Neonatal and very-early-onset diabetes mellitus
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
References (43)
- et al.
Neonatal diabetes mellitus: chromosomal analysis in transient and permanent cases
J Pediatr
(2002) - et al.
Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus
J Pediatr
(1999) - et al.
Glucose regulation of gene transcription
J Biol Chem
(2000) - et al.
Infancy-onset diabetes mellitus and multiple epiphyseal dysplasia
J Pediatr
(1972) - et al.
Perk is essential for translational regulation and cell survival during unfolded protein response
Mol Cell
(2000) - et al.
Diabetes mellitus and exocrine pancreatic dysfunction in Perk −/− mice reveals a role for translational control in secretory cell survival
Mol Cell
(2001) - et al.
Distinct neurological syndrome in two brothers with hyperuricaemia
Lancet
(1992) - et al.
Expression of neuronal traits in pancreatic beta cells
J Biol Chem
(1997) - et al.
Ultralente insulin treatment of transient neonatal diabetes mellitus
J Pediatr
(1996) - et al.
Long-term course of neonatal diabetes
N Engl J Med
(1995)