Elsevier

Seminars in Neonatology

Volume 9, Issue 1, February 2004, Pages 59-65
Seminars in Neonatology

Neonatal and very-early-onset diabetes mellitus

https://doi.org/10.1016/S1084-2756(03)00064-2Get rights and content

Abstract

Transient (TNDM) and permanent neonatal diabetes mellitus (PNDM) are rare conditions occurring in one in 400 000–500 000 live births. In TNDM, growth-retarded infants develop diabetes in the first few weeks of life only to go into remission in a few months with later relapse as permanent type 2 diabetes, often around the time of adolescence. We believe that pancreatic dysfunction in this condition is maintained throughout life with relapse initiated at times of metabolic stress such as puberty or pregnancy. The mechanisms involved in this rare condition may inform on fetal pancreatic development, islet cell physiology and predisposition to type 2 diabetes. In PNDM, insulin secretory failure occurs in the early postnatal period. A number of conditions are associated with PNDM, some of which have been elucidated at the molecular level. Insulin therapy is difficult to manage in the neonatal period, and in experienced hands, the insulin pump may provide a valuable tool to administer insulin.

Section snippets

‘Transient’ neonatal diabetes mellitus

TNDM is a developmental insulin production disorder that resolves postnatally. Between 50 and 60% of cases of NDM are transient.1, 2Intra-uterine growth retardation is usually present, and its high rate is in keeping with the crucial role of insulin in fetal growth, especially during the last trimester of pregnancy. Hyperglycaemia, failure to thrive and, in some cases, dehydration occur after birth. Insulin production is inadequate, requiring exogenous insulin therapy. Tests are negative for

Permanent neonatal diabetes mellitus

In our experience, PNDM is less common than TNDM. By definition, diabetes develops in the neonatal period and never goes into remission. There are no clinical features that can predict whether a neonate with diabetes but no other dysmorphology will eventually have PNDM or TNDM, although cases with PNDM do not always have intra-uterine growth retardation as is universally seen in the transient 6q phenotype6, 7(Table 2). Diabetes in infancy is nearly always unrelated to classical type 1 diabetes.

Management of insulin therapy in the neonatal period

Insulin therapy is crucial in NDM to obtain satisfactory weight gain and growth in these newborns with intra-uterine growth retardation. Sometimes glucose and caloric deprivation is instituted in these newborns in the face of hyperglycaemia to avoid insulin therapy. This leads to further difficulties in weight gain. In fact, high caloric intake should be maintained in these newborns and insulin therapy should be given. Although paediatricians face numerous difficulties in managing insulin

Conclusions

Neonatal diabetes is a very rare condition. However, it is probably of great relevance to our understanding of the causation of type 2 diabetes within the general population. We believe that these rare single gene disorders are natural models identifying new genes that might have relevance to type 2 diabetes. As already illustrated, the IPF-1 mutation is important in MODY 4 and in some familial forms of early-onset type 2 diabetes. In TNDM, Lindsay et al. demonstrated weak linkage of diabetes

Acknowledgements

We thank the non-profit organization Aide aux Jeunes Diabétiques (AJD) and Diabetes UK for its generous support. We thank our collaborators in the network ‘EURONEODIA’ dedicated to neonatal diabetes: Pr P. Czernichow, Paediatric Endocrinology and Dr H. Cavé, Genetic Biochemistry, Hôpital Robert Debré, Paris, France; Dr K. Temple, Wessex Clinical Genetics Service, Department of Human Genetics, Southampton University,Southampton, UK; Drs D. Mackay and D. Robinson, Wessex Regional Genetics

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