:97–101.

    Article  PubMed  CAS  Google Scholar 

  19. Chemausek SD, Beach DC, Banach W, et al. Characteristics of hepatic receptors for somatomedin-C/insulin-like growth factor-1 and insulin in the developing human. J Clin Endocrinol Metab 1987; 64:737 –743.

    Article  PubMed  Google Scholar 

  20. Menon RK, Chemausek SF, Sperling MA. Ontogeny of insulin-like growth factor 1 and insulin receptor kinase activity in rat liver. J Dev Physiology 1991; 16:87 – 97

    Google Scholar 

  21. Sperling MA, Ganguli S. Pre and post-natal development of insulin glucagon receptors: potential role in energy storage and utilization. J Pediatr Gastroenterol Nutr 1983;2[Suppl 1]:S46–S51.

    Article  PubMed  Google Scholar 

  22. Menon RK, Sperling MA. Insulin as a growth factor. Endocrinol Metab Clin North Am 1997; 25:633–647.

    Article  Google Scholar 

  23. Ferguson AW, Milner RDG. Transient neonatal diabetes mellitus in sibs. Arch Dis Child 1970; 45:80–83.

    Article  PubMed  CAS  Google Scholar 

  24. Schiff D, Colle E, Stem L. Metabolic and growth patterns in transient neonatal diabetes NEJM 1972; 287:119–122.

    Article  PubMed  CAS  Google Scholar 

  25. Blethen SL, White NH, Santiago JV, et al. Plasma somatostatins, endogenous insulin secretions, and growth in transient neonatal diabetes mellitus. JCEM 1981; 52:144 –147.

    PubMed  Google Scholar 

  26. Salerno MC, Gasparini N, Sandomerico ML, et al. Two interesting cases of transient neonatal diabetes mellitus. Journal of Pediatric Endocrinology 1994; 7:47–52.

    Article  PubMed  CAS  Google Scholar 

  27. Longo N, Wang Y, Smith SA, et al. Genotype-phenotype correlation in inherited severe insulin resistance. Hum Mol Genet 2002; 11:1465–1475.

    Article  PubMed  Google Scholar 

  28. Coffey Jr. JD, Killelea DE. Transient neonatal diabetes mellitus in half sisters. A sequel Am J Dis Child 1982; 136:626–627.

    Google Scholar 

  29. Abramowicz MJ, Andriien M, Dupont E, et al. Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus. J Clin Invest 1994; 94:418–421.

    Article  PubMed  CAS  Google Scholar 

  30. Das S, Lese CM, Song M, et al. Partial paternal uniparental disomy of chromosome 6 in an infant with neonatal diabetes, microglossia, and craniofacial abnormalities. Am J Hum Genet 2000;57:1586–1591.

    Google Scholar 

  31. Gardner RJ, Robinson DO, Lamont L, et al. Paternal uniparental disomy of chromosome 56 and transient neonatal diabetes mellitus. Clin Genet 1998; 54:522–525.

    Article  PubMed  CAS  Google Scholar 

  32. Varrault A, Bilanges B, MacKay DJ, et al. Characterization of the methylation-sensitive promoter of the imprinted ZAC gene supports its role in transient neonatal diabetes mellitus. J Biol Chem 2001; 276:18653–18656.

    Article  PubMed  CAS  Google Scholar 

  33. Gardner RJ, MacKay DJG, Mungall AJ, et al. An imprinted locus associated with transient neonatal diabetes mellitus. Hum Mol Genet 2000; 9:589–596.

    Article  PubMed  CAS  Google Scholar 

  34. MacKay DJG, Coupe A-M, Shield JPH, et al. Relaxation of imprinted expression of ZAC and HYMAI in a patient with transient neonatal diabetes mellitus. Hum Genet 2002: 110:139–144.

    Article  PubMed  CAS  Google Scholar 

  35. Arima T, Drewell RA; Amey KL, et al. A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus. Hum Mol Genet 2001; 10:1475–1483.

    Article  PubMed  CAS  Google Scholar 

  36. Delepine M, Nicolino M, Barrett T, et al. EBF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat Genet 2000; 25:406–409.

    Article  PubMed  CAS  Google Scholar 

  37. Chatila TA, Blaeser F, Ho N, et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 2000; 106:R75–81.

    Article  PubMed  CAS  Google Scholar 

  38. Wildin RS, Ramsdell F, Peake J, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 2001; 27:18–20.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Sperling, M.A. (2003). Neonatal Diabetes. In: Menon, R.K., Sperling, M.A. (eds) Pediatric Diabetes. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0507-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0507-5_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5111-5

  • Online ISBN: 978-1-4615-0507-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics